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YAMAMOTO MasaakiGraduate School of Medicine / Faculty of Medical SciencesAssistant Professor
Research activity information
■ Award- Jun. 2022 95th Japan Endocrine Society Meeting, Research Award
- Apr. 2018 91th Japan Endocrine Society Meeting, Young Investigator Award
- Mar. 2017 99th Annual Meeting of the Endocrine Society, Outstanding abstract award
- Jan. 2016 上原記念生命科学財団, 海外留学助成金リサーチフェローシップ
- Aug. 2014 公益財団法人 成長科学協会, 留学助成
- Jun. 2014 International Society of Endocrinology, International travel fellowship award
- Jun. 2013 95th Annual Meeting of the Endocrine Society, Featured Poster presentation
- Oct. 2012 The 6th International Congress of the GRS and IGF Society, Poster Prize
- Oct. 2012 The 6th International Congress of the GRS and IGF Society, Travel Grant
- Nov. 2011 38th Japan Neuroendocrine Society Meeting, Young Investigator Award
- Sep. 2011 Kobe University Graduate School of Medicine, Best Paper Award at 2011
- Oct. 2010 The 5th International Congress of the GRS and IGF Society, Travel Grant
- PURPOSE: Approximately 20% of pheochromocytomas are cystic in nature. However, research on the correlation between catecholamine and metanephrine fractions in cystic fluid and peripheral blood is limited. This study investigated the relationship between catecholamine fractions and their metabolites in peripheral blood and cystic fluid. METHODS: Five patients with pathologically diagnosed cystic pheochromocytomas were included in the analysis. Catecholamine fractions and their metabolites in the cystic fluid were measured. The relationship between phenylethanolamine N-methyltransferase (PNMT) expression in tumor tissues and catecholamine fractions of cystic fluid was also assessed. RESULTS: The elevated patterns of catecholamine and metanephrine fractions in the cystic fluid were consistent with those observed in the peripheral blood of two patients. However, in two other patients. discordance was observed, with normetanephrine predominance in the peripheral blood despite adrenaline/metanephrine and noradrenaline/normetanephrine elevations in the cystic fluid. Immunohistochemical analysis revealed that PNMT expression in tumor tissues and the elevated pattern of catecholamine fractions in the peripheral blood were consistent in all patients, except for one patient with non-elevated peripheral blood catecholamines. However, in cystic fluid, the predominantly catecholamine fraction did not consistently align with PNMT expression. CONCLUSION: In cystic pheochromocytoma, the elevation patterns of catecholamine fractions in cysts may not align with those in the peripheral blood and may differ relative to PNMT expression in tumor tissues.Apr. 2025, Journal of endocrinological investigation, English, International magazineScientific journal
- The use of asfotase alfa, a bone-targeted recombinant alkaline phosphatase (ALP) enzyme, for the treatment of adult-onset hypophosphatasia (HPP) remains controversial, particularly in patients without evident bone abnormalities. We report the case of a 41-year-old woman with a history of Graves' disease, who presented with progressive joint pain and severe fatigue. Despite the absence of bone lesions, the patient was diagnosed with HPP based on persistently low alkaline phosphatase levels, family history, and a novel heterozygous ALPL variant (p.Ala205Thr). Functional analysis revealed a dominant-negative effect for this variant. Her symptoms significantly interfered with her daily activities owing to uncontrolled pain and loss of motor function and were so exacerbated that high doses of acetaminophen and NSAIDs were ineffective. Treatment with asfotase alfa was initiated based on multidisciplinary team consensus. Within 3 months of treatment initiation, her pain improved significantly, as indicated by reduced scores on the visual analog scale from 6.6 to 0.9, and elimination of the need for analgesics. Additionally, her grip strength increased, and her urinary phosphoethanolamine levels and serum pyridoxal 5'-phosphate/pyridoxal ratio decreased from 90.4 to 57.8 μmol/g·creatinine and from 4.6 to 0.4, respectively. These improvements have been maintained for more than 2 years. This case highlights the potential of asfotase alfa in effectively alleviating symptoms in patients with adult-onset HPP without bone lesions, emphasizing the importance of patient selection and outcome monitoring. We also discuss the key considerations for future treatment, supported by a literature review of asfotase alfa in adult patients with HPP.Jan. 2025, Endocrine journal, English, Domestic magazineScientific journal
- INTRODUCTION: Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment but can give rise to immune-related adverse events such as ICI-related diabetes mellitus (DM). CASE PRESENTATION: We herein present the case of a 59-year-old Japanese man with malignant melanoma who developed ICI-related DM after 18 months of nivolumab treatment. He experienced marked hyperglycemia and diabetic ketoacidosis without a personal or family history of diabetes. Laboratory findings revealed initial preservation of insulin secretion but a rapid decline in C-peptide levels in the absence of islet autoantibodies. He was therefore diagnosed with ICI-related DM. This case fulfilled the criteria for fulminant type 1 DM but lacked the typical human leukocyte antigen alleles associated with conventional type 1 diabetes. No metastasis or morphological changes were apparent on CT scans of the pancreas, and magnetic resonance cholangiopancreatography did not show dilation or interruption of the main pancreatic duct. However, diffusion-weighted magnetic resonance imaging revealed high signal intensity with low apparent diffusion coefficient values in the pancreas, likely indicative of fibrosis or infiltration of inflammatory cells. DISCUSSION: This case underscores that ICI-related DM should be considered a potential immune-related adverse event as well as pointing to the benefit of diffusion-weighted imaging for assessment of pancreatic involvement at an early stage of the disease.Jan. 2025, Hormones (Athens, Greece), English, International magazineScientific journal
- PURPOSE: To elucidate the long-term efficacy and safety of growth hormone replacement therapy (GHRT) in Japanese patients with adult growth hormone deficiency (AGHD). METHODS: We conducted a retrospective study. A total of 110 patients with AGHD receiving GHRT were enrolled. Clinical and laboratory data were collected annually from the beginning of the study. Statistical analysis was performed using a linear mixed-effects model. RESULTS: Of all patients, 46.4% were males, 70.9% had adult-onset GHD, and follow-up was up to 196 months, with a median of 68 months. The insulin-like growth factor-1 standard deviation score increased after the start of GHRT and remained constant for more than 11 years. Seventeen patients were followed up for more than 11 years. The body mass index increased. Waist circumference decreased in the short term but increased in the long term. The diastolic blood pressure decreased 1-5 years after the start of GHRT, and the systolic blood pressure increased 11 years after GHRT. Moreover, a long-term decrease in low-density lipoprotein cholesterol, an increase in high-density lipoprotein cholesterol, and a decrease in aspartate aminotransferase and alanine aminotransferase levels were observed. The glycosylated hemoglobin level increased after 3 years. The bone mineral density in the lumbar spine and total hip increased significantly 3 years after the start of GHRT. Finally, the number of adverse events was eight. CONCLUSION: We demonstrated the metabolic effectiveness and safety of GHRT in Japanese patients with AGHD over a long follow-up period of 16 years.Corresponding, Sep. 2024, Pituitary, English, International magazineScientific journal
- Cushing's syndrome is characterized by chronic glucocorticoid oversecretion and diverse clinical manifestations. Distinguishing between adrenocorticotropic hormone (ACTH)-independent and ACTH-dependent forms is crucial for determining treatment options. Plasma ACTH levels aid in the differential diagnosis, with undetectable or low levels suggesting ACTH-independent hypercortisolemia. ACTH is derived from pro-opiomelanocortin, and its processing involves prohormone convertase 1/3. High-molecular-weight ACTH is generally found in ACTH-producing pituitary tumors and ectopic ACTH syndrome. The mechanism of negative feedback and the process of high-molecular-weight ACTH alternation during ACTH-independent Cushing's syndrome remain unclear. A 40-year-old woman with hypertension and multiple fractures developed symptoms suggestive of Cushing's syndrome. Computed tomography revealed a left adrenocortical tumor along with atrophy of the right adrenal gland. ACTH levels were undetectable at the previous clinic, indicating ACTH-independent Cushing's syndrome. However, subsequent measurements at our hospital revealed non-suppressed ACTH (18.1 pg/mL), prompting further investigation. Gel exclusion chromatography confirmed the presence of high-molecular-weight ACTH. Metyrapone treatment decreased the cortisol levels. In this situation, in which ACTH levels should be elevated, a decrease in high-molecular-weight ACTH levels was observed. Histological findings revealed cortisol-producing adenoma without ACTH expression. This case highlights the importance of assay differences in evaluating ACTH concentrations and introduces a novel finding of circulating high-molecular-weight ACTH. The observed decline in high-molecular-weight ACTH levels suggests a potential time lag in the negative feedback within the hypothalamic-pituitary-adrenal axis exhibited by glucocorticoids. This temporal aspect of the regulation of ACTH-related molecules warrants further exploration to enhance our understanding of the hypothalamic-pituitary-adrenal axis feedback mechanism.Aug. 2024, Journal of neuroendocrinology, e13438, English, International magazineScientific journal
- OBJECTIVE: To elucidate the fluctuations in glucose levels measured using CGM-metrics during the four distinct seasons of the year in individuals with type 1 diabetes mellitus (T1DM) using an intermittently scanned CGM (isCGM) device or sensor augmented pump (SAP). RESEARCH DESIGN AND METHODS: This retrospective, single-center study enrolled 93 individuals with T1DM who were equipped with an isCGM device or SAP at Kobe University Hospital. The subjects had a median age of 47.0 years [interquartile range, 37.0-62.0 years], 25 individuals (26.9%) were male, median body mass index was 22.0 kg/m2 [20.8-23.8 kg/m2], and median hemoglobin A1c level was 7.4% [6.9-8.0%]. CGM data were reviewed from January to December 2019, and the mean sensor glucose (SG) value, time above range (TAR), time in range (TIR), time below range (TBR), and standard deviation (SD) of SG were calculated for each season (spring, March-May; summer, June-August; autumn, September-November; winter, December-February). RESULTS: Seasonal fluctuations were detected for mean SG, TAR, TIR, and SD, with TIR being lower and mean SG, TAR, and SD being higher in cold seasons (spring or winter) than in warm seasons (summer or autumn). CONCLUSION: Seasonal fluctuations in CGM metrics should be taken into account in future studies performed to evaluate the favorable impact of CGM on glycemic management in individuals with T1DM.Jul. 2024, Endocrine, English, International magazineScientific journal
- SUMMARY: A 52-year-old female patient with breast cancer presented with a history of fatigue and malaise 1 year prior. She was diagnosed with isolated adrenocorticotropic hormone (ACTH) deficiency (IAD) on endocrinological examination. Her pituitary gland showed normal morphology. Paraneoplastic IAD associated with breast cancer was suspected; however, immunofluorescence staining revealed no ectopic ACTH or proopiomelanocortin expression in the tumor tissue. Subsequently, the patient was diagnosed with idiopathic acquired IAD concurrent with breast cancer, ruling out paraneoplastic syndrome. Although malignancy should be considered a potential cause of IAD, not all patients with concurrent IAD and malignancy necessarily develop paraneoplastic syndrome. LEARNING POINTS: Several adrenal insufficiency symptoms are similar to the nonspecific symptoms associated with malignancies, and therefore, the diagnosis of IAD remains challenging, especially in patients with cancer. When we encounter a case of IAD accompanied by a malignant tumor, it is important to suspect that paraneoplastic IAD, a novel clinical condition as secondary hypophysitis, may be the etiologic agent. Although malignant tumours should be considered a potential cause of IAD, not all patients with concurrent IAD and malignancy necessarily develop paraneoplastic autoimmune hypophysitis.Jul. 2024, Endocrinology, diabetes & metabolism case reports, 2024(3) (3), English, International magazineScientific journal
- PURPOSE: Early diagnosis and immediate treatment of Cushing's syndrome (CS) are critical for a better prognosis but remain a challenge. However, few comprehensive reports have focused on this issue or investigated whether patient-reported manifestations are consistent with physician-assessed symptoms of CS. This study aimed to clarify the differences in patient-reported and physician-assessed manifestations of signs and symptoms of CS that prevent early diagnosis. METHODS: This single-center retrospective study included 52 patients with CS (16 with Cushing's disease and 36 with adrenal CS). Upon clinical diagnosis, medical records were used to independently review the patient-reported and physician-assessed manifestations of typical (such as purple striae and proximal myopathy) and nonspecific features (such as hirsutism and hypertension). The correlations and differences between the patient-reported and physician-assessed manifestations were then analyzed. RESULTS: We observed a positive correlation between the total number of manifestations of nonspecific features reported by patients and those assessed by physicians, but not for typical features. Moreover, manifestations reported by the patients were less frequent than those assessed by physicians for typical features, leading to discrepancies between the two groups. In contrast, there were no differences in most nonspecific features between the patient-reported and physician-assessed manifestations. Notably, the concordance between patient-reported and physician-assessed manifestations of typical features was not associated with urinary free cortisol levels. CONCLUSION: Regardless of disease severity, patients often do not complain of the typical features of CS that are crucial for formulating a diagnosis.Jun. 2024, Endocrine, English, International magazineScientific journal
- Orthostatic hypotension (OH) is a common condition. Many potential etiologies of OH have been identified, but in clinical practice the underlying cause of OH is often unknown. In the present study, we identified a novel and extraordinary etiology of OH. We describe a first case of acquired severe OH with syncope, and the female patient had extremely low levels of catecholamines and serotonin in plasma, urine and cerebrospinal fluid (CSF). Her clinical and biochemical evidence showed a deficiency of the enzyme aromatic l-amino acid decarboxylase (AADC), which converts l-DOPA to dopamine, and 5-hydroxytryptophan to serotonin, respectively. The consequence of pharmacologic stimulation of catecholaminergic nerves and radionuclide examination revealed her catecholaminergic nerves denervation. Moreover, we found that the patient's serum showed presence of autoantibodies against AADC, and that isolated peripheral blood mononuclear cells (PBMCs) from the patient showed cytokine-induced toxicity against AADC. These observations suggest that her autoimmunity against AADC is highly likely to cause toxicity to adrenal medulla and catecholaminergic nerves which contain AADC, resulting in hypocatecholaminemia and severe OH. Administration of vitamin B6, an essential cofactor of AADC, enhanced her residual AADC activity and drastically improved her symptoms. Our data thus provide a new insight into pathogenesis and pathophysiology of OH.Jun. 2024, Biochemical and biophysical research communications, 714, 149940 - 149940, English, International magazineScientific journal
- BACKGROUND: A patient with systemic lupus erythematosus (SLE) suffered from acquired thyroid-stimulating hormone (TSH), luteinizing hormone (LH), and follicle-stimulating hormone (FSH) deficiencies. MRI findings revealed a slight atrophy of the pituitary gland. Further, the serum concentration of the covalent alpha subunit (glycoprotein hormones alpha chain [CGA]) in TSH-, LH-, and FSH-positive cells was below the detectable range. Because SLE is an autoimmune disorder, autoimmunity against the pituitary gland was suspected as the cause of pituitary deficiency. METHODS AND RESULTS: Immunofluorescence analysis showed that the patient's immunoglobulin G recognized CGA-positive cells in the pituitary gland; therefore, autoimmunity against CGA-positive cells may have caused TSH, LH, and FSH deficiencies in this patient. Moreover, cell-specific autoimmunity impairs pituitary hormone levels. Further research is required to clarify whether acquired TSH, LH, and FSH deficiencies are common in patients with SLE or other autoimmune diseases. CONCLUSION: Our findings highlight a unique case of acquired TSH, LH, and FSH deficiencies caused by circulating anti-CGA-positive cell antibodies, introducing a novel clinical concept of acquired hypopituitarism.Lead, Jun. 2024, Endocrine, English, International magazineScientific journal
- Anti-pituitary-specific transcription factor-1 (PIT-1) hypophysitis, a paraneoplastic syndrome resulting from an autoimmune response against PIT-1, typically manifests with undetectable levels of growth hormone (GH) and prolactin (PRL), and significantly low levels of serum thyroid-stimulating hormone (TSH) at diagnosis. These hormonal levels are highly specific to this disease and serve as key diagnostic indicators. Herein, we present a detailed clinical course of a 69-year-old male with a history of gastric cancer and lymph node metastases who developed anti-PIT-1 hypophysitis after the initiation of immune checkpoint inhibitor (ICI) therapy, specifically nivolumab, oxaliplatin, and capecitabine. The patient was referred to our department owing to decreased TSH, free triiodothyronine (T3), and free thyroxine (T4) levels after two doses of nivolumab. Initially suspected as central hypothyroidism due to ICI-related hypophysitis, further assessment confirmed the diagnosis of anti-PIT-1 hypophysitis. Notably, GH, PRL, and TSH levels markedly declined, leading to complete deficiencies 2 months after the first nivolumab dose-a pattern consistent with that of previous cases of anti-PIT-1 hypophysitis. Therefore, this report not only presents an atypical subset of ICI-related hypophysitis but also delineates the process of hormone impairment leading to complete deficiencies in anti-PIT-1 hypophysitis. This case highlights the importance of vigilant monitoring for endocrine issues in patients undergoing ICI therapy, given the escalating incidence of immune-related adverse events associated with the extensive use of ICI therapy for various cancers.Apr. 2024, Journal of neuroendocrinology, e13395, English, International magazineScientific journal
- INTRODUCTION: Levels of serum selenium (Se) and zinc (Zn) decrease when total parental nutrition (TPN) is administered without trace element supplementation for just a few weeks. These trace elements are involved in thyroid hormone metabolism and their deficiencies cause thyroid dysfunction. However, there have been few reports on the details of its clinical course. CASE PRESENTATION: A 50-year-old man presented with thyroid dysfunction due to Se and Zn deficiency. He had an approximately 70-cm residual small intestine after undergoing intestinal resection and he received TPN without trace element supplementation for one and a half months. Blood tests revealed high levels of thyroid-stimulating hormone (TSH) and free thyroxine (FT4) and low levels of free triiodothyronine (FT3). An abnormal pattern of thyroid function led to suspicion of Se deficiency. Se supplementation raised FT3 levels and lowered FT4 levels to within their respective reference ranges; however, subclinical hypothyroidism persisted with transient TSH elevation. We suspected that Zn deficiency also contributed to the hypothyroidism and, therefore, initiated Zn supplementation, which resulted in normalization of thyroid function. DISCUSSION: Although thyroid dysfunction has been reported in many studies conducted on Se and Zn deficiencies, hormonal patterns vary between reports. Further accumulation of cases, including detailed data on nutritional status, would be of benefit to elucidate the clinical reality. CONCLUSION: It is important to consider Se and Zn deficiencies when TSH and FT4 levels are elevated. It should also be noted that transient TSH elevation may be observed with Se supplementation.Apr. 2024, Hormones (Athens, Greece), English, International magazineScientific journal
- Immune checkpoint inhibitor (ICI)-related hypophysitis (RH) is a common immune-related adverse event. The early detection of ICI-RH prevents life-threatening adrenal insufficiency. However, good predictors of secondary adrenal insufficiency in ICI-RH have not yet been reported. We hypothesized that fluctuations in serum adrenocorticotropic hormone (ACTH) and cortisol levels occur similarly to those in thyroid-stimulating hormone and thyroid hormone (thyroxine and triiodothyronine) levels in ICI-related thyroiditis. Here, we sought to test this hypothesis. Patients who used ICI and had a history of measurement of serum ACTH and cortisol concentrations were retrieved from electronic medical records, and those with a history of glucocorticoid use were excluded from the analysis. We evaluated fluctuations in serum ACTH and cortisol concentrations and the development of ICI-RH. For patients with ICI-RH, data at three points (before ICI administration (pre), maximum ACTH concentration (peak), and onset of ICI-RH) were analyzed to evaluate hormone fluctuations. A total of 202 patients were retrieved from the medical record. Forty-three patients were diagnosed with ICI-RH. Twenty-six out of 43 patients had sufficient data to evaluate fluctuations in serum ACTH and cortisol concentrations and no history of glucocorticoid use. ACTH concentrations changed from 37.4 (29.9-48.3) (pre) to 64.4 (46.5-106.2) (peak) pg/mL (1.72-fold increase, p=0.0026) in the patients with ICI-RH before the onset. There were no differences in cortisol concentrations between the pre and peak values in patients with ICI-RH. We also evaluated the fluctuations in serum ACTH and cortisol levels in patients who did not receive ICI-RH (62 cases). However, elevation of serum ACTH levels was not observed in patients without ICI-RH, suggesting that transient elevation of serum ACTH levels is a unique phenomenon in patients with ICI-RH. In conclusion, serum ACTH levels were transiently elevated in some patients with ICI-RH before the onset of secondary adrenal insufficiency. Monitoring the ACTH levels and their fluctuations may help predict the onset of ICI-RH.Feb. 2024, Journal for immunotherapy of cancer, 12(2) (2), English, International magazineScientific journal
- BACKGROUND: Corticotrophs are susceptible to lymphocyte cytotoxicity, as seen in hypophysitis, suggesting that an immunological approach may be a potential strategy for corticotroph-derived tumors. OBJECTIVES: We aimed clarify whether corticotroph tumors that induce hypercortisolemia (ACTHomas) could be targets for immunotherapy. METHODS: Tumor-infiltrating immune cells were immunohistochemically analyzed. ACTHomas (Naïve: ACTHomas without preoperative treatment) were compared with other pituitary tumors, and further divided into three different cortisol-exposed milieus: Naïve, Met (ACTHomas with preoperative metyrapone), and SCA (silent corticotroph adenomas). A three-dimensional cell culture of resected tumors was used to analyze the effects of immune checkpoint inhibitors. RESULTS: The number of tumor-infiltrating lymphocytes (TILs) was low in ACTHomas. Among these, the number of CD8+ cells was lower in ACTHomas than in both somatotroph) and gonadotroph tumors (P < 0.01 and P < 0.01, respectively). Then we compared the differences in TILs among Naïve, Met, and SCA. The number of CD4+ cells, but not CD8+ cells, was higher in both Met and SCA than in Naïve. Next, we investigated tumor-associated macrophages, which could negatively affect T cell infiltration. The numbers of CD163+ and CD204+ cells were positively associated with cortisol levels. Moreover, tumor size was positively correlated with the number of CD204+ cells. CONCLUSIONS: We found the possibility that ACTHomas were immunologically cold in a cortisol-independent manner. In contrast, the tumor infiltration of CD4+ cells and M2-macrophages were associated with the cortisol milieu. Future studies are needed to validate these results and develop effective immunotherapy while considering the cortisol milieu.Feb. 2024, Endocrinology, English, International magazineScientific journal
- PURPOSE: Preoperative medical management is critical to prevent intraoperative cardiovascular complications in patients with pheochromocytomas and paragangliomas (PPGLs). Initial treatment involves α-adrenergic receptor blockers. However, while the routine use of metyrosine alongside these blockers is not strongly recommended due to a lack of evidence supporting its efficacy and associated safety concerns, there are previous studies on combination therapy with phenoxybenzamine and metyrosine. There are few reports on combination therapy with the selective α1-adrenergic receptor blocker doxazosin. Therefore, we investigated this combination treatment, which theoretically can affect perioperative outcomes in patients with PPGLs. To our knowledge, this is the first such study. METHODS: This retrospective single-center observational study involved 51 patients who underwent surgical resection of PPGLs at Kobe University Hospital between 2014 and 2022. All patients received doxazosin at maximum doses. Fourteen patients received concomitant metyrosine, while 37 received doxazosin alone. Their perioperative outcomes were compared. RESULTS: No severe event, such as acute coronary syndrome, was observed in either group. Intraoperatively, the doxazosin + metyrosine group exhibited a lower median minimum systolic blood pressure (56 [54-60] vs. 68 [59-74] mmHg, P = 0.03) and required lower median remifentanil (P = 0.04) and diltiazem (P = 0.02) doses than the doxazosin-alone group. CONCLUSION: The combination of metyrosine and doxazosin as a preoperative treatment for PPGLs affects intraoperative circulatory hemodynamics, such as a reduced occurrence of blood pressure elevation during surgery. Further research is necessary to identify patients who will benefit most from this combination treatment.Corresponding, Jan. 2024, Endocrine, English, International magazineScientific journal
- Metyrapone is commonly used in the initial management of Cushing's syndrome to reduce hypercortisolemia, but its optimal dosage and timing can vary significantly between patients. Currently, there are limited guidelines on adjustment methods for its administration to individual needs. This study aimed to evaluate responsiveness of each patient to metyrapone and identify the patient characteristics associated with the indices of cortisol responsiveness following a low-dose metyrapone. This single-center retrospective observational study included 15 treatment-naïve patients, 7 of whom had Cushing's disease and 8 had adrenal Cushing's syndrome. Serum cortisol levels were measured hourly from the time of administration of 250 mg of metyrapone up to four hours afterward. Parameters analyzed included the nadir of serum cortisol levels (Fnadir), the difference between basal and nadir serum cortisol levels (ΔF), the time to nadir, and the characteristics of the patients. As a result, cortisol suppression curves showed significant variability among patients, particularly in the time to nadir. While the median time to nadir was 2 hours, 20% of patients required 4 hours or more, and these responses were not associated with patient characteristics. Fnadir was positively correlated with early-morning serum cortisol levels, serum cortisol levels after low-dose dexamethasone suppression test (LDDST), and urinary free cortisol (UFC) levels, whereas ΔF was positively correlated with late-night serum cortisol levels, serum cortisol levels after LDDST, and UFC levels. In conclusion, the duration of response to metyrapone appeared unpredictable in patients with Cushing's syndrome and did not correlate with patient characteristics at baseline. Tracking the effect of metyrapone following a single low-dose administration may explain this variability and provide insights for optimizing individual dosing regimens. Further studies are required to validate these findings and guide more personalized treatment adjustments.2024, Frontiers in endocrinology, 15, 1511155 - 1511155, English, International magazineScientific journal
- We present a case of type 1 diabetes mellitus (T1DM) that developed in a 53-year-old man after long-term treatment with nivolumab. The patient underwent total gastrectomy for gastric cancer at 40 years of age, and he was started on nivolumab at age 48 years for treatment of a recurrent lesion that proved resistant to standard chemotherapy. Nivolumab treatment resulted in complete response, but, after the 136th infusion of the drug at age 53 years, the patient was hospitalized for sudden onset of diabetic ketoacidosis. He was diagnosed with immune checkpoint inhibitor-induced T1DM (ICI-DM), which developed 1988 days (284 weeks) after initiation of nivolumab. HLA typing revealed disease susceptibility alleles for both fulminant T1DM and ICI-DM. With the increased survival after the ICI treatment, delayed-onset irAEs after long-term use of ICI have been reported; however, delayed-onset ICI-DM remains to be elucidated. This case provides important insight into ICI-DM that develops after prolonged ICI administration, and it suggests that patients should be monitored for ICI-DM regardless of the duration of ICI therapy.Jan. 2024, Diabetology international, 15(1) (1), 130 - 134, English, Domestic magazine
- The pathogenesis of anti-pituitary-specific transcription factor 1 (PIT-1) hypophysitis was gradually revealed as cases emerged. Our comprehensive analysis, including all reported cases, identified a new instance of anti-PIT-1 hypophysitis post-immune checkpoint inhibitor therapy. All nine patients exhibited extremely low GH, PRL, and TSH levels; two had a slightly atrophic pituitary gland; four had thymoma, and five had malignant neoplasms of diffuse large B-cell lymphoma (DLBCL) and other origins. Patients with thymoma showed multiple autoimmune diseases. HLA-A*24:02 and/or A*02:06 were present in six and DR53 in five cases analyzed. High anti-PIT-1 antibody titers and ectopic PIT-1 expression in the cytosol and nucleus of the tumor tissues were observed in patients with thymoma or DLBCL, whereas it was exclusively observed in the nuclei of a bladder cancer patient. These findings provide new insights into the pathophysiology of paraneoplastic autoimmune hypophysitis.Dec. 2023, European journal of endocrinology, English, International magazineScientific journal
- PURPOSE: Predicting the therapeutic effects of first-generation somatostatin receptor ligands (fg-SRLs) is important when assessing or planning effective treatment strategies in patients with acromegaly. The oft-used maximum growth hormone (GH) suppression rate parameter of the octreotide test has a suboptimal predictive value. Therefore, this study explored newer parameters of the octreotide test for predicting the therapeutic effect of long-acting fg-SRLs. METHODS: In this single-center retrospective study, the octreotide test parameters and the therapeutic effects of fg-SRL at 3 months were investigated in 45 consecutive treatment-naïve patients with acromegaly between April 2008 and March 2023. Additionally, the relationship between the octreotide test parameters and the therapeutic effects of fg-SRLs was investigated. Tumor shrinkage was evaluated based on changes in the longitudinal diameter of the macroadenomas. The area GH suppression rate-time under the curve (AUC) and the time to nadir GH level were calculated and compared with the maximum GH suppression rate. RESULTS: The AUC estimated reductions in serum insulin-like growth factor I, and tumor shrinkage. The time to nadir GH level predicted tumor shrinkage more robustly than the maximum GH suppression rate in patients with macroadenoma. CONCLUSION: The AUC and time to nadir GH level may potentially be newer parameters of the octreotide test for estimating the therapeutic effect of fg-SRLs.Corresponding, Nov. 2023, Pituitary, English, International magazineScientific journal
- Pheochromocytomas and paragangliomas (PPGLs) are rare tumors that secrete catecholamines and arise from the adrenal medulla or extra-adrenal sympathetic ganglia. These tumors secrete adrenaline and noradrenaline, but paragangliomas usually produce only noradrenaline because of the lack of phenylethanolamine N-methyltransferase (PNMT) expression. Composite paragangliomas, which are complex tumors consisting of multiple types of neuroblastic cells, are extremely rare. We present the case of a 46-year-old woman with an atypical catecholamine profile who was preoperatively diagnosed with pheochromocytoma. However, postoperative pathology revealed that the patient had an extra-adrenal paraganglioma accompanied by a ganglioneuroma, which led to the diagnosis of a composite tumor. Interestingly, PNMT is expressed in both paragangliomas and ganglioneuromas. In addition, we reviewed reported composite paragangliomas and compared their clinical features with those of composite pheochromocytomas. We also discuss various aspects of the etiology of composite paragangliomas and the mechanism by which PNMT is expressed in tumors.Corresponding, Nov. 2023, Endocrine journal, English, Domestic magazineScientific journal
- GH activates GH receptors, which activates IGF-1 in the liver through a cascade of processes. The GH/IGF-1 axis plays an important role in the regulation of metabolism. Insufficient GH secretion results in short stature in childhood, while adult GH deficiency (AGHD) is observed in adulthood. The early diagnosis of AGHD is important for early initiation of GH replacement therapy. This review described the regulatory mechanisms of GH signaling based on nutritional status and a novel disease concept pathogenesis that causes AGHD. GH-dependent IGF-1 production in the liver is regulated by a complex interplay between nutritional status, hormones, and growth factors. GH resistance is an adaptive response that enhances survival during starvation and malnutrition. Sirtuin 1 (SIRT1) negatively regulates GH-induced IGF-I production in the liver by directly inhibiting STAT5 activation, which causes GH resistance under starvation and malnutrition. The presence of autoantibodies is strongly associated with the disruption of immune tolerance in pituitary cells. Pituitary-specific transcription factors (PIT-1) are essential for the development, differentiation, and maintenance of GH, PRL, and TSH producing cells. However, the underlying mechanism that causes immune intolerance to PIT-1 remain unclear. The GH-IGF-1 system plays a pivotal role in growth, and the involvement of SIRT1 in this regulatory mechanism presents an intriguing perspective on the interplay between nutrient metabolism and lifespan. The discovery of the anti-PIT-1 pituitary antibody, a novel disease concept associated with AGHD, has provided valuable insights, which serves as a significant milestone towards unraveling the complete pathogenesis of the disease.Aug. 2023, Endocrine journal, English, Domestic magazine[Refereed][Invited]Scientific journal
- OBJECTIVE: Thyroid-stimulating hormone (TSH) harmonization is effective in minimizing differences between the results of immunoassays in healthy subjects. However, the effectiveness of TSH harmonization in clinical practice has not been investigated. The aim of this study was to evaluate the instability of TSH harmonization in clinical practice. METHODS: We compared the reactivities of four harmonized TSH immunoassays using combined difference plots of 431 patients. We selected patients with statistically significant deviations in TSH levels and analyzed their thyroid hormone levels and clinical characteristics. RESULTS: The combined difference plots showed that one harmonized TSH immunoassay exhibited markedly different reactivity even after TSH harmonization compared with the other three immunoassays. Among 109 patients with mild-to-moderate elevation of TSH levels, we selected 15 patients with statistically significant deviations in TSH levels according to the difference plots of three harmonized TSH immunoassays, excluding one immunoassay that showed different reactivity. The thyroid hormone levels of three patients were misclassified as hypothyroidism or normal due to deviating TSH levels. In terms of clinical characteristics, these patients were in poor nutritional status and general condition, possibly due to their severe illness (e.g., advanced metastatic cancer). CONCLUSION: We have confirmed that TSH harmonization in clinical practice is relatively stable. However, some patients showed deviating TSH levels in the harmonized TSH immunoassays, indicating the need for caution, particularly in poorly nourished patients. This finding suggests the presence of factors that contribute to the instability of TSH harmonization in such cases. Further investigation is warranted to validate these results.Jun. 2023, Clinical endocrinology, English, International magazineScientific journal
- CONTEXT: The COVID-19 pandemic challenged undertaking gradual educational activities for residency and fellowship trainees. However, recent technological advances have enabled broadening active learning opportunities through international online conferences. OBJECTIVE: The format of our international online endocrine case conference, launched during the pandemic, is introduced. The objective impact of this program on trainees is described. METHODS: Four academic facilities developed a semiannual international collaborative endocrinology case conference. Experts were invited as commentators to facilitate in-depth discussion. Six conferences were held between 2020 and 2022. After the fourth and sixth conferences, anonymous multiple-choice online surveys were administered to all attendees. RESULTS: Participants included trainees and faculty. At each conference, 3 to 5 cases of rare endocrine diseases from up to 4 institutions were presented, mainly by trainees. Sixty-two percent of attendees reported 4 facilities as the appropriate size for the collaboration to maintain active learning in case conferences. Eighty-two percent of attendees preferred a semiannual conference. The survey also revealed the positive impact on trainees' learning regarding diversity of medical practice, academic career development, and confidence in honing of presentation skills. CONCLUSION: We present an example of our successful virtual global case conference to enhance learning about rare endocrine cases. For the success of the collaborative case conference, we suggest smaller cross-country institutional collaborations. Preferably, they would be international, semiannually based, and with recognized experts as commentators. Since our conference has engendered multiple positive effects on trainees and faculty, continuation of virtual education should be considered even after the pandemic era.Feb. 2023, Journal of the Endocrine Society, 7(4) (4), bvad023, English, International magazineScientific journal
- CONTEXT: The occurrence of multiple endocrinopathies due to immune checkpoint inhibitors (ICIs) is a relatively common adverse event. However, the occurrence of a combination of hypophysitis and type 1 diabetes mellitus (T1DM) is extremely rare, and its clinical features are unclear. OBJECTIVE: We comparatively analyzed the clinical features of this combination and each individual ICI-induced endocrinopathy. METHODS: We reported 3 cases that we encountered and reviewed previously reported cases of patients with combined hypophysitis and T1DM due to ICIs. RESULTS: Anti-programmed cell death-1 (anti-PD-1) antibodies were prescribed to all 3 cases. The duration from ICI initiation to the onset of endocrine disease was 12 to 48 weeks. Several human leukocyte antigen (HLA) haplotypes that have disease susceptibility to hypophysitis were detected in all 3 patients. With the 17 previously reported cases, combined endocrinopathies were more common in men (85%). The onset age was in the 60s for both combined and single endocrinopathies. Anti-PD-1 antibodies were used in most of the cases (90%). The time from ICI initiation to the onset of endocrinopathies was 24 (8-76) weeks for hypophysitis and 32 (8-76) weeks for T1DM in patients with combined endocrinopathies, which was not significantly different from that for each single endocrinopathy. CONCLUSION: We presented 3 cases of patients with combined endocrinopathies of hypophysitis and T1DM that may have been caused by anti-PD-1 antibodies. There was no difference in the time from ICI initiation to the onset of endocrinopathies between combined and single endocrinopathies. Further case accumulation and pathogenic investigations are required.Jan. 2023, Journal of the Endocrine Society, 7(3) (3), bvad002, English, International magazineScientific journal
- INTRODUCTION: A recently discovered facet of paraneoplastic adrenocorticotropic hormone (ACTH) deficiency exists in two forms: a paraneoplastic spontaneous isolated ACTH deficiency (IAD) and an immune checkpoint inhibitor (ICI)-related hypophysitis. Autoantibodies against corticotrophs, such as circulating anti-proopiomelanocortin (POMC) antibodies are considered disease markers. However, the number of identified cases was limited, implying that the characteristics of these autoantibodies are not fully understood. METHODS: We investigate circulating autoimmune autoantibodies in detail through a novel case of IAD that developed as a paraneoplastic autoimmune ACTH deficiency. RESULTS: The patient developed IAD after 25 weeks of ICI therapy for metastasis of large-cell neuroendocrine carcinoma at 69 years of age. Ectopic ACTH expression and infiltration of CD3+, CD4+, CD8+, and CD20+ lymphocytes were observed in the tumor tissues and circulating anti-POMC antibodies were detected specifically in the patient's serum. Moreover, detailed analyses of immunofluorescence staining using patient serum revealed that the recognition site of the autoantibody was ACTH25-39, which had not been identified in previous cases of paraneoplastic autoimmune ACTH deficiency. CONCLUSION: This case involved a combination of paraneoplastic spontaneously acquired IAD and ICI-related hypophysitis occupying the middle ground. Moreover, our study reveals new aspects of anti-POMC antibodies in patients with paraneoplastic ACTH deficiency. This report expands our understanding of the immunological landscape and provides new insights for the identification of antibodies associated with paraneoplastic autoimmune ACTH deficiency.2023, Frontiers in immunology, 14, 1284301 - 1284301, English, International magazineScientific journal
- 2023, 月刊糖尿病・内分泌代謝科, 57(3) (3)Adult growth hormone deficiency.
- Pheochromocytoma is a rare but life-threatening condition due to catecholamine release induced by drug treatments such as β-blockers or glucocorticoids. We present a case of hypertensive crisis due to pheochromocytoma, induced after the initiation of dexamethasone and landiolol during intensive care for severe coronavirus disease 2019 (COVID-19). Based on a detailed medical history review, the patient was previously diagnosed with primary aldosteronism by confirmatory tests, moreover, an abdominal computed tomography scan identified an adrenal tumor 2 years before current admission. We tentatively diagnosed the patient with pheochromocytoma and initiated α-blockers without conducting a catecholamine report, leading to stable hemodynamics. We present a successfully managed case of pheochromocytoma concomitant with COVID-19, which has become a global crisis.Corresponding, Nov. 2022, Endocrine journal, English, Domestic magazineScientific journal
- Nov. 2022, The American journal of medicine, English, International magazine
- There is uncertainty regarding the need for COVID-19 peri-vaccination glucocorticoid coverage in patients with adrenal insufficiency. In this survey conducted in a single tertiary medical institution, 167 consecutive outpatients taking physiological glucocorticoids because of adrenal insufficiency were included. The patients declared if they developed an adrenal crisis after vaccination, and the amount and duration of an increase in their glucocorticoid dosage, if any. None of the patients without preventive glucocorticoid increase suffered an adrenal crisis after COVID-19 vaccination. Only 8.3% (14 cases) and 27.5% (46 cases) of the patients needed to escalate the dose of glucocorticoids when systemic symptoms appeared after the first and second injections, respectively. Glucocorticoids were increased in patients <60 years of age more than in patients ≥60 years of age at the time of both the first (p = 0.026) and second injections (p = 0.005). Sex and the causes of adrenal insufficiency were not associated with the frequency of the patients who needed glucocorticoid dose escalation. In the cases with increased glucocorticoids, the median dosage for escalation was 10 mg (hydrocortisone equivalent). In conclusion, even without prophylactic glucocorticoid administration, adrenal crisis did not occur during the peri-COVID-19 vaccination period. The dose escalation of steroid was more frequent in younger patients following the second vaccination. Careful monitoring of adverse effects and the appropriate management of glucocorticoids when necessary are essential following COVID-19 vaccinations.Sep. 2022, Endocrine journal, 70(1) (1), 89 - 95, English, Domestic magazineScientific journal
- Lead, (有)科学評論社, Sep. 2022, 糖尿病・内分泌代謝科, 55(3) (3), 327 - 332, JapaneseGH産生下垂体腺腫
- Acromegaly is caused by excessive secretion of GH and IGF-I mostly from somatotroph tumors. Various genetic and epigenetic factors are involved in the pathogenesis of somatotroph tumors. While somatic mutations of GNAS are the most prevalent cause of somatotroph tumors, germline mutations in various genes (AIP, PRKAR1A, GPR101, GNAS, MEN1, CDKN1B, SDHx, MAX) are also known as the cause of somatotroph tumors. Moreover, recent findings based on multiple perspectives of the pangenomic approach including genome, transcriptome, and methylome analyses, histological characterization, genomic instability, and possible involvement of miRNAs have gradually unveiled the whole landscape of the underlying mechanisms of somatotroph tumors. In this review, we will focus on the recent advances in genetic and epigenetic pathogenesis of somatotroph tumors.Aug. 2022, Cancers, 14(16) (16), English, International magazine[Invited]Scientific journal
- Coronavirus disease 2019 (COVID-19) is associated with endocrine disorders, but their long-term clinical course remains unclear. We here report the 15-month clinical course for an individual with multiple endocrine disorders of the pituitary gland and testis likely triggered by COVID-19. A 65-year-old man with no history of endocrinopathy was admitted for acute COVID-19 pneumonia. Although his respiratory condition improved after administration of antiviral drugs, his blood pressure dropped suddenly to a preshock level and was refractory to vasopressors. The circulating adrenocorticotropic hormone (ACTH) and cortisol concentrations were low, and secondary adrenal insufficiency was suspected. Administration of hydrocortisone rapidly ameliorated the hypotension, and the patient was discharged taking 15 mg of hydrocortisone daily. An insulin tolerance test performed 3 months later revealed impaired ACTH, cortisol, and growth hormone (GH) responses, indicative of combined hypopituitarism. The patient also manifested symptoms of hypogonadism, and a hormonal workup suggested primary hypogonadism. At 12 months after discharge, GH and ACTH responses had recovered completely and partially, respectively. After another 3 months, basal ACTH and cortisol levels had been restored to the normal range and the patient discontinued hydrocortisone replacement without exacerbation of symptoms, although his hypogonadism persisted. The patient thus developed transient GH and ACTH deficiency that lasted for more than a year as well as persistent primary hypogonadism during intensive care for COVID-19. Certain prolonged symptoms of COVID-19 might be accounted for by such hormonal disturbance.Corresponding, Jul. 2022, Endocrine journal, English, Domestic magazineScientific journal
- Cases in which bilateral adrenal 123I-Metaiodobenzylguanidine (123I-MIBG) scintigraphy accumulation is sometimes shown, with mildly elevated catecholamine (CA) or metanephrine (MN) levels (within 3 times the upper reference limit) are diagnostic dilemmas. We experienced 3 cases of adrenal incidentalomas with this dilemma in the differential diagnosis. The clinical diagnosis was subclinical Cushing's syndrome in 2 cases, and primary aldosteronism in 1. Despite suspected CA excess in clinical symptoms and imaging findings, the pathological findings of all these tumors were revealed to be cytochrome P450 family 11 subfamily B member 1 (CYP11B1) positive adrenocortical adenomas. Interestingly, adrenal medullary hyperplasia (AMH) was detected in the adrenal parenchyma of all those backgrounds. To clarify the clinical features of such cases, a cross-sectional study was conducted at the Kobe University Hospital from 2014 to 2020. One-hundred sixty-four patients who had undergone 123I-MIBG scintigraphy were recruited. Among them, 10 patients (6.1%) met the above criteria, including the presented 3 cases. Plasma adrenaline, noradrenaline, urinary metanephrine, and normetanephrine had values of 0.05 ± 0.05 ng/mL, 0.63 ± 0.32 ng/mL, 0.22 ± 0.05 mg/day, and 0.35 ± 0.16 mg/day, respectively. Nine cases were complicated with hypertension, and symptoms related to CA excess were observed. Half of them (5 cases) including presented 3 cases had unilateral adrenal tumors. These suggest that in cases of bilateral adrenal uptake on 123I-MIBG, AMH needs to be considered. Adrenocortical adenomas may be associated with AMH and further larger investigation is needed for this pathology.Jun. 2022, Scientific reports, 12(1) (1), 9276 - 9276, English, International magazineScientific journal
- AIMS/INTRODUCTION: Bone mineral density (BMD) in patients with type 1 diabetes mellitus (T1DM) is reduced due to impaired insulin secretion. However, it is unclear whether the rate of BMD reduction is affected by T1DM subtypes. This study aimed to clarify the difference in BMD across T1DM subtypes: slowly progressive (SP), acute-onset (AO), and fulminant (F). METHODS: This was a retrospective, single-center, cross-sectional study conducted on 98 adult T1DM patients. The main outcome included the BMD Z-score (BMD-Z) measured at the lumbar spine (LS) and femoral neck (FN). RESULTS: The LS BMD-Z was lower in the AO than in the SP (p =0.03). No differences were observed when compared to the F. The FN BMD-Z tended to be higher in the SP than in the AO and F. Multiple regression analyses showed that the LS BMD-Z was associated with subtypes (AO vs. SP) (p =0.01), but not subtypes (F vs. SP), adjusted for sex, duration, retinopathy, and C-peptide immunoreactivity (CPR). When patients were divided into disease duration tertiles, in the first and second tertiles, the CPR levels were lower in the AO or F than in the SP. In contrast, LS and FN BMD-Z differed between the AO and SP only in the second tertiles (both p <0.01), with a similar tendency between the F and SP. CONCLUSIONS: Among T1DM subtypes, BMD has time-dependent changes, which reveals that BMD decline follows impaired insulin secretion. These results provide novel insights into the association between the low insulin exposure duration and BMD.Apr. 2022, Journal of diabetes investigation, 13(9) (9), 1585 - 1595, English, Domestic magazineScientific journal
- PURPOSE: To clarify the characteristics of Cushing's disease (CD) patients who respond to the desmopressin (DDAVP) test and its underlying mechanisms. METHODS: Forty-seven patients with CD who underwent DDAVP testing were included. Patients were divided into two groups: DDAVP test (+) (adrenocorticotropic hormone [ACTH] levels increased by ≥ 1.5-fold during the DDAVP test) and DDAVP test (-) (ACTH levels increased by < 1.5-fold). AVP receptor expression levels in these tumors were quantified using quantitative RT-PCR and immunohistochemistry. AVP receptor promoter activity was analyzed using a dual-luciferase reporter assay system. RESULTS: Females (96.9%) and USP8 mutants (85.7%) were more prevalent in the DDAVP test (+) than in the DDAVP test (-). Indeed, the ACTH and cortisol responsiveness to DDAVP was greater in USP8 mutation positive tumors than that in USP8 wild type tumors (3.0-fold vs. 1.3-fold, 1.6-fold vs. 1.1-fold, respectively). Responsiveness to DDAVP was correlated with the expression levels of AVPR1B, but not with those of AVPR2. Comparably, Avpr1b promoter activity was enhanced by the overexpression of mutant USP8 compared to the wild type. CONCLUSIONS: We found that the responsiveness of ACTH to DDAVP in CD was greater in tumors with USP8 mutations. The present data suggest that USP8 mutations upregulate the AVPR1B promoter activity. Additionally, we showed that the DDAVP test can predict the presence of USP8 mutations.Apr. 2022, Pituitary, 25(3) (3), 496 - 507, English, International magazineScientific journal
- Kenny-Caffey syndrome type 2 (KCS2) is an extremely rare skeletal disorder involving hypoparathyroidism and short stature. It has an autosomal dominant pattern of inheritance and is caused by variants in the FAM111 trypsin-like peptidase A (FAM111A) gene. This disease is often difficult to diagnose due to a wide range of more common diseases manifesting hypoparathyroidism and short stature. Herein, we present the case of a 56-year-old female patient with idiopathic hypoparathyroidism and a short stature. The patient was treated for these conditions during childhood. Upon re-evaluating the etiology of KCS2, we suspected that the patient had the disorder because of clinical manifestations, such as cortical thickening and medullary stenosis of the bones, and lack of intellectual abnormalities. Genetic testing identified a heterozygous missense variant in the FAM111A gene (p.R569H). Interestingly, the patient also had bilateral sensorineural hearing loss and vestibular dysfunction, which have been rarely described in previous reports of pediatric cases. In KCS2, inner ear dysfunction due to Eustachian tube dysfunction may progress in middle age or later. However, this disease is now being reported in younger patients. Nevertheless, our case may be instructive of how such cases emerge chronically after middle age. Herein, we also provide a literature review of KCS2.2022, Frontiers in endocrinology, 13, 1073173 - 1073173, English, International magazine
- Combined pituitary hormone deficiency (CPHD) is not a rare disorder, with a frequency of approximately 1 case per 4,000 live births. However, in most cases, a genetic diagnosis is not available. Furthermore, the diagnosis is challenging because no clear correlation exists between the pituitary hormones affected and the gene(s) responsible for the disorder. Next-generation sequencing (NGS) has recently been widely used to identify novel genes that cause (or putatively cause) CPHD. This review outlines causative genes for CPHD that have been newly reported in recent years. Moreover, novel variants of known CPHD-related genes (POU1F1 and GH1 genes) that contribute to CPHD through unique mechanisms are also discussed in this review. From a clinical perspective, variants in some of the recently identified causative genes result in extra-pituitary phenotypes. Clinical research on the related symptoms and basic research on pituitary formation may help in inferring the causative gene(s) of CPHD. Future NGS analysis of a large number of CPHD cases may reveal new genes related to pituitary development. Clarifying the causative genes of CPHD may help to understand the process of pituitary development. We hope that future innovations will lead to the identification of genes responsible for CPHD and pituitary development.2022, Frontiers in endocrinology, 13, 1008306 - 1008306, English, International magazineScientific journal
- Context: With the increasing number of older patients with acromegaly, it is important to understand the effects of aging on the quality of life (QoL) in acromegaly. Objective: To investigate the factors associated with the QoL of older acromegaly patients. Design: This was a single-center, retrospective, cross-sectional study conducted between 2014 and 2019. Methods: Among 90 acromegaly patients at Kobe University Hospital, 74 who had completed the QoL evaluation under treatment were enrolled (age = 62.0 [50.7-70.0], female 52%). SF-36 and the AcroQoL questionnaire were used to quantify QoL. The patients were divided into two groups: the young and middle-aged group, aged <65 years (51.0 [46.0-59.2], n =42), and the older group, aged ≥65 years (70.5 [69.0-73.0], n =32). The factors associated with the QoL scores were analyzed using univariate and multivariate regression analyses. Results: The scores for the physical component summary of SF-36 were negatively associated with age (P <0.01), while those for the mental or role/social component summary were positively associated (P <0.01, P =0.03, respectively). In contrast, AcroQoL scores were not associated with age. However, the different factors were associated with lower AcroQoL scores; arthropathy and higher BMI in the older group (P <0.01, and P =0.01, respectively), and treatment modalities and size of pituitary tumor in the young and middle-aged group (P <0.01, P =0.04, respectively). Replacement of hydrocortisone was commonly associated both in young and middle-aged group (P =0.04), and in older group (P =0.02). Conclusion: We showed that the factors associated with impaired QoL differed in the young and middle-aged, and older patients with acromegaly. In older patients, arthropathy and higher BMI were associated with poor QoL. These suggest the importance of early diagnosis and appropriate treatment in preventing arthropathy in acromegaly.2022, Frontiers in endocrinology, 13, 819330 - 819330, English, International magazineScientific journal
- Lead, (公社)日本医師会, Oct. 2021, 日本医師会雑誌, 150(特別2) (特別2), S182 - S183, Japanese【内分泌疾患・糖尿病・代謝疾患-診療のエッセンス】(II章)糖尿病 薬物療法 経口薬による治療 α-グルコシダーゼ阻害薬
- (有)科学評論社, Aug. 2021, 糖尿病・内分泌代謝科, 53(2) (2), 230 - 234, Japanese抗PIT-1下垂体炎[Invited]
- Cushing's disease is a syndromic pathological condition caused by adrenocorticotropic hormone (ACTH)-secreting pituitary adenomas (ACTHomas) mediated by hypercortisolemia. It may have a severe clinical course, including infection, psychiatric disorders, hypercoagulability, and metabolic abnormalities, despite the generally small, nonaggressive nature of the tumors. Up to 20% of ACTHomas show aggressive behavior, which is related to poor surgical outcomes, postsurgical recurrence, serious clinical course, and high mortality. Although several gene variants have been identified in both germline and somatic changes in Cushing's disease, the pathophysiology of aggressive ACTHomas is poorly understood. In this review, we focused on the aggressiveness of ACTHomas, its pathology, the current status of medical therapy, and future prospects. Crooke's cell adenoma (CCA), Nelson syndrome, and corticotroph pituitary carcinoma are representative refractory pituitary tumors that secrete superphysiological ACTH. Although clinically asymptomatic, silent corticotroph adenoma is an aggressive ACTH-producing pituitary adenoma. In this review, we summarize the current understanding of the pathophysiology of aggressive ACTHomas, including these tumors, from a molecular point of view based on genetic, pathological, and experimental evidence. The treatment of aggressive ACTHomas is clinically challenging and usually resistant to standard treatment, including surgery, radiotherapy, and established medical therapy (e.g., pasireotide and cabergoline). Temozolomide is the most prescribed pharmaceutical treatment for these tumors. Reports have shown that several treatments for patients with refractory ACTHomas include chemotherapy, such as cyclohexyl-chloroethyl-nitrosourea combined with 5-fluorouracil, or targeted therapies against several molecules including vascular endothelial growth factor receptor, cytotoxic T lymphocyte antigen 4, programmed cell death protein 1 (PD-1), and ligand for PD-1. Genetic and experimental evidence indicates that some possible therapeutic candidates are expected, such as epidermal growth factor receptor tyrosine kinase inhibitor, cyclin-dependent kinase inhibitor, and BRAF inhibitor. The development of novel treatment options for aggressive ACTHomas is an emerging task.Lead, Jun. 2021, Frontiers in endocrinology, 12, 650791 - 650791, English, International magazineScientific journal
- Context: Paradoxical increases in serum cortisol in the dexamethasone suppression test (DST) have been rarely observed in Cushing disease (CD). Its pathophysiology and prevalence remain unclear. Case Description: A 62-year-old woman with suspected CD showed paradoxical increases in cortisol after both 1-mg and 8-mg DST (1.95-fold and 2.52-fold, respectively). The initiation of metyrapone paradoxically decreased plasma adrenocorticotropic hormone (ACTH) levels and suppressed cortisol levels. Moreover, the pituitary tumor considerably shrank during metyrapone treatment. Ex Vivo Experiments: The resected tumor tissue was enzymatically digested, dispersed, and embedded into Matrigel as 3D cultured cells. ACTH levels in the media were measured. In this tumor culture, ACTH levels increased 1.3-fold after dexamethasone treatment (P < 0.01) while control tumor cultures exhibited no increase in ACTH levels, but rather a 20% to 40% suppression (P < 0.05). Clinical Study: A cross-sectional, retrospective, multicenter study that included 92 patients with CD who underwent both low-dose and high-dose DST from 2014 to 2020 was performed. Eight cases (8.7%) showed an increase in serum cortisol after both low-dose and high-dose DST. Conclusion: This is the first report of a patient with glucocorticoid (GC)-driven positive feedback CD who showed both ACTH suppression and tumor shrinkage by metyrapone. Our cohort study revealed that 8.7% of patients with CD patients possibly possess GC-driven positive-feedback systems, thereby suggesting the presence of a new subtype of CD that is different from the majority of CD cases. The mechanisms exhibiting GC positive feedback in CD and the therapeutic approach for these patients remain to be investigated.Jun. 2021, Journal of the Endocrine Society, 5(6) (6), bvab055, English, International magazineScientific journal
- CONTEXT: Mechanisms underlying pituitary corticotroph adenoma ACTH production are poorly understood, yet circulating ACTH levels closely correlate with adenoma phenotype and clinical outcomes. OBJECTIVE: We characterized the 5' ends of proopiomelanocortin (POMC) gene transcripts, which encode the precursor polypeptide for ACTH, in order to investigate additional regulatory mechanisms of POMC gene transcription and ACTH production. METHODS: We examined 11 normal human pituitary tissues, 32 ACTH-secreting tumors, as well as 6 silent pituitary corticotroph adenomas (SCA) that immunostain for but do not secrete ACTH. RESULTS: We identified a novel regulatory region located near the intron2/exon3 junction in the human POMC gene, which functions as a second promoter and an enhancer. In vitro experiments demonstrated that CREB binds the second promoter and regulates its transcriptional activity. The second promoter is highly methylated in SCA, partially demethylated in normal pituitary tissue, and highly demethylated in pituitary and ectopic ACTH-secreting tumors. In contrast, the first promoter is demethylated in all POMC-expressing cells and is highly demethylated only in pituitary ACTH-secreting tumors harboring the USP8 mutation. Demethylation patterns of the second promoter correlate with clinical phenotypes of Cushing's disease. CONCLUSION: We identified a second POMC promoter regulated by methylation status in ACTH-secreting pituitary tumors. Our findings open new avenues for elucidating subcellular regulation of the hypothalamic-pituitary-adrenal axis and suggest the second POMC promoter may be a target for therapeutic intervention to suppress excess ACTH production.Jun. 2021, The Journal of clinical endocrinology and metabolism, English, International magazineScientific journal
- BACKGROUND: Immune checkpoint inhibitors (ICIs) as a cancer immunotherapy have emerged as a treatment for multiple advanced cancer types. Because of enhanced immune responses, immune-related adverse events (irAEs), including endocrinopathies such as hypophysitis, have been associated with the use of ICIs. Most underlying mechanisms of ICI-related hypophysitis remain unclear, especially for programmed cell death-1 (PD-1)/PD-1 ligand 1 (PD-L1) inhibitors. We hypothesized that ICI-related hypophysitis is associated with paraneoplastic syndrome caused by ectopic expression of pituitary-specific antigens. METHODS: Twenty consecutive patients with ICI-related hypophysitis between 2017 and 2019 at Kobe University Hospital were retrospectively analyzed. Circulating anti-pituitary antibodies were detected using immunofluorescence staining and immunoblotting. Ectopic expression of pituitary autoantigens in tumor specimens was also examined. RESULTS: Eighteen patients were treated with PD-1/PD-L1 inhibitors, and two were treated with a combination of cytotoxic T-lymphocyte antigen-4 (CTLA-4) and PD-1 inhibitors. All patients showed adrenocorticotropic hormone (ACTH) deficiency and additionally, three showed thyroid-stimulating hormone (TSH) deficiency, and one showed gonadotropin-releasing hormone (GnRH) deficiency. Among these patients, three exhibited anti-pituitary antibodies, two with anti-corticotroph antibody and one with anti-somatotroph antibody. Interestingly, the anti-corticotroph antibody recognized proopiomelanocortin (POMC) and those two patients exhibited ectopic ACTH expression in the tumor, while the patients without anti-corticotroph antibody did not. CONCLUSIONS: We demonstrated 10% of PD-1/PD-L1 inhibitors-related hypophysitis were associated with the autoimmunity against corticotrophs and maybe caused as a form of paraneoplastic syndrome, in which ectopic expression of ACTH in the tumor was observed. It is also suggested that the pathophysiology is heterogenous in ICI-related hypophysitis.May 2021, Cancer immunology, immunotherapy : CII, 70(12) (12), 3669 - 3677, English, International magazineScientific journal
- (有)科学評論社, May 2021, 糖尿病・内分泌代謝科, 52(5) (5), 453 - 458, Japanese【糖尿病・内分泌代謝疾患とGPCR update】ソマトスタチン受容体
- (株)メディカ出版, Mar. 2021, 糖尿病ケア, (2021春季増刊) (2021春季増刊), 230 - 233, Japanese
- Anti-pituitary-specific transcription factor 1 (PIT-1) hypophysitis (anti-PIT-1 antibody syndrome) is a thymoma-associated autoimmune disease characterized by acquired growth hormone (GH), prolactin (PRL), and thyrotropin (TSH) deficiencies due to autoimmunity against PIT-1. Ectopic expression of PIT-1 in the thymoma plays a causal role in development of the disease. Here, we report 2 cases of anti-PIT-1 hypophysitis exhibiting as a form of paraneoplastic syndrome with conditions other than thymoma. A 79-year-old woman (case 1) and an 86-year-old man (case 2) were referred with a suspicion of anti-PIT-1 hypophysitis because of acquired GH, PRL, and TSH deficiencies. Case 1 was complicated by diffuse large B-cell lymphoma (DLBCL) of the bladder and case 2 was diagnosed with malignancy with multiple metastases of unknown origin. Because circulating anti-PIT-1 antibody was detected, both patients were diagnosed with anti-PIT-1 hypophysitis. Circulating PIT-1-reactive T cells were detected in case 1 via enzyme-linked immunospot (ELISPOT) assay. Interestingly, the PIT-1 protein was ectopically expressed in the DLBCL cells of case 1, whereas DLBCL tissues derived from patients without anti-PIT-1 hypophysitis were negative for PIT-1. In case 2, the materials were not available because of best supportive care was under way. These data show that anti-PIT-1 hypophysitis is associated not only with thymoma but also with other malignancies. Additionally, the ectopic expression of PIT-1 in the DLBCL tissues and presence of PIT-1-reactive T cells suggested that the underlying mechanisms were similar to those observed in thymoma. Thus, anti-PIT-1 hypophysitis is defined as a form of paraneoplastic syndrome.Mar. 2021, Journal of the Endocrine Society, 5(3) (3), bvaa194, English, International magazine
- Cushing's disease caused due to adrenocorticotropic hormone (ACTH)-secreting pituitary adenomas (ACTHomas) leads to hypercortisolemia, resulting in increased morbidity and mortality. Autonomous ACTH secretion is attributed to the impaired glucocorticoid negative feedback (glucocorticoid resistance) response. Interestingly, other conditions, such as ectopic ACTH syndrome (EAS) and non-neoplastic hypercortisolemia (NNH, also known as pseudo-Cushing's syndrome) also exhibit glucocorticoid resistance. Therefore, to differentiate between these conditions, several dynamic tests, including those with desmopressin (DDAVP), corticotrophin-releasing hormone (CRH), and Dex/CRH have been developed. In normal pituitary corticotrophs, ACTH synthesis and secretion are regulated mainly by CRH and glucocorticoids, which are the ACTH secretion-stimulating and -suppressing factors, respectively. These factors regulate ACTH synthesis and secretion through genomic and non-genomic mechanisms. Conversely, glucocorticoid negative feedback is impaired in ACTHomas, which could be due to the overexpression of 11β-HSD2, HSP90, or TR4, or loss of expression of CABLES1 or nuclear BRG1 proteins. Genetic analysis has indicated the involvement of several genes in the etiology of ACTHomas, including USP8, USP48, BRAF, and TP53. However, the association between glucocorticoid resistance and these genes remains unclear. Here, we review the clinical aspects and molecular mechanisms of ACTHomas and compare them to those of other related conditions.Nov. 2020, International journal of molecular sciences, 21(23) (23), English, International magazineScientific journal
- Drivers of sporadic benign pituitary adenoma growth are largely unknown. Whole-exome sequencing of 159 prospectively resected pituitary adenomas showed that somatic copy number alteration (SCNA) rather than mutation is a hallmark of hormone-secreting adenomas and that SCNAs correlate with adenoma phenotype. Using single-gene SCNA pathway analysis, we observed that both cAMP and Fanconi anemia DNA damage repair pathways were affected by SCNAs in growth hormone-secreting (GH-secreting) somatotroph adenomas. As somatotroph differentiation and GH secretion are dependent on cAMP activation and we previously showed DNA damage, aneuploidy, and senescence in somatotroph adenomas, we studied links between cAMP signaling and DNA damage. Stimulation of cAMP in C57BL/6 mouse primary pituitary cultures using forskolin or a long-acting GH-releasing hormone (GHRH) analog increased GH production and DNA damage measured by H2AX phosphorylation and a comet assay. Octreotide, a somatostatin receptor ligand that targets somatotroph adenoma GH secretion in patients with acromegaly, inhibited cAMP and GH and reversed DNA damage induction. In vivo long-acting GHRH treatment also induced pituitary DNA damage in mice. We conclude that cAMP, which induces somatotroph proliferation and GH secretion, may concomitantly induce DNA damage, potentially linking hormone hypersecretion to SCNA and genome instability. These results elucidating somatotroph adenoma pathophysiology identify pathways for targeted treatment.American Society for Clinical Investigation, Nov. 2020, The Journal of clinical investigation, 130(11) (11), 5738 - 5755, English, International magazine[Refereed]Scientific journal
- PURPOSE: Multidisciplinary team meetings (MDMs) to address various clinical problems have become common, especially for cancer care. However, the impact of MDMs on adrenal tumor care has rarely been reported. We organized an endocrine tumor MDM including adrenal tumors in August 2014. The objective of this study was to assess the impact of our adrenal tumor MDMs on patient clinical outcomes. We compared several parameters measuring clinical outcomes before and after MDMs were instituted. METHODS: The adrenal tumor MDMs included an endocrinologists, urologists, radiologists, pathologists, and residents. We analyzed 128 consecutive cases of functioning adrenal tumors (primary aldosteronism (PA), n = 53; Cushing's syndrome (CS), n = 24; pheochromocytoma (PCC), n = 51) who underwent surgery in Kobe University Hospital from 2008 to 2019, and compared clinical parameters before (n = 68) and after (n = 60) MDMs were instituted. RESULTS: Twenty-one selected cases including PA, CS, PCC, adrenocortical carcinoma, and metastatic adrenal tumor were discussed in the MDM. In the analysis of 128 cases, the difference between pre- and postoperative systolic BP (ΔBP) in patients with PA after MDMs were instituted was smaller compared with those before (p = 0.02). In CS, preoperative steroid synthesis inhibitors were used more often (33 vs. 100%, p < 0.01), postoperative plasma ACTH levels were higher (29.1 vs. 84.5 pg/mL, p < 0.01), and postoperative decrease in systolic BP was milder (p < 0.01) after MDMs were instituted. In PCC, doses of preoperative doxazosin were higher (p < 0.01) after MDMs institution. Operating time, bleeding volume, and cure rate did not differ between each tumor type. CONCLUSIONS: These data suggest that instituting MDMs improved the perioperative management of functioning adrenal tumors.Sep. 2020, Endocrine, 69(3) (3), 519 - 525, English, International magazine[Refereed]Scientific journal
- Lead, IntechOpen, Apr. 2020, Growth Disorders and AcromegalyIn book
- Some endocrine disorders, including hypophysitis and isolated adrenocorticotropic hormone (ACTH) deficiency, are caused by an autoimmune response to endocrine organs. Although the pathogenesis of some autoimmune endocrine diseases has been elucidated, it remains obscure for most. Anti-PIT-1 hypophysitis (anti-PIT-1 antibody syndrome) is a newly described pituitary autoimmune disease characterized by acquired and specific growth hormone (GH), prolactin (PRL), and thyroid-stimulating hormone (TSH) deficiencies. This disorder is associated with a thymoma or neoplasm that ectopically expresses pituitary-specific transcription factor 1 (PIT-1) protein. Circulating anti-PIT-1 antibody is a disease marker, and PIT-1-reactive cytotoxic T cells (CTLs) play a pivotal role in disease development. In addition, isolated ACTH deficiency appears to be caused by autoimmunity to corticotrophs; however, the pathogenesis remains unclear. A recently described case of isolated ACTH deficiency with large cell neuroendocrine carcinoma (LCNEC) showed ectopically expressed proopiomelanocortin (POMC), and circulating anti-POMC antibody and POMC-reactive CTLs were also detected. As CTL infiltrations around corticotrophs were also observed, isolated ACTH deficiency may be associated at least in part with a paraneoplastic syndrome. Although several underlying mechanisms for pituitary autoimmunity have been proposed, these observations highlight the importance of paraneoplastic syndrome as a cause of pituitary autoimmune disease. In this review, we focus on the pathophysiology and connection of anti-PIT-1 hypophysitis and isolated ACTH deficiency and discuss the state-of-art knowledge for understanding pituitary autoimmunity.Lead, Apr. 2020, Endocrine reviews, 41(2) (2), English, International magazine[Refereed][Invited]Scientific journal
- Lead, (公社)日本医師会, 2020, 日本医師会雑誌, 149(特別2) (特別2), S285 - S287, Japanese免疫・炎症疾患各論/内分泌疾患 下垂体炎,多腺性自己免疫症候群(APS)
- Aug. 2019, Journal of the Endocrine SocietyPathogenesis of anti-PIT-1 antibody syndrome: PIT-1 presentation by HLA class I on anterior pituitary cells.[Refereed]
- Feb. 2019, Endocrinology, 160(2) (2), 276 - 291[Refereed]
- Feb. 2019, JCI insight, 4(3) (3)[Refereed]
- Pituitary corticotroph somatostatin receptor subtype 5 (SSTR5) signals to inhibit adrenocorticotrophin (ACTH) secretion. As ACTH deficiency results in attenuated adrenal cortisol production and an impaired stress response, we sought to clarify the role of SSTR5 in modifying the hypothalamic/pituitary/adrenal (HPA) axis. We generated Tg HP5 mice overexpressing SSTR5 in pituitary corticotrophs that produce the ACTH precursor proopiomelanocortin (POMC). Basal ACTH and corticosterone were similar in HP5 and WT mice, while HP5 mice showed attenuated ACTH and corticosterone responses to corticotrophin releasing hormone (CRH). HP5 mice exhibited attenuated corticosterone responses upon a restraint stress test and inflammatory stress following LPS injection, as well as increased anxiety-like and depressive-like behavior on open field and forced swim tests. Pituitary corticotroph CRH receptor subtype 1 (CRHR1) mRNA expression and ACTH responses to CRH were also attenuated in HP5 mice. In AtT20 cells stably overexpressing SSTR5, CRHR1 expression and cAMP response to CRH were reduced, whereas both were increased after SSTR5 KO. In elucidating mechanisms for these observations, we show that SSTR5-induced miR-449c suppresses both CRHR1 expression and function. We conclude that corticotroph SSTR5 attenuates HPA axis responses via CRHR1 downregulation, suggesting a role for SSTR5 in the pathogenesis of secondary adrenal insufficiency.Lead, Oct. 2018, JCI insight, 3(19) (19), English, International magazine[Refereed]Scientific journal
- The endocrine system plays an essential role in the physiological adaptation to malnutrition. The adaptive response of various hormones directs the energy utilization toward the survival functions and away from growth and reproduction. Particularly, the hypothalamic pituitary axis plays an integral and a central role in the regulation of endocrine organs. Sirtuin 1 (SIRT1) is a nicotinamide adenine dinucleotide (NAD)-dependent histone deacetylase that is activated in response to calorie restriction (CR). SIRT1 is involved in cellular processes via the deacetylation of histone as well as various transcription factors and signal transduction molecules and thereby modulates the endocrine/metabolic functions. There is much evidence to demonstrate clearly that SIRT1 in the hypothalamus, pituitary gland, and other target organs modifies the synthesis, secretion, and activities of hormones and in turn induces the adaptive responses. In this review, we discussed the role of SIRT1 in the hypothalamic pituitary axis and its pathophysiological significance.Lead, 2018, Frontiers in endocrinology, 9, 605 - 605, English, International magazine[Refereed]Scientific journal
- Acromegaly is a disease associated with an increased risk for several kinds of neoplasms including colon and thyroid cancer. Although the association between acromegaly and pancreatic neoplasms has not been elucidated, it has recently been reported that GNAS gene mutations were found in 58% of intraductal papillary mucinous neoplasms (IPMNs), which are representative pancreatic cystic lesions, suggesting a link between IPMNs and acromegaly. To assess the prevalence of pancreatic cystic lesions in patients with acromegaly, we performed a retrospective cross-sectional single institute study. Thirty consecutive acromegalic patients (20 females and 10 males; mean age, 60.9 +/- 11.9 years) who underwent abdominal contrast-enhanced computed tomography or magnetic resonance imaging between 2007 and 2015 at Kobe University Hospital were recruited. We also analyzed the relationship between presence of pancreatic cystic lesions and somatic GNAS mutations in pituitary tumors. Seventeen of 30 (56.7%) patients studied had pancreatic cystic lesions. Nine of 17 patients (52.9%) were diagnosed with IPMNs based on imaging findings. These results suggest that the prevalence of IPMNs may be higher in acromegalic patients in acromegalic patients than historically observed in control patients (up to 13.5%). In patients with pancreatic cystic lesions, the mean patient age was higher and the duration of disease was longer than in those without pancreatic cystic lesions (67.0 +/- 2.3 vs. 53.0 +/- 2.7 years, p < 0.001, 15.5 +/- 2.4 vs. 7.3 +/- 2.8 years, p = 0.04). There were no differences in serum growth hormone levels or insulin-like growth factor standard deviation scores between these two groups (21.3 +/- 6.4 vs. 23.0 +/- 7.4 ng/ml, p = 0.86, 6.6 +/- 0.5 vs. 8.0 +/- 0.6, p = 0.70). Neither the presence of somatic GNAS mutation in a pituitary tumor nor low signal intensity of the tumor in T2 weighted magnetic resonance imaging was associated with the presence of pancreatic cystic lesions. These data demonstrate that old or long-suffering patients with acromegaly have a higher prevalence of pancreatic cystic lesions. Moreover, the prevalence of pancreatic cystic lesions may be increased in acromegalic patients.SPRINGER, Oct. 2017, PITUITARY, 20(5) (5), 509 - 514, English[Refereed]Scientific journal
- The diagnostic steps for primary aldosteronism (PA) include case screening tests, confirmatory tests, and localization. The aim of this study was to identify useful confirmatory tests and their cut-off values for differentiating the subtype of primary aldosteronism, especially in unilateral PA, such as aldosterone-producing adenoma, and bilateral PA, such as idiopathic hyperaldosteronism. Seventy-six patients who underwent all four confirmatory tests, the captopril-challenge test (CCT), furosemide upright test (FUT), saline infusion test (SIT), and ACTH stimulation test (AST), and who were confirmed to have an aldosterone excess by adrenal venous sampling (AVS) were recruited. Subjects were diagnosed as having unilateral aldosterone excess (n=17) or bilateral aldosterone excess (n=59) by AVS. The SIT-positive rate was significantly higher in the unilateral group (94.1%) than in the bilateral group (57.6%). Multivariable logistic regression analysis showed that tumor on computed tomography (CT) and plasma aldosterone concentration (PAC) max/cortisol on the AST were useful for differentiating the subtype of PA. Receiver operating characteristic (ROC) curve analysis for distinguishing the subtype of PA showed that a cut-off value of 18.3 PAC(max)/cortisol on the AST had a sensitivity of 83% and a specificity of 88%. The area under the ROC curve was 0.918 (95% confidence interval 0.7916-0.9708). These data suggest that abdominal CT and AST are useful for differentiating the subtype of PA and the indication for AVS.JAPAN ENDOCRINE SOC, 2017, ENDOCRINE JOURNAL, 64(1) (1), 65 - 73, English[Refereed]Scientific journal
- Objective Various organs are known to be affected by the comorbidities of acromegaly. However, the involvement of renal structural comorbidities, such as cysts, has so far remained largely unknown. In this single-center study, we aimed to determine the prevalence and factors associated with simple renal cysts in Japanese patients with acromegaly. Methods A total of 71 consecutive patients with acromegaly were analyzed, who all underwent abdominal ultrasonography at diagnosis between 1986 and 2012 at Kobe University Hospital. Results Of these 71 patients, 23 (32.4%) exhibited simple renal cysts. Acromegalic patients with renal cysts tended to be significantly older, had a higher prevalence of smoking- and higher nadir growth hormone (GH) levels during the oral glucose tolerance test (OGTT) than did those without renal cysts. A multivariate logistic regression analysis showed age, smoking, and nadir GH to be independent factors associated with renal cysts. Interestingly, the number of renal cysts positively correlated with both the basal GH levels and nadir GH levels during OGTT (r=0.66, p<0.05 and r=0.70, p<0.05, respectively). In addition, the mean diameter of renal cysts positively correlated with the systolic blood pressure (r=0.84, p<0.005). Conclusion This is the first report to show the prevalence of simple renal cysts in patients with acromegaly. Elevated nadir GH levels during OGTT were found to be associated with an increased risk of simple renal cysts. Therefore, an excessive secretion of GH may be related to the development of renal cysts.Lead, JAPAN SOC INTERNAL MEDICINE, 2016, INTERNAL MEDICINE, 55(13) (13), 1685 - 1690, English[Refereed]Scientific journal
- Colorectal neoplasms are well known to be a complication in cases of acromegaly; however, data on the prevalence of colorectal neoplasms in Asian patients with acromegaly are limited. Further, the factors associated with colorectal neoplasms in cases of acromegaly are controversial. Therefore, we aimed to clarify the prevalence of and factors associated with colorectal neoplasms in Japanese patients with acromegaly in a single center. We analyzed consecutive 57 patients who had undergone full-length colonoscopy at the time of diagnosis at Kobe University Hospital between 1986 and 2012. Of the 57 patients, 22 (38.6 %), 18 (31.6 %) and 3 (5.3 %) patients were diagnosed with hyperplastic polyps, adenomas, and adenocarcinomas, respectively and the prevalence was significantly higher than in a historical control group, Chinese patients with irritable bowel syndrome (The odds ratio was 4.0, 8.7, and 17.5, respectively). The prevalence of adenocarcinomas was also significantly higher in these patients than in the general Japanese population (odds ratio 14.5). Patients with acromegaly who had colorectal neoplasms had longer disease duration than those without colorectal neoplasms. Of note, the area under the growth hormone (GH) concentration-time curve (GH AUC) during the oral glucose tolerance test was significantly higher in patients with adenocarcinomas than in those with no colonic lesion or those with hyperplastic polyps. Japanese patients with acromegaly exhibited an increased risk of colorectal neoplasms, especially colorectal adenocarcinomas. An increased GH AUC was associated with an increased risk for colon adenocarcinomas in patients with acromegaly.Lead, SPRINGER, Jun. 2015, PITUITARY, 18(3) (3), 343 - 351, English[Refereed]Scientific journal
- Anti-PIT-1 Antibody Syndrome; a Novel Clinical Entity Leading to HypopituitarismVarious hypothalamic-pituitary diseases cause hypopituitarism. Inflammation related to autoimmunity also causes hypopituitarism. Hypophysitis is a representative disease caused by autoimmunity. Generally, anterior pituitary hormones are non-specifically impaired in this condition, but specific hormone defects have been reported in some cases. Anti-PIT-1 (pituitary-specific transcription factor 1) antibody syndrome is a novel clinical entity that presents an acquired combined pituitary hormone deficiency characterized by a specific defect in growth hormone, prolactin, and thyroid-stimulating hormone. Circulating anti-PIT-1 antibody along with various autoantibodies are detected with multiple endocrine organopathy, meeting the definition of autoimmune polyglandular syndrome. Mechanistically, cytotoxic T lymphocytes that specifically react with PIT-1 protein play an important role in the development of this syndrome.MEDICAL MEDIA, Mar. 2015, PEDIATRIC ENDOCRINOLOGY REVIEWS PER, 12(3) (3), 290 - 296, English[Refereed]Scientific journal
- Context: Anti-pituitary-specific transcriptional factor 1 (PIT-1) antibody syndrome is characterized by acquired growth hormone (GH), prolactin (PRL), and thyroid-stimulating hormone (TSH) deficiencies associated with circulating anti-PIT-1 antibodies. Although autoimmunity to PIT-1 has been suggested as a pathogenesis, the precise mechanism of the syndrome remains unclarified. Objective: To elucidate the involvement of antibody-or cell-mediated immunity in anti-PIT-1 antibody syndrome. Materials and Methods: To investigate a direct effect of anti-PIT-1 antibody on pituitary cells, cell proliferation, and cytotoxicity detection assays were performed using patient serum. Enzyme-linked immunospot (ELISpot) assay was performed to evaluate the involvement of PIT-1-reactive cytotoxic T lymphocytes (CTLs). An immunohistochemical analysis using anti-CD4 or anti-CD8 antibody was performed to examine tissue infiltration by CTLs. Results: Patient serum did not exhibit any inhibitory effect on cell proliferation and secretion of GH and PRL in GH3 cells. In addition, complement-dependent cytotoxicity was not detected in patient serum on GH3 cells or primary pituitary cells. The ELISpot assay revealed the presence of CTLs that specifically reacted to the recombinant PIT-1 protein in the patient's peripheral lymphocytes. CD8(+) cell infiltrations, which is the characteristic of CTLs, were observed in the pituitary gland, adrenal gland, stomach, thyroid gland, liver, and pancreas of the patient with anti-PIT-1 antibody syndrome. Conclusions: These results suggest that the anti-PIT-1 antibody is not a cause but a marker of anti-PIT-1 antibody syndrome, in which CTLs play a pivotal role in the pathogenesis.ENDOCRINE SOC, Sep. 2014, JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 99(9) (9), E1744 - E1749, English[Refereed]Scientific journal
- Jun. 2014, ENDOCRINE REVIEWS, 35(3) (3)The Increased Area Under the Growth Hormone Concentration-Time Curve during Oral Glucose Tolerance Test Is Associated with Colorectal Adenocarcinoma in Acromegaly[Refereed]International conference proceedings
- Objective: The prevalence and clinical characteristics of IgG4-related hypophysitis remain unclear due to the limited number of case reports. Therefore, in this study, we screened consecutive outpatients with hypopituitarism and/or diabetes insipidus (DI) to estimate its prevalence.Methods: A total of 170 consecutive outpatients with hypopituitarism and/or central DI were screened at Kobe University Hospital for detecting IgG4-related hypophysitis by pituitary magnetic resonance imaging, measuring serum IgG4 concentrations, assessing the involvement of other organs, and carrying out an immunohistochemical analysis to detect IgG4-positive cell infiltration.Results: Among the screened cases, 116 cases were excluded due to diagnosis of other causes such as tumors and congenital abnormalities. Additionally, 22 cases with isolated ACTH deficiency were analyzed and were found not to meet the criteria of IgG4-related hypophysitis. The remaining 32 cases were screened and seven were diagnosed with IgG4-related hypophysitis, of which three cases were diagnosed by analyzing pituitary specimens. IgG4-related hypophysitis was detected in 30% (seven of 23 patients) of hypophysitis cases and 4% of all hypopituitarism/DI cases. The mean age at the onset of IgG4-related hypophysitis was 61.8 +/- 8.8 years, and the serum IgG4 concentration was 191.1 +/- 78.3 mg/dl (normal values 5-105 mg/dl and values in IgG4-related disease (RD) >= 135 mg/dl). Pituitary gland and/or stalk swelling was observed in six patients, and an empty sella was observed in one patient. Multiple co-existing organ involvement was observed in four of the seven patients prior to the onset of IgG4-related hypophysitis.Conclusion: These data suggest that the prevalence of IgG4-related hypophysitis has been underestimated. We should also consider the possibility of the development of hypopituitarism/DI caused by IgG4-related hypophysitis during the clinical course of other IgG4-RDs.BIOSCIENTIFICA LTD, Feb. 2014, EUROPEAN JOURNAL OF ENDOCRINOLOGY, 170(2) (2), 161 - 172, English[Refereed]Scientific journal
- A missense single-nucleotide polymorphism in the sialic acid acetylesterase (SIAE) gene is associated with anti-PIT-1 antibody syndrome.A novel clinical entity related to autoimmune polygladular syndrome (APS) termed "anti-PIT-1 antibody syndrome" is characterized by a presence of circulating autoantibody against the pituitary-specific transcriptional factor-1 (PIT-1) with acquired specific defect in GH, PRL, and TSH. Although autoimmunity to PIT-1 has been suggested, the underlying mechanisms remain to be elucidated. Sialic acid acetylesterase (SIAE) plays a crucial role in regulating the threshold of autoantibody production of B-cells and the defective variants of SIAE are associated with an increased risk of various autoimmune diseases such as type 1 diabetes (T1DM). To explore the link between anti-PIT-1 antibody syndrome and SIAE, we analyzed SIAE gene in 3 patients with anti-PIT-1 antibody syndrome and 200 healthy control subjects, and compared the prevalence of single nucleotide polymorphisms. Intriguingly, we found A467V SIAE variants (c.1400C>T, rs7941523) in a heterozygous state in all the patients with anti-PIT-1 antibody syndrome, while we detected in 6 % of control subjects, in which the prevalence was significantly increased in the patients (P<0.0005). Considering the physiological function of SIAE and the clinical features of anti-PIT-1 antibody syndrome, present data imply a novel aspect of the pathogenesis in this disease.Lead, 2014, Endocrine journal, 61(6) (6), 641 - 4, English, Domestic magazine[Refereed]Scientific journal
- Adaptation under fasting conditions is critical for survival in animals. Sirtuin 1 (SIRT1), a protein deacetylase, plays an essential role in adaptive metabolic and endocrine responses under fasting conditions by modifying the acetylation status of various proteins. Fasting induces growth hormone (GH) resistance in the liver, leading to decreased serum insulin-like growth factor-I (IGF-I) levels as an endocrine adaptation for malnutrition; however, the underlying mechanisms of this action remain to be fully elucidated. Here we report that in vivo knockdown of SIRT1 in the liver restored the fasting-induced decrease in serum IGF-I levels and enhanced the GH-dependent increase in IGF-I levels, indicating that SIRT1 negatively regulates GH-dependent IGF-I production in the liver. In vitro analysis using hepatocytes demonstrated that SIRT1 suppresses GH-dependent IGF-I expression, accompanied by decreased tyrosine phosphorylation on signal transducer and activator of transcription (STAT) 5. GST pull-down assays revealed that SIRT1 interacts directly with STAT5. When the lysine residues adjacent to the SH2 domain of STAT5 were mutated, STAT5 acetylation decreased concomitant with a decrease in its transcriptional activity. Knockdown of SIRT1 enhanced the acetylation and GH-induced tyrosine phosphorylation of STAT5, as well as the GH-induced interaction of the GH receptor with STAT5. These data indicate that SIRT1 negatively regulates GH-induced STAT5 phosphorylation and IGF-I production via deacetylation of STAT5 in the liver. In addition, our findings explain the underlying mechanisms of GH resistance under fasting conditions, which is a known element of endocrine adaptation during fasting.Lead, NATL ACAD SCIENCES, Sep. 2013, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 110(37) (37), 14948 - 14953, English[Refereed]Scientific journal
- 2013, Eur J Endocrinol., Oct 28. [Epub ahead of print], Englishor central diabetes insipidus and review of the literature.[Refereed]Scientific journal
- Efficacy of combined octreotide and cabergoline treatment in patients with acromegaly: A retrospective clinical study and review of the literatureAlthough somatostatin analogues are effective medical therapy for acromegaly, the serum insulin-like growth factor-I (IGF-I) levels remain uncontrolled in 35% of patients. Combined therapy with octreotide LAR and cabergoline has been reported to normalize IGF-I levels in 42-56% of Caucasian patients with acromegaly. However, it remains to be clarified whether combination therapy is effective in Japanese patients and on tumor shrinkage. We conducted a retrospective study on combined therapy in patients with octreotide-resistant acromegaly. Ten patients with acromegaly who showed octreotide-resistance were enrolled in this study. Cabergoline was added in doses of 0.25-2.0mg/week. Serum GH and IGF-I levels and tumor volume were assessed before and after treatment, and factors correlated with effect of the combined therapy were analyzed. Although serum GH levels did not decrease, serum IGF-I levels significantly decreased by 20% after 6 months of combined therapy compared with baseline (p < 0.05). As a result, serum IGF-I levels normalized in 30% of the patients. Tumor volume after combined therapy also significantly decreased (p < 0.01). There were no correlations between the decrease of serum IGF-I levels during combined therapy and the response of GH in a bromocriptine test, random GH, IGF-I, and PRL levels, the tumor volume, and the expression of PRL and dopamine D2 receptor in the tumor. In conclusion, we demonstrated that the addition of cabergoline to octreotide LAR is a beneficial option in Japanese patients with octreotide-resistant acromegaly, irrespective of serum PRL levels and the response of GH levels in a bromocriptine test. © The Japan Endocrine Society.2013, Endocrine Journal, 60(4) (4), 507 - 515, English[Refereed]Scientific journal
- 後天性成長ホルモン(GH)、甲状腺刺激ホルモン(TSH)、プロラクチン(PRL)欠損症をきたした下垂体機能低下症3例において、GH、TSH、PRL産生細胞に必須の転写因子であるPIT-1に対する自己抗体が発見された。また複数の内分泌臓器の自己免疫的障害と多彩な自己抗体を認め多腺性自己免疫症候群(APS)の病像を呈していた。本症候群では、PIT-1に対する免疫寛容の破綻によって特異的ホルモン欠損をきたした新たな症候群と考えられAPSに関連した'抗PIT-1抗体症候群'と名付けられた。(著者抄録)(株)北隆館, Nov. 2012, BIO Clinica, 27(12) (12), 1185 - 1188, Japanese
- (有)医学の世界社, Oct. 2012, ホルモンと臨床, 60(10) (10), 787 - 793, Japanese【下垂体疾患最前線】下垂体疾患の新しい病態 抗PIT-1抗体症候群の病態と自己免疫性下垂体疾患における位置付け
- Cellular senescence is characterized by growth arrest, enlarged and flattened cell morphology, the expression of senescence-associated beta-galactosidase (SA-beta-gal). and by activation of tumor suppressor networks. Insulin-like growth factor-I (IGF-I) plays a critical role in cellular growth, proliferation, tumorigenesis, and regulation of aging. In the present study, we show that IGF-I enhances cellular senescence in mouse, rat, and human primary cells in the confluent state: IGF-I induced expression of a DNA damage marker, gamma H2AX, the increased levels of p53 and p21 proteins, and activated SA-beta-gal. In the confluent state, an altered downstream signaling of IGF-I receptor was observed. Treatment with a reactive oxygen species (ROS) scavenger, N-acetylcystein (NAC) significantly suppressed induction of these markers. indicating that ROS are involved in the induction of cellular senescence by IGF-I. In p53-null mouse embryonic fibroblasts, the IGF-I-induced augmentation of SA-beta-gal and p21 was inhibited, demonstrating that p53 is required for cellular senescence induced by IGF-I. Thus, these data reveal a novel pathway whereby IGF-I enhances cellular senescence in the ROS and p53-dependent manner and may explain the underlying mechanisms of IGF-I involvement in tumorigenesis and in regulation of aging. (c) 2012 Elsevier Inc. All rights reserved.ACADEMIC PRESS INC ELSEVIER SCIENCE, Aug. 2012, BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 425(2) (2), 478 - 484, English[Refereed]Scientific journal
- Background: Liver dysfunction in adult hypopituitary patients with GH deficiency (GHD) has been reported and an increased prevalence of nonalcoholic fatty liver disease (NAFLD) has been suggested. Objective: The objective of the present study was to elucidate the pathophysiology of the liver in adult hypopituitary patients with GHD. Patients and methods: We recruited 69 consecutive Japanese adult hypopituitary patients with GHD and examined the prevalence of NAFLD by ultrasonography and nonalcoholic steatohepatitis (NASH) by liver biopsy. Patients had been given routine replacement therapy except for GH. We compared these patients with healthy age-, gender-, and BMI-matched controls. We further analyzed the effect of GH replacement therapy on liver function, inflammation and fibrotic markers, and histological changes. Results: The prevalence of NAFLD in hypopituitary patients with GHD was significantly higher than in controls (77 vs 12%, P<0.001). Of 16 patients assessed by liver biopsy, 14 (21%) patients were diagnosed with NASH. GH replacement therapy significantly reduced serum liver enzyme concentrations in the patients and improved the histological changes in the liver concomitant with reduction in fibrotic marker concentrations in patients with NASH. Conclusions: Adult hypopituitary patients with GHD demonstrated a high NAFLD prevalence. The effect of GH replacement therapy suggests that the NAFLD is predominantly attributable to GHD.BIOSCIENTIFICA LTD, Jul. 2012, EUROPEAN JOURNAL OF ENDOCRINOLOGY, 167(1) (1), 67 - 74, English[Refereed]Scientific journal
- Objective: This study was performed to clarify the pathophysiology of familial short stature with moderate GH deficiency. Patients: The siblings showed moderate GH deficiency with short stature. Pedigree analysis revealed an accumulation of the history of short stature in father's relatives, although there was no consanguinity. Methods: We performed sequencing analysis of GH1 and GHSR gene in the siblings. Results: We detected SNPs in the GH1 gene in the combination of the -278G, -57T, +1169T, and +2103C in one allele from the father and the -2781, -57G, +1169 A, and +2103T in the other allele from the mother in the siblings. In the previous report, the -278G and -57T allele are associated with low serum IGF-I levels in patients with isolated GH deficiency and the haplotype of the -2781, -57G, +1169 A, and +21031 allele exhibited an impaired GH secretion in vitro. Conclusions: It is suggested that these haplotypes were responsible at least in part for the GH deficiency and short stature in these siblings.Lead, JOHANN AMBROSIUS BARTH VERLAG MEDIZINVERLAGE HEIDELBERG GMBH, May 2012, EXPERIMENTAL AND CLINICAL ENDOCRINOLOGY & DIABETES, 120(5) (5), 308 - 310, English[Refereed]Scientific journal
- Background: Excessive oxidative stress plays a causal role in various diseases such as diabetes, hypertension, atherosclerosis, and heart failure. Acromegaly is a pathological condition associated with excess growth hormone (GH) and insulin-like growth factor-I (IGF-I) and a high prevalence of diabetes, hypertension, atherosclerosis, and heart failure; resulting in premature death. We hypothesized that these conditions may be associated with increased oxidative stress. Objective and methods: We explored the oxidative stress levels in the serum and tissues of GH-transgenic rats as an animal model for acromegaly. We also measured the oxidative stress levels in the serum of patients with acromegaly and age-, sex-, and BMI-matched control subjects. We examined the effects of GH and IGF-I on reactive oxygen species (ROS) production in C2C12 myocytes. Results: The levels of an oxidative stress marker, serum thiobarbituric acid reactive substances (TBARS) were increased in the GH-transgenic rats. Further, tissue oxidative stress damage was enhanced in the cardiomyocytes and vascular smooth muscle cells in the aorta of the GH-transgenic rats. In addition, serum TBARS levels and 8-hydroxy-2-deoxyguanosine (8-OHdG) levels were increased in acromegaly in humans. IGF-I but not GH induced ROS production in C2C12 myocytes in vitro. Conclusions: These data indicate that the increased levels of IGF-I are associated with enhanced oxidative stress in rats and humans. In addition, increased ROS may play an important role in the complications and premature death in acromegaly. (C) 2012 Elsevier Ltd. All rights reserved.CHURCHILL LIVINGSTONE, Apr. 2012, GROWTH HORMONE & IGF RESEARCH, 22(2) (2), 64 - 68, English[Refereed]Scientific journal
- Although various function of chemerin have been suggested, its physiological role remains to be elucidated. Here we show that chemerin-deficient mice are glucose intolerant irrespective of exhibiting reduced macrophage accumulation in adipose tissue. The glucose intolerance was mainly due to increased hepatic glucose production and impaired insulin secretion. Chemerin and its receptor ChemR23 were expressed in beta-cell. Studies using isolated islets and perfused pancreas revealed impaired glucose-dependent insulin secretion (GSIS) in chemerin-deficient mice. Conversely, chemerin transgenic mice revealed enhanced GSIS and improved glucose tolerance. Expression of MafA, a pivotal transcriptional factor for beta-cell function, was downregulated in chemerin-deficient islets and a chemerin-ablated beta-cell line and rescue of MafA expression restored GSIS, indicating that chemerin regulates beta-cell function via maintaining MafA expression. These results indicate that chemerin regulates beta-cell function and plays an important role in glucose homeostasis in a tissue-dependent manner.NATURE PUBLISHING GROUP, Oct. 2011, SCIENTIFIC REPORTS, 1, 123, English[Refereed]Scientific journal
- (有)科学評論社, Sep. 2011, 内分泌・糖尿病・代謝内科, 33(3) (3), 240 - 246, Japanese抗PIT-1抗体による下垂体前葉ホルモン複合分泌不全症
- IGF-I induces skeletal muscle hypertrophy by stimulating protein synthesis and suppressing the protein degradation pathway; the downstream signaling pathways Akt-mammalian target of rapamycin (mTOR)-p70-kDA-S6-kinase (p70S6K), and Forkhead box O1 (FoxO1) play essential roles in this regulation. Reactive oxygen species (ROS) modulate the signaling of various growth factors via redox regulation. However, the role of ROS in IGF-I signaling is not fully understood. In this study, we investigated whether ROS regulate the signaling and biological action of IGF-I in C2C12 myocytes. We found that IGF-I induces ROS in C2C12 myocytes. While treatment with H(2)O(2) significantly enhanced IGF-I-induced phosphorylation of the IGF-I receptor (IGF-IR), IGF-IR phosphorylation was markedly attenuated when cells were treated with antioxidants. The downstream signaling pathway, Akt-mTOR- p70S6K was subsequently down-regulated. Furthermore, the phosphorylation of FoxO1 by IGF-I decreased concomitantly with the restoration of the expression of its target genes, Atrogin-1 and muscle RING finger 1, which are related to muscle atrophy. Nox4 knockdown, which is reportedly to produce ROS in insulin signaling, attenuated IGF-I-induced IGF-IR phosphorylation, indicating that Nox4 is involved in the regulation of IGF-I signaling. Importantly, antioxidant treatments inhibited IGF-I-induced myocyte hypertrophy, demonstrating that ROS are necessary for IGF-I-induced myocyte hypertrophyin vitro. These results indicate that ROS play an essential role in the signaling and biological action of IGF-I in C2C12 myocytes. (Endocrinology 152: 912-921, 2011)ENDOCRINE SOC, Mar. 2011, ENDOCRINOLOGY, 152(3) (3), 912 - 921, English[Refereed]Scientific journal
- The pituitary-specific transcriptional factor-1 (PIT-I, also known as POU1F1), is an essential factor for multiple hormone-secreting cell types A genetic defect in the PIT-1 gene results in congenital growth hormone (GH), prolactin (PRL), and thyroid-stimulating hormone (TSH) deficiency Here, we investigated 3 cases of adult onset combined GH, PRL, and TSH deficiencies and found that the endocrinological phenotype in each was linked to autoimmunity directed against the PIT-1 protein We detected anti-PIT-1 antibody along with various autoantibodies in the patients' sera An ELISA-based screening revealed that this antibody was highly specific to the disease and absent in control subjects Immunohistochemical analysis revealed that PIT-1-, GH-, PRL-, and TSH-positive cells were absent in the pituitary of patient 2, who also had a range of autoimmune endocrinopathies These clinical manifestations were compatible with the definition of autoimmune polyendocrine syndrome (APS) However, the main manifestations of APS-I - hypoparathyroidism and Candida infection were not observed and the pituitary abnormalities were obviously different from the hypophysitis associated with APS These data suggest that these patients define a unique "anti-PIT-1 antibody syndrome" related to APSLead, AMER SOC CLINICAL INVESTIGATION INC, Jan. 2011, JOURNAL OF CLINICAL INVESTIGATION, 121(1) (1), 113 - 119, English[Refereed]Scientific journal
- A 56-year-old patient with postsurgical hypothyroidism and hypoparathyroidism associated with gastrointestinal malabsorption syndrome was prescribed with l-thyroxine and 1 alpha(OH)D-3 at a massive daily dosage of 600 and 39 mu g, respectively. Although the patient became nearly euthyroid, she had been hypocalcemic, requiring frequent intravenous injection of calcium gluconate to prevent tetany. Because the serum level of 1,25(OH)(2)D hardly increased after an oral intake of 21 mu g 1 alpha(OH)D-3, vitamin D-3 was administered intramuscularly. After stoss therapy (600,000 IU), the patient has been receiving 300,000 IU vitamin D-3 at intervals of 2-4 months so that she remained slightly hypocalcemic (7-8 mg/dl). At 1.5 years later, serum levels of 25(OH)D and 1,25(OH)(2)D were maintained at about 60 ng/ml and 30-50 pg/ml, respectively, and renal function was maintained well. These data suggest that intramuscular injection of 300,000 IU vitamin D-3 at an interval of a few months to maintain a slightly increased serum level of 25(OH)D and a slightly decreased serum level of calcium is a safe and cost-effective treatment in such a parathyroid hormone-deficient hypoparathyroid patient with malabsorption syndrome.SPRINGER TOKYO, Mar. 2010, Journal of bone and mineral metabolism, 28(2) (2), 227 - 232, English
- Mar. 2010, ENDOCRINE JOURNAL, 57, S520GH and IGF-I ameliorate inflammation and fibrosis in a mouse model of non alcoholic steatohepatitis[Refereed]
- Empty sella syndrome is frequently accompanied with pituitary dysfunction. Most of the patients with empty sella syndrome demonstrate primary pituitary or stalk dysfunction and few cases show hypothalamic dysfunction. A 71-year-old man manifested appetite loss, nausea and vomiting with hyponatremia and adrenal insufficiency. Hormonal evaluation and cranial MRI revealed a panhypopituitarism with empty sella. Intriguingly, while the response of ACTH to CRH administration was exaggerated, the response to insulin hypoglycemia was blunted. Serum PRL levels were normal. Further, decreased level of fT4, slightly elevated basal levels of TSH, and delayed response of TSH to TRH administration were observed. These findings strongly suggest that the panhypopituitarism is caused by hypothalamic dysfunction. The presence of autoantibodies to pituitary and cerebrum in the patient's serum implies an autoimmune mechanism as a pathogenesis.Jul. 2009, Endocr J, 56(4) (4), 585 - 589, English
- A case of partial central diabetes insipidus associated with sarcoidosis38歳男。4年前より霧視を自覚しサルコイドーシスによるブドウ膜炎と診断され半年間ステロイド内服加療を行ったが自己中断した。3年前より性欲の低下を自覚したが放置した。半年前より口渇、多飲多尿を認め、2ヵ月前より全身倦怠感、下肢の脱力を自覚し、精査入院した。頭部MRIを施行した。強い造影効果を伴う下垂体茎の腫大を認め、T1強調画像では後葉の高信号は消失していた。頭部MRIにおける下垂体茎病変が存在しAVPの分泌不全を認め、DDAVPによる治療を開始した。肺門部リンパ節腫大、脾腫があり、ACEの上昇も認め、下垂体腫大はサルコイドーシスの中枢神経病変と考えプレドニゾロンを開始した。1ヵ月後の頭部MRIでは下垂体茎の腫大は認めず造影効果も消失し、同時に脾腫、脾内病変も改善した。血清ACE、リゾチーム値の低下を認めたが、尿中β2-MGの高値および尿量の抑制が不十分で、尿細管障害の残存が示唆された。Lead, 医学の世界社, Mar. 2009, ホルモンと臨床, 57(3) (3), 289 - 295, Japanese
- A case of osteomalacia with acquired Fanconi syndrome presumably induced by monoclonal gammopathy of undetermined significance (MGUS)症例は60歳女性で、8年前に糖尿病と診断された際に初めて腎機能低下を指摘され、腹部エコーにて右腎萎縮と右腎結石が認められた。4年前には原発性副甲状腺機能亢進症を疑われたが、画像上副甲状腺の腫大は認めず、経過観察となった。2年前に肩甲骨の疼痛が出現、NSAIDs内服で疼痛はコントロール良好であったが、その後疼痛部位が胸骨・肋骨・膝関節・足関節へと拡大してNSAIDsが徐々に無効となった。同時期より骨型ALPの上昇を認め、骨シンチでは肋骨・膝関節・足関節に集積を認めたがPET/CT検査では有意な集積は認めず原因精査目的で紹介入院となった。入院時、全身の骨痛を自覚しており、血液検査では低リン血症・高ALP血症を認め、全身骨X線像では骨透過性亢進と骨変形を認め、骨シンチにて多発集積を認めたことから臨床的に骨軟化症と考えた。糖尿病・リン酸尿・アミノ酸尿に加え、尿酸・カリウムの尿中喪失による低尿酸血症・低カリウム血症を認めたことからFanconi症候群による低リン血症性骨軟化症と診断した。Fanconi症候群の原因としてはmonoclonal gammopathy of undetermined significanceが疑われた。治療として活性ビタミンD3と中性リン製剤の投与を開始、尿中リン排泄量の増加不良の原因であった酸化マグネシウム投与の中止により良好な吸収が得られ、リン内服量1.5gを外来での維持量とした。骨痛に関しては腎機能障害があることからオキシコドン塩酸塩80mg+アセトアミノフェン1600mgの併用で良好なコントロールが得られ、2ヵ月後にはオキシコドン塩酸塩を中止、3ヵ月後にはアセトアミノフェン400mgまで減量したが、疼痛は治療開始前の3/10程度に改善した。Lead, 医学の世界社, Jul. 2008, ホルモンと臨床, 56(7) (7), 757 - 761, Japanese
- A 30-year-old normocalcemic man with hypopituitarism, hypogonadism, diabetes mellitus, and secondary hemochromatosis due to multiple blood transfusions was admitted because of adrenal crisis. After intravenous administration of saline and cortisol, the corrected serum level of calcium decreased to 7.3 mg/dl. This osteoporotic patient had been prescribed alendronate for radial bone fracture. Since the increase in intact PTH (68 pg/ml) was impaired compared to that seen in hypocalcemic patients with secondary hyperparathyroidism, we presume that the patient has had latent hypoparathyroidism, which was unmasked by the administration of glucocorticoid and bisphosphonate. With a supplemented dose of 1 alpha-OHD3, the patient has been eucalcemic.JAPAN SOC INTERNAL MEDICINE, 2008, INTERNAL MEDICINE, 47(6) (6), 515 - 520, English[Refereed]Scientific journal
- McCune-Albright症候群に全身性強皮症を合併した先端巨大症の一例58歳女性。20歳時にMcCune-Albright症候群と診断され、52歳時には全身性強皮症(SSc)と診断された。40歳前後より先端巨大症を疑う身体所見、内分泌学的検査所見を認めており、精査加療目的で入院となった。身体所見にて先端巨大症様顔貌、手指肥大、右背部にカフェオレ斑、左肩甲骨部骨変形を認め、X線所見にて左上腕骨、左尺骨および橈骨の菲薄化膨隆、嚢胞状変化を認めた。内分泌学的検査所見にてGH、IGF-I高値で、75gOGTTでGHは抑制なく、TRH負荷試験でGHの奇異反応を認めた。下垂体MRIを施行したところ9mmの腺腫を認め、GH産生下垂体腺腫の診断で経鼻的下垂体腫瘍摘出術を施行、病理所見より下垂体GH/PRL産生腺腫と確定診断した。術直後の75gOGTTでGHの抑制なくTRHに対するGHの奇異反応は持続し、PRLの高値を認めた。腫瘍の残存を疑いcabergoline内服を追加したところ、5ヵ月後のIGF-I 260ng/ml、PRL 1.8ng/mlと寛解状態に至り、現在経過観察中である。Lead, (一社)日本内分泌学会, Jun. 2007, 日本内分泌学会雑誌, 83(Suppl.) (Suppl.), 102 - 103, Japanese
- (一社)日本内分泌学会, Oct. 2024, 日本内分泌学会雑誌, 100(2) (2), 590 - 590, Japanese急激な症状の顕在化と共に下垂体卒中を来したCushing病の一例
- (一社)日本内分泌学会, Oct. 2024, 日本内分泌学会雑誌, 100(2) (2), 623 - 623, Japanese腫瘍別にMIBG集積性が異なった両側褐色細胞腫の1例
- (一社)日本内分泌学会, Oct. 2024, 日本内分泌学会雑誌, 100(2) (2), 590 - 590, Japanese急激な症状の顕在化と共に下垂体卒中を来したCushing病の一例
- (一社)日本内分泌学会, Oct. 2024, 日本内分泌学会雑誌, 100(2) (2), 623 - 623, Japanese腫瘍別にMIBG集積性が異なった両側褐色細胞腫の1例
- (一社)日本内分泌学会, May 2024, 日本内分泌学会雑誌, 100(1) (1), 332 - 332, JapaneseDailyからweekly GH製剤への切り替え後よりインスリン量の週内調節が必要となった1型糖尿病合併汎下垂体機能低下症の1例
- (一社)日本内分泌学会, May 2024, 日本内分泌学会雑誌, 100(1) (1), 370 - 370, Japaneseメチラポン,カベルゴリン併用からオシロドロスタットへの切り替えを行った94歳Cushing病の一例
- (一社)日本内分泌学会, May 2024, 日本内分泌学会雑誌, 100(1) (1), 426 - 426, JapaneseDOC産生肉腫型副腎皮質癌の1例
- (一社)日本糖尿病学会, Apr. 2024, 糖尿病, 67(Suppl.1) (Suppl.1), S - 176, Japanese抗PD-1抗体阻害薬投与後に発症した膵臓MRI所見と血清CPRの経時的な変化を発症早期より確認し得た劇症1型様の糖尿病の一例
- (一社)日本糖尿病学会, Apr. 2024, 糖尿病, 67(Suppl.1) (Suppl.1), S - 190, Japanese他科入院中患者に対する糖尿病内科医の併診業務の診療実態とその経時的推移
- (一社)日本内分泌学会, Apr. 2024, 日本内分泌学会雑誌, 99(5) (5), 1393 - 1393, Japanese
- (一社)日本内分泌学会, Apr. 2024, 日本内分泌学会雑誌, 99(5) (5), 1423 - 1423, Japanese
- (一社)日本内分泌学会, Apr. 2024, 日本内分泌学会雑誌, 99(5) (5), 1430 - 1430, Japanese
- (一社)日本内分泌学会, Apr. 2024, 日本内分泌学会雑誌, 99(5) (5), 1681 - 1681, Japanese
- (一社)日本糖尿病学会, Feb. 2024, 糖尿病, 67(2) (2), 84 - 84, Japaneseハイブリッドクローズドループ(HCL)療法下でフルマラソンを完走した1型糖尿病の2例
- (一社)日本糖尿病学会, Feb. 2024, 糖尿病, 67(2) (2), 85 - 85, Japanese多職種連携のもとで実施した減量・代謝改善手術4例の経験
- (一社)日本糖尿病学会, Feb. 2024, 糖尿病, 67(2) (2), 87 - 87, Japanese著明なインスリン抵抗性を呈した若年Werner症候群の1例
- (一社)日本糖尿病学会, Feb. 2024, 糖尿病, 67(2) (2), 89 - 89, Japanese緩徐な経過を辿った免疫関連副作用(irAE)による1型様の糖尿病の1例
- (一社)日本糖尿病学会, Feb. 2024, 糖尿病, 67(2) (2), 102 - 102, Japanese複数の膵島関連自己抗体が陽性だがprobable判定であった緩徐進行1型糖尿病の1例
- (一社)日本糖尿病学会, Feb. 2024, 糖尿病, 67(2) (2), 84 - 84, Japaneseハイブリッドクローズドループ(HCL)療法下でフルマラソンを完走した1型糖尿病の2例
- (一社)日本糖尿病学会, Feb. 2024, 糖尿病, 67(2) (2), 85 - 85, Japanese多職種連携のもとで実施した減量・代謝改善手術4例の経験
- (一社)日本糖尿病学会, Feb. 2024, 糖尿病, 67(2) (2), 87 - 87, Japanese著明なインスリン抵抗性を呈した若年Werner症候群の1例
- (一社)日本糖尿病学会, Feb. 2024, 糖尿病, 67(2) (2), 89 - 89, Japanese緩徐な経過を辿った免疫関連副作用(irAE)による1型様の糖尿病の1例
- (一社)日本糖尿病学会, Feb. 2024, 糖尿病, 67(2) (2), 102 - 102, Japanese複数の膵島関連自己抗体が陽性だがprobable判定であった緩徐進行1型糖尿病の1例
- (公財)成長科学協会, 2024, 成長科学協会研究年報, (47) (47), 65 - 66, Japanese下垂体機能低下症におけるオキシトシン分泌不全症の診断法確立とその病態解明
- 2024, ACTH Related Peptides (CD-ROM), 35コルチゾール暴露環境がコルチコトロフ腫瘍における免疫細胞浸潤に与える影響
- (一社)日本内分泌学会, Jan. 2024, 日本内分泌学会雑誌, 99(4) (4), 1130 - 1130, Japanese
- 間脳・下垂体・副腎系研究会, 2024, 間脳・下垂体・副腎系研究会プログラム・抄録集(Web), 35th, 32 - 33, Japaneseコルチゾール暴露環境がコルチコトロフ腫瘍における免疫細胞浸潤に与える影響
- (一社)日本内分泌学会, 2024, 日本内分泌学会雑誌, 100(1) (1), 335 - 335, JapaneseDown症候群に合併したACTH単独欠損症の一例
- (一社)日本内分泌学会, 2024, 日本内分泌学会雑誌, 100(1) (1), 346 - 346, JapaneseACTH産生下垂体腫瘍におけるWW-like領域を含めたUSP8体細胞変異の解析
- (一社)日本内分泌学会, 2024, 日本内分泌学会雑誌, 100(1) (1), 271 - 271, JapaneseGH,PRL完全欠損に至る過程を観察し得た抗PIT-1下垂体炎
- (一社)日本内分泌学会, Jan. 2024, 日本内分泌学会雑誌, 99(4) (4), 1130 - 1130, Japanese成人成長ホルモン分泌不全症UPDATE
- 日本先進糖尿病治療研究会, Nov. 2023, 日本先進糖尿病治療研究会雑誌, 17(2) (2), 92 - 92, JapaneseSAP療法における基礎インスリン設定量とHLC導入後の基礎インスリン注入量の比較検討
- 日本先進糖尿病治療研究会, Nov. 2023, 日本先進糖尿病治療研究会雑誌, 17(2) (2), 105 - 105, Japanese持続皮下インスリンポンプ注入療法(CSII)中の1型糖尿病患者におけるQOLの検討
- (一社)日本内分泌学会, Oct. 2023, 日本内分泌学会雑誌, 99(2) (2), 587 - 587, Japanese
- (一社)日本内分泌学会, Oct. 2023, 日本内分泌学会雑誌, 99(2) (2), 590 - 590, Japanese
- (一社)日本内分泌学会, Oct. 2023, 日本内分泌学会雑誌, 99(2) (2), 608 - 608, Japanese
- (一社)日本内分泌学会, Oct. 2023, 日本内分泌学会雑誌, 99(2) (2), 622 - 622, Japanese
- (一社)日本内分泌学会, Oct. 2023, 日本内分泌学会雑誌, 99(2) (2), 561 - 561, Japanese
- (一社)日本内分泌学会, Oct. 2023, 日本内分泌学会雑誌, 99(2) (2), 561 - 561, Japanese
- (一社)日本内分泌学会, Oct. 2023, 日本内分泌学会雑誌, 99(2) (2), 569 - 569, Japanese
- (一社)日本内分泌学会, Oct. 2023, 日本内分泌学会雑誌, 99(2) (2), 569 - 569, Japanese
- (一社)日本内分泌学会, Oct. 2023, 日本内分泌学会雑誌, 99(2) (2), 581 - 581, Japanese
- (一社)日本内分泌学会, Oct. 2023, 日本内分泌学会雑誌, 99(2) (2), 587 - 587, Japanese
- (一社)日本内分泌学会, Oct. 2023, 日本内分泌学会雑誌, 99(2) (2), 590 - 590, Japanese
- (一社)日本内分泌学会, Oct. 2023, 日本内分泌学会雑誌, 99(2) (2), 608 - 608, Japanese
- (一社)日本内分泌学会, Oct. 2023, 日本内分泌学会雑誌, 99(2) (2), 622 - 622, Japanese
- (一社)日本内分泌学会, Jul. 2023, 日本内分泌学会雑誌, 99(Suppl.) (Suppl.), i - 171, Japanese間脳下垂体機能障害と先天性腎性尿崩症および関連疾患の診療ガイドライン2023年版
- (一社)日本内分泌学会, May 2023, 日本内分泌学会雑誌, 99(1) (1), 228 - 228, Japanese下垂体疾患の診断と治療 Cushing病の診断と治療
- (一社)日本内分泌学会, May 2023, 日本内分泌学会雑誌, 99(1) (1), 295 - 295, Japanese免疫チェックポイント阻害薬が惹起した腫瘍随伴性ACTH単独欠損症
- (一社)日本内分泌学会, May 2023, 日本内分泌学会雑誌, 99(1) (1), 296 - 296, Japaneseゲル濾過分析でACTHの性状を確認し得た異所性ACTH産生腫瘍の一例
- (一社)日本内分泌学会, May 2023, 日本内分泌学会雑誌, 99(1) (1), 301 - 301, Japanese血中に大分子ACTH分泌を認めたコルチゾール産生副腎腺腫の一例
- (一社)日本内分泌学会, May 2023, 日本内分泌学会雑誌, 99(1) (1), 311 - 311, Japanese抗PIT-1下垂体炎新規2例を加えた9症例の臨床的特徴
- (一社)日本内分泌学会, May 2023, 日本内分泌学会雑誌, 99(1) (1), 332 - 332, Japaneseラトケ嚢胞の病理学的診断におけるKRT8の有用性
- (一社)日本内分泌学会, May 2023, 日本内分泌学会雑誌, 99(1) (1), 336 - 336, JapanesePPGLの周術期におけるメチロシン併用に関する検討
- (一社)日本内分泌学会, May 2023, 日本内分泌学会雑誌, 99(1) (1), 395 - 395, JapaneseBMAHにおけるアルドステロン自律性分泌の検討
- 日本先進糖尿病治療研究会, May 2023, 日本先進糖尿病治療研究会雑誌, 17(1) (1), 51 - 51, Japanese間歇スキャン式CGM(isCGM)/Sensor Augmented Pump(SAP)使用中の1型糖尿病患者におけるCGM治療域(TIR)の季節性変動に関する検討
- (一社)日本内分泌学会, May 2023, 日本内分泌学会雑誌, 99(Suppl.Update) (Suppl.Update), 29 - 31, Japanese
- (一社)日本内分泌学会, May 2023, 日本内分泌学会雑誌, 99(Suppl.Update) (Suppl.Update), 51 - 54, Japanese
- (一社)日本糖尿病学会, Apr. 2023, 糖尿病, 66(4) (4), 292 - 292, JapaneseGAD抗体,IA-2抗体重複陽性であった緩徐進行1型糖尿病の1例
- (一社)日本糖尿病学会, Apr. 2023, 糖尿病, 66(4) (4), 302 - 302, Japanese複数の被疑薬が考えられたインスリン自己免疫症候群の1例
- (一社)日本糖尿病学会, Apr. 2023, 糖尿病, 66(4) (4), 307 - 307, Japanese残存インスリン時間の調整が低血糖減少に有効であったHCL加療中1型糖尿病の1例
- (一社)日本内分泌学会, Feb. 2023, 日本内分泌学会雑誌, 98(4) (4), 1035 - 1035, Japanese
- 2023, 日本臨床内分泌病理学会学術総会プログラム・抄録集, 27thBMAHにおけるアルドステロン自律性分泌とその病理学的検討
- (公財)成長科学協会, Dec. 2022, 成長科学協会研究年報, (45) (45), 97 - 98, Japanese成長ホルモン分泌不全症における基礎的・臨床的データの統合的解析による診断予測モデルの構築
- 日本先進糖尿病治療研究会, Dec. 2022, 日本先進糖尿病治療研究会雑誌, 16(2) (2), 63 - 63, Japanese1型糖尿病患者における心エコー図を用いた左室拡張機能の検討
- The Endocrine Society, 01 Nov. 2022, Journal of the Endocrine Society, 6(Supplement{\_}1) (Supplement{\_}1), A499 - A500
- (一社)日本内分泌学会, Oct. 2022, 日本内分泌学会雑誌, 98(2) (2), 552 - 552, Japanese骨粗鬆症を契機に診断に至ったLoeys-Dietz症候群の一例
- (一社)日本内分泌学会, Oct. 2022, 日本内分泌学会雑誌, 98(2) (2), 567 - 567, Japanese局在診断に難渋するACTH依存性Cushing症候群の1例
- (一社)日本内分泌学会, Oct. 2022, 日本内分泌学会雑誌, 98(2) (2), 575 - 575, Japaneseセレン欠乏症により,肝障害と甲状腺機能異常を来した一例
- (一社)日本内分泌学会, Oct. 2022, 日本内分泌学会雑誌, 98(2) (2), 598 - 598, Japanese嚢胞形成を伴う褐色細胞腫4例の嚢胞内カテコラミン分画の検討
- (一社)日本内分泌学会, Oct. 2022, 日本内分泌学会雑誌, 98(2) (2), 605 - 605, JapaneseCushing症候群患者が認識する特異的症候と医師の診断との乖離
- (有)科学評論社, Sep. 2022, 糖尿病・内分泌代謝科, 55(3) (3), 327 - 332, JapaneseGH産生下垂体腺腫
- ACTH産生下垂体腺腫(ACTHoma)において、患者のグルココルチコイドの状態が腫瘍浸潤Tリンパ球に与える影響を明らかにするため2つの検討を行った。検討1として、未治療のACTHoma 29例と対照群(GH産生腫瘍10例、ゴナドトロフ産生腫瘍10例)の浸潤リンパ球数を比較した。検討2として、コルチコトロフ腫瘍53例を対象とし、術前にメチラポンを投与した群(13例)と投与しなかった群(29例)、および臨床的に非機能性腺腫であるsilent corticotroph adenoma群(11例)に分け、浸潤リンパ球数を比較した。その結果、患者のコルチゾールレベルに関係なくコルチコトロフ腫瘍に共通してT細胞浸潤が少ないことと、術前投薬によりコルチゾールを是正することで腫瘍へのCD4陽性T細胞浸潤が回復することが明らかになった。(一社)日本内分泌学会, Aug. 2022, 日本内分泌学会雑誌, 98(Suppl.HPT) (Suppl.HPT), 34 - 37, Japanese
- 32歳男。16歳時に再生不良性貧血と診断され、17歳時から約3週間ごとに赤血球輸血が行われていた。25歳頃から腋毛・恥毛の脱落や精巣の萎縮を自覚していた。今回、再生不良性貧血に対する骨髄移植を目的に当院腫瘍血液内科を受診したさい性腺機能低下症が疑われ、その精査目的に当科入院となった。諸検査の結果と臨床経過から、長期間の輸血による鉄過剰症からゴナドトロピン単独欠損症をきたしたものと判断した。hCG療法を3ヵ月間行ったが性腺機能の明らかな回復はみられなかった。しかし、今後再生不良性貧血の治療により輸血依存状態を脱却し鉄過剰症が改善すれば、hCG/rhFSH療法により性腺機能は回復する可能性があると考えられた。(一社)日本内分泌学会, Aug. 2022, 日本内分泌学会雑誌, 98(Suppl.HPT) (Suppl.HPT), 81 - 83, Japanese
- (一社)日本糖尿病学会, May 2022, 糖尿病, 65(5) (5), 256 - 256, Japanese肺炎治療中に急激に発症し短期間で改善したSLE併発B型インスリン抵抗症の1例
- (一社)日本糖尿病学会, Apr. 2022, 糖尿病, 65(Suppl.1) (Suppl.1), S - 156, JapaneseDTR-QOLを用いた糖尿病患者の教育入院後のQOLの変化の検討
- (一社)日本糖尿病学会, Apr. 2022, 糖尿病, 65(Suppl.1) (Suppl.1), S - 169, Japanese免疫チェックポイント阻害薬投与後に発症した1型糖尿病様の糖尿病の特徴と膵臓MRI所見との関連についての検討
- (一社)日本糖尿病学会, Apr. 2022, 糖尿病, 65(Suppl.1) (Suppl.1), S - 174, Japaneseインスリンポンプの特性を活かした導入支援についての検討
- (一社)日本糖尿病学会, Apr. 2022, 糖尿病, 65(Suppl.1) (Suppl.1), S - 177, JapaneseSGLT2阻害薬投与後のHb増加に伴うGA/HbA1c比への影響に関する検討
- (一社)日本糖尿病学会, Apr. 2022, 糖尿病, 65(Suppl.1) (Suppl.1), S - 199, Japanese肥満症における11の健康障害と長期的な体重変化との関連の検討
- (一社)日本糖尿病学会, Apr. 2022, 糖尿病, 65(Suppl.1) (Suppl.1), S - 238, JapaneseCOVID-19流行下における糖尿病療養支援に関する看護師の意識調査
- (一社)日本糖尿病学会, Apr. 2022, 糖尿病, 65(Suppl.1) (Suppl.1), S - 293, Japaneseメディセーフウィズの導入支援において、看護師が感じる従来型インスリンポンプとの相違について
- (一社)日本糖尿病学会, Apr. 2022, 糖尿病, 65(Suppl.1) (Suppl.1), S - 308, Japanese肥満症患者における食行動質問表の各因子スコアと減量効果予測の検討
- (一社)日本糖尿病学会, Apr. 2022, 糖尿病, 65(Suppl.1) (Suppl.1), S - 308, Japanese肥満症患者に対する術前減量サポートの効果と周術期合併症に関する検討
- (一社)日本肥満学会, Mar. 2022, 肥満研究, 27(Suppl.) (Suppl.), 176 - 176, Japanese肥満のゲノムサイエンス 減量外来受診後にパイロシークエンス法によって診断し得たPrader-Willi症候群の一例
- (一社)日本肥満学会, Mar. 2022, 肥満研究, 27(Suppl.) (Suppl.), 295 - 295, Japanese肥満合併2型糖尿病患者における治療内容ごとの糖尿病QOL質問票(DTR-QOL)に関する検討
- (一社)日本肥満学会, Mar. 2022, 肥満研究, 27(Suppl.) (Suppl.), 335 - 335, Japanese2型糖尿病患者の肥満度別による糖尿病QOL質問票(DTR-QOL)に関する検討
- (一社)日本肥満学会, Mar. 2022, 肥満研究, 27(Suppl.) (Suppl.), 176 - 176, Japanese肥満のゲノムサイエンス 減量外来受診後にパイロシークエンス法によって診断し得たPrader-Willi症候群の一例
- (一社)日本肥満学会, Mar. 2022, 肥満研究, 27(Suppl.) (Suppl.), 295 - 295, Japanese肥満合併2型糖尿病患者における治療内容ごとの糖尿病QOL質問票(DTR-QOL)に関する検討
- (一社)日本肥満学会, Mar. 2022, 肥満研究, 27(Suppl.) (Suppl.), 335 - 335, Japanese2型糖尿病患者の肥満度別による糖尿病QOL質問票(DTR-QOL)に関する検討
- (一社)日本内分泌学会, Mar. 2022, 日本内分泌学会雑誌, 97(5) (5), 1236 - 1236, Japanese
- 2022, 日本臨床内分泌病理学会学術総会プログラム・抄録集, 26thGonadotroph tumorとsomatotroph tumorのcollisionと考えられた一例
- 2022, 糖尿病(Web), 65(Suppl) (Suppl)先端巨大症患者におけるBMIと肥満関連疾患の有病率についての検討
- 2022, 糖尿病(Web), 65(Suppl) (Suppl)1型糖尿病(T1DM)患者におけるIGF-Iと自由行動下のCGM指標に関連する因子の検討
- 2022, 糖尿病(Web), 65(Suppl) (Suppl)肥満症患者における食行動質問表の各因子スコアと減量効果予測の検討
- 2022, 糖尿病(Web), 65(Suppl) (Suppl)Free StyleリブレLink使用者の背景および導入前後におけるスキャン回数,HbA1cの変化の検討
- 2022, 糖尿病(Web), 65(Suppl) (Suppl)肥満症における11の健康障害と長期的な体重変化との関連の検討
- 2022, 糖尿病(Web), 65(Suppl) (Suppl)SGLT2阻害薬投与後のHb増加に伴うGA/HbA1c比への影響に関する検討
- 2022, 糖尿病(Web), 65(Suppl) (Suppl)COVID-19流行下における糖尿病療養支援に関する看護師の意識調査
- 2022, 糖尿病(Web), 65(Suppl) (Suppl)メディセーフウィズの導入支援において,看護師が感じる従来型インスリンポンプとの相違について
- 2022, 糖尿病(Web), 65(Suppl) (Suppl)インスリンポンプの特性を活かした導入支援についての検討
- 2022, 糖尿病(Web), 65(5) (5)インスリン抗体の性質変化に伴いインスリン注射回数の変更を要した1型糖尿病の1例
- 2022, 糖尿病(Web), 65(Suppl) (Suppl)成人成長ホルモン分泌不全症(AGHD)患者におけるGH補充療法による耐糖能への影響に関する検討
- 2022, 糖尿病(Web), 65(5) (5)肺炎治療中に急激に発症し短期間で改善したSLE併発B型インスリン抵抗症の1例
- 2022, 糖尿病(Web), 65(Suppl) (Suppl)免疫チェックポイント阻害薬投与後に発症した1型糖尿病様の糖尿病の特徴と膵臓MRI所見との関連についての検討
- 2022, 糖尿病(Web), 65(Suppl) (Suppl)肥満症患者に対する術前減量サポートの効果と周術期合併症に関する検討
- 2022, 糖尿病(Web), 65(Suppl) (Suppl)DTR-QOLを用いた糖尿病患者の教育入院後のQOLの変化の検討
- 2022, 糖尿病(Web), 65(Suppl) (Suppl)1型糖尿病患者におけるSGLT2阻害薬使用の影響に関する検討
- 2022, 糖尿病(Web), 65(Suppl) (Suppl)若年で糖尿病を発症した小児がん経験者の1例
- 2022, 日本内分泌学会雑誌, 98(1) (1)末梢血FKBP5遺伝子発現はACTH非依存性に血中コルチゾールと関連する
- 2022, 日本内分泌学会雑誌, 98(1) (1)Cushing症候群診断時における自覚症状と他覚所見の乖離について
- 2022, 日本内分泌学会雑誌, 98(1) (1)疾患iPS細胞を用いた自己免疫性下垂体疾患のin vitro疾患モデルの樹立
- 2022, 日本内分泌学会雑誌, 98(1) (1)疾患iPS細胞を用いた自己免疫性下垂体疾患のin vitro疾患モデル樹立と進展防止のための創薬への応用
- 2022, 日本内分泌学会雑誌, 98(1) (1)甲状腺刺激ホルモン(TSH)の測定系のハーモナイゼーションから探る測定系に不安定性を与える因子の検討
- 2022, 日本内分泌学会雑誌, 98(1) (1)先端巨大症患者におけるBMIで層別化した肥満関連疾患の有病率
- 2022, 日本内分泌学会雑誌, 98(1) (1)当院における成人成長ホルモン分泌不全症患者のGH治療による耐糖能変化に寄与する因子の検討
- 2022, 日本内分泌学会雑誌, 98(1) (1)内科における先端巨大症管理~単一施設成績~
- 2022, 日本内分泌学会雑誌, 98(1) (1)下垂体疾患の病因・病態の解明
- 2022, 日本内分泌学会雑誌, 98(1) (1)グルココルチコイド補充中患者におけるCOVID-19ワクチン接種後のステロイドカバーに関する実態調査
- Cushing症候群診断時における自覚症状と他覚所見の乖離について症状・徴候の観点からCushing症候群(CS)の診断が困難である理由について検討した。2004～2022年に当科で副腎性CSと診断した34例(男性4例、女性30例、平均47.7±14.0歳)を対象とした。すべての症状の出現から診断までの期間の中央値は41.5ヵ月であり、最も頻度が多かった症状は体重増加で、症状の出現から診断までの期間も他の症状と比べて長かった。特異的症候に関して、患者の申告では多いものから満月様顔貌41%、近位筋萎縮・筋力低下32%、皮膚菲薄化・易出血性29%といずれも半数以下の申告であったが、医師の診断では満月様顔貌94%、皮膚菲薄化・易出血性79%、中心性肥満・水牛肩79%と高率に認められ、近位筋萎縮・筋力低下以外のすべての特異的症候で医師の診断が患者の申告より有意に多かった。Cushing症候群の診断に時間がかかる要因のひとつとして、特異的症候を患者自身が認知できていないか正確に訴えることができない可能性が示唆された。間脳・下垂体・副腎系研究会, 2022, 間脳・下垂体・副腎系研究会プログラム・抄録集(Web), 33rd, 14 - 16, Japanese
- 2022, 日本間脳下垂体腫瘍学会プログラム・抄録集, 32nd輸血によりゴナドトロピン単独欠損症をきたした再生不良性貧血の一例
- 2022, 日本間脳下垂体腫瘍学会プログラム・抄録集, 32ndグルココルチコイド補充療法患者におけるCOVID-19ワクチン接種後のステロイドカバーに関する実態調査
- 2022, 日本間脳下垂体腫瘍学会プログラム・抄録集, 32ndCorticotroph adenomaにおける腫瘍微小環境とコルチゾールの関連性
- 2022, 日本間脳下垂体腫瘍学会プログラム・抄録集, 32nd重症筋無力症を合併した抗PIT-1下垂体炎の新規症例
- 2022, 日本間脳下垂体腫瘍学会プログラム・抄録集, 32nd神戸大学医学部附属病院におけるクッシング病の診療実態
- 2022, 日本間脳下垂体腫瘍学会プログラム・抄録集, 32ndUSP8変異はAVPR1b受容体高発現を介してクッシング病のDDAVP試験反応性と関連する
- (一社)日本内分泌学会, Dec. 2021, 日本内分泌学会雑誌, 97(4) (4), 907 - 907, Japanese
- (一社)日本内分泌学会, Oct. 2021, 日本内分泌学会雑誌, 97(2) (2), 528 - 528, Japanese
- (一社)日本内分泌学会, Oct. 2021, 日本内分泌学会雑誌, 97(2) (2), 487 - 487, Japanese胸腺腫術後に重症筋無力症を発症した抗PIT-1下垂体炎の1例
- (一社)日本内分泌学会, Oct. 2021, 日本内分泌学会雑誌, 97(2) (2), 501 - 501, JapaneseUSP8変異はV1b受容体発現、DDAVP試験反応性亢進と関連する
- (一社)日本内分泌学会, Oct. 2021, 日本内分泌学会雑誌, 97(2) (2), 505 - 505, Japanese発症36年後に抗ラブフィリン3A抗体陽性を示した尿崩症の1例
- (一社)日本内分泌学会, Oct. 2021, 日本内分泌学会雑誌, 97(2) (2), 533 - 533, JapaneseICIとTKI使用後に原発性副腎不全を生じた腎癌の2例
- (一社)日本内分泌学会, Oct. 2021, 日本内分泌学会雑誌, 97(2) (2), 539 - 539, Japaneseparagangliomaとganglioneuromaの混合腫瘍の1例
- (一社)日本骨粗鬆症学会, Sep. 2021, 日本骨粗鬆症学会雑誌, 7(Suppl.1) (Suppl.1), 346 - 346, JapaneseALP酵素療法により効果を認めた新規ALPL A205T変異による成人発症低ホスファターゼ症の1例
- (一社)日本糖尿病学会, May 2021, 糖尿病, 64(Suppl.1) (Suppl.1), I - 7, Japanese反応性低血糖により診断に至ったA型インスリン抵抗症の1例
- (一社)日本糖尿病学会, May 2021, 糖尿病, 64(Suppl.1) (Suppl.1), I - 3, JapaneseCSII療法施行中1型糖尿病患者の朝食絶食による血中ケトン体推移に関する検討
- (一社)日本糖尿病学会, May 2021, 糖尿病, 64(Suppl.1) (Suppl.1), I - 3, JapaneseDTR-QOLと気分プロフィール検査(POMS短縮版)を用いた教育入院中の糖尿病患者のQOLと感情負担感の変化に関する検討
- (一社)日本糖尿病学会, May 2021, 糖尿病, 64(Suppl.1) (Suppl.1), III - 6, Japanese間歇スキャンCGM(isCGM)使用中の1型糖尿病患者におけるTIR、TAR、TBRの季節性変動に関する検討
- (一社)日本糖尿病学会, May 2021, 糖尿病, 64(Suppl.1) (Suppl.1), III - 1, Japaneseインスリンポンプのトラブルシューティング指導に関わる看護師の理解状況の検討
- (一社)日本糖尿病学会, May 2021, 糖尿病, 64(Suppl.1) (Suppl.1), III - 2, Japaneseチームで取り組む糖尿病教育入院患者の運動療法プログラムが体組成および運動機能に及ぼす影響
- (一社)日本内分泌学会, Apr. 2021, 日本内分泌学会雑誌, 97(1) (1), 122 - 122, Japanese
- (一社)日本内分泌学会, Apr. 2021, 日本内分泌学会雑誌, 97(1) (1), 167 - 167, Japanese
- (一社)日本内分泌学会, Apr. 2021, 日本内分泌学会雑誌, 97(1) (1), 168 - 168, Japanese
- (一社)日本内分泌学会, Apr. 2021, 日本内分泌学会雑誌, 97(1) (1), 224 - 224, Japanese
- (一社)日本内分泌学会, Apr. 2021, 日本内分泌学会雑誌, 97(1) (1), 225 - 225, Japanese
- (一社)日本内分泌学会, Apr. 2021, 日本内分泌学会雑誌, 97(1) (1), 259 - 259, Japanese
- (一社)日本内分泌学会, Apr. 2021, 日本内分泌学会雑誌, 97(1) (1), 262 - 262, Japanese
- (一社)日本内分泌学会, Apr. 2021, 日本内分泌学会雑誌, 97(1) (1), 272 - 272, Japanese
- (一社)日本内分泌学会, Apr. 2021, 日本内分泌学会雑誌, 97(1) (1), 276 - 276, Japanese
- (一社)日本内分泌学会, Apr. 2021, 日本内分泌学会雑誌, 97(1) (1), 286 - 286, Japanese
- (一社)日本内分泌学会, Apr. 2021, 日本内分泌学会雑誌, 97(1) (1), 296 - 296, Japanese
- (一社)日本内分泌学会, Apr. 2021, 日本内分泌学会雑誌, 97(1) (1), 336 - 336, Japanese
- (一社)日本内分泌学会, Apr. 2021, 日本内分泌学会雑誌, 97(1) (1), 347 - 347, Japanese
- (一社)日本内分泌学会, Apr. 2021, 日本内分泌学会雑誌, 97(1) (1), 348 - 348, Japanese
- (一社)日本内分泌学会, Apr. 2021, 日本内分泌学会雑誌, 97(1) (1), 122 - 122, Japanese内分泌研究のインパクト 自己免疫性下垂体疾患の新たな病態の解明と革新的アプローチ
- (一社)日本内分泌学会, Apr. 2021, 日本内分泌学会雑誌, 97(1) (1), 167 - 167, Japanese下垂体の疾患へのアプローチ 下垂体疾患の病態解明を目指したiPS細胞の応用
- (一社)日本内分泌学会, Apr. 2021, 日本内分泌学会雑誌, 97(1) (1), 168 - 168, Japanese下垂体の疾患へのアプローチ POMC遺伝子メチル化とクッシング病の関連性
- (一社)日本内分泌学会, Apr. 2021, 日本内分泌学会雑誌, 97(1) (1), 224 - 224, Japanese高レニン、高アルドステロンを呈したDOC産生副腎皮質癌の一例
- (一社)日本内分泌学会, Apr. 2021, 日本内分泌学会雑誌, 97(1) (1), 225 - 225, Japanese自己免疫性溶血性貧血を伴った悪性胸腺腫合併抗PIT-1下垂体炎の1例
- (一社)日本内分泌学会, Apr. 2021, 日本内分泌学会雑誌, 97(1) (1), 259 - 259, JapaneseACTH産生下垂体腺腫における腫瘍微小環境解析
- (一社)日本内分泌学会, Apr. 2021, 日本内分泌学会雑誌, 97(1) (1), 262 - 262, Japanese疾患iPS細胞/抗原特異的T細胞を用いた抗PIT-1下垂体炎疾患モデルの樹立
- (一社)日本内分泌学会, Apr. 2021, 日本内分泌学会雑誌, 97(1) (1), 272 - 272, Japanese1型糖尿病におけるIGF-I低下と関連する因子の検討
- (一社)日本内分泌学会, Apr. 2021, 日本内分泌学会雑誌, 97(1) (1), 276 - 276, Japaneseパイロシークエンス法によって診断し得たUPD(15)matモザイクによるPrader-Willi症候群の一例
- (一社)日本内分泌学会, Apr. 2021, 日本内分泌学会雑誌, 97(1) (1), 286 - 286, Japanese治療抵抗性高血圧症、低カリウム血症を呈し、レニン産生が疑われた副腎皮質癌の一例
- (一社)日本内分泌学会, Apr. 2021, 日本内分泌学会雑誌, 97(1) (1), 296 - 296, Japaneseメチラポン短期投与でコルチゾールを正常化できた周期性クッシング病の一例
- (一社)日本内分泌学会, Apr. 2021, 日本内分泌学会雑誌, 97(1) (1), 336 - 336, Japanese成人期診断22q11.2欠失症候群における内分泌異常の検討
- (一社)日本内分泌学会, Apr. 2021, 日本内分泌学会雑誌, 97(1) (1), 347 - 347, Japaneseカテコラミン軽度上昇を呈するMIBG両側副腎集積例の検討
- (一社)日本内分泌学会, Apr. 2021, 日本内分泌学会雑誌, 97(1) (1), 348 - 348, Japanese当院PPGL症例におけるメチロシンの使用経験
- (株)メディカ出版, Mar. 2021, 糖尿病ケア, (2021春季増刊) (2021春季増刊), 230 - 233, Japanese【ダウンロードで今すぐ使える!初診・再診・重症化予防の3ステップ 最高で最強の糖尿病患者説明シート57】(第5章)薬物療法の患者説明シート(ステップ2) シックデイってどんな日?薬はどうすればいいの?
- 2021, 日本間脳下垂体腫瘍学会プログラム・抄録集, 31st下垂体腫瘍オルガノイド樹立への挑戦
- (一社)日本内分泌学会, 2021, 日本内分泌学会雑誌, 97(2) (2), 1622 - 1622, Japaneseparagangliomaとganglioneuromaの混合腫瘍の1例
- 2021, 糖尿病(Web), 64(Suppl) (Suppl)CSII療法施行中1型糖尿病患者の朝食絶食による血中ケトン体推移に関する検討
- 2021, 糖尿病(Web), 64(Suppl) (Suppl)反応性低血糖により診断に至ったA型インスリン抵抗症の1例
- 2021, 糖尿病(Web), 64(Suppl) (Suppl)間歇スキャンCGM(isCGM)使用中の1型糖尿病患者におけるTIR,TAR,TBRの季節性変動に関する検討
- 2021, 糖尿病(Web), 64(Suppl) (Suppl)DTR-QOLと気分プロフィール検査(POMS短縮版)を用いた教育入院中の糖尿病患者のQOLと感情負担感の変化に関する検討
- 2021, 糖尿病(Web), 64(Suppl) (Suppl)チームで取り組む糖尿病教育入院患者の運動療法プログラムが体組成および運動機能に及ぼす影響
- 2021, 糖尿病(Web), 64(Suppl) (Suppl)インスリンポンプのトラブルシューティング指導に関わる看護師の理解状況の検討
- (一社)日本内分泌学会, 2021, 日本臨床内分泌病理学会学術総会プログラム・抄録集, 25th(5) (5), 1608 - 1608, JapaneseCorticotroph adenomaにおける腫瘍微小環境は非炎症性を呈する
- (一社)日本内分泌学会, 2021, 日本臨床内分泌病理学会学術総会プログラム・抄録集, 25th(5) (5), 1603 - 1603, Japanese両側副腎での123I-MIBG陽性例における臨床的,病理学的検討
- 2021, 日本神経内分泌学会学術集会プログラム・抄録集, 47thSSTR5の生理的・臨床的意義
- (一社)日本内分泌学会, 2021, 日本神経内分泌学会学術集会プログラム・抄録集, 47th(5) (5), 1236 - 1236, Japanese疾患iPS細胞を用いた自己免疫性下垂体疾患のin vitro疾患モデルの樹立
- (有)科学評論社, 2021, 月刊糖尿病・内分泌代謝科, 53(2) (2), 230 - 234, JapaneseAnti-PIT-1 hypophysitis.
- (一社)日本糖尿病学会, Jan. 2021, 糖尿病, 64(1) (1), 57 - 57, JapaneseNivolumab投与開始1年半後に劇症1型糖尿病様病態で発症した糖尿病の1例
- (一社)日本糖尿病学会, Jan. 2021, 糖尿病, 64(1) (1), 58 - 58, Japanese1型糖尿病患者における、治療法別DTR-QOLスコアの検討
- (一社)日本糖尿病学会, Jan. 2021, 糖尿病, 64(1) (1), 63 - 63, Japanese下垂体腺腫摘出術後に早朝の血糖上昇が改善した先端巨大症の1例
- (一社)日本糖尿病学会, Jan. 2021, 糖尿病, 64(1) (1), 75 - 75, Japanese家族背景から見るDTR-QOLスコアの検討
- (一社)日本糖尿病学会, Jan. 2021, 糖尿病, 64(1) (1), 82 - 82, JapaneseCSII療法中1型糖尿病患者のSGLT2阻害薬服用下での絶食中血中ケトン体変化
- (一社)日本糖尿病学会, Jan. 2021, 糖尿病, 64(1) (1), 84 - 84, Japanese複合要因により自発性低血糖を頻発したアルコール多飲習慣のあるC型肝炎合併透析患者
- (一社)日本内分泌学会, Oct. 2020, 日本内分泌学会雑誌, 96(2) (2), 499 - 499, Japanese
- (一社)日本内分泌学会, Oct. 2020, 日本内分泌学会雑誌, 96(2) (2), 502 - 502, Japanese
- (一社)日本内分泌学会, Oct. 2020, 日本内分泌学会雑誌, 96(2) (2), 561 - 561, Japanese
- (一社)日本内分泌学会, Aug. 2020, 日本内分泌学会雑誌, 96(Suppl.HPT) (Suppl.HPT), 63 - 66, Japaneseプロラクチノーマとして治療されていたaggressiveな機能性FSH産生下垂体腺腫の1例
- (一社)日本内分泌学会, Aug. 2020, 日本内分泌学会雑誌, 96(1) (1), 246 - 246, Japanese
- (一社)日本内分泌学会, Aug. 2020, 日本内分泌学会雑誌, 96(1) (1), 250 - 250, Japanese
- (一社)日本内分泌学会, Aug. 2020, 日本内分泌学会雑誌, 96(1) (1), 251 - 251, Japanese
- (一社)日本内分泌学会, Aug. 2020, 日本内分泌学会雑誌, 96(1) (1), 290 - 290, Japanese
- (一社)日本内分泌学会, Aug. 2020, 日本内分泌学会雑誌, 96(1) (1), 307 - 307, Japanese
- (一社)日本内分泌学会, Aug. 2020, 日本内分泌学会雑誌, 96(1) (1), 360 - 360, Japanese
- (一社)日本内分泌学会, Aug. 2020, 日本内分泌学会雑誌, 96(1) (1), 374 - 374, Japanese
- (一社)日本糖尿病学会, Jul. 2020, 糖尿病, 63(7) (7), 475 - 475, Japanese1型糖尿病患者における心エコー図を用いた左室拡張機能の検討
- (一社)日本糖尿病学会, Jul. 2020, 糖尿病, 63(7) (7), 505 - 505, JapaneseSAP療法中1型糖尿病患者におけるカニューレ交換後の血糖推移に関する検討
- (一社)日本糖尿病学会, Jul. 2020, 糖尿病, 63(7) (7), 505 - 505, JapaneseSAP療法中の1型糖尿病患者におけるPLGS機能導入半年後の効果についての検討
- (一社)日本糖尿病学会, Jul. 2020, 糖尿病, 63(7) (7), 475 - 475, Japanese1型糖尿病患者における心エコー図を用いた左室拡張機能の検討
- (一社)日本糖尿病学会, Jul. 2020, 糖尿病, 63(7) (7), 505 - 505, JapaneseSAP療法中1型糖尿病患者におけるカニューレ交換後の血糖推移に関する検討
- (一社)日本糖尿病学会, Jul. 2020, 糖尿病, 63(7) (7), 505 - 505, JapaneseSAP療法中の1型糖尿病患者におけるPLGS機能導入半年後の効果についての検討
- 日本臨床分子医学会, Apr. 2020, 日本臨床分子医学会学術総会プログラム・抄録集, 57回, 78 - 78, Japanese疾患iPS細胞/抗原特異的T細胞を用いた抗PIT-1下垂体炎疾患モデルの樹立
- 日本臨床分子医学会, Apr. 2020, 日本臨床分子医学会学術総会プログラム・抄録集, 57回, 79 - 79, JapaneseCushing病におけるCRH試験反応性に関連する病態の解明
- 日本臨床分子医学会, Apr. 2020, 日本臨床分子医学会学術総会プログラム・抄録集, 57回, 78 - 78, Japanese疾患iPS細胞/抗原特異的T細胞を用いた抗PIT-1下垂体炎疾患モデルの樹立
- 日本臨床分子医学会, Apr. 2020, 日本臨床分子医学会学術総会プログラム・抄録集, 57回, 79 - 79, JapaneseCushing病におけるCRH試験反応性に関連する病態の解明
- 2020, 日本内分泌学会雑誌, 96(Suppl. HPT (Web)) (Suppl. HPT (Web))プロラクチノーマとして治療されていたaggressiveな機能性FSH産生下垂体腺腫の1例
- 2020, 糖尿病(Web), 63(Suppl) (Suppl)糖尿病教育入院患者におけるDTR-QOLスコアに影響する因子についての検討
- 2020, 糖尿病(Web), 63(Suppl) (Suppl)1型糖尿病患者における発症様式の違いは骨密度に影響を与える
- 2020, 糖尿病(Web), 63(Suppl) (Suppl)当院入院1型糖尿病患者における,入院前後のDTR-QOLスコアの変化
- 2020, プラダー・ウィリ症候群における診療ガイドラインの作成 令和元年度 総括研究報告書(Web)プラダー・ウィリ症候群における診療ガイドラインの作成に関する研究 トランジションを主に
- 2020, 日本間脳下垂体腫瘍学会プログラム・抄録集, 30thAcroQoLを用いた高齢先端巨大症患者QoLの特徴と解析
- 2020, 日本間脳下垂体腫瘍学会プログラム・抄録集, 30th先端巨大症患者のオクトレオチド試験は術前投与における短期間のソマトスタチンアナログ治療効果を予測する
- 2020, 糖尿病(Web), 63(7) (7)1型糖尿病患者における心エコー図を用いた左室拡張機能の検討
- 2020, 糖尿病(Web), 63(7) (7)SAP療法中の1型糖尿病患者におけるPLGS機能導入半年後の効果についての検討
- 2020, 糖尿病(Web), 63(7) (7)SAP療法中1型糖尿病患者におけるカニューレ交換後の血糖推移に関する検討
- (一社)日本内分泌学会, 2020, 日本内分泌学会雑誌, 96(1) (1), 246 - 246, Japanese1型糖尿病ではインスリン分泌能が骨密度に影響を与える
- (一社)日本内分泌学会, 2020, 日本内分泌学会雑誌, 96(1) (1), 250 - 250, Japanese自己免疫性溶血性貧血を伴った悪性胸腺腫合併抗PIT-1下垂体炎の1例
- (一社)日本内分泌学会, 2020, 日本内分泌学会雑誌, 96(1) (1), 251 - 251, JapaneseQT延長,致死性不整脈を呈したACTH分泌不全症の3例
- (一社)日本内分泌学会, 2020, 日本内分泌学会雑誌, 96(1) (1), 290 - 290, JapaneseCushing病におけるCRH試験の反応性と関連する臨床的特徴の検討
- (一社)日本内分泌学会, 2020, 日本内分泌学会雑誌, 96(1) (1), 307 - 307, JapaneseICI関連下垂体炎,1型糖尿病を同時期に発症した一例
- (一社)日本内分泌学会, 2020, 日本内分泌学会雑誌, 96(1) (1), 360 - 360, Japaneseゴナドトロピン単独分泌不全症をきたした再生不良性貧血の一例
- (一社)日本内分泌学会, 2020, 日本内分泌学会雑誌, 96(1) (1), 374 - 374, Japanese高レニン,高アルドステロンを呈したDOC産生副腎皮質癌の一例
- (一社)日本内分泌学会, 2020, 日本内分泌学会雑誌, 96(2) (2), 495 - 495, Japanese免疫チェックポイント阻害薬関連下垂体炎の新たな発症機序の解明
- (一社)日本内分泌学会, 2020, 日本内分泌学会雑誌, 96(2) (2), 506 - 506, Japaneseクッシング病術後に精神症状を生じた1例
- (一社)日本内分泌学会, 2020, 日本内分泌学会雑誌, 96(2) (2), 542 - 542, Japanese血中遊離メタネフリン分画が鑑別に有用であった副腎腺腫の1例
- (一社)日本内分泌学会, 2020, 日本内分泌学会雑誌, 96(2) (2), 564 - 564, JapanesePazopanibにより改善を認めた非膵島細胞腫瘍性低血糖症の一例
- (一社)日本肥満学会, Oct. 2019, 肥満研究, 25(Suppl.) (Suppl.), 312 - 312, Japanese
- (一社)日本内分泌学会, Oct. 2019, 日本内分泌学会雑誌, 95(2) (2), 708 - 708, JapanesebigACTHがないにも関わらずACTH/F高値を認めたクッシング病の1例
- (一社)日本内分泌学会, Oct. 2019, 日本内分泌学会雑誌, 95(2) (2), 706 - 706, Japanese前立腺癌に異所性ACTH発現を認めたACTH単独欠損症の一例
- (一社)日本内分泌学会, Oct. 2019, 日本内分泌学会雑誌, 95(2) (2), 707 - 707, Japanese先端巨大症のオクトレオチド試験は3ヵ月後の薬物効果を予測する
- (一社)日本内分泌学会, Oct. 2019, 日本内分泌学会雑誌, 95(2) (2), 711 - 711, Japanese重症ニューモシスチス肺炎を呈した異所性ACTH症候群の一例
- (一社)日本内分泌学会, Oct. 2019, 日本内分泌学会雑誌, 95(2) (2), 720 - 720, Japanese抗PIT-1抗体症候群は新たな傍腫瘍症候群である
- (一社)日本内分泌学会, Oct. 2019, 日本内分泌学会雑誌, 95(2) (2), 767 - 767, Japanese
- (一社)日本内分泌学会, Oct. 2019, 日本内分泌学会雑誌, 95(2) (2), 781 - 781, Japanese
- (一社)日本内分泌学会, Oct. 2019, 日本内分泌学会雑誌, 95(2) (2), 796 - 796, Japanese
- (一社)日本内分泌学会, Oct. 2019, 日本内分泌学会雑誌, 95(2) (2), 810 - 810, Japanese
- (一社)日本内分泌学会, Oct. 2019, 日本内分泌学会雑誌, 95(2) (2), 815 - 815, Japanese
- (一社)日本内分泌学会, Oct. 2019, 日本内分泌学会雑誌, 95(2) (2), 821 - 821, Japanese
- (一社)日本内分泌学会, Oct. 2019, 日本内分泌学会雑誌, 95(2) (2), 706 - 706, Japanese前立腺癌に異所性ACTH発現を認めたACTH単独欠損症の一例
- (一社)日本内分泌学会, Oct. 2019, 日本内分泌学会雑誌, 95(2) (2), 707 - 707, Japanese先端巨大症のオクトレオチド試験は3ヵ月後の薬物効果を予測する
- (一社)日本内分泌学会, Oct. 2019, 日本内分泌学会雑誌, 95(2) (2), 720 - 720, Japanese抗PIT-1抗体症候群は新たな傍腫瘍症候群である
- (一社)日本内分泌学会, Oct. 2019, 日本内分泌学会雑誌, 95(2) (2), 767 - 767, Japanese高齢先端巨大症患者におけるQOL低下に関連する因子の検討
- (一社)日本内分泌学会, Oct. 2019, 日本内分泌学会雑誌, 95(2) (2), 796 - 796, Japaneseアルドステロン産生腺腫の分泌能は腫瘍径と正の相関を示す
- (一社)日本内分泌学会, Oct. 2019, 日本内分泌学会雑誌, 95(2) (2), 810 - 810, Japanese副甲状腺摘出術によって膵NETの改善を認めたMEN1の1例
- (一社)日本内分泌学会, Oct. 2019, 日本内分泌学会雑誌, 95(2) (2), 815 - 815, Japanese1型糖尿病患者における骨密度低下に関連する因子の検討
- 2019, 日本小児内分泌学会学術集会プログラム・抄録集, 53rd祖母の診断を契機に3歳時に診断に至った家族性中枢性尿崩症の一例
- (一社)日本内分泌学会, 2019, 日本内分泌学会雑誌, 95(3 (Web)) (3 (Web)), 1139 - 1139, Japanese高齢先端巨大症患者におけるQOLの特徴とその低下に寄与する因子の検討
- (一社)日本内分泌学会, 2019, 日本内分泌学会雑誌, 95(3 (Web)) (3 (Web)), 1142 - 1142, Japanese2年間以上形態学的変化のなかった肺腫瘤が原因であった異所性ACTH症候群の一例
- (一社)日本内分泌学会, Apr. 2018, 日本内分泌学会雑誌, 94(1) (1), 290 - 290, Japanese下垂体SSTR5はmicroRNAを介してHPA軸を抑制する
- (一社)日本内分泌学会, Apr. 2015, 日本内分泌学会雑誌, 91(1) (1), 332 - 332, Japanese甲状腺中毒性周期性四肢麻痺を契機にGitelman症候群と診断された一例
- (一社)日本内分泌学会, Oct. 2014, 日本内分泌学会雑誌, 90(3) (3), 950 - 950, JapaneseTSH産生腫瘍、脳塞栓症と抗体陰性のバセドウ病を合併した1例
- (一社)日本内分泌学会, Oct. 2014, 日本内分泌学会雑誌, 90(3) (3), 954 - 954, Japanese低Na血症と視神経脊髄炎関連疾患を合併した一例
- ENDOCRINE SOC, Jun. 2014, ENDOCRINE REVIEWS, 35(3) (3), EnglishThe Significance of Confirmatory Tests in Primary AldosteronismSummary international conference
- ENDOCRINE SOC, Jun. 2014, ENDOCRINE REVIEWS, 35(3) (3), EnglishUsefulness of the Growth Hormone-Releasing Peptide-2 Test in Insulinoma DiagnosisSummary international conference
- (一社)日本糖尿病学会, Jun. 2014, 糖尿病, 57(6) (6), 472 - 472, Japanese挙児希望の1型糖尿病に対し炭水化物制限食を試みた1例
- (一社)日本内分泌学会, Apr. 2014, 日本内分泌学会雑誌, 90(1) (1), 313 - 313, Japanese妊娠中の甲状腺機能亢進症の5例
- (一社)日本内分泌学会, Apr. 2014, 日本内分泌学会雑誌, 90(1) (1), 327 - 327, Japanese原発性アルドステロン症における4種負荷試験の有用性の検討
- (一社)日本糖尿病学会, Apr. 2014, 糖尿病, 57(Suppl.1) (Suppl.1), S - 232, Japaneseインスリン投与開始量の設定法に関する検討
- (一社)日本内分泌学会, Dec. 2013, 日本内分泌学会雑誌, 89(3) (3), 983 - 983, Japaneseカテコラミン合成異常による起立性低血圧の新たな原因疾患の同定
- (一社)日本内分泌学会, Dec. 2013, 日本内分泌学会雑誌, 89(3) (3), 950 - 950, Japanese分娩時大量出血から52年後に診断されたSheehan症候群の一例
- (一社)日本内分泌学会, Dec. 2013, 日本内分泌学会雑誌, 89(3) (3), 976 - 976, Japanese有痛性女性化乳房を契機に診断されたBasedow病の1例
- (一社)日本内分泌学会, Dec. 2013, 日本内分泌学会雑誌, 89(3) (3), 989 - 989, Japanese先端巨大症にPlummer病を合併した一例
- (一社)日本内分泌学会, Dec. 2013, 日本内分泌学会雑誌, 89(3) (3), 991 - 991, JapaneseCRH負荷で奇異性反応を認めた先端巨大症の2例
- (一社)日本内分泌学会, Dec. 2012, 日本内分泌学会雑誌, 88(3) (3), 1013 - 1013, Japanese2型糖尿病における先端巨大症の頻度についての検討
- (一社)日本内分泌学会, Dec. 2011, 日本内分泌学会雑誌, 87(3) (3), 946 - 946, Japaneseミトタンにより長期寛解維持できた周期性クッシング症候群の一例
- (一社)日本内分泌学会, Dec. 2011, 日本内分泌学会雑誌, 87(3) (3), 948 - 948, Japanese糖尿病精査を契機にプレクリニカルアクロメガリーが疑われた2例
- (一社)日本内分泌学会, Sep. 2011, 日本内分泌学会雑誌, 87(2) (2), 597 - 597, JapaneseSirt1は肝臓におけるStat5を脱アセチル化し、GH/GF-I系を抑制する
- (一社)日本内分泌学会, Sep. 2011, 日本内分泌学会雑誌, 87(2) (2), 600 - 600, Japanese下垂体腫瘍を認めない巨人症において同定したSOCS2ミスセンス変異
- (一社)日本内分泌学会, Apr. 2011, 日本内分泌学会雑誌, 87(1) (1), 285 - 285, Japanese下垂体腫瘍を認めない巨人症において同定したSOCS2ミスセンス変異
- (一社)日本内分泌学会, Apr. 2011, 日本内分泌学会雑誌, 87(1) (1), 258 - 258, JapaneseSirt1は肝臓におけるGHシグナルおよびIGF-I産生を調節する
- (一社)日本糖尿病学会, Apr. 2011, 糖尿病, 54(Suppl.1) (Suppl.1), S - 157, Japanese新規アディポカインケマリンは耐糖能および褐色脂肪細胞機能を調節する
- (一社)日本内分泌学会, Apr. 2011, 日本内分泌学会雑誌, 87(1) (1), 280 - 280, Japanese新規アディポカインケマリンは肝糖新生、インスリン分泌、褐色脂肪機能を調節し糖尿病発症と関連する
- 2011, 日本小児内分泌学会学術集会プログラム・抄録集, 45th優性遺伝を呈する低身長の家系でGH1遺伝子に3つのSNPが見いだされたGH分泌不全性低身長症の姉弟例
- (一社)日本内分泌学会, Dec. 2010, 日本内分泌学会雑誌, 86(3) (3), 715 - 715, Japanese先端巨大症におけるOctreotide LARとPegvisomant併用療法の検討
- (一社)日本内分泌学会, Dec. 2010, 日本内分泌学会雑誌, 86(3) (3), 679 - 679, JapaneseGH産生腫瘍を合併したPANCHの一例
- (一社)日本内分泌学会, Dec. 2010, 日本内分泌学会雑誌, 86(3) (3), 714 - 714, Japanese先端巨大症に対するオクトレオチドとカベルゴリン併用療法の検討
- JAPAN ENDOCRINE SOC, Mar. 2010, ENDOCRINE JOURNAL, 57, S538 - S538, EnglishSirt1 negatively regulates IGF-I production by growth hormone in hepatocytesSummary international conference
- (一社)日本内分泌学会, Mar. 2010, 日本内分泌学会雑誌, 86(1) (1), 101 - 101, JapaneseIGF-Iは血管平滑筋細胞において細胞老化を促進する
- (一社)日本内分泌学会, Mar. 2010, 日本内分泌学会雑誌, 86(1) (1), 106 - 106, JapaneseOctreotide LARとPegvisomantの併用療法により初めて寛解に至った浸潤性巨大GH産生腫瘍の一例
- (一社)日本内分泌学会, Mar. 2010, 日本内分泌学会雑誌, 86(1) (1), 155 - 155, Japanese新規アディポカイン、ケマリンはインスリン分泌および感受性を調節し糖尿病の発症と関わる
- (一社)日本内分泌学会, Apr. 2009, 日本内分泌学会雑誌, 85(1) (1), 305 - 305, Japanese重篤な消化吸収障害を伴う術後性副甲状腺機能低下症にビタミンD3大量間欠筋注投与が著効した一例
- (一社)日本内分泌学会, Apr. 2009, 日本内分泌学会雑誌, 85(1) (1), 322 - 322, JapaneseACTH産生カルチノイドによる異所性クッシング症候群の一例 オクトレオチドおよびTAEによる治療
- ライフサイエンス出版(株), Apr. 2009, Osteoporosis Japan, 17(2) (2), 325 - 325, Japanese重篤な消化吸収障害を併発した術後性副甲状腺機能低下症にビタミンD3大量間欠筋注投与が著効した一例
- (一社)日本内分泌学会, Apr. 2009, 日本内分泌学会雑誌, 85(1) (1), 323 - 323, JapaneseIGF-IはNASHモデルマウスの耐糖能および肝線維化を改善する
- (一社)日本内分泌学会, Apr. 2009, 日本内分泌学会雑誌, 85(1) (1), 353 - 353, JapaneseSirt1は肝細胞におけるGHによるIGF-I産生を抑制する
- (一社)日本内分泌学会, Apr. 2009, 日本内分泌学会雑誌, 85(1) (1), 353 - 353, EnglishIGF-1シグナル伝達とその生物学的作用における活性酸素種の重要な役割(Reactive oxygen species play an essential role in IGF-I signaling and its biological action)
- (一社)日本糖尿病学会, Apr. 2009, 糖尿病, 52(Suppl.1) (Suppl.1), S - 27, Japaneseインスリン抵抗性と炎症 アディポサイエンスの臨床応用の視点から 新規アディポカイン、ケマリンの新たな機能 MafAを介して膵β細胞機能を調節し糖尿病発症と関連する
- (一社)日本糖尿病学会, Apr. 2009, 糖尿病, 52(Suppl.1) (Suppl.1), S - 227, Japanese新規アディポカイン、ケマリンは膵β細胞機能を調節し、2型糖尿病患者においてその血中濃度が低下している
- (一社)日本内分泌学会, Dec. 2008, 日本内分泌学会雑誌, 84(3) (3), 853 - 853, Japanese原発性アルドステロン症(PA)における副腎静脈採血の判定基準検討
- (一社)日本内分泌学会, Dec. 2008, 日本内分泌学会雑誌, 84(3) (3), 838 - 838, JapaneseNASHを合併したAGHDにGH補充療法が有効だった一例
- (一社)日本内分泌学会, Apr. 2008, 日本内分泌学会雑誌, 84(1) (1), 300 - 300, Japanese術後性副甲状腺機能低下症に著しい消化吸収障害を合併し、大量の活性型VD内服が全く無効な1症例に対するVD3大量筋注療法
- (一社)日本内分泌学会, Dec. 2007, 日本内分泌学会雑誌, 83(3) (3), 769 - 769, Japanese異所性ACTH産生部位の鑑別のための術中ACTH測定の有用性
- (一社)日本内分泌学会, Dec. 2007, 日本内分泌学会雑誌, 83(3) (3), 782 - 782, Japanese原疾患の診断に苦慮したFanconi症候群による骨軟化症の一例
- (一社)日本内分泌学会, Sep. 2007, 日本内分泌学会雑誌, 83(2) (2), 407 - 407, Japanese下垂体茎の腫大を認めサルコイドーシスによる中枢性尿崩症が疑われた一例
- (一社)日本内分泌学会, Apr. 2007, 日本内分泌学会雑誌, 83(1) (1), 125 - 125, JapaneseGHRP-2負荷でGHが1.8ng/ml以上に反応する重症成人GH分泌不全症の臨床像に関する検討
- (一社)日本内分泌学会, Dec. 2006, 日本内分泌学会雑誌, 82(3) (3), 683 - 683, JapaneseMcCune Albright症候群にPSSを合併した先端巨大症の1例
- Contributor, 成人成長ホルモン分泌不全症と先端巨大症, 医歯薬出版, Aug. 2024医学のあゆみ 内分泌疾患の温故知新 日本内分泌学会創設100周年を目前にして
- Contributor, CQ5 原発巣不明の異所性ACTH症候群の病変検索法は？, 診断と治療社, Jun. 2023内分泌代謝疾患クリニカルクエスチョン100 改訂第2版
- Editor, メディカルレビュー社, May 2023, ISBN: 4779227275糖尿病療養指導ガイドブック: 糖尿病療養指導士の学習目標と課題 (2023)
- Contributor, 自己免疫性多内分泌腺症候群, 診断と治療社, May 2023, ISBN: 9784787826046内分泌代謝・糖尿病内科領域専門医研修ガイドブック
- Contributor, 1)抗精神病薬 2)躁病・躁状態治療薬 3)抗うつ薬, 診断と治療社, Aug. 2022薬剤性内分泌障害診療マニュアル
- Editor, メディカルレビュー社, May 2022糖尿病療養指導ガイドブック: 糖尿病療養指導士の学習目標と課題 (2022)
- Contributor, Chapter 11 Pituitary-Immune Interface, Elsevier, May 2022, ISBN: 9780323998994The Pituitary 5th Edition
- Contributor, Cushing病, 診断と治療社, Dec. 2021下垂体疾患診療マニュアル（第３版）
- Contributor, 多腺性自己免疫症候群, 総合医学社, Sep. 2021最新ガイドラインに基づく 代謝・内分泌疾患 診療指針 2021-’22
- 第23回日本内分泌学会九州支部学術集会, Sep. 2023UPDATE on AGHD[Invited]Invited oral presentation
- 第96回日本内分泌学会学術総会, Jun. 2023クッシング病の診断と治療[Invited]Nominated symposium
- 第95回日本内分泌学会学術総会, Jun. 2022下垂体疾患の病因・病態の解明[Invited]
- 第47回日本神経内分泌学会学術集会, Oct. 2021SSTR5の生理的・臨床的意義[Invited]
- 第92回日本内分泌学会学術総会, May 2019, English, Domestic conferenceSomatostatin Receptor Subtype 5 Modifies Hypothalamic-Pituitary-Adrenal Axis Stress.[Invited]Nominated symposium
- 第29回日本間脳下垂体腫瘍学会, Feb. 2019, Japanese, 大阪, Domestic conferenceCorticotrophにおけるSSTR5の役割～新規モデルマウスから見えてきたこと～[Invited]Nominated symposium
- 第91回日本内分泌学会学術総会, Apr. 2018, Japanese, 宮崎, Domestic conference下垂体SSTR5はmicroRNAを介してストレス応答を制御する.[Invited]Nominated symposium
- Pituitary Society
- The Endocrine Society
- 間脳下垂体腫瘍学会
- Japan Neuroendocrine Society
- THE JAPAN DIABETES SOCIETY
- The Japan Endocrine Society
- THE JAPANESE SOCIETY OF INTERNAL MEDICINE
- 日本学術振興会, 科学研究費助成事業 基盤研究(C), 基盤研究(C), 神戸大学, 01 Apr. 2023 - 31 Mar. 2026マルチオミクス解析を用いた副腎不全の病態解明と新規バイオマーカーの同定
- 日本学術振興会, 科学研究費助成事業 基盤研究(C), 基盤研究(C), 神戸大学, 01 Apr. 2020 - 31 Mar. 2023HPA軸における循環血液中microRNAの生理的・病理的意義の解明今年度は新たに患者をエントリーし入院下でプロトコールに従って副腎不全患者のステロイド補充前後の血液サンプルを採取した。血液サンプルからRNAを抽出しRNAseqを施行し、ステロイド充足前後での発現パターンの変化を検討し、複数のバイオマーカー候補を得た。また本学の質量分析センターとの共同研究により血清のメタボローム解析を行い、複数のアミノ酸がステロイド補充前後で有意に変化していることが明らかとなった。また同様に血清から超遠心法を用いてエクソソームを抽出した。エクソソームの確認としてナノサイトによる粒計測、ウエスタンブロット法によるエクソソーム表面抗原を複数確認し、抽出したRNAをバイオアナライザーにて解析したところ純度の高いRNAが抽出されていることを確認した。 昨年度よりマウス血清からエクソソーム抽出を行っていたが、同定には至らなかった。今年度、超遠心のプロトコールを修正し、抗体の種類を変えることで表面抗原を確認することに成功した。今後ヒト検体で得られたバイオマーカーの生理的意義を検証するためにマウスを用いた実験も展開する予定である。
- Frontiers in Endocrinology, Review EditorFrontiers in Endocrinology, Review Editor26 Feb. 2017 - Present
- The Japan Endocrine Society Young Endocrinologist ConferenceThe Japan Endocrine Society Young Endocrinologist Conference01 Apr. 2021 - 31 Mar. 2025Academic society etc
- 糖尿病療養指導ガイドブック 編集委員糖尿病療養指導ガイドブック 編集委員01 Apr. 2021 - 30 Jun. 2024