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  • The Endocrine Society  (34)
  • 1
    In: JCEM Case Reports, The Endocrine Society, Vol. 2, No. 2 ( 2024-01-08)
    Abstract: Surgical treatment is generally the standard therapeutic regimen used for primary bilateral macronodular adrenal cortical disease (PBMACD). However, in cases for which surgery is difficult or in which there is mild cortisol hypersecretion, metyrapone treatment can be selected. Although hypokalemia has been occasionally noted following metyrapone administration for Cushing syndrome associated with an adrenal adenoma, all such cases have been reported to be transient. Hypokalemia induced by metyrapone treatment is thought to occur due to excessive suppression of cortisol secretion, resulting in overproduction of adrenocorticotropic hormone from the pituitary gland, ultimately leading to excessive production of 11-deoxycorticosterone (DOC) in the adrenal cortex. A 52-year-old man diagnosed with PBMACD and started on metyrapone treatment subsequently presented with persistent hypokalemia. Interestingly, following initiation of metyrapone, blood test findings indicated marginal changes in serum cortisol, adrenocorticotropic hormone, and dehydroepiandrosterone sulfate levels, even when DOC levels were already markedly elevated. In addition to the effects of metyrapone, the present findings suggest a unique DOC synthesis regulatory mechanism involved in the pathogenesis of PBMACD.
    Type of Medium: Online Resource
    ISSN: 2755-1520
    Language: English
    Publisher: The Endocrine Society
    Publication Date: 2024
    detail.hit.zdb_id: 3166308-4
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  • 2
    Online Resource
    Online Resource
    The Endocrine Society ; 2010
    In:  The Journal of Clinical Endocrinology & Metabolism Vol. 95, No. 12 ( 2010-12-01), p. 5457-5457
    In: The Journal of Clinical Endocrinology & Metabolism, The Endocrine Society, Vol. 95, No. 12 ( 2010-12-01), p. 5457-5457
    Type of Medium: Online Resource
    ISSN: 0021-972X , 1945-7197
    RVK:
    Language: English
    Publisher: The Endocrine Society
    Publication Date: 2010
    detail.hit.zdb_id: 2026217-6
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  • 3
    In: The Journal of Clinical Endocrinology & Metabolism, The Endocrine Society, Vol. 99, No. 9 ( 2014-09-01), p. E1744-E1749
    Abstract: 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.
    Type of Medium: Online Resource
    ISSN: 0021-972X , 1945-7197
    RVK:
    Language: English
    Publisher: The Endocrine Society
    Publication Date: 2014
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  • 4
    In: Journal of the Endocrine Society, The Endocrine Society, Vol. 7, No. Supplement_1 ( 2023-10-05)
    Abstract: Disclosure: N. Yamamoto: None. M. Yamamoto: None. N. Kiyota: None. Y. Inaba: None. K. Kanie: None. S. Urai: None. M. Suzuki: None. Y. Sasaki: None. Y. Oi: None. Y. Tsujimoto: None. Y. Motomura: None. Y. Ohmachi: None. H. Bando: None. G. Iguchi: None. M. Nagao: None. I. Fukuda: None. H. Fukuoka: None. W. Ogawa: None. Introduction: Non-islet cell tumor hypoglycemia (NICTH) is a rare paraneoplastic syndrome caused by insulin-like growth factor II (IGF-II) hypersecretion from the tumors. It is characterized by incompletely processed big IGF-II with potent insulin-like activity. We present a case of NICTH complicated with solitary fibrous tumor (SFT) which was ameliorated with the administration of pazopanib, a multi-targeted tyrosine kinase inhibitor. Clinical Case: A 57-year-old man went into a coma and was hospitalized. His plasma glucose levels were 26 mg/dL, and he regained consciousness after glucose administration, leading to a diagnosis of hypoglycemic coma. Moreover, a contrast-enhanced CT scan showed multiple tumors in his liver and right kidney. He was referred to our hospital for further management. After 5 hours of fasting, he had a cold sweat, and his plasma glucose levels dropped to 32 mg/dL with suppressed serum insulin levels of 0.2 U/mL. Serum 3-hydroxybutyrate levels were as low as 21 μmol/L, and plasma glucose levels increased to 83 mg/dL after glucagon administration, suggesting an agent mimicking insulin. Percutaneous liver biopsy was performed, and the tumors were diagnosed with SFT. Immunoblotting for his serum showed big IGF-II, leading to a diagnosis of NICTH, and hypoglycemia due to hypersecretion of IGF-II. Due to multiple metastases, surgery was not indicated and pazopanib was administered. Hypoglycemia during the night was prevented by glucose infusion through the central venous port, and he was discharged. Three months later, when he was re-hospitalized for thrombophlebitis of the right jugular vein, hypoglycemia did not occur even after 10 hours of fasting and CT scan showed the necrotic change of the tumor. Two weeks later of pazopanib discontinuation due to the thrombogenic adverse effect, hypoglycemia recurred accompanied by the tumor enlargement. When the anticoagulation therapy regressed the thrombosis and pazopanib was re-administered, hypoglycemia improved reproducibly and remained stable for more than 2 years although the tumor showed gradual progression. Conclusion: This is the first case in which pazopanib was effective in suppressing NICTH associated with SFT. Presentation: Saturday, June 17, 2023
    Type of Medium: Online Resource
    ISSN: 2472-1972
    Language: English
    Publisher: The Endocrine Society
    Publication Date: 2023
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  • 5
    In: Journal of the Endocrine Society, The Endocrine Society, Vol. 4, No. Supplement_1 ( 2020-05-08)
    Abstract: Background: With rapid aging in the society and the improvement of prognosis in patients with acromegaly, treatment goals have been changed. In elderly patients with acromegaly, improvement in the quality of life (QoL) is one of the most important treatment goals. However, factors associated with QoL in elderly patients with acromegaly remains unclear. Objective: To clarify the differences in the QoL in patients with acromegaly between the young and elderly, and to identify the factors associated with the impairment in the elderly. Patients and Methods: This is a retrospective cross-sectional single-center study. Eighty patients with acromegaly (male 49%, the mean age 59.6±12.6 years, mean IGF-I SD score 0.7±2.3), who had been followed up in the outpatient clinic at Kobe University Hospital, were enrolled. Patients were divided into following 2 groups; Elderly group (E group); 65 years of age or more (n =34, male 41%, mean age 71.4±4.1 years), or Young group (Y group); younger than 65 years old (n =46, male 50.9%, mean age 50.9±9.2 years). We evaluated QoL using AcroQoL and analyzed the associated factors by multivariate analysis. Results: In the comparison of E and Y group, IGF-I SD score (0.4±1.6 in E group vs. 0.9±2.7 in Y group) and the way of treatment (surgery; 65% vs 72%, current medical therapy; 56% vs 43%, past radiation therapy; 15% vs 9%) were comparable, while disease duration was longer in E than Y group (13.7±10.9 vs 8.3±8.1 years, p =0.02). Arthropathy was more frequent in E group (50% vs 11%, p & lt;0.01). In total, current medical therapy and hydrocortisone replacement were associated with lower total scale (β =-0.27, p =0.01 and β =-0.35, p & lt;0.01). Then, we separately analyzed the associated factors in each E and Y group. In Y group, current medical therapy and hydrocortisone replacement were associated with lower total (β =-0.48, p & lt;0.01, and β =-0.35, p & lt;0.01) and physical scales (β =-0.40, p & lt;0.01, and β =-0.31, p & lt;0.01). Past radiotherapy for the pituitary tumor was also associated with lower mental scale (β =-0.40, p & lt;0.01). On the other hand, in E group, arthropathy and high BMI were associated with lower total scale (β =-0.41, p =0.02, and β =-0.40, p =0.02) and current hydrocortisone replacement was associated with lower physical scale (β =-0.36, p =0.03). Conclusions: AcroQoL score was impaired both in E and Y group in patients with acromegaly. In total, current medical therapy and hydrocortisone replacement were associated with lower QoL scale as previously reported; however, when stratified by age, arthropathy and high BMI were associated with lower QoL scale in the elderly. These data clearly indicate that the factors influence on QoL are different depending on the age. Although causal relationship remains unclarified, these data suggest that when treat the patients, it may be important to avoid these complications.
    Type of Medium: Online Resource
    ISSN: 2472-1972
    Language: English
    Publisher: The Endocrine Society
    Publication Date: 2020
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  • 6
    In: Journal of the Endocrine Society, The Endocrine Society, Vol. 4, No. 9 ( 2020-09-01)
    Abstract: Adrenal corticomedullary mixed tumors (CMMTs) are extremely rare; with only 20 cases being reported to date, the pathogenesis has remained elusive. A 31-year-old woman developed gestational hypertension with psychiatric disturbances persistent to postpartum and was diagnosed with pheochromocytoma, for which adrenalectomy was performed. Histological findings showed mixed adrenocortical adenoma and pheochromocytoma. Double immunostaining of inhibin and INSM1 (insulinoma-associated protein 1) showed that the 2 tumor components had distinct functional properties. Exome analysis of peripheral leukocytes and tumor (singular, as anatomically it is only 1 mass) revealed a homozygous germline FGFR4-G388R variant. As a readout of the variant, serine phosphorylation of signal transducer and activator of transcription 3 (STAT3) was detected only in the nucleus of adrenocortical adenoma component but not in the pheochromocytoma component. No tyrosine phosphorylation of STAT3 was detected. We report a case of CMMT with the germline FGFR4-G388R variant. Although additional studies are required, our immunohistochemical analysis suggests that the variant may play a role in the development of the adrenocortical component within the pheochromocytoma, leading to CMMT.
    Type of Medium: Online Resource
    ISSN: 2472-1972
    Language: English
    Publisher: The Endocrine Society
    Publication Date: 2020
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  • 7
    In: Journal of the Endocrine Society, The Endocrine Society, Vol. 5, No. 3 ( 2021-03-01)
    Abstract: 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.
    Type of Medium: Online Resource
    ISSN: 2472-1972
    Language: English
    Publisher: The Endocrine Society
    Publication Date: 2021
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  • 8
    In: Journal of the Endocrine Society, The Endocrine Society, Vol. 5, No. 6 ( 2021-06-01)
    Abstract: 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 & lt; 0.01) while control tumor cultures exhibited no increase in ACTH levels, but rather a 20% to 40% suppression (P & lt; 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.
    Type of Medium: Online Resource
    ISSN: 2472-1972
    Language: English
    Publisher: The Endocrine Society
    Publication Date: 2021
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  • 9
    Online Resource
    Online Resource
    The Endocrine Society ; 2021
    In:  Journal of the Endocrine Society Vol. 5, No. Supplement_1 ( 2021-05-03), p. A984-A984
    In: Journal of the Endocrine Society, The Endocrine Society, Vol. 5, No. Supplement_1 ( 2021-05-03), p. A984-A984
    Abstract: Case: 70 years old woman was pointed out for hypertension at a medical checkup and visited a primary physician. Severe hypokalemia (2.4 mmol/L) was noted, and abdominal CT scan revealed a right 99 mm diameter adrenal tumor adjacent to a 80 mm diameter liver tumor. She was referred to our hospital for further management. Despite treatment with antihypertensive agents, including ARB, MRB, and CCB, her blood pressure remained around 170/90 mmHg. In the meantime, 120 meq of potassium chloride treatment was needed to keep her serum potassium levels around 3.5 mmol/L. Both her plasma renin activity (PRA) and plasma aldosterone concentration (PAC) were high (6.4 ng/mL/h and 376 pg/mL), indicating renin-dependent hypertension. Since CT angiography revealed the right renal artery compressed downward by the adrenal tumor, renovascular hypertension was suspected. Moreover, both early morning plasma ACTH levels and serum cortisol levels were suppressed (8.5 pmol/L and 5.3 μg/dL), despite elevated urinary free cortisol levels (350 μg/day). Urinary steroid profile analysis detected various elevated precursor steroid metabolites, including deoxycorticosterone (DOC) and corticosterone. DOC levels were 5 folds more than the upper normal limit, suggesting one of the causes of her hypertension with hypokalemia, while elevated corticosterone levels were thought to be contributed to suppressing ACTH. After the right adrenalectomy and hepatic segmentectomy, both of her hypertension and hypokalemia rapidly improved with declining PRA and PAC levels to 0.2 ng/mL/h and & lt; 0.7 pg/mL, respectively. Urinary DOC levels also fell into the normal range. From the pathological findings, she was diagnosed with adrenocortical carcinoma (ACC) infiltrating the liver (pT4N0M0, stage IV). The immunohistochemistry analysis showed disorganized expression of steroidogenic enzymes, including CYP11B1, CYP11B2, and 3β-HSD, supporting a variety production of steroid metabolites from the ACC. Although mitotane was initiated as a adjuvant chemotherapy, multiple metastasis was found at her lung, liver, and vertebrae, 6 months after the operation. Along with that, hypertension and hypokalemia recurred gradually with both of PRA and PAC elevation. However, CT angiography detected no apparent renovascular stenosis. We performed renin immunostaining of ACC specimen revealed partially positive, demonstrating renin production from this ACC. Conclusion: Although juxtaglomerular cell tumor is the most common renin-producing tumor, some cases of renin secreting ACC have been reported as a quite rare case. In the present case, renin secretion from ACC might be contributed to severe hypertension and hypokalemia, and both renal artery stenosis and DOC secretion induced by the ACC are considered to be a major cause.
    Type of Medium: Online Resource
    ISSN: 2472-1972
    Language: English
    Publisher: The Endocrine Society
    Publication Date: 2021
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  • 10
    In: Journal of the Endocrine Society, The Endocrine Society, Vol. 7, No. 3 ( 2023-01-06)
    Abstract: 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.
    Type of Medium: Online Resource
    ISSN: 2472-1972
    Language: English
    Publisher: The Endocrine Society
    Publication Date: 2023
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