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Key Clinical Message: Primary hyperaldosteronism with type 3 autoimmune polyendocrine syndrome was a rare combination of both hyper‐ and hypoendocrine gland function. Comprehensive treatment including surgery and replacement therapy might be an effective strategy. Primary aldosteronism (PA) is a common cause of secondary hypertension originating from hormones. Type 3 autoimmune polyendocrine syndrome (APS‐3) is characterized by the simultaneous or subsequent occurrence of autoimmune‐mediated endocrine gland damage, except for Addison disease. Here we reported an extremely rare case of a 63‐year‐old woman with PA and APS‐3 who initially presented with hypertension (HT). The APS‐3 of this patient mainly exhibited type 1 diabetes mellitus (T1DM) and Hashimoto's thyroiditis. She underwent the adrenal adenoma resection with a histopathologic diagnosis of adrenal cortical adenoma. After surgery, the HT of this patient was immediately reversed, and the concentration of serum potassium went back to normal. Then, this patient was administered with replacement therapy of insulin and levothyroxine sodium tablets (L‐T4). [ABSTRACT FROM AUTHOR]

Key Clinical Message: Acute chest pain can be the first manifestation of multiple endocrine neoplasia type 1(MEN1)‐associated thymic neuroendocrine neoplasms (NEN). Comprehensive treatment may be an effective strategy for MEN1‐associated NEN. Multiple endocrine neoplasia type 1(MEN1)‐associated thymic neuroendocrine neoplasms (NEN) is caused by the mutation of tumor suppressor MEN1 gene. Patients with MEN1‐associated NEN initially presenting with acute chest pain are very rare. In the manuscript, we reported a case of a 45‐year‐old man who developed MEN1‐associated NEN with acute chest pain as initial symptom. Thoracoscopic thymotomy was performed and thymic NEN was successfully removed. Genetic test showed a germline mutation of MEN1 gene in this patient. Immunohistochemical staining exhibited Syn(+), CgA(+), INSM1(+), CD56(+) and Ki67‐positive cells (2%) in MEN1‐associated NEN. Further evaluation unveiled MEN1‐associated benign tumors including digestive NEN and pituitary gland adenoma. The 99mTc‐HYNIC‐TOC scintigraphy showed that focally increased radioactivity in the mid‐upper abdomen. This patient was administered with 50Gy/25F of radiation dose to treat the postoperative lesions. Subsequently, sandostatin LAR (30 mg per week) was used as systemic therapy. He had no recurrence or metastasis for 6‐month follow‐up. Thus, acute chest pain can be the first manifestation of MEN1‐associated NEN, and comprehensive treatment including surgery, radiation and systemic treatment may be an effective strategy for MEN1‐associated NEN. [ABSTRACT FROM AUTHOR]

Dysfunction of glucagon-secreting α-cells participates in the progression of diabetes, and glucagon receptor (GCGR) antagonism is regarded as a novel strategy for diabetes therapy. GCGR antagonism upregulates glucagon and glucagon-like peptide 1 (GLP-1) secretion and, notably, promotes β-cell regeneration in diabetic mice. Here, we aimed to clarify the role of GLP-1 receptor (GLP-1R) activated by glucagon and/or GLP-1 in the GCGR antagonism–induced β-cell regeneration. We showed that in db/db mice and type 1 diabetic wild-type or Flox/cre mice, GCGR monoclonal antibody (mAb) improved glucose control, upregulated plasma insulin level, and increased β-cell area. Notably, blockage of systemic or pancreatic GLP-1R signaling by exendin 9-39 (Ex9) or Glp1r knockout diminished the above effects of GCGR mAb. Furthermore, glucagon-neutralizing antibody (nAb), which prevents activation of GLP-1R by glucagon, also attenuated the GCGR mAb–induced insulinotropic effect and β-cell regeneration. In cultured primary mouse islets isolated from normal mice and db/db mice, GCGR mAb action to increase insulin release and to upregulate β-cell–specific marker expression was reduced by a glucagon nAb, by the GLP-1R antagonist Ex9, or by a pancreas-specific Glp1r knockout. These findings suggest that activation of GLP-1R by glucagon participates in β-cell regeneration induced by GCGR antagonism in diabetic mice. Article Highlights: Glucagon receptor (GCGR) antagonism promotes β-cell regeneration in type 1 and type 2 diabetic mice and in euglycemic nonhuman primates. Glucagon and glucagon-like peptide 1 (GLP-1) can activate the GLP-1 receptor (GLP-1R), and their levels are upregulated following GCGR antagonism. We investigated whether GLP-1R activated by glucagon and/or GLP-1 contributed to β-cell regeneration induced by GCGR antagonism. We found that blockage of glucagon–GLP-1R signaling attenuated the GCGR monoclonal antibody–induced insulinotropic effect and β-cell regeneration in diabetic mice. Our study reveals a novel mechanism of β-cell regeneration and uncovers the communication between α-cells and β-cells in regulating β-cell mass. [ABSTRACT FROM AUTHOR]