Bexarotene-induced hypothyroidism and dyslipidemia; a nation-wide study.

Central hypothyroidism and dyslipidemia are well-known adverse events (AEs) of bexarotene therapy. Although hypothyroidism is known to cause dyslipidemia, no study has examined the association between hypothyroidism and dyslipidemia in patients undergoing bexarotene therapy. The aim of this study is to examine this association. A retrospective observational study was performed among 294 patients who initiated bexarotene therapy in Japan (nation-wide postmarketing complete surveillance). Jonckheere-Terpstra (one sided) test was performed to evaluate the effect of the bexarotene dose on lipid metabolisms, and regression analyses were performed to evaluate associations of bexarotene dose, free thyroxine (FT4), body mass index (BMI), and lipid metabolisms. Most patients developed hypothyroidism. Two-third of patients showed FT4 values below the lower limit at 1 week. Triglycerides (TG) increased in a bexarotene dose-dependent manner, and grade ≥3 AEs on hypertriglyceridemia was observed in 39% of the patients. Additionally, one-third of grade ≥3 AEs on hypertriglyceridemia occurred within 1 week. The delta_FT4 (difference in FT4 from baseline) negatively correlated with TG increase at 1 week (p = 0.012) but not with low density lipoprotein cholesterol (LDL-C) increase at any week. Bexarotene-induced hypothyroidism is almost inevitable and occurred quickly. Bexarotene-induced hypertriglyceridemia showed positive bexarotene dose dependency and negative delta_FT4 dependency. Prophylactic and appropriate thyroid hormone compensation therapy and starting bexarotene at low doses with subsequent titration while managing dyslipidemia may have a beneficial effect for the successful continuation of bexarotene therapy without severe endocrine and metabolic AEs.

Recurrent bilateral adrenal infarction with myelodysplastic/myeloproliferative neoplasm-unclassifiable (MDS/MPN-U): a case report.

BACKGROUND: Bilateral adrenal infarction is rare and only a small number of cases have been reported so far. Adrenal infarction is usually caused by thrombophilia or a hypercoagulable state, such as antiphospholipid antibody syndrome, pregnancy, and coronavirus disease 2019. However, adrenal infarction with myelodysplastic/myeloproliferative neoplasm (MDS/MPN) has not been reported. CASE PRESENTATION: An 81-year-old man with a sudden severe bilateral backache presented to our hospital. Contrast-enhanced computed tomography (CT) led to the diagnosis of bilateral adrenal infarction. Previously reported causes of adrenal infarction were all excluded and a diagnosis of MDS/MPN-unclassifiable (MDS/MPN-U) was reached, which was considered to be attributed to adrenal infarction. He developed a relapse of bilateral adrenal infarction, and aspirin administration was initiated. Partial primary adrenal insufficiency was suspected as the serum adrenocorticotropic hormone level was persistently high after the second bilateral adrenal infarction. CONCLUSION: This is the first case of bilateral adrenal infarction with MDS/MPN-U encountered. MDS/MPN has the clinical characteristics of MPN. It is reasonable to assume that MDS/MPN-U may have influenced bilateral adrenal infarction development, considering the absence of thrombosis history and a current comorbid hypercoagulable disease. This is also the first case of recurrent bilateral adrenal infarction. It is important to carefully investigate the underlying cause of adrenal infarction once adrenal infarction is diagnosed, as well as to assess adrenocortical function.

A Novel Pathogenic MEN1 Gene Variant Identified in a Family With Multiple Pancreatic Neuroendocrine Tumors.

Multiple endocrine neoplasia type 1 (MEN1) is a hereditary endocrine tumor syndrome caused by pathogenic variants in the MEN1 gene, and most patients with this syndrome initially develop primary hyperparathyroidism (PHPT). Here, we report the case of a family wherein a germline MEN1 variant was detected and multiple pancreatic neuroendocrine tumors (PanNETs) were observed at the initial evaluation. A 40-year-old woman presented with a complaint of abdominal discomfort, and a close examination revealed multiple pancreatic tumors. Distal pancreatectomy with splenectomy was performed, and the diagnosis was nonfunctional PanNETs. Five years later, her 76-year-old mother was referred to the hospital with multiple pancreatic tumors. A genetic test revealed that both patients harbored a previously unreported germline variant in the MEN1 gene. Although it was classified as a variant of uncertain significance, we suspect that it may be associated with the pathogenesis of these lesions. This case report presents a new disease concept-familial isolated pancreatic neuroendocrine tumors, or FIPNETs-in patients harboring a pathogenic variant in the MEN1 gene who experience only pancreatic lesions. We suggest that clinicians consider genetic testing for the MEN1 gene in patients with multiple pancreatic lesions who show no signs of PHPT.

Association Between Aldosterone and Hypertension Among Patients With Overt and Subclinical Hypercortisolism.

Introduction: Hypertension is one of the most common clinical features of patients with overt and subclinical hypercortisolism. Although previous studies have shown the coexistence of autonomous cortisol and aldosterone secretion, it is unclear whether aldosterone plays a role in hypertension among patients with hypercortisolism. Therefore, we examined the associations of plasma aldosterone concentrations (PACs) with hypertension among patients with overt and subclinical hypercortisolism. Methods: This single-center retrospective cohort study included patients with adrenal tumor and serum cortisol levels after 1-mg dexamethasone suppression test >1.8 µg/dL (50 nmol/L). Using multivariable regression models adjusting for baseline characteristics, we investigated the association of PACs with systolic blood pressure and postoperative improvement of hypertension after the adrenalectomy. Results: Among 89 patients enrolled in this study (median age, 51 years), 21 showed clinical signs of Cushing syndrome (overt hypercortisolism) and 68 did not show clinical presentations (subclinical hypercortisolism). We found that higher PACs were significantly associated with elevated systolic blood pressure among patients with subclinical hypercortisolism (adjusted difference [95% CI] = +0.59 [0.19-0.99], P = 0.008) but not among those with overt hypercortisolism. Among 33 patients with subclinical hypercortisolism and hypertension who underwent adrenalectomy, the postoperative improvement of hypertension was significantly associated with higher PACs at baseline (adjusted risk difference [95% CI] = +1.45% [0.35-2.55], P = 0.01). Conclusion: These findings indicate that aldosterone may contribute to hypertension among patients with subclinical hypercortisolism. Further multi-institutional and population-based studies are required to validate our findings and examine the clinical effectiveness of the intervention targeting aldosterone for such patients.

Two Cases of Thyrotoxicosis and Euglycemic Diabetic Ketoacidosis Under Sodium-glucose Transport Protein 2 Inhibitor Treatment.

Thyrotoxicosis and sodium-glucose transport protein 2 inhibitors (SGLT2is) are associated with the induction of euglycemic diabetic ketoacidosis (euDKA). We herein report two cases of euDKA in patients with diabetes mellitus wherein both thyrotoxicosis and SGLT2i treatment were the underlying causes. One patient developed thyrotoxicosis during the course of type 2 diabetes mellitus, whereas the other patient was suspected of developing slowly progressive insulin-dependent diabetes mellitus during the course of Graves' disease. Although such cases are rare, there is some concern that similar cases may occur because of the increased frequency of SGLT2i use in recent years.

Successful prednisolone or calcimimetic treatment of acquired hypocalciuric hypercalcemia caused by biased allosteric CaSR autoantibodies.

Biased agonism is a frontier field in GPCR research. Acquired hypocalciuric hypercalcemia (AHH) is a rare disease caused by calcium-sensing receptor (CaSR) autoantibodies, to date, showing either simple blocking or biased properties (i.e., stimulatory or blocking effects on different downstream signaling pathways). This emphasizes the importance of the Gi/o (pertussis toxin-sensitive G proteins, whose ßγ subunits activate multiple signals, including ERK1/2) in regulating parathyroid hormone secretion. We here describe 3 patients with symptomatic AHH who shared characteristics with the 2 cases we previously reported as follows: (a) elderly (74-87 years at diagnosis), (b) male, (c) unexpectedly showed no other autoimmune diseases, (d) showed spontaneously fluctuating Ca levels from approximately normal to near fatally high ranges, (e) acute exacerbations could be successfully treated with prednisolone and/or calcimimetics, (f) the presence of CaSR autoantibodies that operated as biased allosteric modulators of CaSR, and (g) were likely to be conformational (i.e., recognizing and, thereby, stabilizing a unique active conformation of CaSR that activates Gq/11, activating phosphatidylinositol turnover, but not Gi/o). Our observations with these prominent commonalities may provide new insights into the phenotype and characteristics of AHH and the mechanisms by which the biased agonism of GPCRs operate.

Salvage from hemodialysis via percutaneous transluminal renal artery stenting for a jeopardized solitary functioning kidney: A case report.

Atherosclerotic renal artery stenosis (ARAS) causes resistant hypertension, progressively declining renal function, and cardiac destabilization syndromes, including heart failure. We report a patient who underwent successful percutaneous transluminal renal angioplasty (PTRA) for anuretic acute kidney injury (AKI) due to ARAS. This patient, admitted to our hospital with congestive heart failure, developed anuretic AKI and started hemodialysis 3 days after admission. Computed tomography and magnetic resonance angiograms showed total occlusion of the proximal right renal artery, with atrophy of the right kidney and severe stenosis of the proximal left renal artery. These findings suggested that only the left kidney was functioning. We performed PTRA of the left renal artery in which the culprit lesion causing the AKI appeared to be located. Using intravascular ultrasound, severe calcification in the ostium of the left renal artery and a necrotic core with plaque rupture in the culprit lesion were observed. Kidney function recovered immediately after revascularization, which permitted successful withdrawal of hemodialysis. There is no clear consensus regarding the indication for PTRA in patients with ARAS; however, our experience suggests that PTRA may be beneficial for patients with a jeopardized solitary functioning kidney. .