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BackgroundIodine deficiency has long been recognized as an important public health problem. Global approaches such as salt iodization that aim to overcome iodine deficiency have been successful. Meanwhile, they have led to excessive iodine consumption in some populations, thereby increasing the risks of iodine-induced thyroid dysfunction, as well as the comorbidities and mortality associated with hypothyroidism and hyperthyroidism. This study aimed to elucidate whether iodine intake is associated with mortality among U.S. adults.MethodsThis was an observational study to estimate mortality risks according to urinary iodine concentration (UIC) utilizing a nationally representative sample of 12,264 adults aged 20-80 years enrolled in the National Health and Nutrition Examination Survey (NHANES) III. Crude and multivariable Cox proportional hazards regression models were employed to investigate the association between UIC (

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Context Tumor-induced osteomalacia (TIO) is one of the most common forms of acquired fibroblast growth factor 23 (FGF23)-related hypophosphatemia and is usually caused by phosphaturic mesenchymal tumors (PMTs). Although the complete resection of PMTs can cure TIO, preoperative localization of tumors by standard imaging modalities is often challenging. In addition to 18F-fluoro-2-deoxy-D-glucose positron emission tomography–computed tomography (FDG-PET) and 111In-pentetreotide scintigraphy (SRS), systemic FGF23 venous sampling (FGF23VS) has been used to help localize PMTs in specialized institutions. Objective This study aimed to evaluate the diagnostic performance of each imaging test and their combinations in localizing PMTs. Methods In an observational retrospective study of patients with adult-onset FGF23-related osteomalacia who underwent all 3 imaging studies (FDG-PET, SRS, and FGF23VS), the rate of successful preoperative localization of the tumors was evaluated only in the patients with pathological diagnoses of PMTs, considering the possibility that pathogenesis of patients without identified tumors might be due to other causes such as late-onset hereditary FGF23-related hypophosphatemia. Results A total of 30 Japanese patients with TIO (median age, 60 years [range, 28-87 years]; 10 women [33.3%]) were included in the study. The success rate of preoperative localization for each test and combinations of 2 or 3 tests among 18 patients with PMTs was as follows: 72% (FDG-PET), 72% (SRS), 94% (FGF23VS), 89% (FDG-PET, SRS), 100% (FDG-PET, FGF23VS), 94% (SRS, FGF23VS), and 100% (FDG-PET, SRS, and FGF23VS). Conclusion We observed the highest localization rate of PMTs in patients with identified PMTs with the combination of FDG-PET and FGF23VS. [ABSTRACT FROM AUTHOR]

Homozygous ENPP1 mutations are associated with autosomal recessive hypophosphatemic rickets type 2 (ARHR2), severe ossification of the spinal ligaments, and generalized arterial calcification of infancy type 1. There are a limited number of reports on phenotypes associated with heterozygous ENPP1 mutations. Here, we report a series of three probands and their families with heterozygous and compound heterozygous ENPP1 mutations. The first case (case 1) was a 47‐year‐old male, diagnosed with early‐onset osteoporosis and low‐normal serum phosphate levels, which invoked suspicion for hypophosphatemic rickets. The second and third cases were 77‐ and 54‐year‐old females who both presented with severe spinal ligament ossification and the presumptive diagnosis of diffuse idiopathic skeletal hyperostosis (DISH). Upon workup, fibroblast growth factor 23 (FGF23) was noted to be relatively high in case 2 and serum phosphorous was low‐normal in case 3, and the diagnoses of X‐linked hypophosphatemic rickets (XLH) and ARHR2 were considered. Genetic testing for genes related to congenital hypophosphatemic rickets was therefore performed, revealing heterozygous ENPP1 variants in cases 1 and 2 (case 1, c.536A>G, p.Asn179Ser; case 2, c.1352A>G, p.Tyr451Cys) and compound heterozygous ENPP1 variants in case 3 constituting the same variants present in cases 1 and 2 (c.536A>G, p.Asn179Ser and c.1352A>G, p.Tyr451Cys). Several in silico tools predicted the two variants to be pathogeneic, a finding confirmed by in vitro biochemical analysis demonstrating that the p.Asn179Ser and p.Tyr451Cys ENPP1 variants possessed a catalytic velocity of 45% and 30% compared with that of wild‐type ENPP1, respectively. Both variants were therefore categorized as pathogenic loss‐of‐function mutations. Our findings suggest that ENPP1 mutational status should be evaluated in patients presenting with the diagnosis of idiopathic DISH, ossification of the posterior longitudinal ligament (OPLL), and early‐onset osteoporosis. © 2022 American Society for Bone and Mineral Research (ASBMR). [ABSTRACT FROM AUTHOR]

Pseudohypoparathyroidism type Ia (PHP-Ia) results from the loss of one allele of [G.sub.s[alpha]], causing resistance to parathyroid hormone and other hormones that transduce signals via [G.sub.s]. Most [G.sub.s[alpha]]mutations cause the complete loss of protein expression, but some cause loss of function only, and these have provided valuable insights into the normal function of G proteins. Here we have analyzed a mutant [G.sub.s[alpha]] ([alpha]s-AVDT) harboring AVDT amino acid repeats within its GDP/GTP binding site, which was identified in unique patients with PHP-Ia accompanied by neonatal diarrhea. Biochemical and intact cell analyses showed that [alpha]s-AVDT is unstable but constitutively active as a result of rapid GDP release and reduced GTP hydrolysis. This instability underlies the PHP-Ia phenotype. [alpha]s-AVDT is predominantly localized in the cytosol, but in rat and mouse small intestine epithelial cells (IEC-6 and DIF-12 cells) [alpha]s-AVDT was found to be localized predominantly in the membrane where adenylyl cyclase is present and constitutive increases in cAMP accumulation occur in parallel. The likely cause of this membrane localization is the inhibition of an activation-dependent decrease in [alpha]s palmitoylation. Upon the overexpression of acyl-protein thioesterase 1, however, [alpha]s-AVDT translocates from the membrane to the cytosol, and the constitutive accumulation of cAMP becomes attenuated. These results suggest that PHP-Ia results from the instability of [alpha]s-AVDT and that the accompanying neonatal diarrhea may result from its enhanced constitutive activity in the intestine. Hence, palmitoylation may control the activity and localization of [G.sub.s[alpha]] in a cell-specific manner. disease | G protein | lipid modification | localization | activity

To establish real‐world evidence about the safety and efficacy of bexarotene for Japanese patients with cutaneous T‐cell lymphoma, we conducted a nationwide cohort study using data from post‐marketing surveillance for bexarotene treatment. In total, 294 patients with cutaneous T‐cell lymphoma were identified between June 2016 and June 2018. Of these, 267 patients were included as the safety analysis set. Of the 267 patients, 175 were included in the efficacy analysis set. Of these, 139 patients had mycosis fungoides, including 46 with early stage disease and 93 with advanced stage disease. Among the 139 patients with mycosis fungoides, the objective response rate was 46.8%. A significant difference in objective response rate was detected between patients who started with bexarotene at 300 mg/m2 (61.6%) and patients who started with bexarotene at less than 300 mg/m2 (22.6%, p < 0.001). Of the 139 patients with mycosis fungoides, 92 were treated with a combination of bexarotene plus photo(chemo)therapy. A significant difference in objective response rate was seen between bexarotene with a combination of photo(chemo)therapy (57.6%) and bexarotene without a combination of photo(chemo)therapy (25.5%, p < 0.001). Starting bexarotene at 300 mg/m2 and combination with photo(chemo)therapy were detected as independent factors influencing response. Common treatment‐related adverse events included hypothyroidism (85.8%), hypertriglyceridemia (68.5%), hypercholesterolemia (43.8%), and neutropenia (21.3%). Hypertriglyceridemia, hypercholesterolemia, and neutropenia occurred more frequently in patients who started with bexarotene at 300 mg/m2 than patients who started with bexarotene at less than 300 mg/m2 (hypertriglyceridemia, 76.4% vs. 57.0%, p = 0.001; hypercholesterolemia, 49.0% vs. 36.4%, p = 0.045; neutropenia, 28.0% vs. 12.1%, p = 0.002; respectively). The present study indicates that starting bexarotene at 300 mg/m2 and combination of photo(chemo)therapy offer a promising efficacy for the treatment of patients with mycosis fungoides. Efficacy of low‐dose bexarotene plus photo(chemo)therapy should be evaluated in future. [ABSTRACT FROM AUTHOR]