Oncocytic Adrenocortical Carcinoma With Low 18F-FDG Uptake and the Absence of Glucose Transporter 1 Expression.

Adrenocortical carcinoma (ACC) is a rare tumor, and some histological variants (oncocytic, myxoid, and sarcomatoid ACCs) have been reported in addition to the conventional ACC. Among these subtypes, oncocytic ACC is histologically characterized by the presence of abundant eosinophilic granular cytoplasm in the carcinoma cells owing to the accumulation of mitochondria, which generally yields high 18F-fluorodeoxyglucose (FDG) uptake on positron emission tomography (PET). Herein, we report the case of a 21-year-old woman with oncocytic ACC with low FDG uptake on PET scan. Her circulating levels of androgens were high, and androgen-synthesis enzymes were detected in carcinoma cells. The patient also had hypocholesterolemia. However, glucose transporter 1 (GLUT1) was not detected in the tumor, which was considered to account for the low FDG uptake by the tumor. To the best of our knowledge, this is the first case of low FDG uptake by oncocytic ACC without GLUT1 expression. Additionally, since hypocholesterolemia was reported in 3 previous reports of androgen-producing tumors, a possible correlation between androgenicity in adrenal tumors and the development of hypocholesterolemia could be postulated; however, further investigations are needed for clarification. This case highlights important information regarding the diversity of ACC and its impact on hypocholesterolemia.

Clinical and genetic determinants of urinary glucose excretion in patients with diabetes mellitus.

AIMS/INTRODUCTION: Glucosuria is a representative symptom in diabetes patients with poor glycemic control and in those treated with sodium-glucose cotransporter 2 inhibitors. Renal threshold levels of glucose excretion are known to vary among individuals, but factors contributing to glucosuria are not well characterized. The present study aimed to clarify clinical and genetic determinants of glucosuria in individuals with diabetes mellitus. MATERIALS AND METHODS: The 24-h urinary glucose excretion was measured in 135 hospitalized patients on admission, with continuous measurement for five consecutive days in 75 patients. Genetic and clinical factors contributing to glucosuria were studied. As a genetic factor, SLC5A2 polymorphism was genotyped. A total of 476 participants (266 participants with type 2 diabetes and 210 healthy controls) were additionally genotyped for the association study of SLC5A2 with type 2 diabetes. A meta-analysis was carried out with the present study and previous association studies. RESULTS: Multiple regression analysis showed that the independent variables of average blood glucose (ß = 0.41, P = 1.4 × 10-7 ), estimated glomerular filtration rate (ß = 0.28, P = 6.0 × 10-5 ), sex (ß = 0.28, P = 5.7 × 10-5 ) and SLC5A2 rs9934336 polymorphism (ß = 0.17, P = 0.02) were significantly correlated with urinary glucose excretion. The frequency of the A allele of rs9934336 tended to be lower in participants with type 2 diabetes than in controls (odds ratio 0.78, 95% confidence interval 0.53-1.13, not significant), and meta-analysis showed a significant association between the A allele and type 2 diabetes (summary odds ratio for minor allele [A] 0.86, 95% confidence interval 0.78-0.94, P < 0.002). CONCLUSIONS: Blood glucose, estimated glomerular filtration rate, sex and SLC5A2 polymorphism were independent determinants of glucosuria in diabetes mellitus.

Contribution of Asian Haplotype of KCNJ18 to Susceptibility to and Ethnic Differences in Thyrotoxic Periodic Paralysis.

CONTEXT AND OBJECTIVES: Thyrotoxic periodic paralysis (TPP) is an acute complication of thyrotoxicosis that can be lethal. TPP is rare in Caucasians but often affects young men in East Asian populations. This study aimed to clarify the contribution of KCNJ18 to susceptibility to TPP in East Asian populations. PARTICIPANTS AND METHODS: The study comprised 635 participants including 13 Japanese patients with TPP, 208 Japanese patients with Graves disease without TPP, and 414 healthy control subjects from the Japanese (n = 208), Korean (n = 111), and Caucasian populations (n = 95). DNA samples from 29 participants (13 with TPP, 8 with Graves disease, and 8 controls) were sequenced for KCNJ18, and all participants (n = 635) were genotyped for six variants of KCNJ18 and a polymorphism of KCNJ2 (rs312691). RESULTS: Six single-nucleotide variants (SNVs) with amino acid substitutions were identified by direct sequencing of KCNJ18. Among these, four SNVs comprised three haplotypes under strong linkage disequilibrium. Haplotype 1 (AAAG) of KCNJ18 was significantly associated with susceptibility to TPP in the Japanese population (OR = 19.6; 95% CI, 1.5 to 256.9; P = 0.013). Haplotype frequencies in the general East Asian (Japanese and Korean) and Caucasian populations differed significantly (haplotype 1: 80.8% vs 48.4%, P = 1.1×10-27). CONCLUSION: A major haplotype of KCNJ18 in East Asian populations is significantly associated with susceptibility to TPP. The haplotype is much more common in East Asian than Caucasian populations, suggesting its contribution to the high prevalence of TPP in East Asian populations.