Unresolved subclinical hypothyroidism is independently associated with progression of chronic kidney disease.

BACKGROUND AND AIM: Patients with chronic kidney disease (CKD) often have subclinical hypothyroidism. However, few reports have investigated changes in the status of subclinical hypothyroidism in CKD patients and its clinical significance in CKD progression. METHODS: We included 168 patients with nondialysis-dependent CKD stages 2-4. The normalization of subclinical hypothyroidism during follow-up was assessed, and the association between transitions in subclinical hypothyroid status and the rate of decline of the estimated glomerular filtration rate (eGFR) was investigated. RESULTS: At baseline, 127 patients were euthyroid and 41 (24.4%) patients were diagnosed with subclinical hypothyroidism. Of these 41 patients, 21 (51.2%) spontaneously resolved to euthyroid during follow-up. The rate of eGFR decline of patients with resolved subclinical hypothyroidism was similar to that of euthyroid patients. The patients with unresolved subclinical hypothyroidism showed a steeper renal function decline than patients with euthyroidism or resolved subclinical hypothyroidism (all p < 0.05). The progression to end-stage renal disease was more frequent in those with unresolved subclinical hypothyroidism than in those who were euthyroid (p = 0.006). In multivariate linear regression for rate of eGFR decrease, unresolved subclinical hypothyroidism (ß = -5.77, p = 0.001), baseline renal function (ß = -0.12, p < 0.001) and level of proteinuria (ß = -2.36, p = 0.015) were independently associated with the rate of renal function decline. CONCLUSIONS: Half of the CKD patients with subclinical hypothyroidism did not resolve to euthyroidism, and this lack of resolution was independently associated with rapid renal function decline.

Germline Mutations and Phenotypic Associations in Korean Patients With Pheochromocytoma and Paraganglioma: A Multicenter Study and Literature Review.

Genetic testing is recommended for all patients with pheochromocytomas and paragangliomas (PPGL) to establish genotype-phenotype associations. We investigated germline mutations in 59 patients with PPGL at six Korean university hospitals using next-generation sequencing (NGS) targeting 38 PPGL-associated genes, including those recommended by the Korean PPGL Task Force. Germline mutations were identified in 13 patients (22%), and affected four genes: RET, NF1, VHL, and SDHD. Germline mutations were significantly associated with a family history of PPGL, smaller tumor size, and the presence of other types of tumors. Using 95 Korean PPGL cases with germline mutations identified through a literature review and 13 cases from our cohort, we characterized genotype-phenotype correlations. Mutation hotspots were identified in specific codons of RET (codons 631 and 634), VHL (157 and 167), and SDHB (131 and 253). NF1 mutations varied, indicating the absence of common hotspots. These findings highlight the efficacy of the recommended NGS panel for Korean patients with PPGL and the importance of genetic testing in establishing clinical management and personalized therapeutic strategies.

Muscular sarcoidosis detected by F-18 FDG PET/CT in a hypercalcemic patient.

Sarcoidosis is a systemic granulomatous disease of unknown etiology that involves many organs, occasionally mimicking malignancy. We herein report a 50-yr-old woman of muscular sarcoidosis of chronic myopathic type, manifested by hypercalcemia and muscle wasting. Besides insignificant hilar lymphadenopathy, her sarcoidosis was confined to generalized atrophic muscles and therefore, F-18 FDG PET/CT alone among conventional imaging studies provided diagnostic clues for the non-parathyroid-related hypercalcemia. On follow-up PET/CT during low-dose steroid treatment, FDG uptake in the muscles disappeared whereas that in the hilar lymph nodes remained. PET/CT may be useful in the evaluation of unexpected disease extent and monitoring treatment response in suspected or known sarcoidosis patients.

Exenatide reverses dysregulated microRNAs in high-fat diet-induced obese mice.

Exenatide has beneficial effects on insulin sensitivity in several animal models; however, its mechanism of action remains unclear. Furthermore, the relationship between the effect of exenatide on the changes in the relative abundance of microRNAs (miRNAs), which play a role in regulating glucose and lipid metabolism, is not fully understood. Therefore, we assessed the effect of exenatide on miRNA expression in a high-fat diet (HFD)-induced mouse model of obesity. Both HFD control and exenatide-treated HFD mice showed similar body weight gain and increase in ß-cell mass. Insulin levels were significantly lower in exenatide-treated mice than in HFD control mice. The levels of miRNA-15a, 29c, 124a, and 375 in the pancreas were significantly increased in HFD control mice. Furthermore, the levels of miRNA-29c, 124a, and 146a in the liver and miRNA-15a, 29c, 124a, and 146a in the muscle were significantly increased. In contrast, the levels of miRNA-15a, 29c, 124a, and 375 in the serum were significantly decreased. These effects were reversed by treatment with exenatide. Our results provide experimental evidence that exenatide-mediated amelioration of insulin sensitivity is associated with antagonistic changes in the relative abundance of miRNA-15a, 29c, 124a, and 375 in tissues and serum, thus highlighting their usefulness as biomarkers for monitoring insulin sensitivity and response to exenatide treatment in experimental diabetes.

Factors influencing the detection of the BRAF T1799A mutation in papillary thyroid carcinoma.

The BRAF T1799A mutation is a heterozygous point mutation and its reported prevalence in papillary thyroid carcinoma (PTC) has varied from 29 to 83%, with an overall mean of 44%. In Korea, the reported mutation rate reached 83% in PTC and 52% in micropapillary carcinoma. We hypothesized that the differences in prevalence may be influenced by the methods of mutation analysis, the sizes of tumor and ethnic differences. Three types of DNA samples from the same PTC mass (0.4-1.6 cm, mean 0.83 cm sized) per each patient (n=17) were isolated. The first type was obtained from frozen PTC tissues using laser-captured microdissection (Frozen-laser, n=17), the second was obtained from frozen tissue by manual tumor margin dissection using a blade (Frozen-blade, n=17) and the third was obtained from formalin-fixed, paraffin-embedded tissue by manual margin dissection (Paraffin-blade, n=15, 2 failed). The mutation rates of the three-matched DNA samples were compared by the SNP mode and AQ mode of pyrosequencing, and direct DNA sequencing. Both the AQ mode of pyrosequencing and the direct DNA sequencing detected the BRAF T1799A mutation in 100% of the 'Frozen-laser' samples, but the mutation was omitted in 1/17 of the 'Frozen-blade' samples and in 5/15 of the 'Paraffin-blade' samples, while the former was more rapid and objective than the latter. The SNP mode of pyrosequencing variably detected the mutation from 40 to 100%, and it showed the lowest sensitivity. Our results indicate that the reported prevalence of the BRAF T1799A mutation in PTC can be underestimated due the mutation analysis methods, and especially in small PTCs. The BRAF T1799A mutation may be an early and essential carcinogenic event in nearly all Korean PTCs, and even in micro-PTCs. For the accurate detection of the BRAF T1799A mutation from small PTCs, fresh or frozen tissues and more cautious microdissection are required, and the AQ mode of pyrosequencing assay is preferred.