Genetics of Congenital Isolated TSH Deficiency: Mutation Screening of the Known Causative Genes and a Literature Review.

CONTEXT: Congenital isolated TSH deficiency (i-TSHD) is a rare form of congenital hypothyroidism. Five genes (IGSF1, IRS4, TBL1X, TRHR, and TSHB) responsible for the disease have been identified, although their relative frequencies and hypothalamic/pituitary unit phenotypes have remained to be clarified. OBJECTIVES: To define the relative frequencies and hypothalamic/pituitary unit phenotypes of congenital i-TSHD resulting from single gene mutations. PATIENTS AND METHODS: Thirteen Japanese patients (11 boys and 2 girls) with congenital i-TSHD were enrolled. IGSF1, IRS4, TBL1X, TRHR, and TSHB were sequenced. For a TBL1X mutation (p.Asn382del), its pathogenicity was verified in vitro. For a literature review, published clinical data derived from 74 patients with congenital i-TSHD resulting from single-gene mutations were retrieved and analyzed. RESULTS: Genetic screening of the 13 study subjects revealed six mutation-carrying patients (46%), including five hemizygous IGSF1 mutation carriers and one hemizygous TBL1X mutation carrier. Among the six mutation carriers, one had intellectual disability and the other one had obesity, but the remaining four did not show nonendocrine phenotypes. Loss of function of the TBL1X mutation (p.Asn382del) was confirmed in vitro. The literature review demonstrated etiology-specific relationship between serum prolactin (PRL) levels and TRH-stimulated TSH levels with some degree of overlap. CONCLUSIONS: The mutation screening study covering the five causative genes of congenital i-TSHD was performed, showing that the IGSF1 defect was the leading genetic cause of the disease. Assessing relationships between serum PRL levels and TRH-stimulated TSH levels would contribute to predict the etiologies of congenital i-TSHD.

Comparison of brachial artery flow-mediated dilation in youth with type 1 and type 2 diabetes mellitus.

AIMS/INTRODUCTION: Brachial artery flow-mediated dilation (FMD) is a method of evaluating the function of vascular endothelial cells and is utilized for early diagnosis of atherosclerotic diseases. Only a few studies evaluated the risks for major vascular complications in youth with type 1 and 2 diabetes mellitus from the aspect of the early development of atherosclerosis. We studied whether there is a difference in vascular endothelial cell function between youth with type 1 and 2 diabetes mellitus. MATERIALS AND METHODS: We assessed %FMD of 24 patients with type 1 diabetes mellitus and 27 patients with type 2 diabetes mellitus aged 12-20 years along with glycated hemoglobin, lipid metabolism markers such as triglycerides, and inflammatory biomarkers such as total adiponectin levels in adolescent patients with type 1 or 2 diabetes mellitus. The significance of the difference in each factor between the type 1 and type 2 diabetes groups was assessed using Student's t-test. RESULTS: The %FMD was significantly lower in patients with type 2 diabetes. The body mass index and blood pressure were significantly higher, and total and high-molecular-weight adiponectin levels were significantly lower in patients with type 2 diabetes. %FMD significantly correlated with systolic blood pressure. CONCLUSIONS: The results suggest that youth with type 2 diabetes have more advanced damage of the vascular endothelium and therefore are at higher risk for major vascular complications. Therefore, monitoring the progression of atherosclerosis would also be beneficial in youth with diabetes mellitus, and measurement of FMD could be further warranted.