ABSTRACT
INTRODUCTION: Individuals with Turner syndrome (TS) are at increased risk of developing diabetes mellitus (DM). Currently, annual DM screening with hemoglobin A1c (HbA1c) with or without fasting blood glucose (FBG) is recommended starting at age 10. However, the optimal DM screening for individuals with TS is not known. The purpose of this study was to evaluate the correlation between HbA1c, FBG, and the 2-hour oral glucose tolerance test (OGTT). A second goal was to query whether optimal HbA1c and fasting (FBG) cut points for TS-associated DM and impaired glucose tolerance (IGT), as defined by the OGTT 2-hour blood glucose (BG), might differ from those for the general population. METHODS: Individuals with TS ≥ age 10 from the TS: Genotype Phenotype study in the National Institute of Child Health and Human Development's Data and Specimen Hub (DASH) who had 2-hour OGTT BG, HbA1c, and FBG were included. Correlations between HbA1c, FBG, and 2-hour OGTT BG were evaluated. Areas under the receiver operative characteristic (ROC-AUC) curves were generated. Optimal cut points for predicting TS-associated IGT (2-hour BG ≥ 7.77 mmol/L ) and DM 2-hour BG ≥11.10 mmol/L) were determined. RESULTS: 348 individuals had complete data (2-hour OGTT BG < 7.77 mmol/L, n = 239; TS-associated IGT, n = 79; DM, n = 30). ROC-AUC was poor for HbA1c to predict IGT (0.57, 0.49-0.65) but better for DM (0.81, 0.71-0.90). ROC-AUC was also poor for FBG to predict IGT (0.63, 0.56-0.70) but better for DM (0.85, 0.77-0.93). At a cut point of 38 mmol/mol (5.6%), HbA1c had 67% sensitivity (95% CI: 47-83%) and 86% specificity (95% CI: 82-90%) for identifying TS-associated DM defined by 2-hour OGTT BG. DISCUSSION/CONCLUSIONS: The correlation of HbA1c and 2-hour OGTT BG are lower in TS than other published studies regarding type 2 DM. HbA1c is fairly specific for DM in TS but lacks sensitivity especially at currently utilized levels. Future research should focus on characterizing individuals with TS whose glycemic status is discordant, as this may provide additional insights into the pathophysiology of glucose metabolism in TS. Longitudinal assessement of glycemia as it relates to micro- and macrovascular complications in individuals with TS will further inform DM screening in this population.
ABSTRACT
Objective: Peripheral precocious puberty (PP) is an infrequent etiology for early sexual development. Intracranial germ cell tumors (GCTs) are rare but can present infrequently with PP with the rate of development affected by the degree of tumor hormone production. Our objective was to describe a young boy with a ß-human chorionic gonadotropin (hCG)-secreting intracranial GCT with an extremely elevated testosterone level, who presented with rapidly progressive PP. Case Report: A 5-year-old boy presented with penile growth plus pubic hair, deepening voice, and body odor for 3 months. Physical examination revealed a height velocity of 16.25 cm/year, Tanner stage 3 pubic hair, and enlarged penis for age. Laboratory results revealed elevated serum and cerebrospinal fluid ß-hCG and 17-hydroxyprogesterone progesterone levels. The testosterone level was above the initial detection range at 2700 ng/dL. Follicle-stimulating hormone and luteinizing hormone were prepubertal with normal serum and cerebrospinal fluid alpha-fetoprotein levels. Imaging showed a pineal mass diagnosed as a ß-hCG-secreting GCT. During chemotherapy, the physical signs of PP remitted and laboratory values normalized. Discussion: Intracranial tumors can cause peripheral PP in boys. If the tumor produces high ß-hCG levels, this could cause severe hyperandrogenemia resulting in the rapid development of secondary sexual signs. GCTs should be considered in male patients with rapidly progressive PP, even in those lacking other signs of a brain tumor. Conclusion: When presented with a boy with PP, a GCT should be considered if workup shows an elevated testosterone level in conjunction with an elevated ß-hCG level, especially if with rapid development.
