Relationship Between the Serum FGF21 Level and Growth in Children of Short Stature.

BACKGROUND: This study investigated the relationship between fibroblast growth factor 21 (FGF21) levels and growth in children with growth hormone deficiency (GHD) and idiopathic short stature (ISS), and the effects of the FGF21 level on response to growth hormone (GH) treatment. METHODS: We included 171 pre-pubertal children with a GHD (n = 54), ISS (n = 46), and normal height (n = 71). Fasting FGF21 levels were measured at baseline and every 6 months during GH treatment. Factors associated with growth velocity (GV) after GH therapy were investigated. RESULTS: The FGF21 level was higher in short children than in the controls without significant difference between the GHD and ISS groups. In the GHD group, the FGF21 level was inversely associated with the free fatty acid (FFA) level at baseline (r = -0.28, P = 0.039), however, was positively correlated with the FFA level at 12 months (r = 0.62, P = 0.016). The GV over 12 months of GH therapy was positively associated with the delta insulin-like growth factor 1 level (ß = 0.003, P = 0.020). The baseline log-transformed FGF21 level was inversely associated with GV with marginal significance (ß = -0.64, P = 0.070). CONCLUSION: The FGF21 level was higher in children of short stature, both those with GHD and the ISS, than in children with normal growth. The pretreatment FGF21 level negatively affected the GV of children with GH-treated GHD. These results suggest the existence of a GH/FFA/FGF21 axis in children.

Persistent goiter with congenital hypothyroidism due to mutation in DUOXA2 gene.

Thyroid hormones are crucial for development of the central nervous system. Congenital hypothyroidism (CH) is the most common preventable disease resulting in mental retardation. A neonatal screening test (NST) can detect a mild form of CH that can be treated at an early age. Generally after 3 years of age, when most of the brain has matured, clinicians consider reevaluation of thyroid function for CH patients that have been identified with a normal thyroid gland at a normal position. This report presents three CH patients that developed normally, with persistent goiter despite thyroid hormone supplements. The patients' initial thyroid-stimulating hormone (TSH) level after NST was 47, 157, and 57 mIU/L, respectively. Levothyroxine administration began at 1 or 2 months of age and was terminated after reevaluation at the age of 3, 15, and 5 years, respectively. However, 1 or 2 years later, they all resumed their medication due to increased TSH level coupled with newly developed or enlarged goiter. They all showed dual oxidase maturation factor 2 (DUOXA2) gene mutation: a homozygous mutation with DUOXA2 (c.413dupA; p.Tyr138*) in case 1, a presumed compound heterozygotic mutation with DUOXA2 (p.Tyr138*/p.Tyr246*) in case 2, and heterozygous mutations with DUOXA2 (c.738C>G; p.Tyr246*) and TPO (c.2268dupT; p.Glu757*) in case 3. When goiter persists or is newly developed despite a maintained euthyroid status, for those with transient CH history, follow-up to assess the thyroid function is recommended for at least 1 or 2 years, and genetic testing would be helpful. This study presents the first clinical cases of DUOXA2 mutation in Korea.

Nonalcoholic fatty liver disease in long-term survivors of childhood-onset craniopharyngioma.

PURPOSE: Hypothalamic obesity in childhood-onset (CO-) craniopharyngioma patients may predispose to nonalcoholic fatty liver disease (NAFLD). This study reviewed the characteristics of NAFLD associated with CO-craniopharyngioma. METHODS: This study retrospectively reviewed 75 patients who underwent surgery for craniopharyngioma while younger than 15 years of age between 2000 and 2016. RESULTS: Elevated aspartate aminotransferase (AST) or alanine aminotransferase (ALT) above 40 IU/L was observed in 51 of the 75 (68%) CO-craniopharyngioma patients. Imaging studies were performed in 32 patients with elevated liver enzymes. The estimated prevalence of NAFLD in CO-craniopharyngioma was 47%. NAFLD was detected in 22 patients (male 59%, 4.3±4.0 years after first surgery). The mean age at the time of the initial operation was 9.1±2.9 years. Six patients (27.3%) were diagnosed within 1 year. Among the 19 patients with initial height and weight data, the body mass index (BMI) z-score (BMI_Z) at the time of diagnosis with NAFLD was 1.37±1.01 (range, -0.75 to 3.18), with 4 patients (18.2%) being overweight and 9 (40.9%) being obese. BMI_Z increased above BMI_Z at the time of the operation in 13 patients (68.4%). The increment in BMI_Z was 1.13 (range, 0.10-2.84). Seventeen patients did not receive growth hormone. An insulin-like growth factor-I level <3rd percentile was observed in 19 patients. CONCLUSIONS: NAFLD is common in survivors of CO-craniopharyngioma and may develop earlier. If the ALT or AST is above 40 IU/L, a diagnostic work-up should be started.

Unfavorable Course of Subclinical Hypothyroidism in Children with Hashimoto's Thyroiditis Compared to Those with Isolated Non-Autoimmune Hyperthyrotropinemia.

Subclinical hypothyroidism (SCH) is a common problem in pediatric population, and the natural history of SCH varies depending on its etiology. Whether Hashimoto's thyroiditis (HT) negatively affects the natural course of SCH was investigated in pediatric patients without concomitant diseases. Predictors for levothyroxine medication were also evaluated. Medical records of 109 children with SCH (91 girls, 5?18 years) diagnosed between 2005 and 2014 were retrospectively reviewed. Patients were classified into HT (n = 37) and isolated non-autoimmune hyperthyrotropinemia (iso-NAHT, n = 72). During median 2 years of follow-up, only 10.1% of SCH patients eventually initiated levothyroxine, and HT patients showed a higher probability of requiring levothyroxine medication than iso-NAHT patients (21.6% vs. 4.2%). Underlying HT independently predicted deterioration of thyroid function, leading to levothyroxine medication (hazard ratios [HRs], 4.6 vs. iso-NAHT, P = 0.025). High titers of anti-thyroglobulin antibodies (TGAbs) predicted later medication in the HT group (HRs, 28.2 vs. normal TGAbs, P = 0.013). Most pediatric SCH showed benign and self-remitting courses. Underlying HT significantly increases the risk for levothyroxine medication, especially with high titers of TGAbs.