Background: Discontinuing growth hormone (GH) treatment during the transition to adulthood has been associated with adverse health outcomes in patients with childhood-onset growth hormone deficiency (CO-GHD). This study investigated the metabolic changes associated with interrupting GH treatment in adolescents with CO-GHD during the transition period.Methods: This study included 187 patients with CO-GHD who were confirmed to have adult GHD and were treated at six academic centers in Korea. Data on clinical parameters, including anthropometric measurements, metabolic profiles, and bone mineral density (BMD) at the end of childhood GH treatment, were collected at the time of re-evaluation for GHD and 1 year after treatment resumption.Results: Most patients (n=182, 97.3%) had organic GHD. The median age at treatment discontinuation and re-evaluation was 15.6 and 18.7 years, respectively. The median duration of treatment interruption was 2.8 years. During treatment discontinuation, body mass index Z-scores and total cholesterol, low-density lipoprotein, and non-high-density lipoprotein (HDL) cholesterol levels increased, whereas fasting glucose levels decreased. One year after GH treatment resumption, fasting glucose levels, HDL cholesterol levels, and femoral neck BMD increased significantly. Longer GH interruption (>2 years, 60.4%) resulted in worse lipid profiles at re-evaluation. The duration of interruption was positively correlated with fasting glucose and non-HDL cholesterol levels after adjusting for covariates.Conclusion: GH treatment interruption during the transition period resulted in worse metabolic parameters, and a longer interruption period was correlated with poorer outcomes. GH treatment should be resumed early in patients with CO-GHD during the transition period.

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 (β = 0.003, P = 0.020). The baseline log-transformed FGF21 level was inversely associated with GV with marginal significance (β = −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.

Objectives Prolactin (PRL) stimulates the mammary glands development; however, it also inhibits gonadotropin-releasing hormone (GnRH) secretion. We evaluated the relationship between PRL levels and puberty in girls with precocious breast development. Methods This study included 244 girls with breast development < 8 years of age. Patients were categorized as central precocious puberty (CPP) [peak luteinizing hormone (LH) levels ≥ 5 IU/L after GnRH stimulation] versus non-CPP (NPP) group. High PRL was defined as serum PRL > 17.9 ng/mL. Results High PRL was more common in NPP than in CPP group (17.6 vs. 8.1%, p=0.025), although mean PRL levels did not differ. In NPP group, the high PRL group had lower peak LH/follicle-stimulating hormone (FSH) ratio, and later LH peak time after GnRH stimulation than normal PRL group (all p < 0.05). PRL levels of the subgroups according to the peak LH time (15, 30, 45, 60, and 90 min after GnRH stimulation) were different in NPP group, but not in CPP group. PRL levels tended to be higher as the peak LH time was delayed. High PRL was associated with decreased odds for CPP (OR=0.42, p=0.043). Conclusions Girls with NPP showed higher proportion of high PRL than CPP group. High PRL group showed more features of prepubertal response in NPP group, and associated with decreased odds for CPP, suggesting the possibility of PRL role on breast development while suppressing hypothalamic–pituitary–gonadal axis activation in NPP girls.

Cerebrotendinous xanthomatosis (CTX) is a rare genetic disease caused by a deficiency of enzymes for the synthesis of bile acid, resulting in the accumulation of cholestanol with reduced chenodeoxycholic acid (CDCA) production and causing various symptoms such as chronic diarrhea in infancy, juvenile cataracts in childhood, tendon xanthomas in adolescence and young adulthood, and progressive neurologic dysfunction in adulthood. Because oral CDCA replacement therapy can effectively prevent disease progression, early diagnosis and treatment are critical in CTX. This study reports the case of CTX in a 10-year-old male who presented with Achilles tendon xanthoma and mild intellectual disability. Biochemical testing showed normal cholesterol and sitosterol levels but elevated cholestanol levels. Genetic testing showed compound heterozygous variants of CYP27A1, c.379C>T (p.Arg127Trp), and c.1214G>A (p.Arg405Gln), which confirmed the diagnosis of CTX. The patient had neither cataracts nor other focal neurologic deficits and showed no abnormalities on brain imaging. The patient received oral CDCA replacement therapy without any adverse effects; thereafter, the cholestanol level decreased and no disease progression was noted. The diagnostic possibility of CTX should be considered in patients with tendon xanthoma and normolipidemic conditions to prevent neurological deterioration.