Search

Context: Management of GH-treated children with idiopathic short stature (ISS) with early puberty and adolescents in midpuberty at initiation of treatment is challenging., Objective: To assess the effect of combined GH/GnRHa therapy during puberty on achieved adult height (AHt) in these children with ISS and to determine whether outcome depended on sex and pubertal status at initiation of GH therapy., Design: Retrospective, single-center observational study from 2003-2018., Setting: Tertiary endocrine center., Patients: One hundred ninety-two GH-treated children with ISS; 58 of 192 were treated by GH/GnRHa during puberty; 31 of 58 were prepubertal (19 girls) and 27 of 58 pubertal (19 girls) at initiation of GH., Main Outcome Measures: AHt, gain-in-height standard deviation score (SDS), AHt vs predicted adult height (PAHt), AHt vs target height (THt)., Results: Most boys and girls attained AHt SDS within the normal range (-0.73 ± 0.60 and -0.85 ± 0.65, respectively). Treatment modality, pubertal status, and sex were tested for their joint effect on growth outcome measures. Combined GH/GnRHa therapy increased AHt vs PAHt (P < 0.001) and AHt vs THt (P = 0.035). Prepubertal status at onset of GH treatment increased AHt (P = 0.049), gain-in-height SDS (P < 0.001), AHt vs PAHt (P < 0.001), and AHt vs THt (P = 0.042). Female sex increased AHt vs PAHt (P < 0.001)., Conclusions: Our study demonstrated a beneficial effect of combined GH/GnRHa therapy in increasing AHt outcome in children with ISS with early/normal puberty and in adolescents naïve to GH treatment who are in midpuberty at initiation of therapy. This effect was more pronounced in the prepubertal group and in girls. Prospective randomized controlled trials are needed to assess whether GnRHa can increase AHt in GH-treated children with ISS., (Copyright © 2019 Endocrine Society.)

Objective: To assess clinical variables, including early thyroid scintigraphy, in predicting the outcome (permanent vs transient) in term infants with congenital hypothyroidism (CH)., Methods: In a retrospective study, 142 full-term infants with CH diagnosed between 2000 and 2012 were categorized into three groups: agenesis/ectopic thyroid and permanent CH; eutopic thyroid and permanent CH; and eutopic thyroid and transient CH. All underwent early thyroid scintigraphy and were under regular follow-up in our tertiary Pediatric Endocrine Institute., Results: Thyroid scan showed agenesis/ectopic thyroid in 58 (41%) and eutopic thyroid in 84 (59%) infants. Imaging findings were similar in eutopic-permanent and eutopic-transient groups. At initial evaluation, TSH levels were higher in the agenesis/ectopic group than in the eutopic-permanent and eutopic-transient groups (71.5 ± 11.2 mIU/L vs 49.1 ± 27.9 mIU/L and 42.5 ± 29.1 mIU/L, respectively; P < 0.001). Higher l-T4 doses were required from the third month in the agenesis/ectopic than in the eutopic-permanent group (P < 0.001) and from the sixth month in the eutopic-permanent than in the eutopic-transient group (P < 0.01). Initial TSH >63.5 mU/L (P < 0.001) and l-T4 dose >4.6 μg/kg/d at age >6 months (P < 0.001) were found to be predictors for an agenesis/ectopic gland using receiver operating characteristic analysis, as was an l-T4 dose >2.2 μg/kg/d at age >6 months (P < 0.01) for permanent CH in patients with a eutopic gland., Conclusions: Although early thyroid scintigraphy is reliable in predicting permanent CH when detecting agenesis or ectopic gland, it cannot differentiate between permanent and transient CH in cases with a eutopic thyroid. Confirmatory TSH at diagnosis and the l-T4 dose through treatment may better distinguish between permanent and transient CH.

Context: Central precocious puberty (CPP) may have clinical implications in adulthood., Objective: To assess the prevalence of obesity, metabolic outcome (hyperlipidemia, diabetes, and hypertension), and malignancy rate of former CPP women between the third and fifth decades of life., Design: This was a case control study of a historical cohort using the computerized database of a health management organization., Setting: The setting was the Institute for Endocrinology and Diabetes, Schneider Children's Medical Center of Israel, and Clalit Health Services., Participants: The study group comprised of 142 CPP women aged 27-50 years [100 GnRH analog (GnRHa) treated; 42 untreated]. The control group comprised of 413 women randomly matched for age, year of birth, and community clinic (283 for the GnRHa treated; 130 for the untreated)., Methods: Extracted from the database were demographic data, medical history, medications dispensed, recorded anthropometric measurements, vital signs, and laboratory data., Results: At young adulthood, body mass index (percentile and distribution) of treated and untreated former CPP women was comparable to that of their respective controls. Elevated body mass index at presentation was a risk factor for obesity in adulthood in the GnRHa-treated group (r = 0.257; P = .01). The prevalence of metabolic comorbidities (16 vs 13.4%; 21.4 vs 24.6%) and malignancy rate (1.0 vs 1.5%; 4.8 vs 1.5%) were similar in the former CPP women and their controls, with no significant difference between CPP groups., Conclusion: CPP (treated or untreated) is not associated with increased risk of obesity, metabolic derangements, or cancer morbidities in young adulthood. The finding that the health status of former CPP women is similar to that of the general population is reassuring.

Context: Because clinical manifestations of thyroid disorders are variable and subtle in children and adolescents, thyroid function tests are often repeated in patients with nonspecific symptoms., Objectives: The objective of the study was to determine the natural history of initial abnormal TSH and define populations at greater risk for developing a subsequent thyroid dysfunction., Methods: A total of 121,052 of 1.043 million outpatients aged 0.5-16 yr insured by the Clalit Health Medical Organization had a TSH determination in 2002 and follow-up to 2007. Extracted from the Clalit Health Medical Organization database were their demographic data, referral diagnoses, and laboratory results (TSH, free T(4), thyroid antibodies). Excluded were patients with overt hypothyroidism or hyperthyroidism on initial testing., Results: Results of 96.5% of initial serum TSH concentrations were normal (0.35-5.5 mIU/liter), 0.2% were low (<0.35 mIU/liter), 2.9% elevated (>5.5 to 10 mIU/liter). The frequency of TSH testing increased with age and female gender. During follow-up, repeated (two to more than four) TSH tests were performed in 45.7% of the patients. In the second TSH determination, normal TSH was documented in 40, 73.6, and 78.9% of those whose initial serum TSH was highly elevated, elevated, and low, respectively, and in 97% of those with normal initial TSH. Predictive factors for a sustained highly elevated TSH were initial TSH greater than 7.5 mIU/liter (P = 0.014) and female gender (P = 0.047)., Conclusions: In the pediatric population, initial normal or slightly elevated TSH levels are likely to remain normal or spontaneously normalize without treatment. Patients with initial levels greater than 7.5 mIU/liter, particularly girls, are at a greater risk for sustained abnormal TSH levels.