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Subclinical hypothyroidism (SH) is biochemically defined as serum TSH levels above the upper limit of the reference range in the presence of normal free T4 (FT4) concentrations. While there is a general agreement to treat subjects with serum TSH levels above 10 mU/L, the management of mild form (TSH concentrations between 4.5 and 10 mU/L) is still a matter of debate. In children, mild SH is often a benign and remitting condition and the risk of progression to overt thyroid dysfunction depends on the underlying condition, being higher in the autoimmune forms. The major concern is to establish whether SH in children should always be considered an expression of mild thyroid dysfunction and may deserve treatment. Current data indicate that children with mild SH have normal linear growth, bone health and intellectual outcome. However, slight metabolic abnormalities and subtle deficits in specific cognitive domains have been reported in children with modest elevation of TSH concentration. Although these findings are not sufficient to recommend levothyroxine treatment for all children with mild SH, they indicate the need for regular monitoring to ensure early identification of children who may benefit from treatment. In the meanwhile, the decision to initiate therapy in children with mild SH should be based on individual factors.

Background: Long-term consequences of mild subclinical hypothyroidism (SH) in children are still unclear, and the need for levothyroxine (L-T4) supplementation remains controversial. We designed a 2-year, case-control, prospective study of a cohort of children with SH to evaluate the effects of L-T4 therapy on neurocognitive outcome., Methods: Thirty-four children, age 9.1 ± 2.6 years, with long-lasting, idiopathic, and mild SH, and 34 healthy matched controls, were enrolled. Twenty SH children underwent a 2-year L-T4 treatment (group A), whereas 14 refused treatment and were reevaluated after a 2-year-follow-up (group B). IQ and specific cognitive domains were evaluated in all children at study entry and after 2 years of therapy (group A) or observation (group B) in SH individuals., Results: In SH children baseline IQ scores were normal and comparable to controls (full-scale IQ [FSIQ] 100.4 ± 11.3 vs 101.8 ± 14.2, verbal IQ [VIQ] 99.7 ± 13.7 vs 98.3 ± 14.9 and performance IQ [PIQ] 101.2 ± 10.4 vs 105 ± 10.4).In group A, L-T4 treatment was associated with normalization of thyrotropin (6.3 ± 1.0 mIU/L at baseline vs 2.8 ± 1.4 mIU/L at 2 years, P < .001). However, 2-year L-T4 therapy was not associated with a change in IQ scores (FSIQ 104.4 ± 13.8 vs 102.7 ± 11.0; VIQ 101.8 ± 14.9 vs 102.3 ± 11.9; and PIQ 106.5 ± 13.9 vs 102.7 ± 10.7) or in verbal or performance subtest scores. No significant differences were found in IQ scores after 2 years of treatment in group A compared to group B after a 2-year follow-up., Conclusions: Our data suggest neurocognitive function in children is not impaired by persistent, mild, untreated SH and is not significantly modified by 2-year L-T4 supplementation., (© Endocrine Society 2020. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Context: Growth hormone deficiency (GHD) in children may be associated with early cardiovascular risk factors and alterations in left ventricular (LV) structure and function; data on cardiopulmonary functional capacity are lacking., Objectives: Aim of the study was to evaluate the effect of GHD and growth hormone (GH) therapy on cardiopulmonary functional capacity, left and right cardiac structure and function, and body composition in children and adolescents., Design: Prospective, case-control study., Patients and Methods: Twenty-one untrained GHD children (11.3 ± 0.8 years) underwent cardiopulmonary exercise testing, echocardiography and dual-energy x-ray absorptiometry, before and after 12 months of GH therapy. Twenty-one controls matched for sex, pubertal status, body mass index, and physical activity (PA) were evaluated at baseline and after 1 year., Results: At baseline, GHD patients showed reduced LV mass (LVM; 63.32 ± 7.80 vs 80.44 ± 26.29 g/m2, P = 0.006), peak oxygen consumption (VO2peak; 22.92 ± 4.80 vs 27.48 ± 6.71 mL/Kg/min, P = 0.02), peak workload (80.62 ± 29.32 vs 103.76 ± 36.20 W, P = 0.02), and O2 pulse (4.93 ± 1.30 vs 7.67 ± 2.93 mL/beat, P = 0.0003), compared with controls. GHD patients also exhibited lower lean body mass (LBM 65.36 ± 7.84% vs 76.13 ± 8.23%, P < 0.001), and higher fat mass (FM 30.84 ± 7.92% vs 22.19 ± 8.18%, P = 0.001) than controls. GH therapy resulted in a significant increase of LVM (72.01 ± 15.88, P = 0.03), VO2peak (26.80 ± 4.97; P = 0.01), peak workload (103.67 ± 32.24, P = 0.001), O2 pulse (6.64 ± 1.68, P = 0.0007), and LBM (75.36 ± 7.59%, P = 0.0001), with a reduction in FM (22.62 ± 7.73%, P = 0.001). No difference was found in either left or right ventricular function., Conclusion: Our results suggest that cardiac structure, body composition and cardiopulmonary functional capacity are impaired in children with untreated GHD and can be restored after short-term GH replacement therapy., (Copyright © 2017 Endocrine Society)

Context: PATIENTS with classic congenital adrenal hyperplasia (CAH) are treated with lifelong glucocorticoids (GCs). Cardiovascular and metabolic effects of such therapy in adolescents have never been quantified., Objective: Our objective was to investigate left ventricular (LV) morphology, function, and exercise performance in adolescents with CAH., Design and Setting: We conducted a cross-sectional and controlled study conducted at a tertiary referral center., Patients: Twenty patients with classic CAH (10 females) aged 13.6 ± 2.5 years and 20 healthy controls comparable for sex and pubertal status were enrolled in the study and compared with a group of 18 patients without CAH receiving a similar dose of GCs for juvenile idiopathic arthritis., Main Outcomes Measures: Echocardiographic assessment and symptom-limited exercise testing were performed. Anthropometric, hormonal and biochemical parameters were also measured., Results: Compared with healthy controls, patients with CAH exhibited an increased body mass index (P < .001), waist-to-height ratio (P < .001), and percent body fat (P < .001) as well as higher insulin concentrations and homeostasis model assessment of insulin resistance index even after adjustment for body mass index (P = .03 and P = .05, respectively). Moreover, CAH patients exhibited an impaired exercise capacity as shown by reduced peak workload (99 ± 27 vs 126 ± 27 W, P < .01) and higher systolic blood pressure response at peak (156 ± 18 vs 132 ± 11 mm Hg, P < .01; Δ = 45 ± 24 vs 22 ± 10 mm Hg, P = .05) with respect to healthy controls. CAH males displayed mild LV diastolic dysfunction as documented by significant prolongation of both isovolumic relaxation time (118 ± 18 vs 98 ± 11 milliseconds, P < .05) and mitral deceleration time (138 ± 25 vs 111 ± 15 milliseconds, P < .01). No significant differences in cardiovascular function were found between CAH and juvenile idiopathic arthritis patients., Conclusion: Adolescents with CAH exhibit impaired exercise performance and enhanced systolic blood pressure response during exercise. In our population, such abnormalities appear related to GC therapy rather than CAH per se. CAH males, but not females, present mild LV diastolic dysfunction that correlates with testosterone concentrations suggesting a sex hormone-related difference.

Objective: The treatment of children with subclinical hypothyroidism (SH) is controversial for TSH values between 4.5 and 10 mU/l. The aim of this cross-sectional, controlled study was to evaluate growth and intellectual outcome in children with persistent SH who have never been treated with levothyroxine., Design and Methods: Clinical and auxological parameters, thyroid function, and intellectual outcome were evaluated in 36 children with persistent SH at the age of 9.7±0.6 (range 4-18.0) years. Children had been followed longitudinally for 3.3±0.3 (range 2.0-9.3) years, from first diagnosis of SH until enrollment in the study. Thirty-six age- and sex-matched children were enrolled in the study as controls., Results: At study entry, height (-0.8±0.2 SDS), bone age/chronological age (BA/CA ratio 0.92±0.6), and body mass index (BMI -0.1±0.2 SDS) in SH children were normal. Despite long-term duration of SH, none of these parameters showed a worsening with respect to height (-0.7±0.2 SDS), BA/CA (0.97±0.03), and BMI (-0.1±0.2) at the time of first SH detection. None of the children showed overt signs or symptoms of hypothyroidism during the follow-up. Verbal (99.1±2.2), performance (100.4±1.9), and full-scale (99.7±1.9) intelligence quotient (IQ) scores in SH children were normal and comparable to those of controls. No relationship was detected between IQ scores and the degree or duration of SH., Conclusions: Persistent SH in children is not associated with alterations in growth, bone maturation, BMI, and cognitive function or other complaints that could be ascribed to SH even after several years without therapeutic intervention.