Update on Neonatal Isolated Hyperthyrotropinemia: A Systematic Review.

The purpose of this paper was to systematically summarize the published literature on neonatal isolated hyperthyrotropinemia (HTT), with a focus on prevalence, L-T4 management, re-evaluation of thyroid function during infancy or childhood, etiology including genetic variation, thyroid imaging tests, and developmental outcome. Electronic and manual searches were conducted for relevant publications, and a total of 46 articles were included in this systematic review. The overall prevalence of neonatal HTT was estimated at 0.06%. The occurrence of abnormal imaging tests was found to be higher in the persistent than in the transient condition. A continuous spectrum of thyroid impairment severity can occur because of genetic factors, environmental factors, or a combination of the two. Excessive or insufficient iodine levels were found in 46% and 16% of infants, respectively. Thirty-five different genetic variants have been found in three genes in 37 patients with neonatal HTT of different ethnic backgrounds extracted from studies with variable design. In general, genetic variants reported in the TSHR gene, the most auspicious candidate gene for HTT, may explain the phenotype of the patients. Many practitioners elect to treat infants with HTT to prevent any possible adverse developmental effects. Most patients with thyroid abnormalities and/or carrying monoallelic or biallelic genetic variants have received L-T4 treatment. For all those neonates on treatment with L-T4, it is essential to ensure follow-up until 2 or 3 years of age and to conduct medically supervised trial-off therapy when warranted. TSH levels were found to be elevated following cessation of therapy in 44% of children. Withdrawal of treatment was judged as unsuccessful, and medication was restarted, in 78% of cases. Finally, data extracted from nine studies showed that none of the 94 included patients proved to have a poor developmental outcome (0/94). Among subjects presenting with normal cognitive performance, 82% of cases have received L-T4 therapy. Until now, the precise neurodevelopmental risks posed by mild disease remain uncertain.

The relationship between hyperthyrotropinemia and metabolic and cardiovascular risk factors in a large group of overweight and obese children and adolescents.

PURPOSE: Mild TSH elevations are frequently observed in obese patients, in the absence of any detectable thyroid disease. Our objective is to evaluate the relationship between the raised TSH levels and the biochemical and clinical consequences of obesity. METHODS: This is a retrospective cross-sectional study of a large population of obese children and adolescents. We evaluated 833 subjects (340 m, 493 f), aged 14.4 ± 2.5 (range 5.2-18.5) years, height SDS 0.27 ± 1.04 (-3.49-4.35), and BMI SDS 2.94 ± 0.59 (1.60-4.68). Body composition, free T4, TSH, anti-TPO antibodies, anti-TG antibodies, inflammation markers (total WBC and the subtypes, ultrasensitive C-reactive protein), and metabolic parameters [AST, ALT, γGT, ALP, glycaemia, insulin, total cholesterol (TC), HDL-cholesterol (HDL-C), and LDL-cholesterol (LDL-C), triglycerides (TG)] were measured, and oral disposition index (ODI) and cardiovascular risk factors (TC/HDL-C and TG/HDL-C) were calculated. After exclusion of the subjects showing anti-thyroid antibodies, the remaining 779 (325 m, 454 f) were then subdivided into two subgroups according to a TSH value below (group A) or above (group B) 4.5 mU/L. RESULTS: Clinical characteristics and hematological markers of patients with and without positive anti-thyroid antibodies were similar, with the exception of higher TSH levels in the latter group. Using analysis of covariance, the subjects of group B had significantly higher values of TC (170.3 ± 28.7 vs 163.3 ± 32.9 mg/dL; p < 0.05), systolic (125.8 ± 13.5 vs 124.5 ± 13.1 mm/Hg), and diastolic blood pressure (79.2 ± 8.0 vs 77.9 ± 8.2 mm/Hg) than subjects of group A. No difference was observed in body composition, ODI, and the cardiovascular risk factors between these two groups. CONCLUSION: TSH elevation in overweight and obese children and adolescents, being associated with a higher TC and blood pressure, might negatively influence the cardiac status. Longitudinal studies are requested, however, to confirm this hypothesis and, therefore, to conclude whether a substitutive treatment with l-thyroxine is really needed in these patients.

Thyroid hormone receptor ß mediates thyroid hormone effects on bone remodeling and bone mass.

Excess thyroid hormone (TH) in adults causes osteoporosis and increases fracture risk. However, the mechanisms by which TH affects bone turnover are not elucidated. In particular, the roles of thyroid hormone receptor (TR) isotypes in the mediation of TH effects on osteoblast-mediated bone formation and osteoclast-mediated bone resorption are not established. In this study we have induced experimental hypothyroidism or hyperthyroidism in adult wild-type, TRα- or TRß-deficient mice and analyzed the effects of TH status on the structure and remodeling parameters of trabecular bone. In wild-type mice, excess TH decreased bone volume and mineralization. High TH concentrations were associated with a high bone-resorption activity, assessed by increased osteoclast surfaces and elevated concentrations of serum bone-resorption markers. Serum markers of bone formation also were higher in TH-treated mice. TRα deficiency did not prevent TH action on bone volume, bone mineralization, bone formation, or bone resorption. In contrast, TRß deficiency blocked all the early effects of excess TH observed in wild-type mice. However, prolonged exposure to low or high TH concentrations of TRß-deficient mice induced mild modifications of bone structure and remodeling parameters. Together our data suggest that TRß receptors mediate the acute effects produced by transient changes of TH concentrations on bone remodeling, whereas TRα receptors mediate long-term effects of chronic alterations of TH metabolism. These data shed new light on the respective roles of TRs in the control of bone metabolism by TH.