Very young children with Prader-Willi syndrome are refractory to growth hormone-associated decreases in free thyroxine levels

Abstract

The earlier initiation of growth hormone (GH) treatment for patients with Prader-Willi syndrome (PWS) who are younger than 2 years has become more prevalent. Because free thyroxine (FT4) levels are low during this period, GH may induce further reductions; however, limited information is currently available on this issue. Therefore, we herein performed age-dependent and time-course analyses of thyroid hormone levels in GH-treated PWS children. This retrospective analysis included genetically diagnosed PWS patients (N = 37, median age of 26 months). An age-dependent analysis was performed by subdividing subjects based on age [a younger group aged between 1 and 24 months (N = 16) and an older group between 25 and 84 months (N = 21)] and was followed by a multiple regression analysis with adjustments for sex and the cumulative GH dose per bodyweight. A time-course analysis of subjects who had not received levothyroxine during the first 18 months of GH treatment (N = 28) was conducted. A one-month treatment with GH decreased FT4 levels in the older group, but not in the younger group, and this was associated with increases in thyroid-stimulating hormone levels. A positive correlation was noted between age and decreases in FT4 levels independent of the cumulative GH dose per bodyweight. The time-course analysis revealed no changes in FT4 levels in the younger group, while transient decreases were observed in the older group. In conclusion, GH treatment causes age-dependent changes in FT4 levels. This result will help clinicians establish a therapeutic strategy to decide the necessity of levothyroxine supplementation in GH-treated children with PWS.

Endocrine features of Prader-Willi syndrome: a narrative review focusing on genotype-phenotype correlation

“…The relationship between thyroid function and recombinant human (rhGH) therapy, particularly the influence of rhGH on serum thyroid hormone levels and increased conversion of thyroxine (T4) to triiodothyronine (T3), has been evaluated in some studies (41,46). RhGH therapy does not seem to increase the prevalence of different forms of hypothyroidism in PWS (41,46), but it is important to evaluate thyroid hormones before, during, and after rhGH treatment to confirm euthyroidism and prevent the possible risks of previously unmasked and/or untreated hypothyroidism.…”