The occurrence of hypothyroidism during the initial phase of GH replacement therapy in children with GH deficiency: clinical implications
Joanna Smyczynska1,2, Renata Stawerska1,2, Andrzej Lewinski2,3 & Maciej Hilczer1,2
Normal thyroid hormone secretion (or appropriate L-thyroxin substitution) is necessary for the optimal effect GH administration on growing rate. The decrease of free thyroxin (FT4) levels at GH therapy onset was reported in several studies.
The aim of our study was to assess the incidence of hypothyroidism (HT) during the initial phase of GH administration in previously euthyroid children with GH deficiency (GHD) and to compare the first-year response to the therapy in the patients with and without HT.
The analysis comprised 67 children (53 boys, 14 girls), age 12.3±2.2 years (mean±S.D.), with GHD (GH secretion <10.0 ng/ml, decreased IGF1 levels), who were treated with GH in a dose of 0.20±0.02 mg/kg per week for at least 1 year. In all the patients TSH and FT4 concentration was assessed after 36 months of GH administration and HT was diagnosed in 17 of them (25.4%) on the ground of either decreased FT4 level (eight cases) or increased TSH (eight cases), or both (one case). The appropriate L-thyroxin substitution was administered very soon. Height velocity (HV), IGF1 secretion (expressed as IGF1 SDS for age and sex) and its bioavailability (IGF1/IGFBP3 molar ratio) before and after 1 year of GH therapy was compared in both groups.
There were no significant differences in any of the analysed parameters among the groups before GH therapy. The increase of IGF1 SDS presented significant (P<0.001) and similar in both groups (from −2.01±0.97 to 0.61±0.67 in euthyroid children and from −1.99±1.00 to 0.83±0.83 in those who developed HT). The increase of IGF1/IGFBP3 molar ratio was also significant (P<0.001) and similar in both groups (from 0.19±0.07 to 0.41±0.09 and from 0.18±0.05 to 0.45±0.12, respectively). However, the increase of HV presented significantly (P<0.01) lower in children with HT (from 3.8±0.9 to 9.3±2.0 cm/year) than in those who remained euthyroid all the time (from 3.5±1.0 to 10.0±2.1 cm/year).
The incidence of HT during the initial phase of GH treatment in children with GHD and the negative effect of even transient thyroid hormone deficiency on growing rate should be taken into account. Further studies on the possibility of predicting the occurrence of HT in particular patients seem advisable.