The relationships between GH secretion and thyroid function, as well as the effects of rhGH administration on thyroid hormone levels have been the subject of numerous studies.
The data of Cacciari et al. [
1], presented 30 years ago, indicated that the risk of inducing an alteration in thyroid function in hypopituitary patients during rhGH therapy was only slight and that the abnormal values of thyroxine (T4) and triiodothyronine (T3) returned to normal limits during follow-up.
Next, Gács and Bános [
2] reported that rhGH therapy in children with idiopathic GHD reduced T4 secretion and affected the peripheral metabolism of thyroid hormones, resulting in an increase of T3.
In 1994, Jørgensen et al. [
3] reported that, in GH-deficient adults, rhGH administration stimulated peripheral T4 to T3 conversion in a dose-dependent manner and influenced circadian rhythm of thyrotropin (TSH) secretion. Moreover, in some of those patients before rhGH administration, serum T3 levels were subnormal despite T4 substitution and normalised during the therapy.
As it was shown that rhGH administration might induce a fall in serum T4, it seemed probable that GHD could mask secondary hypothyroidism in some patients with hypopituitarism. Recently, Agha et al. [
4] proved that rhGH administration really led to „unmasking” hypothyroidism in hypopituitary adults. Similar were the observations of Losa et al. [
5], who reported that, in adults with GHD, administration of rhGH therapy was associated with a significant decrease of free T4 (FT4) in first 6 months of treatment.
[OA] Smyczynska J, Hilczer M, Stawerska R, Lewinski A. Thyroid function in children with growth hormone (GH) deficiency during the initial phase of GH replacement therapy - clinical implications. Thyroid Res 2010;3(1):2. http://thyroidresearchjournal.biomedcentral.com/articles/10.1186/1756-6614-3-2
BACKGROUND: Normal thyroid hormone secretion or appropriate L-thyroxine (L-T4) substitution is necessary for the optimal effect of the growth hormone (GH) administration on growth rate. The decrease of free thyroxine (FT4) levels at recombinant human GH (rhGH) therapy onset has been reported in several studies. The aim of the present study was to evaluate the effect of rhGH administration on thyrotropin (TSH) and FT4 serum concentrations in children with GH deficiency (GHD) during the 1st year of therapy, as well as to assess potential indications to thyroid hormone supplementation in them.
PATIENTS AND METHODS: The analysis involved data of 75 children (59 boys, 16 girls) with disorders of GH secretion (GHD, neurosecretory dysfunction - NSD) and partial GH inactivity (inactGH), who were treated with rhGH for - at least - one year. In all the children, body height and height velocity (HV) were assessed before and after 1 year of therapy, while TSH, FT4, IGF-I and IGFBP-3 before treatment and after 3-6 months and 1 year of treatment. In the patients, who revealed hypothyroidism (HypoT), an appropriate L-T4 substitution was introduced immediately. The incidence of HypoT, occurring during the initial phase of rhGH therapy, was assessed, as well as its influence on the therapy effectiveness.
RESULTS: Before rhGH substitution, there were no significant differences in either auxological indices or TSH and FT4 secretion, or IGF-I concentration and its bioavailability among the groups of patients. During the initial 3-6 months of rhGH administration, a significant decrease of FT4 serum concentration, together with a significant increase of IGF-I SDS and IGF-I/IGFBP-3 molar ratio was observed in all the studied groups. In 17 children, HypoT was diagnosed and L-T4 substitution was administered. Despite similar IGF-I secretion increase, the improvement of HV presented significantly lower in children with HypoT than in those who remained euthyroid all the time.
CONCLUSIONS: The incidence of HypoT during the initial phase of GH treatment in children with GHD and the negative effect of even transient thyroid hormone deficiency on the growth rate should be taken into account.
