The effect of recombinant human growth hormone on thyroid function in patients with growth hormone deficiency

To evaluate the effect of growth hormone treatment on thyroid function of growth hormone deficient children, 19 (18M/1F) euthyroid children of growth hormone deficiency (GHD) were treated with Genotropin, a recombinant human growth hormone (rhGH) for 12 months. rhGH was injected subcutaneously with a daily dosage of 0.1 IU/kg. All the patients were diagnosed by two GH provocative stimulating tests with the serum GH peak level < 7 micrograms/L. During the treatment, blood was drawn before or 6 and 12 months after the initiation of therapy to measure serum T3, T4, FT3, FT4, rT3 and thyroid-stimulating hormone (TSH) levels. In the meantime, thyrotropin releasing hormone (TRH) stimulating test was performed by an i.v. injection of 200 micrograms synthetic TRH. The results showed that (1) the average serum levels of T4 and FT4 decreased significantly 6 at the 6th and 12th month (P < 0.001), while the serum FT3 level decreased only at the 6th month (P < 0.05). The serum T3, rT3 and TSH concentrations remained unchanged. (2) 8 euthyroid patients (45%) became subclinical hypothyroidism after 12 months' treatment with rhGH for their serum FT4 levels fell to below the normal range. The 19 patients were divided into thyroid function normal (n = 11) and subnormal group (n = 8) according to their posttreatment thyroid functions. (3) The TSH response to TRH was evaluated by the area under the curve (AUC) of serum TSH. The average AUC was greater in the subnormal group than in the normal group whether before or 6 and 12 months after the treatment. The greater TSH response to TRH among patients with decreased posttreatmental FT4 levels suggests that latent TRH deficiency has already existed, which may be the pathogenetic basis of the hypothyroidism developped after rhGH treatment. Thus the thyroid function of GHD patients should be monitored during rhGH treatment in order that the thyroxine replacement therapy can be given in time.