Growth hormone administration stimulates energy expenditure and extrathyroidal conversion of thyroxine to triiodothyronine in a dose‐dependent manner and suppresses circadian thyrotrophin levels: studies in GH‐deficient adults

OBJECTIVE: The impact of exogenous GH on thyroid function remains controversial although most data add support to a stimulation of peripheral T4 to T3 conversion. For further elucidation we evaluated iodothyronine and circadian TSH levels in GH-deficient patients as part of a GH dose-response study. PATIENTS: Eight GH-deficient adults, who received stable T4 substitution due to central hypothyroidism; two patients, who were euthyroid without T4 supplementation were studied separately. DESIGN: All patients were initially studied after at least 4 weeks without GH followed by 3 consecutive 4-week periods in fixed order during which they received daily doses of 1, 2 and 4 IU of GH/m2 body surface area. The patients were hospitalized for 24 hours at the end of each period. MEASUREMENTS: Circulating total and free concentrations of T4 and T3, total rT3 and TSH were measured once at the end of each study period. Circadian TSH levels were recorded during the period without GH and during GH treatment with 2 IU GH. RESULTS: Highly significant GH dose-dependent increases in total and free T3 and a reduction in rT3 were observed. The T3/T4 ratio also increased with increasing GH dosages (P < 0.001). In seven patients subnormal T3 levels were recorded in the period off GH, despite T4 levels well within the normal range. Resting energy expenditure also increased and correlated with free T3 levels (r = 0.47, P < 0.05). The circadian TSH levels exhibited a significant nocturnal increase during the period without GH, whereas GH therapy significantly suppressed the TSH levels and blunted the circadian rhythm (mean TSH levels (mU/l) 0.546 +/- 0.246 (no GH) vs 0.066 +/- 0.031 (2 IU GH) (P < 0.05)). The two euthyroid non-T4 substituted patients exhibited qualitatively similar changes in all parameters. CONCLUSIONS: GH administration stimulated peripheral T4 to T3 conversion in a dose-dependent manner. Serum T3 levels were subnormal despite T4 substitution when the patients were off GH but normalized with GH therapy. Energy expenditure increased with GH and correlated with free T3 levels. GH caused a significant blunting of serum TSH. These findings suggest that GH plays a distinct role in the physiological regulation of thyroid function in general, and of peripheral T4 metabolism in particular.