Growth hormone replacement improves thyroxine biological effects: implications for management of central hypothyroidism.

Abstract

The biological significance of GH-induced changes in serum TH concentrations is unknown. It has been suggested that serum free T(4) (FT(4)) should be targeted at the high-normal range during GH replacement. Our objective was to evaluate the effects of GH replacement on T(4) biological effects. If GH modulates thyroxine biological effects, serum FT(4) should be targeted accordingly. We conducted observational (study 1) and interventional (studies 2 and 3)/outpatient studies. Thirty-two GH-deficient patients (13 off GH; 22 on l-T(4)) participated in the study. In study 2, levothyroxine was administered to increase FT(4) (>1.0 ng/dl). In study 3, GH was administered or withdrawn. We measured FT(4), total T(3) (TT(3)), myocardial isovolumic contraction time (ICT), and resting energy expenditure (REE). In study 1, off-GH and on-GH groups had similar FT(4), but off GH showed lower TT(3) (P < 0.01) and REE (P = 0.02), higher ICT (P < 0.05) than on-GH and controls. On GH, ICT and REE correlated only with TT(3) (r = -0.48; r = 0.58; P < 0.05). Off GH, ICT correlated only with FT(4) (P < 0.01). In study 2, off GH, levothyroxine intervention increased FT(4) (P = 0.005) and TT(3) (P = 0.012), decreased ICT (P = 0.006), and increased REE (P = 0.013); ICT and FT(4) changes correlated (r = -0.72; P = 0.06). On GH, levothyroxine increased FT(4) (P = 0.0002), TT(3) (P = 0.014), and REE (P = 0.10) and decreased ICT (P = 0.049); REE and TT(3) changes correlated (r = 0.60; P = 0.05). In study 3, GH decreased FT(4), increased TT(3), decreased ICT, and increased REE (P < 0.05). REE correlated (P < 0.05) with IGF-I (r = 0.57) and TT(3) (r = 0.64). ICT correlated only with TT(3) (r = -0.46). GH replacement improves the biological effects of T(4). Serum FT(4) should be targeted at the high-normal range in GH-deficient patients only off GH replacement.