Context: 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.
Objective: Our objective was to evaluate the effects of GH replacement on T(4) biological effects.
Hypothesis: If GH modulates thyroxine biological effects, serum FT(4) should be targeted accordingly.
Design and setting: We conducted observational (study 1) and interventional (studies 2 and 3)/outpatient studies.
Patients: Thirty-two GH-deficient patients (13 off GH; 22 on l-T(4)) participated in the study.
Interventions: In study 2, levothyroxine was administered to increase FT(4) (>1.0 ng/dl). In study 3, GH was administered or withdrawn.
Main outcome measures: We measured FT(4), total T(3) (TT(3)), myocardial isovolumic contraction time (ICT), and resting energy expenditure (REE).
Results: 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).
Conclusions: 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.