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


OBJECTIVE
If GH modulates thyroxine biological effects, serum FT(4) should be targeted accordingly.


METHODS
We conducted observational (study 1) and interventional (studies 2 and 3)/outpatient studies.


METHODS
Thirty-two GH-deficient patients (13 off GH; 22 on l-T(4)) participated in the study.


METHODS
In study 2, levothyroxine was administered to increase FT(4) (>1.0 ng/dl). In study 3, GH was administered or withdrawn.


METHODS
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.
Martins
Manoel R A
MR
Division of Endocrinology, da Escola Paulista de Medicina-Universidade Federal de São Paulo, Rua Pedro de Toledo 910, São Paulo, Brazil 04039-002.
Doin
Fabio C
FC
Komatsu
William R
WR
Barros-Neto
Turibio L
TL
Moises
Valdir A
VA
Abucham
Julio
J
D000293:Adolescent; D000328:Adult; D002648:Child; D004359:Drug Therapy, Combination; D004452:Echocardiography; D004734:Energy Metabolism / Q000187:drug effects; D005260:Female; D013006:Growth Hormone / Q000627:therapeutic use*; D020249:Hormone Replacement Therapy; D019382:Human Growth Hormone / Q000172:deficiency; D006801:Humans; D007037:Hypothyroidism / Q000188:drug therapy*; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D013963:Thyroid Hormones / Q000097:blood; D013974:Thyroxine / Q000627:therapeutic use*; D014284:Triiodothyronine / Q000097:blood