The effect of growth hormone replacement on the thyroid axis in patients with hypopituitarism: in vivo and ex vivo studies.
OBJECTIVE
Alterations in the hypothalamic-pituitary-thyroid axis have been reported following growth hormone (GH) replacement. The aim was to examine the relationship between changes in serum concentration of thyroid hormones and deiodinase activity in subcutaneous adipose tissue, before and after GH replacement.


METHODS
A prospective, observational study of patients receiving GH replacement as part of routine clinical care.


METHODS
Twenty adult hypopituitary men.


METHODS
Serum TSH, thyroid hormones - free and total thyroxine (T4) and triiodothyronine (T3) and reverse T3, thyroglobulin and thyroid-binding globulin (TBG) levels were measured before and after GH substitution. Changes in serum hormone levels were compared to the activity of deiodinase isoenzymes (DIO1, DIO2 and DIO3) in subcutaneous adipose tissue.


RESULTS
The mean daily dose of growth hormone (GH) was 0·34 ± 0·11 mg (range 0·15-0·5 mg). Following GH replacement, mean free T4 levels declined (-1·09 ± 1·99 pmol/l, P = 0·02). Reverse T3 levels also fell (-3·44 ± 1·42 ng/dl, P = 0·03) and free T3 levels increased significantly (+0·34 ± 0·15 pmol/l, P = 0·03). In subcutaneous fat, DIO2 enzyme activity declined; DIO1 and DIO3 activities remained unchanged following GH substitution. Serum TSH, thyroglobulin and TBG levels were unaltered by GH therapy.


CONCLUSIONS
In vitro analysis of subcutaneous adipose tissue from hypopituitary human subjects demonstrates that GH replacement is associated with significant changes in deiodinase isoenzyme activity. However, the observed variation in enzyme activity does not explain the changes in the circulating concentration of thyroid hormones induced by GH replacement. It is possible that deiodinase isoenzymes are differentially regulated by GH in other tissues including liver and muscle.
Department of Endocrinology, Beaumont Hospital & RCSI Medical School, Dublin 9, Ireland.
Nigel
http://orcid.org/0000-0002-9248-8191
N
Glynn
School of Health and Human Performance, Dublin City University, Dublin, Ireland.
Helena
H
Kenny
Division of Endocrinology, Department of Internal Medicine, Texas Tech University Health Science Center-School of Medicine, Lubbock, TX, USA.
Leah
L
Quisenberry
Department of Clinical Biochemistry, Addenbrooke's Hospital, Cambridge, UK.
David J
DJ
Halsall
Department of Chemical Pathology, University Hospital Southampton, Southampton, UK.
Paul
P
Cook
Department of Endocrinology, Connolly Hospital, Dublin, Ireland.
Tommy
http://orcid.org/0000-0002-7570-3953
T
Kyaw Tun
Department of Endocrinology, Connolly Hospital, Dublin, Ireland.
John H
JH
McDermott
Department of Endocrinology, Beaumont Hospital & RCSI Medical School, Dublin 9, Ireland.
Diarmuid
D
Smith
Department of Endocrinology, Beaumont Hospital & RCSI Medical School, Dublin 9, Ireland.
Christopher J
CJ
Thompson
School of Health and Human Performance, Dublin City University, Dublin, Ireland.
Donal J
DJ
O'Gorman
Department of Endocrinology and Metabolism, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
Anita
A
Boelen
Division of Endocrinology, Department of Internal Medicine, Texas Tech University Health Science Center-School of Medicine, Lubbock, TX, USA.
Joaquin
J
Lado-Abeal
Department of Endocrinology, Beaumont Hospital & RCSI Medical School, Dublin 9, Ireland.
Amar
A
Agha
D000328:Adult; D000368:Aged; D013006:Growth Hormone / Q000008:administration & dosage / Q000494:pharmacology*; D020249:Hormone Replacement Therapy / Q000379:methods*; D006801:Humans; D007018:Hypopituitarism / Q000097:blood / Q000188:drug therapy / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D050507:Subcutaneous Fat, Abdominal / Q000187:drug effects / Q000378:metabolism*; D016896:Treatment Outcome; D055815:Young Adult
D013006:Growth Hormone