Impact of growth hormone (GH) deficiency and GH replacement upon thymus function in adult patients.
BACKGROUND
Despite age-related adipose involution, T cell generation in the thymus (thymopoiesis) is maintained beyond puberty in adults. In rodents, growth hormone (GH), insulin-like growth factor-1 (IGF-1), and GH secretagogues reverse age-related changes in thymus cytoarchitecture and increase thymopoiesis. GH administration also enhances thymic mass and function in HIV-infected patients. Until now, thymic function has not been investigated in adult GH deficiency (AGHD). The objective of this clinical study was to evaluate thymic function in AGHD, as well as the repercussion upon thymopoiesis of GH treatment for restoration of GH/IGF-1 physiological levels.


RESULTS
Twenty-two patients with documented AGHD were enrolled in this study. The following parameters were measured: plasma IGF-1 concentrations, signal-joint T-cell receptor excision circle (sjTREC) frequency, and sj/beta TREC ratio. Analyses were performed at three time points: firstly on GH treatment at maintenance dose, secondly one month after GH withdrawal, and thirdly one month after GH resumption. After 1-month interruption of GH treatment, both plasma IGF-1 concentrations and sjTREC frequency were decreased (p<0.001). Decreases in IGF-1 and sjTREC levels were correlated (r = 0.61, p<0.01). There was also a decrease in intrathymic T cell proliferation as indicated by the reduced sj/beta TREC ratio (p<0.01). One month after reintroduction of GH treatment, IGF-1 concentration and sjTREC frequency regained a level equivalent to the one before GH withdrawal. The sj/beta TREC ratio also increased with GH resumption, but did not return to the level measured before GH withdrawal.


CONCLUSIONS
In patients with AGHD under GH treatment, GH withdrawal decreases thymic T cell output, as well as intrathymic T cell proliferation. These parameters of thymus function are completely or partially restored one month after GH resumption. These data indicate that the functional integrity of the somatotrope GH/IGF-1 axis is important for the maintenance of a normal thymus function in human adults.


BACKGROUND
ClinicalTrials.gov NTC00601419.
Morrhaye
Gabriel
G
University of Liege Center of Immunology, Laboratory of Immunoendocrinology, Institute of Pathology CHU-B23, Liege-Sart Tilman, Belgium.
Kermani
Hamid
H
Legros
Jean-Jacques
JJ
Baron
Frederic
F
Beguin
Yves
Y
Moutschen
Michel
M
Cheynier
Remi
R
Martens
Henri J
HJ
Geenen
Vincent
V
D000328:Adult; D000368:Aged; D000375:Aging / Q000378:metabolism; D005260:Female; D020249:Hormone Replacement Therapy; D019382:Human Growth Hormone / Q000172:deficiency* / Q000627:therapeutic use*; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D013950:Thymus Gland / Q000502:physiology*
D011948:Receptors, Antigen, T-Cell; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I