Long-term effects of growth hormone replacement therapy on thyroid function in adults with growth hormone deficiency.
BACKGROUND
Clinical studies on the effect of growth hormone (GH) on thyroid function in patients with GH deficiency are contradictory. Further, the majority of published observations are limited to the first 6-12 months of GH replacement therapy. The aim of our study was to estimate the incidence of clinically relevant hypothyroidism in a cohort of patients with adult GH deficiency (AGHD) during long-term therapy with recombinant human GH (rhGH).


METHODS
The study was designed as a retrospective collection of data on thyroid function in 49 AGHD patients of whom 44 (90%) had multiple hormone deficiency. Thirty-seven patients (76%) were on stable levothyroxine (LT4) replacement therapy (HYPO), and 12 (24%) were euthyroid (EUT). Therapy with rhGH was started at a dose of 3.5 microg/kg body weight and adjusted according to insulin-like growth factor-I (IGF-I) levels. At baseline, 6 months, 12 months, and yearly thereafter we measured free triiodothyronine (fT3), free thyroxine (fT4), thyroid-stimulating hormone, and IGF-I. Study outcome was fT4 level below the normal range (9 pmol/L), irrespectively of fT3 or thyroid-stimulating hormone levels.


RESULTS
During a follow-up of 115 patient-years, mean fT4 level decreased significantly, although remaining within the normal range (p = 0.0242; month 48 vs. baseline). The largest decrease was between baseline and month 6, when fT4 decreased of 1.43 pmol/L (95% confidence interval, 0.33-2.53) per 1 unit (microg/kg body weight) increase in rhGH dose. The incidence of hypothyroidism was 1.2 (HYPO group) and 6.7 (EUT group) events per 100 patient-years.


CONCLUSIONS
We confirm that in patients with AGHD, rhGH therapy is associated with a small, although significant, decrement of fT4 in the first 6 months of replacement therapy. However, the incidence of hypothyroidism is low. Monitoring of thyroid function during rhGH therapy is advisable, particularly in the first year of therapy when the largest decrease in fT4 occurs.
Losa
Marco
M
Department of Neurosurgery, Istituto Scientifico San Raffaele, Università Vita-Salute, Milan, Italy. losa.marco@hsr.it
Scavini
Marina
M
Gatti
Elisa
E
Rossini
Alessandro
A
Madaschi
Sara
S
Formenti
Ilaria
I
Caumo
Andrea
A
Stidley
Christine A
CA
Lanzi
Roberto
R
D000328:Adult; D002648:Child; D004393:Dwarfism, Pituitary / Q000151:congenital / Q000188:drug therapy*; D005260:Female; D005500:Follow-Up Studies; D020249:Hormone Replacement Therapy; D019382:Human Growth Hormone / Q000009:adverse effects / Q000172:deficiency / Q000627:therapeutic use*; D006801:Humans; D007037:Hypothyroidism / Q000453:epidemiology / Q000209:etiology; D015994:Incidence; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins / Q000627:therapeutic use; D012189:Retrospective Studies; D013961:Thyroid Gland / Q000502:physiology*; D013974:Thyroxine / Q000097:blood / Q000627:therapeutic use
D011994:Recombinant Proteins; D019382:Human Growth Hormone; D013974:Thyroxine