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GH therapy alters circulating thyroid hormones, deiodinase activity in men
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In men with hypopituitarism, treatment with growth hormone therapy is associated with changes in circulating thyroid hormone levels and deiodinase enzyme activity, although the mechanism behind the changes remains unclear, study findings show.
In a prospective, observational study, Nigel Glynn, MBChB, of the department of endocrinology at Beaumont Hospital and RCSI Medical School in Dublin, and colleagues analyzed data from 20 men with severe-onset GH deficiency who were GH-naive at enrollment (mean age, 53 years; mean BMI, 31.3 kg/m²). All men received 0.3 mg per day subcutaneous recombinant GH (Saizen, Merck), with the dose titrated at 1 month to achieve an insulin-like growth factor I level in the upper half of the age-related reference range (mean daily dose, 0.34 mg). Participants underwent a biopsy of subcutaneous fat before initiating therapy. Serum thyroid-stimulating hormone, free and total thyroxine, free and total triiodothyronine, reverse T3, thyroxine-binding globulin (TBG), thyroglobulin, antithyroid peroxidase (anti-TPO) antibody titer, selenium, IGF-I, testosterone and electrolytes were assessed before and at 3 to 6 months after initiation of GH therapy (mean duration of therapy before testing, 5.3 months). Changes in serum hormone levels were compared with the activity of deiodinase isoenzymes (DIO1, DIO2 and DIO3) in subcutaneous adipose tissue.
After initiation of GH therapy, the men experienced declines in free T4 (mean, –1.09 pmol/L) and reverse T3 (mean, –3.44 pmol/L), whereas free T3 levels increased (mean increase, 0.34 pmol/L); the serum T3/T4 and free T3/reverse T3 ratios also rose. Researchers observed an association between a higher dose of GH and greater decline in serum T4 (r = –0.583; P = .007). Serum TSH levels did not change during the study period, nor did serum thyroglobulin or TBG, according to researchers.
“Our results demonstrate a decreased circulating concentration of free T4 in conjunction with an increase in free T3 following replacement of GH,” the researchers wrote. “These alterations occurred despite TSH levels remaining unchanged.”
In subcutaneous fat, DIO2 enzyme activity declined (–11.08 fmol/mg/min; 96% CI, –28.95 to 0.19); DIO1 and DIO3 activities remained unchanged after GH substitution. Researchers noted that the decline of DIO2 activity correlated with the fall in serum T4 and total T4, but not with the changes in T3 or reverse T3.
“Direct measurement of DIO2 enzyme activity did not reveal changes that would explain the alterations observed in the serum levels of thyroid hormones,” the researchers wrote. “Paradoxically, DIO2 activity, in subcutaneous fat, declined following GH replacement.”
The researchers suggested several possible mechanisms for the unexpected observation. GH therapy is known to cause lipolysis, they wrote, and a reduction in DIO2 activity could be an attempt to protect fat tissue from the additional lipolytic action of T3. The rise in T3 could also be explained by a reduced clearance of T3 due to attenuated DIO3 activity, they wrote. – by Regina Schaffer
Disclosure: The researchers report no relevant financial disclosures.
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