Thyroid Function during Growth Hormone Therapy

Abstract

Administration of growth hormone (GH) in GH-deficient patients has been reported to cause a variety of perturbations in thyroid function. Reports range from decreased sensitivity of thyrotropin (TSH) to thyrotropin-releasing hormone (TRH) stimulation and induction of hypothyroidism to increased energy expenditure and enhanced peripheral thyroxine (T₄) to triiodothyronine (T₃) conversion. Some of the diversities may relate to the fact that earlier studies were uncontrolled case reports, which furthermore employed pituitary GH preparations, which may have been contaminated with TSH. A confounding variable in terms of incipient TSH insufficiency in some patients may also have been present. Data from a placebo-controlled crossover study of 4-months GH therapy in GH-deficient adults, some of whom were on ongoing T₄ substitution, revealed that the most prominent effect on thyroid function was increased peripheral T₄ to T₃ conversion without significantly affecting TSH levels or secretion from the thyroid gland. It was furthermore observed that T3 levels during placebo were significantly decreased compared to an untreated healthy control group. Comparable findings have been made in a controlled study of 6-months GH therapy in adult-onset GH-deficient patients. More recent data suggest that these effects prevail after long-term (16 months) therapy. Similar findings have also been reported in healthy subjects receiving pharmacological GH doses. It is likely that this effect is not caused by GH per se inasmuch as reduced T₄ to T₃ conversion is a common observation in catabolic states with concomitant GH hypersecretion. It remains to be shown whether insulin-like growth factor I (IGF-I) stimulates peripheral deiodination.

Growth Hormone Treatment of Adults with Prader-Willi Syndrome and Growth Hormone Deficiency Improves Lean Body Mass, Fractional Body Fat, and Serum Triiodothyronine without Glucose Impairment: Results from the United States Multicenter Trial

“…To our knowledge, the observed baseline T 3 abnormalities in 20% of GHD PWS subjects and their normalization with GH therapy are unique. However, they are consistent with reports in children with PWS (30) and in non-PWS GHD adults, documenting dose-dependent enhancement of extrathyroidal T 4 to T 3 conversion (13)(14)(15)31) and suppression of circadian TSH levels after the administration of GH (15,32) as well as with other widely reported subtle, but notable complexities in the interaction of GH with the hypothalamic-pituitary-thyroid axis (32). The concomitant group mean reduction in total T 4 levels after GH (8.6 to 7.9 ng/dl, P ϭ 0.05) provides additional evidence of increased deiodination of T 4 in our PWS subjects and supports the hypothesis that peripheral conversion of T 4 to T 3 may contribute to GH-mediated enhancement of resting energy expenditure and LBM (15).…”

Correlation between Severity of Growth Hormone Deficiency and Thyroid Metabolism and Effects of Long-Term Growth Hormone Treatment on Thyroid Function in Children with Idiopathic Growth Hormone Deficiency

“…In our patients, a significant increase in fT 3 at 12 months of therapy is documented in the majority of cases, in line with the data of Seminara et al [16], without a significant relationship with IGF-1 and without any impact on catch-up growth. These changes, independently of TSH levels, might be an expression of the metabolic status of patients at that moment and could be explained by an increased GH-induced T 4 to T 3 deiodination, as previously reported [12,14,36]. The evidence that GHD reduces T 4 to T 3 conversion and GH improves T 4 to T 3 conversion through iodothyronine deiodinase activity is well known in animal models [37,38,39].…”

The Growth Hormone/Insulin-Like Growth Factor-I Axis in Exercise and Sport

“…Thyroid hormone replacement in the hypopituitary patient cannot be titrated against serum TSH, the most sensitive index of tissue activity of thyroid hormones, and thus subtle degrees of overand underreplacement with thyroid hormones likely occur in hypopituitarism. GH, through increased 5Ј-deiodinase activity, increases conversion of T 4 to metabolically active T 3 (7), and it has been suggested that this effect might underlie some of the metabolic changes observed with GH replacement (107,108). Untreated testosterone deficiency in males is associated with reduced LBM, increased body fat, and reduced exercise capac- ity, whereas orally administered estrogen reduces fat oxidation and increases body fat in normal women (109,110).…”