The interaction between growth hormone and the thyroid axis in hypopituitary patients: in vivo and ex vivo studies

Alterations in the hypothalamo-pituitary-thyroid (HPT) axis have been reported following growth hormone (GH) replacement. The aim of this study was to examine potential mechanisms responsible for GH-induced changes in the HPT axis. Furthermore, we aimed to explore the relationship between changes in the serum concentration of thyroid hormones and peripheral biomarkers of thyroid hormone action, before and after GH replacement.

Twenty men with severe GH deficiency participated in a prospective, observational study of physiological GH replacement. Research measurements were conducted immediately prior to commencing and 3-6 months after GH replacement.

Following GH replacement, the ratio of freeT3:freeT4 in serum increased. In subcutaneous fat, Type 2 deiodinase enzyme activity declined. Type 1 and Type 3 deiodinase activity remained unchanged following GH substitution. Serum TSH, thyroglobulin and thyroid binding globulin levels were unchanged by GH therapy.

Hepatic-derived serum markers of thyroid hormone action, including ferritin and caeruloplasmin, declined following GH replacement. In contrast, serum markers of bone turnover increased in parallel with changes in serum concentration of thyroid hormones. Resting energy expenditure and cardiac time intervals did not change throughout the study. Health-related quality of life (QOL) improved following GH replacement in the full study group. However, the improvement in QOL was poorer than expected in subjects who experienced a fall in serum free T4.

This study confirms the significant impact of GH replacement on the thyroid axis. In vitro analysis of subcutaneous fat from hypopituitary subjects demonstrates that GH replacement is associated with significant changes in deiodinase isoenzyme activity. However, the observed variation in enzyme activity does not explain changes in the circulating concentration of thyroid hormones induced by GH replacement. Notwithstanding the underlying mechanism, changes in the HPT axis, induced by GH replacement, have complex clinical implications for patients with hypopituitarism.