Effect of Growth Hormone Replacement Therapy on Pituitary Hormone Secretion and Hormone Replacement Therapies in GHD Adults

Abstract

Objective: We tested the impact of commencement of GH replacement therapy in GH-deficient (GHD) adults on the circulating levels of other anterior pituitary and peripheral hormones and the need for re-evaluation of other hormone replacement therapies, especially the need for dose changes. Methods: 22 GHD patients were investigated in a double-blind randomized study and 90 GHD patients in an open study at baseline and after 6 and 12 months of GH replacement therapy. Results: In the placebo-controlled trial, the FT₃ levels increased after 6 months in the GH-treated group, and in the open study the FT₃ levels tended to increase. Other hormone concentrations did not change in either part of the study. Four patients required an increase in thyroxine dose, while 2 patients needed dose reduction. One originally euthyroid patient required thyroxine replacement. Two patients with originally conserved pituitary-adrenal function developed ACTH insufficiency. The hydrocortisone dose was increased in 1 and decreased in 1 of the 66 patients with secondary hypocortisolism. None of the females required any adjustment of sex hormone replacement therapy. Two of 37 males needed dose increase of testosterone, while 1 needed dose reduction. Conclusion: GH replacement therapy required dose adjustments regarding other hormone replacement therapies in 12.2% (n = 11), while initiation of new hormone replacement was performed in 3.3% (n = 3) of the 90 patients during the 1-year follow-up. Monitoring of pituitary hormone axes is advisable after commencement of GH replacement therapy, since changes of hormone replacement therapy was observed in a small but clinically significant number of patients.

Growth hormone and thyroid function—interaction and inhibition

“…Although the findings of Agha et al were comparable to those of previous reports, Hubina et al 1 reported that only 1 of 35 adults with organic hypopituitarism and severe GHD developed secondary hypothyroidism and the need to begin levothyroxine therapy during rhGH administration. In the same study, only 4 of 65 patients with secondary hypothyroidism who were receiving levothyroxine at the start of rhGH treatment required increases in levo thyroxine dosage during rhGH therapy.…”

“…In patients with subclinical adrenocortico tropic hormone deficiency, therefore, administration of rhGH might unmask the need for cortisol replacement therapy. 1,5 …”

GH replacement in adults: interactions with other pituitary hormone deficiencies and replacement therapies

“…This effect is also seen in children with MHPD, but not in children with IGHD (81). The same mechanism may induce high FT 4 in a previously wellreplaced patient when GH treatment is started (80). Also to be considered is that both transdermal and oral estrogens increase thyroxin-binding globulin and patients may need higher L-T 4 replacement doses when these therapies are combined (75).…”

“…Therefore, careful monitoring of thyroid function is mandatory during GH treatment (78), as it may indicate changes in the T 4 dose needed. Patients with untreated GHD may have higher FT 4 levels than on GH replacement; GH therapy may, therefore, unmask undiagnosed CH (74,79,80). This effect is also seen in children with MHPD, but not in children with IGHD (81).…”

Predictors and Growth Consequences of Central Hypothyroidism in Pediatric Patients Receiving Recombinant Human Growth Hormone

“…Studies suggest that rhGH may induce or unmask central hypothyroidism, or increase dose requirement for thyroid hormone among patients already receiving levothyroxine (in as many as 12-16% of patients) [3][4][5][6] . Proposed mechanisms include increased peripheral conversion of T4 to T3 by type I and II deiodinase 7,8 , increased thyroxine binding globulin (TBG) levels and subsequent lower free T4 9 , and decreased secretion of TSH per se 5,8 .…”