Effects of methimazole treatment on growth hormone (GH) response to GH-releasing hormone in patients with hyperthyroidism

Abstract

Abstract. In vitro studies have demonstrated that thyroid hormones can enhance basal and stimulated growth hormone secretion by cultured pituitary cells. However, both in man and in the rat the effects of high thyroid hormone levels on GH secretion are unclear. The aim of our study was to test the GH response to human GHRH in hyperthyroid patients and to evaluate the effects on GH secretion of short- and long-term pharmacological decrease of circulating thyroid hormones. We examined 10 hyperthyroid patients with recent diagnosis of Graves' disease. Twelve healthy volunteers served as controls. All subjects received a bolus iv injection of GHRH(1-29)NH2, 100 μg. Hyperthyroid patients underwent a GHRH test one and three months after starting antithyroid therapy with methimazole, 10 mg/day po. GH levels at 15, 30, 45, 60 min and GH peak after stimulus were significantly lower in hyperthyroid patients than in normal subjects. The GH peak was also delayed in hyperthyroid patients. After one month of methimazole therapy, most of the hyperthyroid patients had thyroid hormone levels in the normal range, but they did not show significant changes in GH levels after GHRH, and the GH peak was again delayed. After three months of therapy with methimazole, the hyperthyroid patients did not show a further significant decrease in serum thyroid hormone levels. However, mean GH levels from 15 to 60 min were significantly increased compared with the control study. The GH peak after GHRH was also earlier than in the pretreatment study. In conclusion, the GH response to GHRH is inhibited and delayed by hyperthyroidism and returns to the normal pattern after long-term euthyroidism has been achieved with methimazole.

Acute Effects of Clonidine and Growth-Hormone-Releasing Hormone on Growth Hormone Secretion in Patients with Hyperthyroidism

“…Our data confirm that hyperthyroid patients show blunted GH responses to GHRH [9]. The mechanism by which the elevation in the serum concentration of thy roid hormones inhibits GH secretion remains to be explained.…”

“…pretreating animals with thyroxine has been reported to decrease the GH response to GHRH as com pared to the euthyroid state [11], In man, several studies have reported that hyperthyroid patients have reduced spontaneous GH secretion (21) and that the GH re sponse to various stimuli, such as insulin-induced hypo glycemia [8,9] and p-adrenergic blockers [22,23] is impaired in hyperthyroidism. The GH response to GHRH in hyperthyroid patients has also been reported to be blunted [9,12]. a-Adrenergic pathways play an important role in reg ulating GH secretion.…”

“…6]. In patients with hyper thyroidism reduced GH responses to pharmacological stimuli [7][8][9] and reduced spontaneous nocturnal GH secretion have been reported [10], In the hyperthyroid rat the GH response to GHRH has also been described to be decreased [11]. Recently, studies in man have shown that the blunted GH response to GHRH in hyperthyroid patients is normalized by long-term antithyroid therapy [9.…”

Effect of Arginine on the GHRH-Stimulated GH Secretion in Patients with Hyperthyroidism

“…The hypothesis that arginine sup presses endogenous somatostatin release is also supported by the observation that arginine is able to enhance the TSH response toTRH in normal human subjects [14] and to normalize the GH response to GHRH in patients thought to have high somatostatin tone, e.g. under chronic glucocorticoid treatment [28], Our data confirm that hyperthyroid patients have blunted GH responses to GHRH [9], The mechanism by which the elevation in the serum concentration of thyroid hormones inhibits GH secretion remains to be explained. We have shown that, in hyperthyroid patients, pretreat ment with the P-blocker propranolol enhances the GH response to GHRH ( 1-29)NH: [29], On the basis of these results, it has been hypothesized that GH inhibition in hyperthyroid patients is mediated, at least in part, as in patients treated with glucocorticoids [30], by an increase in the hypothalamic secretion of somatostatin.…”

“…9] and p-adrenergic block ers [21,22], is impaired in hypertyroidism. The GH response to GHRH in hyperthyroid patients has also been reported to be blunted [9,12], Moreover, pharmacologi cal substances thought to stimulate endogenous GHRH secretion, such as clonidine [23] and galanin [24]. are not able to reverse GH inhibition in hyperthyroidism [25,26] Arginine is a well-known GH secretagogue [13].…”