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

Abstract

Patients with hyperthyroidism have reduced growth hormone (GH) responses to pharmacological stimuli and reduced spontaneous nocturnal GH secretion. The stimulatory effect of clonidine on GH secretion has been suggested to depend on an enhancement of hypothalamic GH-releasing hormone (GHRH) release. The aim of our study was to evaluate the effects of clonidine and GHRH on GH secretion in patients with hyperthyroidism. Eight hyperthyroid females with recent diagnosis of Graves’ disease (age range 20–55 years, body mass index range 19.2–26.2 kg/m²) and 6 healthy female volunteers (age range 22–35 years, body mass index range 19–25 kg/m²) underwent two experimental trials at no less than 7-day intervals: (a) an intravenous infusion of clonidine 150 µg in 10 ml of saline, or (b) a bolus intravenous injection of human GHRH (1–29)NH₂, 100 µg in 1 ml of saline. Hyperthyroid patients showed blunted GH peaks after clonidine (7.1 ± 1.7 µg/l) as compared to normal subjects receiving clonidine (28.5 ± 4.9 µg/l, p < 0.05). GH peaks after GHRH were also significantly lower in hyperthyroid subjects (8.0 ± 1.7 µg/l) as compared to normal subjects receiving GHRH (27.5 ± 4.4 µg/l, p < 0.05). No significant differences in the GH values either after clonidine or GHRH were observed in the two groups of subjects examined. Our data demonstrate that the GH responses to clonidine as well as to GHRH in patients with hyperthyroidism are inhibited in a similar fashion with respect to normal subjects. That clonidine is not able to reverse the blunted GH secretion in hyperthyroidism suggests that hyperthyroxinemia may either cause an increase in somatostatin release by the hypothalamus or block GH secretion acting directly at the pituitary level.

Decreased ghrelin-induced GH release in thyrotoxicosis: comparison with GH-releasing peptide-6 (GHRP-6) and GHRH

“…Moreover, in hyperthyroidism peak GH values after GHRH were also blunted, confirming earlier studies [25][26][27]. However, surprisingly, we also found a decrease in GH response to GHRP-6, which is in contrast to our previous report showing normal GH response to GHRP-6 associated with blunted GH responsiveness to GHRH in thyrotoxicosis [28].…”

“…Impaired GH release has been found in patients with thyroid dysfunctions [22]. In hyperthyroidism a blunted GH response to several pharmacological stimuli, such as GHRH, has been demonstrated [24][25][26][27]. We have previously shown that GH response to GHRP-6 is normal in thyrotoxicosis while GH responsiveness to GHRH is decreased [28].…”

Iopanoic acid‐induced decrease of circulating T3 causes a significant increase in GH responsiveness to GH releasing hormone in thyrotoxic patients

“…A decrease in circulating T3 could interfere with GH secretion at hypothalamic and/or pituitary level. It has previously been suggested that an increase in hypothalamic somatostatinergic tone could participate in the blunted GH response to pharmacological stimuli in thyrotoxicosis ( Giustina et al ., 1990 , 1991; Valcavi et al ., 1992 ). Indeed, it has been shown that T3 increases somatostatin release from rat hypothalamic fragments in vitro ( Berelowitz et al ., 1980 ).…”

“…Impaired GH release has been found in patients with thyroid disturbances. In hyperthyroidism, a blunted GH response to several pharmacological tests, such as GHRH, has been found ( Burgess et al ., 1966 ; Giustina et al ., 1991 , 1992; Valcavi et al ., 1993 ; Ramos‐Dias et al ., 1995 ). The mechanisms involved in this alteration have not been fully elucidated.…”

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

“…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]. Re cently, the mechanism through which arginine stimulates GH secretion has been elucidated.…”