The Effects of Endogenous Opioids and Cortisol on Thyrotropin and Prolactin Secretion in Patients with Addison’s Disease¹

Abstract

This study assessed the controversial role of endogenous opioids and cortisol in the regulation of TSH and PRL secretion in humans. Seven euthyroid male patients with Addison's disease were studied four times, with an interval of 1-3 months, as follows: 1) during normocortisolism [graduated infusion of hydrocortisone, 0.4 mg/kg, over 19.5 h]; 2) normocortisolism and coadministration of naloxone, at 25 g/kg⅐h during the last 6.5 h; 3) hypocortisolism (24 h withdrawal of hydrocortisone, followed by 19.5 h saline infusion); and 4) hypocortisolism plus naloxone administration. The TSH and PRL levels were measured every 15 min, from 0800 -1530 h. A TRH test was performed at 1300 h and 1400 h (10 g and 200 g of TRH, respectively). The mean TSH level increased significantly during hypocortisolism, compared with normocortisolism (1.78 Ϯ 0.04 vs. 0.84 Ϯ 0.02 mU/L; P Ͻ 0.001). The administration of naloxone suppressed the TSH levels during hypo-and normocortisolism (1.78 Ϯ 0.04 vs. 1.50 Ϯ 0.03 and 0.84 Ϯ 0.02 vs. 0.61 Ϯ 0.02 mU/L, respectively; P Ͻ 0.001). During hypocortisolism, the TSH responses to small and high doses of TRH were significantly higher than during normocortisolism (P Ͻ 0.02). Naloxone had no effect on the TSH responses to TRH, neither during hypo-nor during normocortisolism. The mean PRL level increased significantly during hypocortisolism, compared with normocortisolism (5.8 Ϯ 0.4 vs. 3.6 Ϯ 0.2 g/L; P Ͻ 0.001), and naloxone induced an increase in PRL levels both during hypo-and normocortisolism (7.1 Ϯ 0.7 vs. 4.7 Ϯ 0.5 g/L, respectively; P Ͻ 0.01). The PRL responses to TRH were similar during hypo-and normocortisolism and without any change during opioid receptor blockade. In conclusion, cortisol suppressed basal TSH and PRL secretion and reduced the sensitivity of the thyrotrophs to TRH, without affecting the PRL response to TRH. Our results suggest that endogenous opioids act at the hypothalamic level to stimulate TSH secretion and to suppress the PRL secretion, but these results argue against an essential role of endogenous opioids in the physiological regulation of TSH and PRL secretion in humans. (J Clin Endocrinol Metab 84: 1595-1601, 1999 T HE ENDOCRINE mechanisms subserving an increased TSH and PRL secretion during acute stress (1) and suppressed TSH and PRL levels during more prolonged stress situations are not fully understood. The endogenous opioids have been clearly implicated in the control of secretion of gonadotropins, ACTH, and vasopressin (2-5); but their role, if any, in controlling TSH and PRL is disputable.In rats, opioid peptides have an inhibitory influence on TSH secretion, apparently mediated via a decreased TRH release from the hypothalamus (6), although an involvement of opioid receptors, both inside and outside the blood-brainbarrier, has been suggested (7). Human studies, evaluating the effect of exogenous opiates or the effect of the opioid receptor antagonist naloxone, have led to conflicting results, depending on the dose and duration of treatment used in different...

Thyroid hormones alterations during acute liver failure: possible underlying mechanisms and consequences

“…Some studies have proposed cytokines, mainly interleukin-6 (IL-6), as possible mediators of NTIS [13,14]. A role for endogenous opioids was also suggested by few studies, but their alterations during ALF and their clinical significance are still unclear [15,16]. Peripheral mechanisms, normal tissue activity despite decreased serum levels, and the presence of a circulating inhibitor have also been proposed, but no single mechanism has proven satisfactory [17,18].…”