Corticotrope hypersecretion coupled with cortisol hypo-responsiveness to stimuli is present in patients with autoimmune endocrine diseases: evidence for subclinical primary hypoadrenalism?

Abstract

Objective: In autoimmune polyglandular syndrome types 1, 2, and 4 primary adrenal insufficiency is present, but its diagnosis is often late. We investigated the function of the hypothalamic-pituitaryadrenal axis in a group of patients with autoimmune diseases (AP) without any symptoms and signs of hypoadrenalism. Design: In 10 AP and 12 normal subjects (NS), we studied cortisol (F), aldosterone (A), and DHEA responses to 0.06 mg adrenocorticotropin (ACTH) (1-24) followed by 250 mg, ACTH and F responses to human corticotropin-releasing hormone (hCRH; 100 mg) and insulin tolerance test (ITT) (0.1 UI/kg). Results: Basal F, A, DHEA, as well as urinary free cortisol and plasma renin activity levels in AP and NS were similar, whereas ACTH levels in AP were higher (P!0.05) than in NS. NS showed F, A, and DHEA response to both consecutive ACTH doses. In AP, the F, A, and DHEA responses to 250 mg ACTH were similar to those in NS, whereas the 0.06 mg ACTH dose did not elicit any significant response. The ACTH responses to hCRH and ITT in AP were higher (P!0.05) than in NS. The F response to hCRH in AP was lower (P!0.05) than in NS, whereas the F response to ITT in AP did not significantly differ from NS. Conclusions: Enhancement of both basal and stimulated corticotrope secretion coupled with reduced adrenal sensitivity to low ACTH dose is present in AP patients without symptoms and signs of hypoadrenalism. This functional picture suggests that normal adrenal secretion is maintained due to corticotrope hyperfunction, suggesting the existence of some subclinical primary hypoadrenalism. European Journal of Endocrinology 155 421-428

Adrenocortical function in young adults with diabetes mellitus type 1

“…It was evidenced that local tissue bioavailability of F participates at regulation of many metabolic processes, including glucose metabolism and glycaemia [34,35]. The mechanism enabling to maintain normal adrenal cortisol secretion in immunopathies may be also compensatory increased ACTH stimulation [36]. It may be speculated that ACTH hypersecretion could play in LR a similar role for maintaining practically the same daily profile of salivary F as was found in NR.…”

Cortisol hyporesponsiveness to the low dose ACTH test is a frequent finding in a pediatric population with type 1 diabetes mellitus

“…Certain inflammatory mediators induced by the process of beta‐cell autoimmune destruction are able to stimulate immune function and the HPA axis. This event could explain the increase in basal and stimulated ACTH in patients with autoimmune disease and no signs of hypocortisolism. The increased activity of the HPA axis in diabetic patients may be also attributable to an alteration of the release of ACTH by the corticotroph, in addition, to the action of corticotrophin releasing hormone (CRH) on the adrenal gland independent of the action of ACTH .…”

Ghrelin and GHRP-6-induced ACTH and cortisol release in thyrotoxicosis

“…Although controversial, it has been suggested that severely thyrotoxic patients might have an impaired cortisol response to insulin-induced hypoglycemia [5] and to both high and low-dose ACTH stimulation, associated or not with dexamethasone [6,7,13,34]. After normalization of thyroid function this impairment disappears, which suggests that adrenal autoimmune disease is an unlikely cause for the reduced adrenocortical reserve [7,13].…”