Endocrine Abstracts

In overt or subclinical ACTH-independant Cushing’s syndrome (CS), aberrant adrenal receptors may control cortisol secretion.

We systematically studied the 20 patients with adrenal incidentaloma screened in our department for illegitimate adrenal receptors between 2000 and 2006. We investigated plasma cortisol level during successive stimulation tests performed while dexamethasone was given orally every 8 h (upright posture, meal, hypothalamic hormones, terlipressin, angiotensin II, metoclopramide and/or octreotide). Subjects were considered as responders if their plasma cortisol level increased at least by 25% after one or several tests without any parallel elevation of ACTH.

Fourteen patients were responders, 11 of them responded to several tests. The most constant responses occurred after terlipressin (85% of explored subjects), suggesting aberrant vasopressin receptors in these patients. Neither clinical, biological or hormonal features nor adrenal tumour dimension nor noriodocholesterol uptake were predictive of illegitimate cortisol response. The responders rate did not differ significantly between unilateral adrenal adenomas (69.2%, n=13) and bilateral macronodular adrenal hyperplasias (71.4%, n=7). Ten patients with features of subclinical CS, including eight responders, underwent adrenal surgery. Metabolism abnormalities and bone mineral density did not improve clearly afterwards.

In 3 prospective studies evaluating aberrant adrenal receptors in subclinical CS, each patient presented with illicit cortisol response(s). In accordance with our results, vasopressin and its analogues induced the most constant responses in these studies. They differed from our procedure in 2 points: dexamethasone was administered during explorations in only two of these studies and cortisol responses mediated through an elevation of plasma ACTH were excluded in none of them. Adrenalectomy is still controversial in the management of subclinical CS. In our study, it resulted in no obvious metabolic or bone benefit. In the future, medications targeting aberrant responses may be an alternative for these patients.