Endocrine Abstracts

In ACTH-independent macronodular adrenal hyperplasia (AIMAH) causing Cushing’s syndrome, cortisol secretion is controlled by illegitimate membrane receptors. In the normal adrenal gland, agonists of 5-HT4 receptors have a powerful effect on aldosterone secretion but little effect on cortisol secretion in vitro.

The aim of our study is to describe the clinical and hormonal features of patients diagnosed with aberrant serotonin receptor expression.

We report the cases of three patients diagnosed with bilateral AIMAH. All patients were females, aged 40, 30 and 74 years respectively. The AIMAH was associated with clinical Cushing’s syndrome in a patient and a subclinical Cushing’s syndrome in two others. The presence of aberrant serotonin receptors was associated with aberrant GIP and angiotensin receptors in a patient, to catecholamine receptors in the second and isolated in the third.

Serotonin receptors are probably the most functional receptors in AIMAH. Indeed, their frequency is high in many published series. The simultaneous expression of several aberrant receptors linked to G protein makes difficult to identify the action of each receptor and the part of cooperation between the different receptors. The characterization of the pharmacological profiles of ectopic receptors in AIMAH provides opportunities for development of new pharmacological therapies. Because numerous adrenal hyperplastic tissues express more than one type of illegitimate receptor, drugs targeted to common transduction mechanisms of illegitimate receptors, including T-type calcium channel blockers, may prove to be useful for reducing cortisol synthesis and/or cellular proliferation in AIMAH.