CORTISOL PRODUCTION BY ALDOSTERONE‐PRODUCING ADENOMAS IN VITRO

Abstract

1. In vitro short-term production of cortisol by dispersed tumour and non-tumourous adrenal cortical cells was measured with and without added angiotensin II (AII) or adrenocorticotrophin (ACTH) in adrenals removed from five patients with primary aldosteronism. 2. Aldosterone-producing adenomas (APA) were classified as angiotensin responsive (AII-R) or angiotensin unresponsive (AII-U) based on pre-operative behaviour in vivo. 3. Cortisol was produced by both tumour and cortex in vitro without stimulation, and significantly more cortisol was generated by the cortex. 4. Addition of AII significantly increased cortisol production by both tumour and cortex to an equal extent. 5. Addition of ACTH also significantly increased cortisol production by both tumour and cortex, but tumours were more responsive than cortex. The response to ACTH exceeded the response to angiotensin in both tumour and cortex. 6. There was no obvious difference between AII-R and AII-U APA in terms of cortisol production.

Combined Primary Aldosteronism and Cushing's Syndrome Due to a Single Adrenocortical Adenoma Complicated by Hashimoto's Thyroiditis.

“…Another possibility is that APAis composed of both aldosterone-producing cells and cortisol-producing cells. The reports describing the APAcontaining zona glomerulosa, zona fasciculate and their hybrid cells (9,18,19) support this possibility. In our case, the latter possibility is more likely considering the result of immunohistochemical studies.…”

“…In most cases, the secretion of cortisol is kept under ACTH feedback control (9) and the amount of cortisol secreted from APAis too small to induce overt Cushingoid signs. Therefore, autonomousproduction of cortisol is rare and hypersecretion of cortisol, leading to typical clinical manifestations of Cushing's syndrome, is extremely rare in aldosterone-producing tumor(s) (10)(11)(12)(13).…”

Steroidogenesis in human aldosterone-secreting adenomas and adrenal hyperplasias: effects of hypoxia in vitro

“…Although patients with aldosterone-secreting adenomas do not usually have clinical hypercortisolism or hyperandrogenism (14), this in vitro phenomenon has been described previously (13,25) and has the potential to be helpful diagnostically (8).…”

“…The primary treatment for solitary tumors is usually surgical removal, whereas therapy for bilateral hyperplasia is more complex (14). A number of studies have characterized the expression and function of these different abnormal adrenal tissues, but none have evaluated their sensitivity to oxygen delivery (5,8,10,13,25).…”

Sporadic solitary aldosterone- and cortisol-co-secreting adenomas: endocrine, histological and genetic findings in a subtype of primary aldosteronism

“…Stowasser and Gordon differentiated between angiotensin II (AngII)-responsive and AngII-unresponsive APAs, [34][35][36] which can be distinguished by the production of cortisol, cell type, extent of steroid suppression with dexamethasone and secretion of hybrid steroids, including 18-OH-F. Therefore, mildly elevated levels of 18-OH-F can be found in ordinary APAs.…”