Aldosterone- and cortisol-co-secreting adrenal tumors: the lost subtype of primary aldosteronism

Abstract

Current guidelines suggest proving angiotensin-independent aldosterone secretion in patients with primary aldosteronism (PA). It is further recommended to demonstrate unilateral disease because of its consequence for therapy. A general screening for excess secretion of other hormones is not recommended. However, clinically relevant autonomous aldosterone production rarely originates in adrenal tumors, compromised of zona glomerulosa cells only. This article reviews published data on aldosterone-and cortisol-co-secreting tumors and shows that pre-operative diagnosis of such a lesion is beneficial for patients. Overt or subclinical glucocorticoid hypersecretion may interfere with diagnostic studies, e.g. adrenal venous sampling, screening of familial forms of PA on the basis of serum 18-hydroxy-cortisol (18-OH-F) determination, and provoke glucocorticoid deficiency after surgical removal of the tumor. In addition, knowledge from histological and molecular studies in patients with aldosterone-and cortisol-co-secreting tumors challenges some concepts of the development of adrenal autonomy. The presence of an aldosterone-and cortisol-co-secreting adrenocortical tumor should be considered if a patient has i) PA and an adenoma that is larger than 2.5 cm, ii) cortisol that is nonsuppressible with overnight low-dose dexamethasone, or iii) grossly elevated serum levels of hybrid steroids, such as 18-OH-F.

KCNJ5 mutations in aldosterone- and cortisol-co-secreting adrenal adenomas [Rapid Communication]

“…but showing the autonomous secretion of cortisol have been identified as having preclinical (or subclinical) Cushing's syndrome [20,21]. Although the concept of preclinical (or subclinical) CS is not universally accepted [14], Spath et al recently reported that we should consider an APA with co-secretion of cortisol if a patient has 1) PA and an adenoma that is larger than 2.5 cm, 2) cortisol that is non-suppressible with overnight low-dose dexamethasone, or 3) grossly elevated serum levels of hybrid steroids, such as 18-OH-F [22]. In fact, although we did not have a chance to measure serum hybrid steroids, all three cases had a tumor larger than 2.5 cm.…”

“…Hogan et al first reported an aldosterone-and cortisol-producing adenoma in 1977 [23]. Subsequently, several papers have been published regarding the association of PA with the autonomous secretion of cortisol [22,24,25]. Many such reports have come from Japan or Europe.…”

PRKACA mutations in cortisol-producing adenomas and adrenal hyperplasia: a single-center study of 60 cases

“…In rare cases, secretion of aldosterone is the main cause of hypertension and optional hypokalemia, and co-secretion of cortisol may play a minor role. Some of the corresponding tumors have been shown to carry activating mutations in the KCNJ5 potassium channel gene that are specific to aldosterone-producing adenomas (15,16,17). Only one study screened for PRKACA mutations in these tumors, but did not report any (7).…”

Indication and Technical Aspects of Adrenal Blood Sampling

“…It should be presumed a diagnosis of bilateral hyperplasia (BAH) is provided in approximately 50 % of patients, whereas in the remaining cases an aldosteroneproducing adenoma (APA) and asymmetrical aldosterone excess is present. Rarer entities include adrenal cortex carcinoma, which occurs in < 1 % of cases [12,13]. Patients with Conn's syndrome have a significantly increased risk of cardiac and vascular diseases, even when compared with patients with similarly poor blood pressure values, but without hyperaldosteronism [14,15].…”

“…▶ It should likewise be taken into account that larger APAs can also secrete relevant quantities of cortisol such that lateralization due to cortisol co-secretion can no longer be identified computationally [13]. Further, the selectivity index on the contralateral side will be erroneously low.…”