Mixed Aldosterone and Cortisol Secretion in Patients with Adrenal Incidentalomas: Different Faces of the Old Concept of Connshing Syndrome.

backgroundCo-secretion of aldosterone and cortisol from an adrenal adenoma is considered a clinically significant condition that can negatively affect blood pressure (BP) control and metabolic status. Studies in cohorts with primary aldosteronism (PA) have identified autonomous cortisol secretion (ACS) in a significant proportion of these patients. However, the frequency and clinical characteristics of this so-called "Connshing syndrome" among patients with adrenal incidentalomas (AIs) remain not sufficiently evaluated.

objectiveThe main aim of the study was to investigate, in a prospective design, the prevalence and the clinical characteristics of mixed aldosterone and cortisol secretion among patients with AIs referred to our expert center. According to our hypothesis, we expected a low prevalence and an atypical clinical presentation in these patients.

methodsPA was diagnosed based on the aldosterone/renin ratio (ARR) as a screening test, followed by two confirmatory tests: the captopril challenge test (CCT) and the dexamethasone-captopril-valsartan test (DCVT). Unilateral aldosterone-cortisol oversecretion was confirmed by imaging studies (computed tomography (CT) or magnetic resonance imaging (MRI)) in all patients and adrenal venous sampling (AVS) in the single patient with bilateral adenomas. ACS was confirmed via the overnight 1 mg dexamethasone suppression test (DST).

resultsWe conducted a prospective study on 399 patients with AIs referred to our expert center during the last three years (from May 10, 2022, to May 10, 2025). Aldosterone and cortisol co-secretion (A/C-CoS) was identified in four patients (≈1%), presenting different clinical manifestations. Three patients had well-controlled hypertension on conventional antihypertensive therapy, and one was normotensive. Three of the four patients had dyslipidemia. Carbohydrate disturbances were found in two patients with normal body mass index (BMI) (one woman with impaired fasting glucose and one man with overt diabetes mellitus (DM)). The other two subjects were slightly overweight with normal glucose tolerance.

conclusionMixed aldosterone and cortisol hypersecretion is usually associated with poor BP control and metabolic disturbances, but in real clinical practice, a wide range of disorders is observed, from severe resistant hypertension to rare cases of normotension and from pronounced metabolic syndrome to a complete absence of metabolic abnormalities. Atypical presentation of A/C-CoS is more likely to be found among patients with AIs. This observation confirms the need for a comprehensive hormonal evaluation of all patients with AIs, regardless of their clinical presentation.