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Concurrent primary aldosteronism and subclinical cortisol hypersecretion: a prospective study

Fallo, Francescoa; Bertello, Chiarab; Tizzani, Davideb; Fassina, Ambrogioc; Boulkroun, Sheerazedd; Sonino, Nicolettae; Monticone, Silviab; Viola, Andreab; Veglio, Francob; Mulatero, Paolob

doi: 10.1097/HJH.0b013e32834937f3
Original papers: Aldosteronism

Background Primary aldosteronism is the most frequent cause of secondary hypertension and is responsible for an increased risk of cardiometabolic complications. A concomitant subtle cortisol hyperproduction could enhance cardiovascular risk. We prospectively estimated the occurrence of subclinical hypercortisolism in primary aldosteronism patients.

Methods In a large population of hypertensive patients without clinical signs of hypercortisolism, 76 consecutive patients with primary aldosteronism were investigated. Differential diagnosis between unilateral and bilateral aldosterone hypersecretion was made by computed tomography/MRI and/or adrenal venous sampling (AVS). Subclinical hypercortisolism was defined as failure to suppress plasma cortisol to less than 50 nmol/l after 1 mg-overnight dexamethasone, used as screening test, and at least one of two other abnormal hormonal parameters, that is, adrenocorticotrophin (ACTH) less than 2 pmol/l and urinary cortisol more than 694 nmol/24 h.

Results Three out of 76 patients had postdexamethasone plasma cortisol more than 50 nmol/l. Only one also showed low-normal ACTH and mildly elevated urinary cortisol. The patient had a right 4 cm adrenal mass. Laparoscopic adrenalectomy was followed by short-term steroid replacement to prevent adrenal insufficiency. In-situ hybridization showed CYP11B1 expression exclusively in tumoral tissue, whereas CYP11B2 was expressed only in a peritumoral region composed of zona glomerulosa-like cells, suggesting the co-existence of a cortisol-producing adenoma and an aldosterone-producing hyperplasia in the same adrenal. The restoration of hormone abnormalities to normal levels was confirmed at 12 months of follow-up.

Conclusion Concurrent aldosterone and subclinical cortisol hypersecretion seems to be a rare event in primary aldosteronism patients; however, its detection by appropriate testing is important to avoid AVS misinterpretation.

aDepartment of Medical and Surgical Sciences, University of Padova, Padova

bDivision of Internal Medicine and Hypertension, Department of Medicine and Experimental Oncology, University of Torino, Turin

cSurgical Pathology and Cytopathology Unit, University of Padova, Padova, Italy

dINSERM, U970, Paris Cardiovascular Research Center, University Paris Descartes, Paris, France

eDepartment of Statistical Sciences, University of Padova, Padova, Italy

Correspondence to Francesco Fallo, MD, Department of Medical and Surgical Sciences, University of Padova, Via Ospedale 105, 35128 Padova, Italy Tel: +39 049 8212654; fax: +39 049 8218744; e-mail:

Abbreviations: ACTH, adrenocorticotrophin; APA, aldosterone-producing adenoma; AVS, adrenal vein sampling; CT, computed tomography; MRI, magnetic resonance imaging; PRA, plasma renin activity; UAH, unilateral adrenal hyperplasia

Received 31 March, 2011

Revised 16 May, 2011

Accepted 25 May, 2011

© 2011 Lippincott Williams & Wilkins, Inc.