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JCI Insight. 2017 Apr 20;2(8). pii: 93136. doi: 10.1172/jci.insight.93136. eCollection 2017 Apr 20.

Steroid metabolome analysis reveals prevalent glucocorticoid excess in primary aldosteronism.

Author information

Institute of Metabolism and Systems Research, University of Birmingham, Birmingham, United Kingdom.
Centre for Endocrinology, Diabetes and Metabolism, Birmingham Health Partners, Birmingham, United Kingdom.
Institute for Applied Health Research, University of Birmingham, Birmingham, United Kingdom.
Medizinische Klinik und Poliklinik IV, Ludwig-Maximilians-Universität München, Munich, Germany.
Division of Endocrinology, Metabolism and Nutrition, Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota, USA.
Research Unit Analytical Pathology, Helmholtz Zentrum Munich, Oberschleißheim, Germany.
Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, United Kingdom.
Neurosciences and Mental Health Research Institute, School of Medicine, Cardiff University, Cardiff, United Kingdom.
Department of Medicine I, Endocrine and Diabetes Unit, University Hospital Würzburg, Würzburg, Germany.
Endocrinology in Charlottenburg, Berlin, Germany.
Department of Internal Medicine, Radboud University Medical Centre, Nijmegen, Netherlands.
Johann Bernoulli Institute for Mathematics and Computer Science, University of Groningen, Groningen, Netherlands.
Department of Clinical Biochemistry, University Hospital South Manchester, Manchester, United Kingdom.
University of California at San Francisco Benioff Children's Hospital, Oakland, California, USA.



Adrenal aldosterone excess is the most common cause of secondary hypertension and is associated with increased cardiovascular morbidity. However, adverse metabolic risk in primary aldosteronism extends beyond hypertension, with increased rates of insulin resistance, type 2 diabetes, and osteoporosis, which cannot be easily explained by aldosterone excess.


We performed mass spectrometry-based analysis of a 24-hour urine steroid metabolome in 174 newly diagnosed patients with primary aldosteronism (103 unilateral adenomas, 71 bilateral adrenal hyperplasias) in comparison to 162 healthy controls, 56 patients with endocrine inactive adrenal adenoma, 104 patients with mild subclinical, and 47 with clinically overt adrenal cortisol excess. We also analyzed the expression of cortisol-producing CYP11B1 and aldosterone-producing CYP11B2 enzymes in adenoma tissue from 57 patients with aldosterone-producing adenoma, employing immunohistochemistry with digital image analysis.


Primary aldosteronism patients had significantly increased cortisol and total glucocorticoid metabolite excretion (all P < 0.001), only exceeded by glucocorticoid output in patients with clinically overt adrenal Cushing syndrome. Several surrogate parameters of metabolic risk correlated significantly with glucocorticoid but not mineralocorticoid output. Intratumoral CYP11B1 expression was significantly associated with the corresponding in vivo glucocorticoid excretion. Unilateral adrenalectomy resolved both mineralocorticoid and glucocorticoid excess. Postoperative evidence of adrenal insufficiency was found in 13 (29%) of 45 consecutively tested patients.


Our data indicate that glucocorticoid cosecretion is frequently found in primary aldosteronism and contributes to associated metabolic risk. Mineralocorticoid receptor antagonist therapy alone may not be sufficient to counteract adverse metabolic risk in medically treated patients with primary aldosteronism.


Medical Research Council UK, Wellcome Trust, European Commission.


Cardiology; Endocrinology

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