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Endocrine Abstracts (2017) 49 S30.3 | DOI: 10.1530/endoabs.49.S30.3

ECE2017 Symposia Moving away from old-fashioned steroidogenesis: what are the clinical implications? (3 abstracts)

Glucocorticoid production in primary aldosteronism – from mechanisms to clinical implications

Felix Beuschlein


Adrenal aldosterone excess is the most common cause of secondary hypertension and is associated with increased cardiovascular morbidity and mortality. 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 but would rather be associated with oversecretion of glucocorticoids. Over the last years, exome sequencing has provided new insights into the genetic set-up of adrenal adenomas highlighting the concept of calcium dependent signalling being the main driver for aldosterone secretion while the cAMP/PKA pathway can be considered of particular importance for cortisol production. In rare examples somatic mutations in genes involved in cAMP signalling could be identified. However, in the majority of cases the contribution of glucocorticoid oversecretion in patients with primary aldosteronism has remained uncertain. Recently, we have performed mass spectrometry-based steroid metabolome profiling in 24-h urines from consecutively recruited patients with primary aldosteronism. Comparisons were made with healthy controls, patients with endocrine inactive adrenal adenoma, and patients with mild subclinical and clinically overt adrenal cortisol excess. Based on these measurements, patients with primary aldosteronism had significantly increased cortisol and total glucocorticoid metabolite excretion, 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. We analysed the expression of cortisol-producing CYP11B1 and aldosterone-producing CYP11B2 enzymes in adrenal adenoma tissue from patients with primary aldosteronism, employing immunohistochemistry with digital image analysis. Intra-tumoral expression of CYP11B1 correlated significantly with glucocorticoid excretion, whereas CYP11B2 expression correlated with aldosterone output. Unilateral adrenalectomy for adenoma removal resolved both mineralocorticoid and glucocorticoid excess. Postoperative evidence of adrenal insufficiency was found in roughly one third of tested patients. These data show that glucocorticoid co-secretion is a prevalent feature in primary aldosteronism and significantly 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.

Volume 49

19th European Congress of Endocrinology

Lisbon, Portugal
20 May 2017 - 23 May 2017

European Society of Endocrinology 

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