Endocrine Abstracts

Bilateral Macronodular Adrenal Hyperplasia (BMAH) is an uncommon cause (<2%) of endogenous Cushing’s syndrome, characterized by enlarged adrenal glands Althought the exact pathogenetic mechanism remains unclear, recently, it has been reported that aberrant expression of ectopic receptors, such as AVP, GIP, angiotensin II (AT1 receptor) catecholamine, LH, 5HT4 agonists, and leptin, evoked cortisol secretion, which escapes from cortisol-mediated feedback in BMAH. Here we report a case of BMAH that suggested an aberrant response to angiotensin II via AT1 receptor in cortisol hypersecretion. A 66-yr-old man was admitted to a hospital for stroke, medically treated since beyond the established thrombolytic window. On admission he presented severe hypertension (BP 230/140 mmHg). On the hypothesis of secondary hypertension we performed in−depth analysis. Laboratory test documented undetectable plasma ACTH level (1,6 pg/ml) and high level of 24−h urinary free cortisol (983 mg/die). Plasma cortisol was not suppressed (12,8 μg/dl) after the administration of 1 mg dexamethasone overnight. Abdominal Magnetic Resonance Imaging demostrated nodular enlargement of bilateral adrenal glands. Moreover, renine and aldosterone levels were high (respectively 83 mU/ml and 74 ng/dl) and Angio-CT revealed right renal artery stenosis. These results indicated a diagnosis of Cushing’s syndrome due to BMAH with suspected adrenal hypersensitivity to angiotensin II. Therefore, Renal Artery Stenosis Angioplasty (PTA) was performed and the patient underwent a revised assessment which revelead normal level of plasma ACTH, urinary free cortisol and renine and aldosterone. Although it is well known that angiotensin II stimulates aldosterone secretion mainly through angiotensin II receptor (AT1), there has been no evidence, to our knowledge, that angiotensin II affects cortisol secretion in vivo. In our case, PTA blocked the aberrantly increase of plasma cortisol level. Therefore, it is possible that the adrenal hypersensitivity to angiotensin II is involved in the pathogenesis of BMAH and that angiotensin II aberrantly stimulated cortisol secretion via AT1 receptor. A similar case report described a case of BMAH with adrenal hypersensitivity to angiotensin II, treated with bilateral adrenalectomy [1]. In summary, we have reported a case of BMAH with possible hypersensitivity to angiotensin II. Further investigations are required to clarify the significance of abnormal adrenal response to angiotensin II.

1. ACTH-Independent Macronodular Adrenal Hyperplasia. Nakamura et al. Endocrine, vol. 15, 2001