Endocrine Abstracts

Introduction: Congenital adrenal hyperplasia (CAH) encompasses a group of enzymatic defects in cortisol biosynthesis resulting in adrenal hyperplasia through chronic compensatory ACTH stimulation. Aldosterone synthase deficiency, however, is associated with normal cortisol secretion and there are no reports on whether it may be associated with adrenocortical hyperplasia.

Case Presentation: A 37-year-old, Greek female was referred for further investigation of excessive diffuse bilateral adrenal hyperplasia discovered during investigations for post-partum weight gain (25 kg), fatigue, hirsutism, easy bruising, and depression associated with borderline cortisol status abnormalities (cortisol post-1mg dexamethasone: 100 nmol/l, basal ACTH: 7.3 pg/ml and 24-h urinary free cortisol (UFC): 1.32×ULN; androgens, as well as 17-hydroxyprogesterone, were normal). In infancy, the patient was erroneously diagnosed with CAH when she presented with failure to thrive, hyponatremia and hyperkalemia. She was treated with methylprednisolone and fludrocortisone until the age of 2, when she was re-evaluated with a Cosyntropin Stimulation Test (CST) with normal basal and stimulated cortisol levels (0’/30’: 811/822 nmol/l). Aldosterone was 13 ng/dl with PRA>40 ng/ml/h and 11-Deoxycortisol 2,2 ng/ml. On repeated testing, aldosterone was 15,6 ng/dl, PRA: 2,2 ng/ml/h, 17OHPR: 0,2 ng/ml and the diagnosis of pseudo-hypoaldosteronism was made. Subsequently, the patient had normal growth and pubertal development; she had oligomenorrhea until pregnancy and subsequently normalization of menstrual cycles. The coding regions of CYP11B2, CYP21A2 and CYP11B1 genes underwent Sanger sequencing.

Results: On physical examination, she had no clinical stigmata of Cushing’s Syndrome. Cortisol post-dexamethasone was borderline (63 nmol/l) without any other features of hypercortisolism (normal midnight serum cortisol and UFC). Basal aldosterone levels were 5/4.4 ng/dl with marginally elevated renin levels (56/40 mcU/ml). Given her PMH we performed a CST, in which she had a normal cortisol response, a borderline increase of 17-OH PRG (0’/30’: 7/30.2 nmol/l) but a remarkable lack of aldosterone response (0’/60’:6.3/6.9 ng/dl). We suspected CYP11B2 gene deficiency, which was confirmed by genetic testing, that revealed compound heterozygosity for two pathogenic variants (p.T185I and p.E255X). No mutations were identified in CYP21A2 and CYP11B1 genes.

Conclusion: To our knowledge, this is the first report that associates diffuse bilateral adrenal hyperplasia with CYP11B2 deficiency, a rare defect that is usually diagnosed during infancy and improves with age so that adults are asymptomatic. Our patient presented with impressively enlarged adrenals without discrete nodules and no other evident cause of adrenal hyperplasia.