Endocrine Abstracts

Introduction: Endogenous subclinical hypercortisolism occurs in 5-30% of patients with adrenal incidentalomas. Adrenal adenoma is the commonest cause of autonomous cortisol secretion (ACS), while primary bilateral macronodular adrenal hyperplasia (PBMAH) is rare. In both, ACS results from activation of the cAMP/PKA pathway. This may be triggered by ligands, other than ACTH, acting upon aberrant G-protein coupled receptors (GPCRs), which may also control locally produced ACTH in paracrine/autocrine fashion. In this setting, diagnosis is challenging due to intermittent hypercortisolism and fluctuations of ACTH level.

Case presentation: We present the case of a 65-year old lady with large bilateral adrenal incidentalomas and imaging features compatible with adenomas. Initial hormonal work-up revealed ACS {cortisol post low dose dexamethasone suppression test (LDDST): 13.92 mg/dl, midnight salivary cortisol: 0,8 mg/dl, ACTH=9.2 pg/mg}. She was not Cushingoid, but had obesity, osteoporosis, hypertension and anxiety disorder. On accounts of the size of her left adrenal adenoma (4.9 x 1.9 cm), she underwent unilateral adrenalectomy. Initial histology demonstrated adrenal adenoma (Weiss score 0/10). During hormonal follow-up, she had persistent hypercortisolism with fluctuating plasma ACTH level (11.5-44.2 pg/ml). Considering the latter, we proceeded to pituitary magnetic resonance imaging, which showed a 3mm incidentaloma. At this point, we repeated LDDST with ACTH measurement: despite adequate ACTH suppression (2.2 pg/ml) cortisol was unsuppressed (6.26 mg/dl). Thus, ACS was confirmed. Imaging-wise, the size of her right adrenal adenoma increased from 4.2 x 1.6 cm to 4,8 x 2.2 over 3 years. Pathology review of the resected left adrenal revealed absence of non-neoplastic adrenal tissue and extended nodular appearance, establishing PBMAH diagnosis. Dynamic testing for aberrant receptors post dexamethasone suppression was performed, demonstrating partial response to posture (25%) and meal (26%). In the absence of overt hypercortisolism and given that PBMAH is a benign condition, we considered medical treatment as more appropriate. To control hypercortisolism, we modified hypertension regime to propranolol and valsartan with later addition of low dose of metyrapone.

Conclusions: Patients with bilateral adrenal adenomas may represent PBMAH, in which aberrant receptor expression is present in 80% of cases. The recognition of aberrant receptor-mediated hypercortisolaemia in patients with PBMAH and unilateral adenomas is important as it may lead to targeted therapies. In this context, b-blockers, angiotensin II blockers, GnRH and somatostatin analogues have been used. Additionally, steroid enzymes inhibitors were found to restore normal circadian secretion of cortisol. Nevertheless, existing data originate from small case series and larger prospective studies are needed.