FRI189 Alcohol-induced Non-neoplastic Hypercortisolism: Report Of Eight Cases And Review Of The Literature

Abstract

Abstract Disclosure: A. Surani: None. T.B. Carroll: Consulting Fee; Self; Corcept Therapeutics. Research Investigator; Self; Corcept Therapeutics, Recordati. B.R. Javorsky: Consulting Fee; Self; Clarus. Research Investigator; Self; Recordati, Amryt Pharma. H. Raff: Consulting Fee; Self; Cerium Pharmaceuticals, Corcept Therapeutics. Research Investigator; Self; Cerium Pharmaceuticals. J.W. Findling: Consulting Fee; Self; Corcept Therapeutics, Recordati. Research Investigator; Self; Recordati. Alcohol intake stimulates the hypothalamic-pituitary-adrenal (HPA) axis. Alcohol-induced hypercortisolism (AIH) is an underrecognized clinical phenomenon thought to be of hypothalamic etiology. Patients with alcohol use disorder may masquerade as neoplastic hypercortisolism [Cushing syndrome (CS)] thus obscuring its diagnosis. We addressed this issue using newer, more accurate biochemical testing for the diagnosis of CS. We evaluated eight patients with AIH referred for possible CS (six for inferior petrosal sinus sampling, one with persistent CS after removal of an adrenal adenoma, and one for pituitary surgery). All patients had clinical features of hypercortisolism and plasma ACTH levels within or above the reference interval (RI) confirming a centrally mediated mechanism. All eight patients had abnormal low-dose dexamethasone suppression test (DST) [post DST serum cortisol 2.2-19.1 mcg/dL (RI<1.8)] and increased late-night salivary cortisol [8.2-71.0 nmol/L (RI<3.2)]. Only one patient had increased urine cortisol excretion. In contrast to patients with pituitary CS, the 5 patients tested had blunted or absent ACTH and cortisol responses to dDAVP. Two patients had adrenal nodules and one patient had abnormal pituitary imaging. Most patients initially underreported their alcohol consumption and one patient denied alcohol use. A marked elevation of blood phosphatidylethanol (PEth) was required in one patient to confirm excessive alcohol use. All the patients had significant elevations of liver function tests (LFTs) with AST>ALT. Review of the literature discovered 37 reported cases of AIH. These cases also had clinical and many biochemical findings that were similar to neoplastic hypercortisolism. Conclusion: AIH is an under-appreciated potentially reversible cause of non-neoplastic hypercortisolism that may be indistinguishable from neoplastic ACTH-dependent CS. Incidental pituitary and adrenal imaging abnormalities as well as under-reporting of alcohol consumption may further confound the diagnosis. Elevations of LFTs (AST>ALT) and subnormal ACTH and cortisol responses to dDAVP may be helpful in distinguishing AIH from neoplastic hypercortisolism. Measurement of PEth helps to confirm an alcohol use disorder. Presentation: Friday, June 16, 2023