Nonfunctional Adrenal Adenomas: Truth or Myth? Presentation and Treatment of 2 Patients

ABSTRACT Objective: Autonomous adrenal cortisol secretion is associated with increased frequency of cardiovascular events; however, there is little consensus on what clinical/biochemical criteria should be employed to establish its diagnosis and treatment. Reported here are two cases of autonomous adrenal cortisol secretion that challenge the currently recommended post-dexamethasone suppression test (post-DST) threshold (>1.8 μg/dL) for diagnosing hypercortisolism. Methods: Patient 1, a 64-year-old Caucasian man, presented with hypertension, nephrolithiasis, obesity, and history of a left adrenal tumor (2.1 × 2.9 cm). Baseline morning adrenocorticotropic hormone (ACTH) and dehydroepiandrosterone sulfate (DHEA-S) were normal; 2-day low-dose DST (LDDST) cortisol was 1.2 μg/dL. Patient 2, a 58-year-old Caucasian woman, presented with bilateral adrenal hyperplasia, obesity, depression, and diabetes. Biochemical evaluation showed low-normal morning ACTH (9 pg/mL), low DHEA-S (<15 μg/dL), and 2-day LDDST cortisol of 1.5 μg/dL. Results: Patient 1 underwent left adrenalectomy because of an increase in the size of his tumor. Postoperatively, he developed adrenal insufficiency, which was treated with hydrocortisone. By 3 months postsurgery, he had lost 35 pounds and his blood pressure had improved substantially. Patient 2, based on the equivocal LDDST cortisol results, was treated medically, rather than surgically, with mifepristone (600 mg daily final dose) for 6 months. During treatment, her diabetes and psychological well-being improved, and she lost 18 pounds. Conclusion: The diagnosis of hypercortisolism is evolving. In cases where a link between autonomous adrenal cortisol secretion and related comorbidities is difficult to establish, a therapeutic trial of a glucocorticoid receptor antagonist may be a useful diagnostic/treatment approach. Abbreviations: ACTH adrenocorticotropic hormone; CS Cushing syndrome; DHEA-S dehydroepiandrosterone sulfate; DST dexamethasone suppression test; GR glucocorticoid receptor; HPA hypothalamic-pituitary-adrenal; UFC urine free cortisol