Clinical features of cortisol- and androgen-secreting adrenocortical adenomas: a systematic review of published cases with an illustrative case

Background Adrenocortical adenomas (ACA) co-secreting cortisol and androgens are rare. The concomitant production of these steroid classes frequently raises suspicion for adrenocortical carcinoma (ACC). Purpose This study aims to present a case of a 48-year-old female with an ACA co-secreting cortisol and androgens, and to provide a systematic review of previously reported cases, focusing on clinical presentation, biochemical findings, imaging characteristics, histopathological features, and follow-up outcomes. Methods The case report was prepared in accordance with the CARE guidelines. A systematic review was conducted in line with PRISMA recommendations and registered in the PROSPERO database (CRD420250637314). A search of PubMed, Scopus, and Web of Science was performed to identify full-text case reports and case series of adult patients with pathologically confirmed ACA co-secreting cortisol and androgens. Only cases meeting predefined eligibility criteria, including evidence of ACTH-independent cortisol secretion, were included. Extracted data were synthesized descriptively. Results A total of 16 cases of ACA co-secreting cortisol and androgens met the inclusion criteria and were included in the systematic review. All patients were female. The median tumor size was 42 mm, and lesions were more frequently located in the left adrenal gland (9/16, 56%). Long-standing hyperandrogenemia was the predominant clinical manifestation. Biochemical evidence of autonomous cortisol and androgen secretion was confirmed in all cases, with marked interindividual variability. In 5/5 cases, unenhanced CT attenuation was ≥10 HU. Laparoscopic adrenalectomy was performed more frequently than open surgery. Histopathological examination confirmed ACA in all tumors. Postoperative adrenal insufficiency following unilateral adrenalectomy occurred in 10 patients. Median duration of glucocorticoid replacement therapy was 6 months. Conclusions Cortisol- and androgen-co-secreting ACA may closely mimic ACC, including in urinary steroid profiling. A prolonged clinical course and predominant hyperandrogenism were observed in the analyzed cases but cannot reliably indicate a benign lesion. Systematic review registration https://www.crd.york.ac.uk/PROSPERO/ , identifier CRD420250637314.