Benign androgen-producing adrenal tumors: A systematic review of cases and case series

Abstract

Purpose: To characterize the clinical, biochemical, radiological, and histological features of benign androgen-producing adrenal tumors in adults. Methods: Systematic review of published case reports and case series. A systematic search of PubMed, Web of Science, and Scopus was conducted for studies published between 1980 and 2024. Eligible cases included adults (≥ 19 years) with histologically confirmed benign adrenal tumors, biochemical evidence of androgen excess with postoperative normalization, and available individual patient data. Extracted variables included demographics, clinical signs, hormonal values, imaging, and histopathology. Results: Ninety-seven cases from 81 publications fulfilled inclusion criteria. Most were women (96/97), with a mean age of 42.1 years. Hirsutism (87.5%) and clitoromegaly (55.2%) were the most common features, though a minority of tumors were discovered incidentally, often in postmenopausal women. While most tumors were unilateral adenomas, 18% showed alternative histologies, including oncocytomas and ganglioneuromas. Total testosterone was elevated in 93.4% of women, DHEAS in 69.4%; combined assessment achieved 100% sensitivity. However, 25.9% of cases did not exceed thresholds commonly used to suggest tumoral hyperandrogenism (7 nmol/L for testosterone, 18.5 µmol/L for DHEAS), highlighting a risk of underdiagnosis. A paradoxical androgen rise after dexamethasone was observed in ~ 30% of tested cases. Cortisol co-secretion was present in 28% of cases. Conclusion: Benign androgen-producing adrenal tumors are rare but clinically significant. They predominantly affect women and may present with subtle or atypical findings, or be discovered incidentally. Reliance on strict hormonal cut-offs may overlook some cases. Broader biochemical assessment and clinical suspicion are crucial to ensure accurate diagnosis.