Feminizing Adrenocortical Carcinoma in Men: A Rare Cause of Persistent Gynecomastia and a Contemporary Literature Review

Feminizing adrenocortical tumors (FATs) represent an exceedingly rare subset of primary adrenal neoplasms, characterized by elevated estrogen levels and suppressed gonadotrophin concentrations. These tumors predominantly affect adult males and are commonly associated with clinical manifestations such as gynecomastia, features of hy-pogonadism and unintended weight loss. The vast majority of FATs are malignant in nature, exhibiting an unfavorable prognosis and a high likelihood of recurrence. We present the case of a 24-year-old male diagnosed with adrenocortical carcinoma, characterized by elevated estrogen levels (90.1 pg/mL), who initially presented with symptoms related to abdominal mass effect and bilateral gynecomastia. Notably, the patient reported one year of unexplained infertility, which resolved spontaneously postoperatively at three months following surgical intervention. Another distinctive feature of this case was the patient's adrenal hormonal profile, which revealed suppressed ACTH (2.6 pg/mL) in the presence of inappropriately normal cortisol levels (12,1 ug/dL). The patient underwent right adrenalectomy, and histo-pathological along with immunohistochemical analyses confirmed a diagnosis of stage II adrenocortical carcinoma (T2, Nx, M0) with autonomous estradiol production. The case was reviewed by a multidisciplinary tumor board for consideration of mitotane therapy; however, the patient was not enrolled due to a completely resected stage T2NxM0 adrenocortical carcinoma with negative margins and a Ki-67 index of 10%. This case underscores the rare presentation of feminizing adrenocortical carcinoma and emphasizes the importance of early diagnosis and close postoperative surveillance, given the tumor’s high recurrence potential. In addition, we conducted a systematic review of the literature from 2015 to 2025, identifying 12 male cases of estrogen-secreting adrenocortical carcinoma (ES-ACC) pre-senting initially with gynecomastia. Data on presentation, hormonal profile, treatment, recurrence and survival were analyzed. Our review highlights a potential paradigm shift in the management of selected low-risk ACC cases, where active surveillance may rep-resent a safe and effective alternative to adjuvant mitotane therapy.