Serum PAPP-A as a potential biomarker for early detection of ectopic pregnancy: an exploratory case-control study.

Adrenocortical carcinoma (ACC) is a rare and highly aggressive malignancy originating from the adrenal cortex. According to data from the National Cancer Institute’s Surveillance, Epidemiology and End Results database, the age-adjusted annual incidence of ACC in the United States ranges from 0.72 to 1.02 per million (, ). The disease exhibits a bimodal age distribution, with incidence peaks in both the first and fourth decades of life () and demonstrates a slight female predominance (). Clinically, approximately 60% of ACC patients present with hormone excess syndromes, including Cushing’s syndrome, virilization, or feminization (). Despite advancements in treatment, the prognosis of ACC remains poor, with a median overall survival of 3.21 years and a 5-year survival rate ranging from 15% to 44% (). Radical surgery remains the only potentially curative treatment for localized ACC (). However, many cases are diagnosed at advanced stages, where surgical resection is often unfeasible. Even in patients who underwent complete surgical resection, the risk of recurrence remains high, with local recurrence rates ranging from 19% to 34% (). Owing to the aggressive biology of ACC and its high risk of recurrence, effective therapeutic options beyond surgery remain limited. Mitotane (o, p’-DDD), a derivative of dichlorodiphenyltrichloroethane, is the only pharmacological agent specifically approved by the U.S. Food and Drug Administration (FDA) and the European Medicines Agency for ACC treatment (). Mitotane both exerts cytotoxic effects and suppresses steroidogenesis, selectively targeting adrenocortical cells () (). Retrospective studies suggest that adjuvant mitotane therapy following surgery may improve disease-free survival and overall survival (–). Consequently, clinical guidelines recommend mitotane for patients at high risk of recurrence post-surgery (–). Schematic overview of mitotane’s anatomical target and its adverse event profile. The left panel depicts the anatomical and histological structure of the adrenal cortex, the primary target where mitotane exerts its selective cytotoxic effects. The right panel provides a comprehensive mapping of common adverse events associated with mitotane.