Metastatic adrenocortical carcinoma in an adult with 21-Hydroxylase deficiency

Abstract

21-hydroxylase deficiency (21-HD) is a rare enzyme defect in the cortisol synthesis pathway. Left untreated, chronic elevations of adrenocorticotropic hormone induce adrenal cortex hyperplasia and may result in the formation of adrenal gland tumors. Benign myelolipomas and testicular adrenal rest tumors are commonly seen, but adrenocortical carcinomas (ACC) are extremely rare with a poor prognosis. We present the case of a 34-year old Caucasian man with untreated 21-HD, and a family history of liver, pancreatic and colon cancer, as well as 21-HD. Incidental computed tomography (CT) imaging for hip pain, and subsequent cancer work up, identified primary ACC with metastasis to the liver, lungs, bones, testicles and contralateral adrenal gland. After a precipitous decline in clinical status on the eighth day of admission, repeat CT imaging revealed worsening hepatomegaly and an interval enlarged left adrenal mass with active hemorrhage. The patient expired the following day due to rapid progression of aggressive metastatic cancer causing multi-organ failure. ACC is associated with hereditary cancer syndromes including Multiple Endocrine Neoplasia 1 (MEN-1), Lynch Syndrome, and Familial Adenomatous Polyposis (FAP). The association of MEN-1 with pancreatic cancer, and of Lynch and FAP with colon cancer, suggests the patient’s robust family history may have contributed to early tumorigenesis and rapid progression of disease in the setting of 21-HD. This case emphasizes the significance of compliance with steroid treatment in patients with 21-HD, as well as highlights the importance of early genetic testing when there is a concomitant family history of cancer.