# A Corticotropin-Secreting Adenoma in the Setting of von Hippel-Lindau Disease

## TL;DR

A 19-year-old with von Hippel-Lindau disease developed a rare ACTH-secreting tumor, expanding the known tumor types linked to this genetic disorder.

## Contribution

This is the first reported case of an ACTH-secreting adenoma in a patient with von Hippel-Lindau disease.

## Key findings

- The patient had a germline VHL gene variant (c.227_229del, p.76delF) and an ACTH-secreting pituitary tumor.
- The tumor showed immunoreactivity for HIF-1α and had a Ki-67 index of 3%.
- The case expands the tumor spectrum associated with von Hippel-Lindau disease to include ACTH-secreting adenomas.

## Abstract

Von Hippel-Lindau (VHL) disease is an autosomal dominant disorder caused by germline pathogenic variants of the VHL gene, which can lead to abnormal growth of blood vessels and cause the development of benign or malignant tumors, as well as cysts in diverse organs. To date, no case reports have documented adrenocorticotropic hormone (ACTH)-secreting adenomas in individuals with VHL disease. We present the case of a 19-year-old female individual with VHL disease who developed an ACTH-secreting adenoma alongside hemangioblastomas in the central nervous system (CNS) and cystic lesions in diverse organ systems. Genetic testing and immunohistochemistry of the pituitary tumor were performed. Genetic testing revealed that the patient carried the familial germline pathogenic variant located in the first exon of the VHL gene (c.227_229del, p.76delF). Immunohistochemical staining of the pituitary tumor demonstrated positive for ACTH, chromogranin A, and synaptophysin, with Ki-67 index at 3%. In addition, tumor cells showed scattered immunoreactivity for the α subunit of hypoxia-inducible factor (HIF-1α). This case suggests that VHL disease might be associated with ACTH-secreting adenomas and broadens the tumor spectrum.