# Recurrent Pituitary Adenoma Causing Cushing’s Disease in a Patient With Lynch Syndrome

## TL;DR

A patient with Lynch syndrome developed a recurring pituitary tumor causing Cushing’s disease, highlighting a rare connection between genetic mutations and endocrine disorders.

## Contribution

This is the second reported case linking MSH6 mutations in Lynch syndrome to ACTH-secreting pituitary adenomas.

## Key findings

- The patient had a pathogenic MSH6 variant confirmed as the cause of Lynch syndrome.
- The patient's pituitary adenoma was successfully treated with repeat surgery and radiosurgery.
- The case suggests a possible association between Lynch syndrome and ACTH-secreting pituitary tumors.

## Abstract

Cushing’s disease (CD) is a severe endocrine disorder caused by an adrenocorticotropic hormone (ACTH)-secreting pituitary microadenoma. The diagnosis of CD remains one of the most challenging in endocrinology due to a wide array of symptoms caused by the extensive distribution of glucocorticoid receptors. Transsphenoidal surgery (TSS) is the first-line treatment, but recurrence following TSS is not uncommon. Repeat TSS and pituitary radiotherapy are among the second-line treatments of CD. Separately, Lynch syndrome (LS) is an autosomal dominant disorder caused by mutations in DNA mismatch repair (MMR) genes and is typically associated with colorectal, endometrial, and ovarian cancer. In this context, we describe the investigation and management of a 45-year-old female patient with a known family history of ovarian cancer and myocardial infarction who developed clinical features of hypercortisolism.

Endocrine evaluation demonstrated elevated cortisol and ACTH levels. The MRI revealed a microadenoma for which the patient underwent repeat TSS and Gamma Knife radiosurgery, leading to resolution of the pituitary adenoma. Subsequently, endometrioid adenocarcinoma was diagnosed, and in view of the family history, an underlying genetic disorder was suspected and later confirmed as LS with a pathogenic MSH6 variant, representing only the second reported case of MSH6-associated pituitary adenoma. Surgical management included hysterectomy with bilateral salpingo-oophorectomy, aortopelvic lymphadenectomy, and omental biopsy. This case underscores the importance of early diagnosis and lifelong monitoring in CD to reduce mortality from uncontrolled hypercortisolism, while highlighting a possible association between LS and ACTH-secreting pituitary adenomas, particularly those with MSH6 mutations.