Endocrine Abstracts

Background: Gastrinoma is a functional neuroendocrine neoplasm (NEN) most commonly located in the duodenum (70%) and the pancreas (25%). The initial confirmation of NEN’s secretion profile does not exclude the possibility of a new hormonal activity of the tumor occurring in the course of the disease. Ectopic Cushing syndrome has been described in up to 5% of gastrinoma cases and hypercortisolemia may worsen the patient’s prognosis.

Case presentation: A 38-year-old transgender male with advanced metastatic functional PanNEN - gastrinoma was admitted to the Department of Endocrinology due to new symptoms and signs of severe ACTH-dependent hypercortisolemia. The patient’s medical history included non-functional adrenal adenoma and chronic gender-affirming hormone treatment with testosterone after the female-to-male surgical intervention at the age of 28 years. Two years before the admission an advanced pancreatic gastrinoma with liver metastases (NET G2, with Ki-67 4-5%) was diagnosed. The patient was disqualified from surgical intervention and the disease was initially managed with somatostatin receptor ligand. Later he was shortly treated with everolimus but it was ceased due to drug-induced interstitial pneumonia. After the diagnosis of ACTH-dependent ectopic hypercortisolemia the patient was qualified for bilateral adrenalectomy after preoperative treatment with metyrapone. Finally, the patient underwent a resection of the left adrenal gland with the tumor, as the right adrenal was surgically inaccessible. Surprisingly, that resulted in a significant decrease in ACTH and cortisol levels leading to clinical remission of Cushing syndrome. Pathology report revealed an adenoma of the adrenal cortex with positive ACTH staining. The result of the simultaneous liver lesion biopsy confirmed a metastatic NEN G2 with positive ACTH immunostaining as well. Subsequently, due to progression of liver metastases in CT and somatostatin receptor scintigraphy, and further increase in gastrin and chromogranin A levels, the patient was qualified for a temozolomide and capecitabine chemotherapy. Although the therapy was discontinued after 4 courses, due to life-threatening anaemia, the patient’s NEN is stable and normalisation of ACTH and cortisol levels persists after a one year follow-up.

Conclusion: We present a rare case of the ectopic Cushing’s syndrome complicating metastatic gastrinoma. Hypercortisolemia significantly worsens the prognosis of patients with NEN, thus a multimodal approach might be needed, as in presented case. We found it very unusual that the remission of ACTH-dependent hypercortisolemia was noted after removal of one adrenal gland with previously non-functioning adenoma. Furthermore, it is interesting if the gender-affirming hormone treatment influence the neuroendocrine tumor development and progression.