Endocrine Abstracts

Introduction: ACTH-secreting pituitary adenomas occasionally present as aggressive pituitary tumors (APT), with invasion of surrounding structures, rapid growth, resistance to conventional therapies and multiple recurrences. In rare cases they can progress to pituitary carcinomas (PC) in several years, diagnosis being made upon the documentation of systemic or central nervous system (CNS) metastatic spread. Among pituitary carcinomas, the most common malignant subtypes are lactotroph and corticotroph carcinomas.

Case report: We present the case of a 66 years-old female diagnosed with an invasive ACTH-secreting pituitary macroadenoma in 2015. She underwent transsphenoidal surgery followed by Gamma-knife radiation due to recurrent disease. Pasireotide was initiated but discontinued after only two months due to serious side effects, including corticotroph insufficiency. After 2 years of remission, hypercortisolism reappeared but in the absence of approachable residual tumor Cabergoline treatment was initiated, to which she responded well, developing adrenal insufficiency. One year later, considering the increase in tumor size, the second course of Gamma-knife radiosurgery was performed with no efficacy, and in 2020 she underwent transcranial adenomectomy. The immunohistochemistry revealed high agressiveness of the tumor - Ki67 5% and mitotic index was greater than 10 mitoses per 10HPF. The last MRI showed a 9 mm tumor at the vermis and the immunohistopathology report described a pituitary carcinoma metastasis (ACTH intense positive, p53 expression in 40% of the cells and Ki67 5%). External radiotherapy was performed; Temozolomide therapy was contraindicated due to poor clinical condition of the patient. She ultimately died just 2 months following the diagnosis of carcinoma.

Conclusion: The evolution of APTs may have periods of radiological and hormonal quiescence. Morbidity and mortality are increased, even in the absence of progression to PC, especially in functioning corticotroph APTs, where they exacerbate in relation to cortisol excess. So far, no pathological marker has been shown yet to reliably predict pituitary tumor behavior. Early diagnosis would offer the chance for prompt intensive treatment in an attempt to reduce overall morbidity and possible progression to carcinomas.

Keywords: pituitary carcinoma, Cushing’s disease;