Endocrine Abstracts

Introduction: Corticotropinomas constitute up to 45% of aggressive pituitary tumors, which characterized by rapid and invasive growth, a high Ki-67 index, resistance to conventional treatments and recurrence in 15-20% of the cases. Progression of corticotroph tumor after bilateral adrenalectomy or Nelson’s syndrome is a frequent severe complication and may present with aggressive tumor behavior.

Clinical case: A Cushing disease was diagnosed in a woman of 19 years of age (2010) for which she underwent a transsphenoidal adenomectomy in 2010 and 2011 (immunohistochemical study was not performed) with the development of secondary hypothyroidism and hypogonadism. Then due to persistence of the disease in 2012 a stereotactic radiosurgery (Gamma-knife, 36 Grey) was performed. Due to its absent effect on ACTH secretion (>2000 pg/l) in 2014 the patient had a bilateral laparoscopic adrenalectomy which led in 2017 to development of Nelson’s syndrome with right sided diplopia, ptosis, and severe headache; MRI noted a tumor 25x24x38 mm with invasive growth to the right cavernous sinus, spreading forward to the entrance to the right orbit. The patient was treated by repeated transsphenoidal adenomectomy followed by conformal external stereotactic radiotherapy (morphology - pituitary adenoma of oxyphilic cells with a solid alveolar structure; immunohistochemistry - ACTH expression in most tumor cells with uneven nuclear expression of Ki-67 (label index from 3,8% to 9,4%) and negative expression of P53; absent methylation of MGMT gene) with complete elimination of neurophthalmic features. In 2023 these clinical features returned, MRI described tumor measuring 27×20×38 mm in the right cavernous sinus with involvement and narrowing of the right carotid artery, extending to the right orbit and the right contour of the pons. The patient was consulted by a neurosurgeon, however, due to the fact that surgical treatment for this patient seemed overly traumatic and non-radical, by decision of the council temozolomide therapy was prescribed at a dose of 150-200 mg/m² daily for 5 days every 4 weeks for 3 courses followed by MRI control in order to determine further treatment tactics. The treatment led to clinically significant reduction in diplopia and headache.

Conclusion: This clinical case demonstrates aggressive corticotropinoma and progression of the rapid and invasive growth despite multimodal treatment even with repetitions. Total adrenalectomy avoided the complications of hypercortisolism for more than 10 years, but the patient needs further treatment of the most aggressive adenoma using oncological therapy methods of which temozolomide is recognized as the first line of therapy.