Introduction: Cushing disease is the most common cause of endogenous hypercortisolemia and most frequently is caused by microadenomas, but rarely, only in 10% to 20% of cases, the adenomas are large enough to produce mass effect.1
Case report: We present the case of a 63 years old female patient, diagnosed in 2007 with a 22/18 mm non-secreting pituitary adenoma and panhypopituitarism. She undergone transsphenoidal surgery twice, followed by gamma knife irradiation, resulting in progressive tumoral regression and empty sella until 2014, when a follow-up CT scan revealed a 15/13/11 mm tumoral recurrence, with rapid tumoral growth in the next couple of months to 27/24/17 mm and invasion in the adjacent structures. The third transsphenoidal surgery and the second gamma knife irradiation followed, without much tumoral mass reduction. IHC revealed and biochemistry confirmed an ACTH secreting aggressive pituitary macroadenoma (ACTH=70.2 pg/ml, 8 am serum cortisol after 1 mg dexamethasone suppression test=13.8 mg/dl, Ki67=25%). Cabergoline therapy was tried without benefit on cortisol secretion (ACTH=211.4 pg/ml, 24-hours urinary free cortisol=1965 nmol/24h, 24 pm salivary cortisol=18.75 nmol/l) or tumor mass which continued progressing to 31/35/34 mm and determined complications such as right eye blindness, right eyelid ptosis and severe trigeminal neuralgia. Pasireotide therapy was initiated but discontinued due to worsening of diabetes mellitus control, even though there were beneficial effects on cortisol secretion. In 2018 temozolomide therapy was decided. The clinical, imagistic and biological follow-up showed improvement on ACTH and cortisol secretion (ACTH=148.8 pg/ml, 8 AM serum cortisol=6.34 ug/ml and 24- hours urinary free cortisol=286.58 nmol/24h), improvement of trigeminal neuralgia, excellent control of the secondary diabetes mellitus and high blood pressure with minimal therapy and stable tumor mass (38/30/29 mm). After five cycles of therapy, temozolomide had to be, at least temporary, discontinued because the patient developed venous catheter related sepsis.
Conclusions: ACTH secreting aggressive pituitary adenomas are rare, but due to their aggressive behaviour and high recurrence rate after surgery and radiotherapy, must be early diagnosed, appropriately treated and followed-up. Temozolomide is an effective therapeutic agent for aggressive pituitary adenomas, that showed significant improvement on clinical and paraclinical parameters and should be used when other treatment options fail.
Bibliography: 1. Gandhi, C. and Post, K. (2019). ACTH-Secreting Adenomas. [online] Ncbi.nlm.nih.gov. Available at: https://www.ncbi.nlm.nih.gov/books/NBK12462/ [Accessed 3 Feb. 2019].
18 - 21 May 2019
European Society of Endocrinology