Endocrine Abstracts

Pasireotide (Pas) is a multireceptor-targeted somatostatin analogue approved for the treatment of patients with Cushing’s Disease (CD) who fail or are poor candidates to surgery. Pas markedly improves signs and symptoms of the disease, reduces urinary free cortisol (UFC) up to its normalization in 55% of patients and pituitary tumour size in up to 100%. Here we present a patient with severe recurrent CD treated with Pas and showing opposite results between hormonal levels and pituitary tumour size. A 54-year-old woman was diagnosed with CD in 2008. A right 8 mm intrasellar adenoma was totally removed by TNS. After seven years the disease recurred (UFC 4x Upper Limit of Normal Range (ULNR), ACTH 60 pg/ml, reference range 9-52) and MRI showed an intrasellar right adenoma tightly close to cavernous sinus (CS). She underwent a second TNS surgery, but, in spite of an apparent total removal of the adenoma, hypercortisolism worsened (UFC 40x ULNR, ACTH 237 pg/ml). MRI showed a tiny remnant of the adenoma adjacent to CS and ketoconazole (Kcz) was started at 800 mg/daily dose. Due to the persistence of pathological UFC levels, sc 600 µg bid Pas was added. The combination therapy firstly induced UFC and ACTH normalization (0.8x ULNR, 33 pg/ml, respectively) and later on hypoadrenalism, so that Kcz was withdrawn and Pas maintained, due to its higher efficacy and aiming to control the size of the adenoma remnant. Pas obtained a marked clinical improvement, diabetes mellitus occurred requiring metformin and dulaglutide. Three months after Pas starting the pituitary MRI showed a slight tumor shrinkage. Due to the occurrence of hypoadrenalism, a steroid replacement therapy was started. Adrenal insufficiency persisted notwithstanding the orogressive tapering of Pas dose to 150 mg once daily. Pituitary MRI performed at 12 and 24 mos during low (150 mg once daily) Pas dose showed a few millimeters increase of the remnant, whereas ACTH levels remained normal (31 pg/ml). Diabetes mellitus remitted, requiring only dietotherapy. This report suggests that in CD Pas induces an opposite effect between hormonal profile and the increase of pituitary tumor size. This peculiar phenomenon might be a consequence of unusual low doses of Pas needed to control hormonal hypersecretion