Endocrine Abstracts

JOINT877

Silent corticotrope pituitary adenomas (SCPAs) comprise approximately 20% of all corticotrope adenomas and 3-19% of non-functioning pituitary adenomas (NFPAs), and are considered high-risk pathologies. Therefore, appropriate treatment decisions and a close follow-up should be tailored to improve patient outcomes. A 43-year-old male patient with fatigue, decreased libido, frontal headaches, right eye strabismus and ptosis was referred to our Endocrinology Department due to an invasive giant pituitary tumor in November 2022. MRI revealed a large sellar-mass with invasion of both cavernous sinus with right dominance and progression towards the sphenoid sinus, and ethmoidal cells on the right and clivus [diameter: 70 mm anterior-posterior, 73 mm cranio-caudal, and 57 mm transversal; pituitary stalk presented slight displacement to the left]. Transcranial surgery was conducted to decompress the optical nerve of the right eye, with improvement in visual acuity, ptosis and headaches. Post-surgery lab tests revealed normal TSH, FT4, cortisol, prolactin, IGF-I levels, but low LH, FSH and total free and bioavailable testosterone levels. A second surgery (transsphenoidal) was performed and pathological report showed a neoplastic proliferation that infiltrated the stroma below the pavement cells with some intraluminal tumor emboli, increase in the mitotic number and absence of necrosis. Immunostaining and molecular studies showed: CK++, SYN+++, CK8.18++ with perinuclear rings, P53++, KI 67<1%, ACTH isolated positivity and negative prolactin/GH/TSH/LH/FSH/TSH/FSH and PIT 1, but T-PIT positive ++ nuclear and GATA 3 positive +++ in all cells. Moreover, tumor sample expresses high POMC levels (ACTH-precursor), DR1 (only dopamine-receptor subtype significantly expressed) and GHRH-R. Interestingly, oncogenic splicing events of key genes were significantly expressed in tumor sample, including high expression of the splicing-variant of the SSTR5 with 4 transmembrane-domains (SSTR5TMD4; no expression of other SSTRs was found), and of In1-ghrelin and GHRH-R spliced-variants. Due to the extensive tumor persistence, we decided to begin Temozolomide in a multidisciplinary-session, but no response was found after receiving 4-cycles. PD-L1 expression and Microsatellite instability were negative. Then, Stereotactic Fractionated radiotherapy was performed. MRI showed slight decrease of the tumor size. Current treatment: cabergoline 2 mg/week, hydrocortisone and testosterone, being tumor stable and the patient is being closely followed-up. The treatment of aggressive NFPAs is a challenge because patients usually need combined therapies such as multiple surgeries, radiotherapy and oncologic drugs. Molecular studies are necessary to identify tumors’ features to select adequate treatments. Oncogenic splicing variants expressed in this tumor might be associated to the aggressive-features found in this patient.