P-57 A case of pituitary carcinoma treated with osilodrostat for severe Cushing's syndrome
Authors: Golounina Olga O , Rozhinskaya Liudmila Ya , Naskhletashvili David R , Mel’nichenko Galina A , Belaya Zhanna E 
Published: January 2024

Abstract

Introduction
Pituitary carcinoma is a rare disorder accounting for 0.1–0.2% of pituitary tumors. We present a case of a male subject with ACTH-secreting pituitary carcinoma with metastasis to the spine, achieving eucortisolism on osilodrostat treatment.

Clinical Case
A 31-year-old male presented with complaints of pain in the rear-left thigh, numbness in the left-hand fingers and shoulder. MRI revealed an invasive pituitary tumor which had spread to the left frontal and temporal lobes with infiltration of the dura mater and compression of the left part of the optic chiasm, multiple formations in the large hemispheres, hemispheres of the cerebellum, in the right internal auditory meatus and at the level of the C1 vertebra compatible with metastasis. Spinal MRI showed a mass at Th6, L1-S2 level compatible with metastasis (Fig.1).
The patient was diagnosed with Cushing's disease (CD) at 23 (late-night serum cortisol 1450 nmol/L (64–327), late-night salivary cortisol (LNSC) 66.4 nmol/L (0.5–9.65), 24hUFC 608 nmol/L (100–379), ACTH 107.3 pg/mL (7.2–63.3)) and underwent transsphenoidal pituitary surgery for pituitary macroadenoma 26×18×29 mm with biochemical remission. Two years later his symptoms of CD relapsed and he had a second transsphenoidal surgery. Histological examination showed an atypical corticotroph tumor with Ki67 – 11.6%. Two months after surgery, Kiber knife surgery was performed. However, 2 years later he had gradual deterioration of vision due to loss of lateral margins. A third transcranial adenomectomy was performed with following panhypopituitarism and diabetes insipidus. The tumor was positively stained for ACTH and also contained some atypical features including nuclear pleomorphism. Postoperative chemotherapy adjuvant treatment with Temozolomide and Carboplatin was prescribed. After 6 cycles, proton radiotherapy was done. In order to control hypercortisolism the patient received ketoconazole 800 mg per day, cabergoline 1 mg twice weekly and pasireotide 1.8 mg per day. However, it was not possible to achieve remission of hypercortisolism. As an adverse event of pasireotide, diabetes mellitus developed, which required insulin therapy and finally lead to pasireotide cessation. Ketoconazole and cabergoline were discontinued and osilodrostat treatment was initiated with a final dose of 5 mg daily over 2 years. He also received another course of radiation therapy at the age of 31 years. Over the past 2 years of observation, his ACTH level ranged from 37 pg/mL to 325.1 pg/ml. In spite of tumor progression and raised ACTH, the patient remains in eucortisolism (late-night serum cortisol 163.3 nmol/L, LNSC 5.21 nmol/L, 24hUFC 70.14 nmol/L) on osilodrostat 10 mg daily.

Conclusion
In this case osilodrostat was effective at controlling hypercortisolism, but its effects on the tumor are unknown. As this patient is the first described case of corticotroph carcinoma tumor treated with Osilodrostat, the results should be taken with caution.Figure 1.Pituitary and spinal MRI of the patientT1-weighted MRI demonstrating (A) chiasmal-sellar region formation, (B) formation in the rigt internal auditory meatus, (C) a highly invasive sacral L1–S2 metastasis