Endocrine Abstracts

JOINT2674

Introduction: Cushing disease is a very challenging endocrine disorder treated ideally by transsphenoidal surgery, with variable aggressiveness and resistance to medical treatment.

Case Report: A 44-year-old woman known with Cushing disease diagnosed 8 years ago with macroadenoma partially resected (2018) by transsphenoidal surgery (Ki67 10%), with significant tumor remnant, followed by stereotaxic radiotherapy -25Gy/5 sessions (2018). Due to bitemporal hemianopsia, a second surgery was unsuccessfully attempted (2019). In March 2020, the tumor relapse required Pasireotide 1.8 mg/day and cabergoline 1.5 mg/week increased at 8 mg/week with no biochemical or morphological response. In 2021 a partial left adrenalectomy was done. The patient presents typical symptoms of complicated Cushing’s disease, including a generally altered state, a moon-shaped face, erythema and chin hirsutism. She has purple striae on the abdomen, skin and vascular fragility in the lower limbs, with multiple bruises and muscular weakness which made her unable to walk by herself. She has secondary hypertension, diabetes, secondary osteoporosis, hypercholesterolemia, gonadotropin deficiency, growth hormone deficiency, hypothyroidism under substitution therapy with Levothyroxinum. Due to local and systemic progression of the disease, she started Temozolomide with in 2022 with no results. Since 2022 she was enrolled on Relacorilant in GRACE clinical trial (CORT125134-455) with clinical response, until June 2024. Afterwards she was treated with Metyrapone 750 mg/day, followed by Ketoconazole 800mg/day without significant improvement. Last imaging showed bilateral macronodular adrenal hyperplasia. As a last therapy, right adrenalectomy was performed, considering the increased hormonal activity (ACTH 540.9 pg/mL, cortisol 48.67 µg/mL). Four days after surgery cortisol decreased to 36.5 mg/dl, and 2 weeks after the surgery, at 15.84 µg/mL. At the time of submission she is recovering from adrenal surgery.

Conclusion: This case highlights the multifactorial treatment of Cushing’s disease and emphasizes the aggressiveness that this pathology can have, even after all available lines of treatment were used. Nevertheless, after the adrenalectomy, there was a noticeable improvement in biological markers. The surgery continues to represent a vital stage in the treatment journey.