Endocrine Abstracts

Introduction: Pancreatic neuroendocrine neoplasms (Pan-NENs) account for 1-2% of all pancreatic tumors. Adrenocorticotropic hormone (ACTH)-producing PanNEN is an extremely rare neuroendocrine tumor that accounts for approximately 4-16% of ectopic ACTH-dependent Cushing’s syndrome.

Clinical case : A 58-year-old female with arterial hypertension and type 2 diabetes was referred to the Endocrinology Department due to abdominal pain, muscle weakness, and unintentional weight gain. The hormonal evaluation confirmed ACTH-dependent hypercortisolemia: serum cortisol at 2000 h. 29.65 µg/dl, midnight serum cortisol 30.89 μg/dl, ACTH 87.6 pg/ml, UFC: 388.5 µg/24h, serum cortisol after 1 mg of dexamethasone: 22.71 μg/dl. MRI visualized a lesion measuring 8x5 mm and infiltrating the right cavernous sinus. Both the CRH stimulation test and high-dose dexamethasone suppression test were negative, whereas the combined dexamethasone-desmopressin test was positive. Given the inconclusive results, diagnostic imaging of the chest and abdomen was performed but revealed no signs of a tumor. Due to the presence of a focal lesion in the pituitary region, exploration of the sella turcica was undertaken; however, the lesion was beyond resectability. For this reason, pharmacological treatment was started. Inferior petrosal sinus sampling was performed twice, with inconclusive results. Pharmacological treatment of hypercortisolemia (pasireotide s.c., ketoconazole, cabergoline) was introduced. The patient remained in follow-up, lasting about ten years, despite pharmacotherapy, the features of ACTH-dependent hypercortisolemia persisted, and finally, in 2022, a full-body CT, visualized a focal lesion measuring 15x14mm in the pancreas tail. SPECT-CT somatostatin-receptor scintigraphy and Ga-68-HA-DOTATATE PET-CT did not reveal increased tracer accumulation and proliferative process features with high expression of somatostatin receptors. 18F-FDG PET/CT showed no proliferative hypermetabolic changes. The patient underwent endoscopic ultrasound with tumor biopsy, and histological examination identified neuroendocrine cells with positive ACTH, CD 56, and chromogranin staining. Since the patient did not consent to surgery, treatment with lanreotide autogel 120 mg was introduced, which led to the normalization of hypercortisolemia. The dimensions of the pancreatic lesion remained stable. After the patient’s consent, one year later, a tail resection of the pancreas was performed, resulting in complete normalization of the pituitary-adrenal axis.

Conclusions: The case described shows that extensive diagnostics and patient compliance are crucial in managing Pan-NENs. Ectopic ACTH production syndrome can be caused by very small focal lesions, so diagnostics of their location may last many years. Somatostatin analogs may be a treatment of choice in preparation for surgical treatment.