Endocrine Abstracts

JOINT3540

Introduction: Cushing’s syndrome (CS) is a rare disease, with 10–15% of cases caused by ectopic ACTH secretion. Clinical presentation ranges from mild to severe hypercortisolism with high mortality. The etiology includes well-differentiated neuroendocrine tumors (NETs) or undifferentiated tumors, complicating diagnosis and management. A multidisciplinary approach and advanced diagnostic techniques are essential. This case highlights the complexity of early diagnosis, comprehensive management, global support, and prolonged evaluation.

Objective: To describe a case of ACTH-dependent ectopic CS, emphasizing the integration of diagnostic methods and the importance of a multidisciplinary approach.

Case Report: A 34 year-old male with a history of anxiety-depressive disorder and progressive obesity was admitted for Fournier’s gangrene requiring secondary intention wound closure. He developed severe hypokalemia (2.5mEq/l)resistant to treatment, new-onset Diabetes Mellitus (HbA1c 8.2%) requiring insulin therapy, and fluctuating psychiatric symptoms, including mutism and treatment refusal. PE revealed moon facies, dorsal fat pad, central obesity, violaceous abdominal striae, and significant proximal muscle weakness with generalized sarcopenia. CS was suspected and confirmed by endocrinological evaluation: - 24-hour urinary free cortisol: 3672.0µg/24h (normal 13-75µg/24h). - Serum cortisol: 22.80µg/dl (normal 5-25µg/dl). - Plasma ACTH: 89.95pg/ml (normal 10-50pg/ml). - Late-night salivary cortisol: 3.170µg/dl (normal <0.208µg/dl). Given the hypercortisolism severity, ectopic ACTH secretion was suspected.

Clinical Course: The patient was transferred to the ICU for hypokalemia management and psychiatric stabilization. Treatment with metyrapone and ketoconazole was initiated, rapidly escalating doses with a block-and-replace strategy using hydrocortisone. Spironolactone was added for hypokalemia and hypertension control. Thromboprophylaxis with heparin and antibiotic prophylaxis with TMP-SMX were implemented. Thoracoabdominopelvic CT revealed a 10×15mm pulmonary nodule in the left lower lobe. 68Ga-DOTATOC PET/CT confirmed a high-uptake pulmonary nodule (SUVmax21.9), suggesting SSTR overexpression without metastases. A multidisciplinary team recommended surgery after hypercortisolism control. Nutritional support with high-protein supplements and rehabilitation were initiated. Following hypercortisolism control and clinical stabilization, left lower lobectomy was performed. Pathology confirmed a typical G1 pulmonary NET (WHO2021), 2cm in size, with clear surgical margins (Ki-67 1.7%). A supradiaphragmatic lymph node revealed metastatic typical carcinoid NET G1 with extracapsular extension (Ki-67 2.1%), pT1bN2. Immunohistochemistry was positive for TTF1, INSM1, chromogranin, synaptophysin, ACTH, and SSTR. Surgery allowed cessation of hypercortisolism treatment, where psychiatric symptoms corrected and Fournier’s gangrene healed.

Conclusions: A multidisciplinary approach is essential for diagnosing and treating NET-associated CS. Advanced techniques such as 68Ga-DOTATOC PET/CT are crucial for early diagnosis. Management of complications are fundamental to successful treatment and patient recovery.