Endocrine Abstracts

Introduction: Ectopic Cushing’s syndrome (ECS) is a rare endocrine condition caused by corticotrophin (ACTH) hypersecretion of nonpituitary neoplasms. Thymic neuroendocrine tumours (NETs) account for about 5-10% of ECS cases, typically with aggressive clinical course.

Case Report: A 31-year-old previously healthy female presented to the emergency department with a 3-week history of fatigue, muscle weakness, headaches and generalized swelling. Physical examination revealed peripheral oedema, high blood pressure (170/100 mmHg) and tachycardia (170 beats/min). Laboratory tests showed leukocytosis (13.95 x10⁹/l), hyperglycemia (478 mg/dl) and metabolic alkalosis with profound hypokalaemia (2.5 mmol/l). She was started on insulin therapy along with aggressive hypokalemia repletion and antihypertensive treatment. Given the overall clinical presentation and resistance to initiated treatment, aggressive CS was suspected. Hormonal tests were as follows: midnight serum cortisol 69.17 mg/dl, urinary free cortisol 11587.5 μg/24h, ACTH 963.7 pg/ml. Chromogranin A (CgA) level was notably elevated (1385.0 ng/ml). Negative HDDDST and CRH tests, negative pituitary imaging with short duration and rapid progression of symptoms were highly suggestive of ECS. To control hypercortisolemia, continuous etomidate infusion was started with significant improvement in the patient’s general condition, oedema reduction and normalization of blood pressure, glycemia and potassium level. Computed tomography (CT) revealed a left adrenal mass measuring 80x56x39 mm infiltrating the diaphragm. Whole-body 18F-FDG-PET/CT showed a metabolically active lesion of the left adrenal gland and multiple active bone lesions suggestive of metastatic malignancy. The patient underwent laparoscopic left adrenalectomy with a postoperative significant decline in cortisol level (4.08 mg/dl) and required hydrocortisone replacement. However, histopathology showed adrenal adenoma with extensive necrosis. A follow-up (8 weeks) whole-body PET/CT finally revealed 18F-FDG-avid (SUVmax 9.3) 42x33 mm lesion in the anterior mediastinum. Due to the local invasion, only a partial resection was performed. Histopathology revealed a thymic large cell neuroendocrine carcinoma with atypical thymic carcinoid component [ACTH(+), CgA(+), synaptophysin(+), CD56(+), MGMT:70%, Ki-67:30%, p53: <1%]. Thymectomy was followed by mediastinal radiotherapy and chemotherapy with the ADOC regimen. The patient has been under endocrine and oncological follow-up for almost 3 years, however, due to the progression of the disease, the prognosis is poor.

Conclusions: The diagnosis and management of ECS remain challenging. ACTH-secreting thymic NETs often behave aggressively and lead to the rapid development of severe hypercortisolism causing uncontrolled hypertension and hyperglycemia with hypokalaemic alkalosis requiring prompt intervention. Due to the rarity and complexity of the disease, management of ECS caused by malignant thymic NETs needs a personalized and multidisciplinary approach.