Endocrine Abstracts

Background: Ectopic Cushing Syndrom (ECS) represents approximately 12% of all patients with Cushing´s disease. Either ACTH (5–10%), CRH or cortisol is produced uncontrolled from nonpituitary tissue. Half of ECS cases are neuroendocrine lung tumors [carcinoid tumors > small cell lung carcinoma (SCLC)], but ECS is clinically apparent only in 1–5% of SCLC cases. Clinical features vary according to extent and duration of exposure to ACTH/Cortisol excess and include rounded erythematous face, acne, purple striae, proximal muscle wasting, edema, hypertension and metabolic alkalosis with hypokalemia. If possible, radical tumor excision is the treatment of choice. Ketoconazole, metyrapone, etomidate, mitotane, and mifepristrone and octreotied are second line options whereas bilateral adrenalectomy is the ultima ratio in case of pharmacological failure. Patients with ECS due to SCLC usually present at an advanced stage.

Case report: A 67-year-old male patient (BMI 26.5 kg/m²) with deterioration of known hypertension, diabetes mellitus on oral treatment (metformin/empagliflozin/saxagliptin) and psoriasis but also hyperhidrosis, bruising, dizziness. Smoking history of 40 pack years. Severe hypokalemia with 2.17 mmol/l (3.3–4.5) and hyperglycaemia (plasma glucose: 20.3 mmol/l; HbA1c: 9.0%;) resulted from corticotropic excess [serum cortisol in nmol/l (101–536): max. 2710; profile: 2033 (0600 h) – 1266 (2400 h) – 1158 (1800 h) – 922 (1200 h); ACTH 339.8 pg/ml (4.7–48.8)]. No increase of ACTH seen in the CRH-test (−15 min: 350.0 – 0‘: 339.7 - … - 120‘ 345.9). Computed tomography (CT) scanning identified tumor lesions of the right lung, liver and bilateral adrenal glands. Liver biopsy provided histologic diagnosis for liver metastasis of a low differentiated, high proliferative SCLC (cT1bN3M1c, G3, extensive disease; MNF116 positive, AE1/AE3 positive, synaptophysin positive, CD56 positive, TTF-1 positive, KI-67-index 90%). Serum NSE was elevated: 51.5 ng/ml (0–12.5). Bradycard episodes (heart rate 35/min) due to reduced potassium levels were seen and cardiovascular surveillance and compensation of electrolyte imbalance at ICU was necessary. Cortisol excess led to susceptibility for infections and soor-esophagitis and aspergillosis of the lungs occured. Adrenostatic therapy with metyrapone (3500 mg/day) was started and serum cortisol normalized to 424 nmol/l. According to tumor board recommendation palliative systemic chemotherapy with etoposid and carboplatin was commenced. Dismissal from hospital was possible after 49 days and after 2 chemotherapy regimes. Medication at dismissal: metyrapone 3000 mg/day, spironolactone 200 mg/day, insulin therapy. Continuation of chemotherapy is planned.

Conclusions: Severe hypokalemia and cortisol excess in combination with brief disease duration should be suspected for ECS. Interdisciplinary therapy by endocrinologists, intensive care unit and oncologists is needed. Severity of hypercortisolism and tumor histology affect mortality and morbidity.