Abstract
Background: Paraneoplastic Cushing’s syndrome is a rare cause of hypercortisolism associated with high morbidity, especially in patients with small cell lung cancer. Therefore, early diagnosis and treatment are critical.
Clinical Case: Herein we present the case of a 58-year-old man who was referred to the endocrinology department, because of refractory hypokalemia (potassium 2.4 mmol/l; RI: 3.4 - 4.5 mmol/l) despite high potassium supplements and spironolactone therapy. History was remarkable for a metabolic syndrome with newly aggravated hypertension and a 60-pack-year smoking history. The patient reported a 20 kg weight gain in 6 weeks and proximal muscle weakness. On examination, he was overweight (BMI 44.8 kg/m²) with bilateral pitting edema. Other features of hypercortisolism such as striae rubrae, facial plethora or ecchymoses, respectively, were not apparent. Initial biochemical tests showed severe hypokalemia and metabolic alkalosis. Night-time salivary cortisol (205 nmol/l; RI: < 2.5 nmol/l), 24-hour urinary free cortisol (> 4357 nmol/24h; RI: 99 - 378 nmol/24h) and serum ACTH (158 ng/l; RI: < 61 ng/l) were markedly elevated. While the MRI of the head demonstrated no pituitary pathology, the CT of thorax and abdomen revealed a pulmonary mass as well as an incidental right adrenal mass. Bronchoscopic biopsy of the pulmonary mass confirmed the suspected diagnosis of ACTH-producing small cell lung cancer. The dignity of the right adrenal mass remained unclear, since the radiologic features per se could not differentiate between adrenal adenoma and metastasis. Chemotherapy with cisplatin/etoposide and inhibition of steroidogenesis with ketoconazole were initiated, which largely controlled the hypercortisolism. Imaging studies after completion of two cycles of chemotherapy showed a tumor response with regression of the pulmonary mass. The right adrenal mass remained stationary under chemotherapy. Thus, an adrenal metastasis could be excluded as potential cause of the adrenal mass, suggesting an incidental adrenal adenoma as the most likely diagnosis.
Conclusion: Paraneoplastic Cushing’s syndrome requires high clinical suspicion for early diagnosis, since many of the classical clinical features of hypercortisolism may still be absent, even if the underlying cancer is already advanced. In patients suspected to have Cushing’s syndrome a three-step diagnostic approach is recommended: (1) biochemical confirmation of hypercortisolism, (2) differentiation between ACTH-dependant and -independant hypercortisolism and (3) identification of its source. This approach helps avoiding misdiagnosis in patients who have both an ACTH-producing cancer and an adrenal adenoma [1].
References: [1] Lacroix et al. Cushing’s syndrome. Lancet 2015; 386: 913-927.
Cardio-respiratory failure secondary to ectopic Cushing's syndrome as the index presentation of small-cell lung cancer
