Abstract
Background: Ectopic ACTH syndrome accounts for about 14% of Cushing syndrome cases. Small cell lung cancer is the most common cause. A few case reports described ectopic ACTH syndrome in patients with parotid acinic cell carcinoma. Parotid carcinoma ex pleomorphic adenoma is a malignant transformation within a pleomorphic adenoma, which is mostly adenocarcinoma not otherwise specified, but other subtypes can occur.
Clinical Case: A 41-year old man with parotid cancer and hypothyroidism was admitted to the hospital for hypokalemia (2.1 mmol/L, n: 3.5-5 mmol/L). Parotid cancer was diagnosed a year before admission. At that time, he underwent left parotidectomy, and pathology showed carcinoma ex pleomorphic adenoma with areas of acinic cell carcinoma. Despite chemoradiation, he was diagnosed with metastasis in the lungs, for which pembrolizumab was started. Over the two months prior to admission, he gained 20 lb, and developed lower extremity weakness, acne, erectile dysfunction and loss of libido. He was also diagnosed with hypertension and started to have mild hypokalemia. Suspecting hyperaldosteronism, oncology team ordered labs just prior to admission, which showed the hypokalemia of 2.1 mmol/L, hypernatremia (147 mmol/L, n: 133-143 mmol/L), normal aldosterone and renin, and high cortisol (59.12 mcg/dL, n: 3-22 mcg/dL) and ACTH (121 pg/mL, n: 9-50 pg/mL).
In the hospital, potassium was slowly improving despite aggressive replacement, and blood pressure was still elevated despite increasing his lisinopril dose. Screening for Cushing syndrome revealed an abnormal 1 mg dexamethasone suppression test (cortisol 51.9 mcg/dL, n: <1.8 mcg/dL), and high 24-hour urinary free cortisol (6495 mcg/24h, n: 3.5-45 mcg/24h) and midnight salivary cortisol (2610 ng/dL and 4250 ng/dL, n: <100 ng/dL). Cortisol was not suppressed after 8 mg dexamethasone (cortisol 47.85 mcg/dL, pretest cortisol 48.73 mcg/dL) pointing toward ectopic ACTH syndrome. Spironolactone was started and titrated up to 100 mg BID with better control of hypertension and normalization of potassium. Ketoconazole was started at 200 mg TID and increased gradually as outpatient to 400 mg TID within three weeks. A repeat 24-hour urinary free cortisol was done five weeks after ketoconazole was started showing significant improvement (110 mcg/24h, n: 3.5-45 mcg/24h). Potassium requirements remarkably decreased from 80 mEq TID to 40 mEq daily. Of note, chest CT done during hospitalization showed new lung lesions despite treatment with pembrolizumab.
Conclusion: This is the first case of ectopic ACTH syndrome to be described in a patient with parotid carcinoma ex pleomorphic adenoma, though areas of acinic cell carcinoma within the tumor can be the source of ACTH. Hypercortisolism due to ectopic ACTH secretion is usually of rapid onset, and can present with severe hypokalemia. Steroid synthesis inhibitors seem to be an effective therapy.
Fine Structure of an Oat Cell Carcinoma of the Lung Associated with Ectopic ACTH Syndrome