Case Presentation: A 83-year-old female with PMH of hypertension, type II diabetes mellitus, and prior tobacco use initially presented to the ED for generalized weakness. Initial exam was notable for hypertension and slowly healing wound on her right leg s/p mechanical fall several weeks prior. Her labs revealed hyperglycemia with serum glucose > 500 in addition to hypokalemia. During hospitalization, electrolyte derangements were thought to be secondary to recent initiation of hydrochlorothiazide and empagliflozin as an outpatient. She was discharged home with potassium supplementation and discontinuation of her recently started medications. One week following, patient returned to the ED with exertional dyspnea, ongoing generalized weakness, and bilateral lower extremity weakness. Patient was markedly hypertensive with SBP in 200s, and she was once again hyperglycemic and hypokalemic. Cardiac work up was unremarkable and CXR was normal. Despite initiation of insulin and repeated adjustments to her antihypertensive regimen, the medical team struggled to achieve sustained control of her hypertension or diabetes. She had ongoing hypokalemia despite supplementation and initiation of spironolactone. Given overall clinical trajectory, work up was broadened to include possible endocrinopathy and random cortisol was elevated at 49 ug/dl (AM 5.27 – 22.45 ug/dl) which was confirmed on repeat level. MRI abdomen revealed metastatic disease throughout the liver, right adrenal gland, and spine. ACTH level was markedly elevated at 301 pg/ml (10 – 60 pg/ml) which confirmed ACTH-dependent Cushing’s syndrome. Further imaging was notable for a 2.8 cm pulmonary nodule with tissue obtained via endobronchial biopsy. Pathology revealed a combined large cell neuroendocrine and small cell carcinoma. Patient initially pursued treatment with platinum-etoposide based chemotherapy which she did not tolerate. Patient transitioned care to hospice and died about two months after her initial diagnosis.
Discussion: Ectopic ACTH production accounts for about 5-10% of Cushing’s Syndrome, and is a well-described phenomenon associated with small cell lung cancer. Ectopic ACTH production in patients with small cell lung cancer is associated with worse prognosis as there is often more extensive disease at diagnosis and decreased response to treatment. For those with nonresectable ACTH producing tumors, treatment can include adrenal enzyme inhibitors such as ketoconazole. Given the aggressive nature of small cell lung cancer, patients with ectopic ACTH production resulting in Cushing’s Syndrome do not typically exhibit the classic symptoms associated with prolonged exposure to cortisol including significant weight gain, buffalo hump, round face, and striae. Instead, they are more likely to exhibit acute symptoms of hypercortisolism including fatigue, hypertension, hyperglycemia, and hypokalemia. Patients with ectopic ACTH production are more likely to be older, to have a shorter duration of clinical findings (11.6 vs 39.9 months), and to have hypokalemia (50% vs 8.6%)1.
Conclusions: Clinicians should be aware that the presenting symptoms of ectopic ACTH production in patients can be insidious, particularly in patients with co-morbidities that may mimic symptoms of hypercortisolism. Thus, it is important to consider hypercortisolism related to ectopic ACTH production as seen with small cell lung cancer and other malignancies in patients with uncontrolled and unexplained hypertension, hyperglycemia, and hypokalemia.