Case Presentation: A 59-year-old white female with past medical history of 30 pack-year tobacco use, HTN, T2DM, and MS presented with malaise, fatigue, and diarrhea for the past two months. During this time period she also experienced consistent hyperglycemia and HTN, despite continued use of her prescribed medications. Upon admission, she was found to have significant hypokalemia. A random urine potassium:creatinine ratio was <1.5, suggesting an extra-renal loss consistent with her history of chronic diarrhea. An arterial blood gas revealed pH 7.57, pCO2 32.3, and HCO3 29. Physical examination was unremarkable. Blood pressure was consistently elevated in the 180/100 range despite adequate treatment with three antihypertensive medicines. A renal ultrasound to investigate resistant HTN revealed incidental liver masses. A follow-up chest/abdomen/pelvis CT showed left supraclavicular and large mediastinal lymph nodes, a 13 mm left upper lobe lung lesion, and multiple mildly enhancing hepatic lesions with central necrosis. Fine needle aspiration of the supraclavicular node revealed histology consistent with small cell lung cancer. ACTH was obtained and found to be 226pg/mL (normal is <60pg/mL). Renin was 0.7ng/mL/hr and aldosterone was <4.0ng/dL.
Discussion: Ectopic ACTH secretion accounts for 10% of Cushing’s syndrome with small cell lung carcinoma (SCLC) being the most common source. Ectopic ACTH syndrome has a typical presentation of hypokalemia, hypertension, hyperglycemia, metabolic alkalosis, and cushingoid features. Rarely, as in this patient’s case, hypokalemia refractory to aggressive potassium supplementation can be the presenting feature. Hypokalemia occurs in the setting of ectopic ACTH secretion because cortisol is molecularly very similar to aldosterone and is capable of binding to mineralocorticoid receptors. In a healthy individual this is prevented by the local action of 11 beta-hydroxysteriod dehydrogenase, the rate-limiting enzyme in the conversion of cortisol to inactive cortisone. In the setting of hypercortisolism the action of this enzyme is insufficient, allowing for mineralocorticoid effects of hypokalemia and metabolic alkalosis to be seen.
Conclusions: This case demonstrates the need to consider the possibility of ectopic ACTH secretion in patients with refractory hypokalemia. While ectopic ACTH secretion is a classic phenomenon associated with SCLC, this combination is rarely observed in clinical practice. In this case, the resultant Cushing’s syndrome from ectopic ACTH secretion lead to both the patient’s admission to the hospital, due to significant hypokalemia, as well as to her diagnosis of SCLC, due to work-up of her resistant hypertension. This finding has a prognostic value, as SCLC patients whom present with ectopic ACTH secretion have a significantly shortened survival when compared to those who develop ectopic ACTH secretion later in the disease course (4 months and 11 months, respectively).