Levetiracetam Treatment Causing False Negative Screening Test in a Woman With Aldosterone Producing Adenoma

Background: Endocrine hypertension accounts for 5–10% of hypertensive population, with primary hyperaldosteronism being the most frequently encountered diagnosis. Biochemical tests are subject to interference with many drugs that may lead to false positive or negative results. We present a case of aldosterone producing adenoma associated with false negative screening test due to Levetiracetam use. Clinical Case: A 30 year-old Middle Eastern woman was referred to endocrinology clinic for evaluation of secondary hypertension and persistent hypokalemia. Six years ago, she presented to emergency room during the 3rd trimester of her second pregnancy with severe preeclampsia and seizure. Postpartum, she was discharged on Levetiracetam (Keppra) 500 mg orally BID. Upon follow up visits, she continued to have persistent elevation of blood pressure readings with spontaneous hypokalemia ranging 2.5–3.2 mEq/L. She was started on Perindopril 10 mg daily and potassium supplement. Amlodipine 5 mg daily was added shortly later on. Clinically, she had regular menstrual cycle. She did not have plethora, central obesity, easy bruising, or proximal muscle weakness. Her review of systems including thyroid-related symptoms were normal. There was no family history of hypertension or adrenal tumors. On examination, BP 180/110, pulse rate 78, weight 58 kg and BMI 25. Her physical examination was otherwise unremarkable. After holding Perindopril for 4 weeks, biochemical tests showed creatinine 0.52 mg/dL (0.49–1.1), urea 16.8 mg/dL, potassium 2.9 mEq/L (3.5–5.2), direct renin concentration (DRC) 100.6 pg/mL, aldosterone 54.25 ng/dL. Plasma fractionated metanephrines were normal and morning cortisol level after 1 mg overnight dexamethasone suppression test was 0.72 mcg/dL. Renal arterial doppler showed normal renal blood flow without any significant stenosis. Despite increasing potassium supplement she continued to have hypokalemia. As levetiracetam was reported by literature review to cause severe hypokalemia, it was stopped after discussion with neurology. Four weeks later, repeated DRC was suppressed 4.0 pg/mL with elevated aldosterone 62.73 ng/dL. Furthermore, primary hyperaldosternism was confirmed after normal saline suppression test revealed unsuppressed aldosterone 15 ng/dL. An Adrenal CT scan showed a small hypodense right adrenal lesion measuring 11x9 mm with a pre-contrast density of 7 HU and post contrast absolute washout more than 60%. Patient elected to undergo right adrenalectomy. 24 hours post surgery, aldosterone level dropped to 4.0 ng/dL and potassium increased to 5 mEq/L. Fortunately, hypertension and hypokalemia have both resolved after surgery. Conclusion: We are first to report that Levetiracetam can cause unsuppressed direct plasma rennin concentration (DRC) and potentially could result in a false negative screening test for primary hyperaldosteronism.