Abstract
Disclosure: A.K. Jain: None. J. Cheng: None. Introduction: Obesity is a complex disease that requires lifestyle and pharmacologic interventions to reduce cardiovascular disease, insulin resistance, and metabolic syndrome. Hyporeninemic hypoaldosteronism (HH), characterized by insufficient plasma renin and aldosterone activity, impairs sodium retention and blood pressure homeostasis. Here we describe a patient with HH maintained on a stable dose of fludrocortisone that recently initiated phentermine for weight loss and presents with recurrent syncope. Case: A 40 year-old female with a history of HH, morbid obesity (BMI 42 kg/m2), premature ovarian insufficiency, non-functional left adrenal incidentaloma, Factor V Leiden mutation, and pulmonary embolism presented to the hospital with progressive, position-independent, recurrent syncope for two weeks. She first experienced syncopal episodes 8 years ago after a 36-week delivery of a stillbirth. After diagnosis of HH, she took fludrocortisone 0.1 mg twice a day. With resolution of syncope, she decreased her evening dose to 0.05 mg. Two weeks ago, she was prescribed phentermine 37.5 mg daily for weight loss. EEG, CT Head, and tilt table test were negative. EKG with normal sinus rhythm. Supine blood pressure was 105/50 mmHg. Standing blood pressure was 90/45 mmHg. Electrolytes, thyroid function, plasma metanephrines, and glucose levels were within range. DHEAS was 255 ug/dL, renin 0.08 ng/mL/h, aldosterone 2 ng/dL, ACTH 21 pg/mL, and AM cortisol 7.15 mcg/dL. 60 minutes post-ACTH stimulation test, cortisol was 23.27 mcg/dL. After immediate discontinuation of phentermine, she demonstrated improvement in energy and no further syncope. She was discharged with fludrocortisone 0.1 mg twice a day and midodrine 0.5 mg three times daily. Discussion: In patients with HH, compensatory mechanisms for maintaining blood pressure and volume are impaired, predisposing them to orthostatic hypotension and syncope. Fludrocortisone, a synthetic mineralocorticoid, helps to retain sodium, expand blood volume, and increase blood pressure. Phentermine, a stimulant prescribed for obesity management, increases norepinephrine and dopamine which can also elevate blood pressure. The combined effects of phentermine's sympathetic stimulation and fludrocortisone’s fluid retention in the context of impaired baroreceptor responsiveness and insufficient aldosterone-mediated regulation may exacerbate recurrent episodes of syncope. Phentermine increases risk of dehydration and fludrocortisone alters potassium and sodium levels, furthering the potential of cardiovascular instability. Till date, there are only two existing case reports that illustrate this adverse drug interaction. Conclusion: This case aims to bring awareness to the adverse drug interaction between phentermine and fludrocortisone in managing patients with both obesity and hyporeninemic hypoaldosteronism. Presentation: Saturday, July 12, 2025