MON-355 Recurrent Adrenal Crisis Secondary to Rifampin-Induced Hepatic Microsomal Enzyme Metabolism

Rifampin is a widely known antibiotic used to treat several types of bacterial infections including tuberculosis (TB) in a combination therapy setting. Rifampin is also known to have a profound drug-drug interaction profile. We describe here a case of rifampin induced hepatic microsomal enzyme causing accelerated hydrocortisone metabolism in a patient with panhypopituitarism resulting in multiple admissions with adrenal crisis. This is a 73-year-old male with a history of pituitary sarcoidosis since the 1980s with subsequent panhypopituitarism requiring replacement with levothyroxine, testosterone, desmopressin, and hydrocortisone in a stable dose pattern of 15 mg in the morning and 5 mg in the evening. He had been recently started on multi-drug therapy for military TB in the setting of an iliopsoas abscess. Initial therapy consisted of the following drug combination: rifampin, isoniazid, pyrazinamide, and ethambutol. After initiation of TB therapy, he presented with signs and symptoms of adrenal crisis that included: fatigue, hypotension, hyponatremia, hyperkalemia, and metabolic acidosis. Despite attempts at increasing the hydrocortisone dose over multiple hospital admissions, the patient had recurrent admissions for adrenal crisis episodes. These events occurred despite changes in his TB therapy regimen (therapy changed to rifampin and levofloxacin followed by the addition of meropenem, Augmentin and cycloserine for suspected resistant TB). Eventually, a stable dose of hydrocortisone 80 mg daily divided into 40/40 mg in the morning and evening stabilized the patient with no further adrenal crisis episodes. Rifampin is considered to be the most powerful known inducer of the hepatic cytochrome P450 enzyme system. It is known to increase the metabolism of many drugs that leads to those drugs being partially or totally ineffective. The list of drugs influenced by this mechanism includes: warfarin, contraceptive pills, anti-retroviral therapy, statins and many more.1 In addition, case reports have been described of hypothyroid patients requiring significantly higher doses of thyroid hormone replacement while on rifampin as compared to their original weight-based dosing requirements. However, in the literature, rifampin inducing increased steroid replacement therapy requirements in adrenally insufficient patients has been rarely reported. This case illustrates the need for increased awareness of higher steroid dose requirements, namely hydrocortisone, in patients on steroid replacement therapy with concomitant use of rifampin to avoid the sequelae of adrenal crisis which can be life threatening. 1. Hardman, Joel G., Lee E. Limbird, and Alfred G. Gilman, eds. "Rifampin." The Pharmacological Basis of Therapeutics. 10th ed. United States of America: The McGraw-Hill Companies, 2001. pp. 1277-1279.