REFRACTORY SIADH IN A PATIENT WITH MYCOBACTERIUM AVIUM COMPLEX PNEUMONIA DUE TO INCREASED METABOLISM OF TOLVAPTAN FROM RIFAMPIN UPREGULATION OF CYP45O ENZYMES

Abstract

SESSION TITLE: Medical Student/Resident Chest Infections Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: October 18-21, 2020 INTRODUCTION: Hyponatremia has been associated with Mycobacterial tuberculosis (MTB) infections in the medical literature since the 1930s but it wasn’t until the 1960s that SIADH was suggested as the cause. This case highlights the difficulty of treating combined Mycobacterial infections and SIADH. CASE PRESENTATION: A 56-year-old woman with no past medical history presented to the pulmonology clinic with a 1 year complaint of chronic cough. A CT scan showed upper lobe fibrosis, multiple nodules, and calcified lymph nodes. Bronchoscopy or needle-biopsy was recommended but she declined further testing. 10 months later, she returned to the clinic with new complaints of fever and fatigue. A repeat CT scan showed extensive destruction of the both upper lobes. Bronchoscopy was performed which was notable for purulent sputum. Bronchial cultures grew Mycobacterium avium complex (MAC). She was prescribed rifampin, ethambutol, and azithromycin as an outpatient, but was admitted to the hospital for treatment. On admission, her initial serum sodium was 132mmol/L. Nephrology was consulted on hospital day 8 for worsening hyponatremia. By then, her serum sodium had dropped to 124mmol/L and her serum osmolality was 270 mosm/kg. Urine studies showed an osmolality of 548 mosm/kg, and sodium of 135mmol/L. She was diagnosed with SIADH secondary to MAC pneumonia and placed on a 600mL fluid restriction and given salt tablets. The patient’s sodium remained under 130, so she was started on tolvaptan 7.5mg daily. Over the next 5 days, the dose of tolvaptan was increased to 30mg daily with improvement of her sodium to 138. Later, the patient was transferred to the medical ICU for worsening respiratory failure and was intubated. Despite maximal resuscitative measures, the patient died from multi-organ failure on hospital day 38. DISCUSSION: Multiple theories have been proposed to explain how MTB infections cause SIADH, including hypoxemia, reset osmoregulation, and ectopic ADH production. Nontuberculous Mycobacterial infections are much rarer than MTB, so the relationship between SIADH and them has not been studied as extensively. This case suggests that all patients with Mycobacterial infections are susceptible to developing SIADH. This case also illustrates the difficulty in treating refractory SIADH from Mycobacterial pneumonias due to the drug-drug interaction of rifampin and tolvaptan. Rifampin is a potent inducer of the CYP450 liver enzymes, which results in the increased metabolism of tolvaptan, necessitating larger tolvaptan doses to have a therapeutic response. CONCLUSIONS: Drug-drug interactions must be taken into consideration when simultaneously treating patients with MAC pneumonia and SIADH. Reference #1: Weiss H, Katz S. Hyponatremia resulting from apparently inappropriate secretion of antidiuretic hormone in patients with pulmonary tuberculosis. American Review of Respiratory Disease. 1964; 92:609-616. Reference #2: Bhatt PR, McNeely EB, Lin TE, Adams KF, Patterson JH. Review of tolvaptan’s pharmacokinetic and pharmacodynamic properties and drug interactions. Journal of Clinical Medicine. 2014; 3: 1276-1290. Reference #3: Vinnard C, Blumberg EA. Endocrine and metabolic aspects of tuberculosis. Microbiology spectrum Spectrum. 2017; 5(1). TNMI7-0035-2016 DISCLOSURES: No relevant relationships by Karl Andersen, source=Web Response No relevant relationships by Amanda Kamar, source=Web Response No relevant relationships by Arvey Stone, source=Web Response