2403 Adefovir-Induced Fanconi Syndrome: Missed Diagnosis and Misdiagnosis

Abstract

INTRODUCTION: Nucleotide reverse transcriptase inhibitors (NRTIs), e.g., adefovir (ADV), are commonly used to treat chronic hepatitis B, which affects approximately 240 million worldwide and 2.2 million in the US. We report a case of ADV-induced Fanconi Syndrome (AIFS) in a patient who was undiagnosed for 5 y. CASE DESCRIPTION/METHODS: A 75 yo Spanish female with history of osteoporosis and CHB on ADV 10 mg/d for 15 y presents to the ED for bilateral hip pain. Over the past 2 y, her hip pain was refractory to steroid injections and complicated by traumatic bilateral hip and atraumatic clavicular fractures. One year ago she was diagnosed with osteoporosis and started on teriparatide (synthetic parathyroid hormone). Exam reveals bilateral hip tenderness and she is unable to bear weight. Labs reveal renal phosphorous wasting and glucosuria, proteinuria, hyperaminoaciduria and low fibroblast growth factor 23 confirm diagnosis of FS (Table 1). Bone scan is consistent with osteomalacia (Figure 1). Teriparatide is stopped to prevent worsening of osteomalacia. Lab review shows otherwise normal phosphorous prior to starting ADV (Table 2), and patient is diagnosed with AIFS. Phosphorous supplementation is started and ADV is changed to entacavir (ETV) due to decreased renal toxicity. Patient reports complete resolution of hip pain within 1 week, over which time labs also improve (Table 2). DISCUSSION: heavy metal or drug toxicity. Classic features include hyperphosphaturia, hyperuricosuria, hypercalciuria, modest proteinuria and glycosuria. In addition to hyperchloremic acidosis, rickets or osteomalacia are the predominant effects of FS. Osteomalacia can exist despite normal calcium and vitamin D levels. FS and osteomalacia affect 30% and 10% of patients on long-term NRTI therapy, respectively. Nephrotoxicity is reported at dosages of 10-120 mg. Risk factors for developing AIFS include old age, low BMI and >8 y treatment with ADV, all of which apply to this patient. While this patient's CMP was checked yearly, her metabolic derangements were overlooked for 5 y. Treatment of her osteoporosis likely worsened her underlying FS. This highlights the need for awareness of this clinically significant syndrome as a more timely diagnosis may have prevented fractures. While AIFS is well reported in Endocrine literature, it is not as widely reported in GI literature, which may contribute to this knowledge gap in Gastroenterologists. GI clinicians should consider FS in patients on longstanding ADV with low phosphorous.