Rhabdomyolysis and Acute Kidney Injury Associated with Hypothyroidism and Statin Therapy
A 63-year-old female patient presented to our hospital complaining of edema, fatigue, and numbness in the right femoral region. She had normal appetite, but her urine output had gradually decreased over the course of the 15 days prior to visiting the hospital. Oliguria began 8 to 9 days after making Kimchi in squat position. Her systemic edema had worsened over the three days prior to presentation, and she was experiencing asthenia and numbness of the right femoral region, which prompted her to visit the hospital through the emergency room. She did not complain of any respiratory distress or chest pain.\nShe had a medical history of hypertension and cerebral hemorrhage 7 years previously and her current medications were aspirin 100 mg, clinidipine 10 mg, valsartan 160 mg, thiazide 12.5 mg, and bisoprolol 5 mg. During the regular follow-up at the cardiology department of our hospital, hyperlipidemia (total cholesterol, 273 mg/dL; low density lipoprotein cholesterol [LDL-C], 167 mg/dL) was developed, and she was treated with rosuvastatin 20 mg starting 40 days before presentation. There were no specific findings in her family history.\nBlood pressure at the time of presentation was 120/90 mm Hg, pulse rate was 54 beats per minute, and body temperature was 35℃. Heart and breath sounds were normal. The skin tugor was decreased, the femoral region was tender to palpation, and she had systemic nonpitting edema especially on the face and periocular region. There was no sign of goiter. Muscle strength was slightly decreased in the bilateral lower extremities, but the remainder of the motor exam was unremarkable. There were no sensory abnormalities in the lower extremities, and the results of straight leg raise test, patellar subluxation test, tarsal test, and ankle clonus reflex test were normal. The pulse on both dorsalis pedis and popliteal arteries was palpated normally.\nBlood tests performed at presentation demonstrated white blood cell, hemoglobin, and platelets of 11,890/mm3, 15.5 g/dL, and 249,000/mm3, respectively. Blood urea nitrogen and serum creatinine were 89.1 and 9.8 mg/dL. Serum Na/K/Cl/total CO2, serum calcium/phosphate, plasma total cholesterol, triglycerides, and LDL-C were 131/4.1/91/17.5 mmol/L, 7.7/7.6 mg/dL, 111, 158, and 42 mg/dL. Aspartate aminotransferase/alanine aminotransferase, creatine kinase, and lactate dehydronase (LDH) were increased to 1,521/360, 72,850, and 1,974 IU/L, respectively. A whole-body bone scan showed diffuse isotope uptake in the muscle of right pelvis and both lower extremities, consistent with rhabdomyolysis (). Urinalysis revealed hematuria and 2+ proteinuria but urine myoglobin was negative.\nTo rule out hypothyroidism, as a possible risk factor for statin-induced muscle injury and as a cause of nonpitting edema and hypercholesterolemia, thyroid function test was performed. T3, free T4, and thyroid-stimulating hormone (TSH) were <25 ng/dL (normal range, 58 to 159), <0.4 ng/dL (normal range, 0.7 to 1.48), and 100 µIU/mL (normal range, 0.35 to 4.94), respectively. In addition, the patient had high titer of thyroid peroxidase autoantibody (1:6,400) and thyroglobulin autoantibodies (1:6,400). Based on all of the aforementioned findings, the patient was diagnosed as hypothyroidism associated with Hashimoto thyroiditis.\nDespite fluid resuscitation with normal saline and administration of a diuretic, the patient failed to maintain adequate urine output of ≥30 mL/hr. Instead, she developed symptoms of fluid overload. Accordingly, she was treated by continuous venovenous hemofiltration (CVVH; Prisma, Gambro, Lund, Sweden) with 2 L per hour of filtration volume via internal jugular venous catheter. Her hypothyroidism was also treated with levothyroxine 50 µg once daily starting from the second day of hospitalization immediately after she was diagnosed with hypothyroidism. After the second day of CVVH, urine output increased to ≥100 mL per hour and renal replacement therapy was stopped on the third day of hospitalization. The patient was discharged from the hospital on the 19th day with the following biochemical values: creatine kinase 507 IU/L, LDH 445 IU/L, blood urea nitrogen 24 mg/dL, and creatinine 2.3 mg/dL. Serum creatinine recovered to the normal range of 1.2 mg/dL 2 months after discharge. Due to the diagnosis of statin induced rhabdomyolysis, rosuvastatin was discontinued at discharge; however, plasma total cholesterol and LDL-C were again elevated to 232 and 151 mg/dL, respectively, 2 months after discharge. Therefore, we began treatment with another type of hydrophilic statin, pravastatin, at a dose of 20 mg per day. At 6 months after discharge, the patient's kidney function remained stable and T3, free T4, and TSH were 89.3 ng/mL, 1.19 ng/dL, and 6.181 µIU/mL, respectively. We continued levothyroxine 50 µg/day and slowly adjusted the dose depending on thyroid function tests.