Year : 2009 | Volume
: 20 | Issue : 1 | Page : 127--129
Severe rhabdomyolysis and acute renal failure secondary to use of simvastatin in undiagnosed hypothyroidism
Faiza A Qari
King Abdul Aziz University, Jeddah, Saudi Arabia
Faiza A Qari
King Abdul Aziz University, P.O. Box 80215, Jeddah 21589
A 52-year-old Indian woman with underlying diabetes mellitus and hyperlipidemia, presented with generalized musculoskeletal pain and oliguria for three days. The patient was taking 80 mg of simvastatin initiated 20 days earlier after cardiac catheterization for an inferior myocardial infarction. Laboratory investigations revealed the following serum levels: creatine kinase 81,620 U/L, aspartate aminotransferase 2497 U/L, alanine aminotransferase 1304 U/L, blood urea nitrogen 21.7 mmol/L, creatinine 447 µmol/L, Free T4 12.6 pmol/L, and thyroid stimulating hormone (TSH) 22.7 µIU/L. Simvastatin was discontinued and the patient received forced alkaline diuresis. Her hypo thyroidism was treated with thyroxin, which was continued upon discharge, and her renal function recovered within two months. This case report discusses the incidence of rhabdomyolysis in a patient with primary hypothyroidism receiving large doses of simvastatin.
|How to cite this article:|
Qari FA. Severe rhabdomyolysis and acute renal failure secondary to use of simvastatin in undiagnosed hypothyroidism.Saudi J Kidney Dis Transpl 2009;20:127-129
|How to cite this URL:|
Qari FA. Severe rhabdomyolysis and acute renal failure secondary to use of simvastatin in undiagnosed hypothyroidism. Saudi J Kidney Dis Transpl [serial online] 2009 [cited 2021 Sep 21 ];20:127-129
Available from: https://www.sjkdt.org/text.asp?2009/20/1/127/44720
3-Hydroxy-3-Methylglutaryl co-enzyme A (HMG Co A) reductase inhibitors are effective in primary as well as secondary prevention of coronary disease.  Therefore, these agents are used as the first choice for hypercholesterolemia, especially atrovstatin and simvastatin.  HMG Co A reductase inhibitors represent the top drug class in sales in the United States; atorvastatin and simvastatin were the first and second most prescribed statins in 2006 respectively.  They are usually well tolerated in most patients. However, they can cause a variety of several musculoskeletal complications including clinical mysotitis and rhabdomyolysis. 
This case report discusses rhabdomyolysis in a patient with primary hypothyroidism receiving large doses of simvastatin.
A 52-year-old Indian woman presented to King Abdulaziz University Hospital's emergency department with complaints of generalized, dull, and constant muscle pain. She expressed an "inability to put her weight on her feet". These symptoms persisted for three days and were associated with weakness, fatigue, and decreased urine output for two days. Her medical history included diabetes mellitus on insulin, hypertension, anemia secondary to fibroids, and coronary artery disease with an inferior myocardial infraction (twenty days earlier). The patient has no history of renal disease with a baseline creatinine of 106 µmol/L. Simvastatin, 80 mg daily, was initiated by her cardiologist after undergoing cardiac catheterization twenty days prior to presentation. In addition, she was taking insulin, diuretics, losartan, aspirin, and clopidogrel.
The patient's vital signs were as follows: temperature 37°C, pulse 60 beats per minute (paced), blood pressure 130/65 mmHg, and respiration 18 breaths per minute. Physical examination showed pale, obese, dull looking woman. Her system examination was largely unremarkable. No palpable goiter was observed on neck examination and there was no delayed relaxation of ankle jerk. Laboratory evaluation at admission revealed creatinine kinase of 81,660 U/L, aspartate aminotransferase 2497 U/L, alanine aminotransferase 1304 U/L, blood urea nitrogen 21.7 mmol/L, creatinine 447 µmol/L, and potassium 6.2 mmol/L. Arterial blood gases showed mild metabolic acidosis. The thyroid stimulating hormone (TSH) was 22.7 U/L (NR 0.27-4.2) and serum free thyroxin (FT4) 12.1 pmol/L. Serum cholesterol level was 6.68 mmol/L, triglyceride 2.21 mmol/L, and LDL level 3.46 mmol/L (NR 0-3.57).
The patient was diagnosed to have rhabdomyolysis and acute oliguric renal failure. Simvastatin was discontinued, and she received forced alkaline dieresis including intravenous normal saline with bicarbonate. L-thyroxin 25 mcg was initially administered, and subsequently the dose was increased to 50 mcg daily.
At discharge, 15 days after hospitalization, the laboratory results included creatine kinase level of 1865 U/L and serum creatinine 138 µmol/L. The patient continued her thyroxin as an outpatient; however, no HMG CoA reductase inhibitor was restarted in view of the severe rhabdomyolysis.
At the patient's follow-up visit one month after hospitalization, she continued to report some mild residual weakness. However, after six weeks, her creatine kinase level was 151 U/L, creatinine 111 mmol/L, aspartate aminotransferase 186 U/L, and alanine aminotransferase 51U/L. FT4 level was 14.5 pmol/ L and TSH 2.06 U/L.
The reported risk of rhabdomyolysis with simvastatin monotherapy is low and dose related (0.02% at 20mg daily, 0.07% at 40mg daily, and 0.3% at 80mg daily).  Several factors have been identified that increase the risk for both myopathy and rhabdomyolysis, including advanced age, chronic renal insufficiency, metabolic disorders such as diabetes or hypothyroidism, major surgery, alcohol abuse and medications that inhibit cytochrome P450 (CYP) 3 A-4. 
Hypothyroidism frequently leads to asymptomatic mild to moderate creatine kinase elevation.  Marked creatine kinase elevation with rhabdomyolysis have been reported only in a very small number of cases with unnoticed hypothyroidism using HMG Co A reductase inhibitors. ,
Our patient received 80 mg of simvastatin with primary hypothyroidism. The severity of elevation of CK might be associated with hypothyroidism. The mechanism by which CK elevation occurs in individuals with hypothyroidism who simultaneously receive HMG Co A reductase inhibitors remains unclear.  This group of drugs may represent an additional risk factor for myopathy and rhabdomyolysis in patients with hypothyroidism.
In conclusion, the case report discussed a patient with severe rhabdomyolysis with primary hypothyroidism receiving a large dose of simvastatin. In order to avoid the serious deleterious complication, vigilant screening with CK levels both upon initiation and during continued treatment with HMG Co A reductase inhibitors, especially in individuals with hypothyroidism.
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