Simvastatin‐induced bilateral leg compartment syndrome and myonecrosis associated with hypothyroidism

Abstract

A 54‐year‐old hypothyroid male taking thyroxine and simvastatin presented with bilateral leg compartment syndrome and myonecrosis. Urgent fasciotomies were performed and the patient made an uneventful recovery with the withdrawal of simvastatin. It is likely that this complication will be seen more often with the increased worldwide use of this drug and its approval for all arteriopathic patients.

Compartment syndrome occurs when there is compression of nerves, blood vessels and muscle within a defined fascial envelope as can occur within the compartments of the leg. Aetiologies include limb trauma, ischaemia, fractures and drugs causing myonecrosis and subsequent swelling. The perfusion pressure falls below the tissue pressure resulting in a compromise to the circulation. It is essential to reduce the compartmental pressures at an early stage in order to minimise tissue oedema and myonecrosis and allow reperfusion of the compartmental tissues. This is done by compartment fasciotomy which can be a limb salvaging procedure.

We report a case of bilateral leg compartment syndrome and myonecrosis in a 54‐year‐old hypothyroid male on thyroxine and simvastatin. This patient initially presented to his general practitioner with weight loss and sweating. His thyroid function tests revealed a reduced thyroid stimulating hormone level of 0.03 and an elevated free T4 level of 63.2. A thyroid scan revealed an enlarged thyroid gland with increased homogenous uptake supporting a diagnosis of Graves' disease. The patient was treated with radioiodine isotopes and thereafter on follow‐up commenced on thyroxine 25 μg daily for subsequent hypothyroidism.

In routine follow‐up his blood cholesterol levels were elevated at 6.5 mmol/l and he was started on simvastatin 20 mg nocte by his general practitioner. The patient acutely developed generalised muscle pains and was unable to walk with intense bilateral calf pain after 1 month. At the time of presentation, both legs were tense, swollen and tender with creatinine kinase levels in the range of 6000 IU/l. Blood results were: urea 6.4, creatinine 149 and cholesterol 5.9 mmol/l.

Urgent fasciotomies were performed and the patient made an uneventful recovery with the withdrawal of simvastatin. The fasciotomy wounds healed very well and did not require any skin grafting for closure. A yellow card report was sent to the Medicines and Healthcare products Regulatory Agency (MHRA) for the adverse drug reaction.

Discussion

Myopathy and myoglobulinuria are rare with the use of simvastatin, and compartment syndrome needing fasciotomies is extremely rare. There are two reported cases of this phenomenon, one occurring in a patient with schizophrenia on risperidone and simvastatin¹ and the second in a patient on simvastatin alone.² It was postulated in the first case that there was an effect on the cytochrome P450 enzymes leading to elevated drug levels. There is also an association with the use of simvastatin for hypercholesterolaemia in hypothyroidism causing myositis.³,⁴ There has also been a report of myopathy and rhabdomyolysis in a patient with hypothyroidism, diabetes mellitus and hypertension.⁵

With the increased worldwide use of this drug and its approval for all arteriopathic patients it is likely that this complication will be seen more often. We present this case for our fellow physicians to be more vigilant with monitoring for myonecrosis and particularly compartment syndrome when prescribing this drug.

Figure 1 Fasciotomies for simvastatin induced compartment syndrome showing myonecrosis. Informed consent was obtained for publication of this figure.