DESTIN, FLA. – Myopathy that occurs following initiation of statin therapy certainly may result from the drug, but don’t be too quick to rule out other causes.
In one case described by Dr. Robert Wortmann at the Congress of Clinical Rheumatology, the problem was actually profound hypothyroidism.
The 58-year-old patient, a physician who presented with muscle weakness of 6 months’ duration, had started taking a statin 1 month prior as treatment for hyperlipidemia. The patient’s creatine phosphokinase (CPK) values ranged from 1,100 to 1,500 U/L, and both the muscle weakness and CPK elevations persisted at 3 months after discontinuation of the statin.
Dr. Robert Wortmann
Statins, as well as fibric acid derivatives and niacin, are important considerations in patients with myopathic symptoms. They can be associated with asymptomatic "hyper-CPK-emia"; transient myalgia and cramps with increased or normal CPK levels; persistent myalgia and cramps or weakness with increased or normal CPK levels; and rhabdomyolysis with myoglobinuria, renal failure, and, when these are unrecognized and untreated, death, said Dr. Wortmann, professor of medicine at Dartmouth Medical School, Lebanon, N.H.
Statin myopathies can occur due to various triggers.
"We know that when you take a statin and interfere with cholesterol synthesis, you can interfere with membrane formation, and this can lead to specific membrane effects and damage and myopathy," he explained, adding that certain genetic polymorphisms – particularly those associated with statin metabolism – also seem to put some people at greater risk for statin myopathies, as does the unmasking of underlying metabolic disorders by statins in some patients.
A particularly interesting statin myopathy is immune-mediated necrotizing myopathy, Dr. Wortmann said.
This potentially painful and debilitating myopathy appears to be associated with anti-HMG CoA reductase antibodies, and it is believed to be immune mediated because it responds to immunosuppressive therapy, he noted.
Patients with this necrotizing myopathy typically require multiple drugs given simultaneously to control the disease.
In the case presented by Dr. Wortmann, however, the problem was much simpler.
"I share this with you because I walked right by this. This was my mistake," he said, explaining that he had arranged for the physician to undergo an electromyogram and muscle biopsy.
"Fortunately, he went and saw his primary care physician again before we could get those done, [who] checked his [thyroid stimulating hormone] and it was way up there. He treated the hypothyroidism, his CPK went back to normal, his muscle symptoms went away, and he was continued on his statin," Dr. Wortmann said.
The most common musculoskeletal manifestation of hypothyroidism is carpal tunnel syndrome, but it can also be associated with sensory or sensorimotor polyneuropathy, asymptomatic hyper-CPK-emia, and myopathy. Myopathy is usually proximal, and may involve myalgias and cramps, with normal or high CPK levels, he noted, adding that although one older case report involved a patient with levels as high as 21,000 U/L, most are in the 700- to 1,200-U/L range.
"So hypothyroidism is a good thing to screen for if you see someone with muscle weakness, because if you pick it up, it’s easy [to manage]," he said. "The take-home message is that just because you see a patient who’s taking a drug [then] experience a side effect that may be found from that drug, it doesn’t mean that’s where it’s coming from."
Dr. Wortmann reported that he had no financial conflicts of interest that were relevant to his presentation.