Asymptomatic hypothyroidism and statin-induced myopathy

Discussion

We describe a case of hypothyroidism-induced dyslipidemia that illustrates a few important points.

First, hypothyroidism, even when profound, might be nearly asymptomatic. Despite the fact that our patient had a thyroid-stimulating hormone level higher than 100 mU/L, he did not have classic hypothyroid symptoms, although he recognized some drowsiness and muscle wasting retrospectively.

Second, use of statins in hypothyroid patients is dangerous. Although the biochemical mechanism of both hypothyroid myopathy and SIM remain unclear, hypothyroidism increases the risk of SIM.3,4 With respect to the mechanism of hypothyroid myopathy, some have hypothesized that defects in glycogenolysis or impaired mitochondrial oxidation are responsible.6 Theories for the cause of SIM include reduction in small guanosine 5’-triphosphate–binding proteins and reduced cholesterol synthesis causing skeletal myocyte membrane instability.10 Presumably, these mechanisms are synergistic when statins are prescribed to hypothyroid patients. Generally, myopathy is more likely to occur at higher statin doses.11 Other lipid-lowering medications, such as fibrates and even ezetimibe, an inhibitor of intestinal cholesterol absorption, can cause myopathy.12

Third, although the patient’s initial response to rosuvastatin monotherapy was good (Table 1), in our experience, hypothyroidism-induced dyslipidemia sometimes is resistant to lipid-lowering therapy. This is true whether a patient has an underlying primary dyslipidemia that is exacerbated by hypothyroidism or a purely secondary dyslipidemia. Although all patients should be assessed for hypothyroidism and, if necessary, treated to attain a euthyroid state before beginning statin therapy, the unfortunate reality is that many are not. Thus, for patients in whom biochemical responses to lipid-lowering therapy are suboptimal, the history should be reviewed to see whether thyroid status has in fact been previously evaluated. Further, if a patient’s dyslipidemia gets worse without apparent cause or he or she develops SIM unexpectedly, hypothyroidism should be considered.

Next, the case demonstrates that patients must report the development of muscle pains to their physicians. It also shows that biochemical testing is imperative in patients with possible myopathic symptoms. The Adult Treatment Panel III of the National Cholesterol Education Program13 and the ACC/AHA/NHLBI Clinical Advisory on the Use and Safety of Statins11 recommend that a baseline CK measure be established before initiating statin therapy and that CK be remeasured and compared with the baseline if patients report any muscle symptoms. More frequent measurements of CK and transaminases might be indicated among patients receiving maximal doses of medications and those receiving combination therapy, typically with fibrates.

Finally, statins are not necessarily contraindicated in patients who have developed SIM while hypothyroid.10,14 However, caution must be exercised with reinitiating statin therapy in this context, and patients should always be instructed that, if muscle pains or flulike symptoms develop, the statin should be immediately discontinued and their physicians contacted.