Abstract
Introduction
Rhabdomyolysis is a syndrome characterized by muscle necrosis and the release of intracellular muscle constituents, namely myoglobin, creatine kinase (CK), aldolase, lactate dehydrogenase (LDH), aspartate aminotransferase, and potassium into the circulation. 1 It manifests as limb weakness, myalgia, swelling, and gross pigmenturia without hematuria. CK levels are typically elevated at least fivefold or greater above the upper threshold of normal. Myoglobinuria may be present. The severity of illness ranges from asymptomatic elevations in serum muscle enzymes to life-threatening disease associated with electrolyte imbalances and acute kidney injury. Causes of rhabdomyolysis can be classified as traumatic or compression and non-traumatic, which include electrolyte imbalance, endocrinopathy, infections, toxic, heavy exercise, heat exposure and seizures. 2
Case report
A 24-year-old Indian man presented with a history of choking sensation on-and-off for one day with no associated chest pain, palpitations or diaphoresis. He also complained of lethargy, lower backache and facial swelling lasting two weeks. He denied any recent trauma or muscle ache and strenuous activity prior to this. He had no significant past medical history, was not on any regular medication including traditional herbal medicines and did not consume alcohol. He had no family history of thyroid or autoimmune conditions. He had no cold intolerance, dry skin, depression, weight gain or constipation.
On examination, the patient was afebrile with a pulse rate of 80 beats per minute and blood pressure was 120/80 mmHg. He had mild facial puffiness when compared to his identity card (IC) photo, and a diffuse, non-tender thyroid gland measuring 2 × 2 cm. Cardiovascular, respiratory and abdominal examination was normal. There were no signs of proximal myopathy or neurological deficits. There were no features to suggest hypothyroidism, namely dry skin, coarse facies, brittle hair, alopecia, loss of lateral third of eyebrows, bradycardia, delay in relaxation phase of deep tendon reflexes or hoarse voice.
The blood investigations (Table 1) were suggestive of rhabdomyolysis with a significantly raised serum CK: 9318 U/l, CK-MB: 93.8 UG/l, troponin T: 0.04 U/l, aldolase: 33.6 U/l, alanine transaminase: 101 U/l, aspartate transaminase: 261 U/l and LDH: 1945 U/l. This was associated with acute kidney injury, with a raised creatinine at 129 Umol/l. Serum electrolytes were normal.
Patient laboratory values.
CK: creatine kinase; LDH: lactate dehydrogenase; FT4: free thyroxine; TSH: thyroid-stimulating hormone; TPO: thyroid peroxidase; AST: aspartate aminotransferase; ALT: alanine aminotransferase.
The urine myoglobin was less than 21. On further investigations he had a free T4 <3.2 pmol/l with markedly elevated thyroid-stimulating hormone (TSH) at 243 MU/l. Subsequent tests were suggestive of Hashimoto’s thyroiditis with raised thyroid peroxidase antibodies (8329 U/l) and positive anti-thyroglobulin antibody.
He was treated with aggressive hydration and started on Levothyroxine, causing a fall in rhabdomyolysis markers and resolution of his symptoms prior to discharge. Further tests to exclude muscle disease were therefore not deemed necessary. Two months later at follow-up he was well and compliant on Levothyroxine. The repeat creatinine, CK and transaminases were completely normal.
Discussion
Hypothyroidism, a common endocrine disorder, is well known to be associated with musculoskeletal problems including myopathy. Roughly a third of patients with hypothyroidism present with proximal muscle weakness, pain, stiffness or cramps. Additional risk factors for myopathy include advancing age, diabetes mellitus, liver disease, renal impairment, and alcoholism. Rhabdomyolysis due to hypothyroidism is, however, very rare. There have been very few case reports of hypothyroidism causing rhabdomyolysis,1–6 but in most of them, a precipitating factor like exercise, trauma, drugs, most commonly statins or alcohol, had been identified. 4
The present case describes a patient with rhabdomyolysis due to undiagnosed hypothyroidism and no precipitating factors. He had no significant past medical history, was not on any long-term medication, and did not consume alcohol. There was no history of recent trauma or strenuous activities.
He presented with generalized weakness but there was no clinical evidence of proximal myopathy. The very high CK level prompted the workup for rhabdomyolysis, which was confirmed by the high LDH, aldolase, creatinine and aminotransferases. There was no myoglobinuria, which, however, does not exclude the diagnosis, since myoglobin is rapidly cleared from the plasma through renal excretion and metabolized to bilirubin.
Myoglobin levels may return to normal within six hours after the onset of muscle injury. In one study, only 19% of patients with rhabdomyolysis had myoglobinuria. 5
Of note, our patient had no clinical features of hypothyroidism except for the mild facial puffiness, despite the severe biochemical abnormality. However, in the absence of an obvious cause for the rhabdomyolysis, namely inflammatory myopathies, congenital deficiency of muscular enzymes, trauma, infection, electrolyte disorders, drugs and toxins, hypothyroidism was considered in the diagnosis, and this was confirmed by the blood tests. Some patients with hypothyroidism may have no symptoms at all, or they are just so subtle that they go unnoticed. We postulate that this could be due to the normal circulating unbound T3 levels found in about 25% of patients, from adaptive deiodinase (the enzyme which is responsible for converting T4 to T3) responses to hypothyroidism. Hence we wish to emphasize the importance of keeping in mind this diagnosis even if there are no clinical features.
The cause of rhabdomyolysis in hypothyroidism is unclear. Various hypotheses including impaired mitochondrial oxidative metabolism, 6 induction of insulin-resistant state, 7 and decreased muscle carnitine levels including autoimmune mechanism, 8 have been proposed. Thyroxine affects energy metabolism and its deficiency leads to abnormal glycogenolysis, mitochondrial oxidative metabolism and triglyceride turnover, which impair muscle function by causing a switch of fast-twitching type 2 muscle fibers to slow-twitching type 1 fibers, low myosin ATPase activity and low adenosine triphosphate (ATP) turnover in skeletal muscle. 9
The fact that the degree of weakness often does not correlate with the biochemical severity of hypothyroidism suggests that muscle injury, rather than impaired muscle function alone, plays a prominent role in some patients. 10
Conclusion
Although hypothyroidism is a rare cause of rhabdomyolysis, it should be suspected in patients presenting with muscle aches and very high CK concentrations in the absence of other, more common causes of rhabdomyolysis, even in the absence of its clinical features. As soon as the diagnosis is made, hydration and thyroid hormone replacement should be promptly instigated, as this will lead to complete recovery. Patients with newly diagnosed hypothyroidism should be advised to avoid factors which may precipitate rhabdomyolysis, namely vigorous exercise, alcohol, and drugs such as high-dose statins.