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Difficulty: HardFormulating a Differential Diagnosis

A 55-year-old woman presents to the clinic complaining of generalized weakness, muscle aches, and difficulty climbing stairs that has progressively worsened over the past three months. She also notes increasing fatigue, a 4-kg (8.8-lb) weight gain, and persistent constipation during this time. Two weeks ago, she was diagnosed with a mild upper respiratory infection and completed a 5-day course of azithromycin. Her chronic medical conditions include hypertension and hyperlipidemia, for which she takes amlodipine and rosuvastatin. She has been on both of these daily medications for four years without any recent dose adjustments. Vital signs show a blood pressure of 132/84 mm Hg, heart rate of 56/min, respiratory rate of 14/min, and temperature of 36.4°C (97.5°F). Physical examination reveals 4/5 muscle strength in the bilateral deltoids and hip flexors. Deep tendon reflexes are 1+ at the patella and Achilles, demonstrating a noticeably delayed relaxation phase. The remainder of the physical examination is unremarkable. Laboratory studies reveal a serum creatine kinase (CK) level of 1,850 U/L and a normal serum creatinine. Which of the following is the most likely underlying cause of this patient's findings?

  1. Hypothyroid myopathyAnswer
  2. B
    Primary statin-induced myonecrosis
  3. C
    CYP3A4 inhibitor-induced statin toxicity
  4. D
    Polymyositis
  5. E
    Polymyalgia rheumatica

Answer

Hypothyroid myopathy
The correct diagnosis is hypothyroid myopathy. This patient's presentation of proximal muscle weakness, myalgias, and an elevated creatine kinase (CK) level requires a broad differential. However, the accompanying systemic symptoms—fatigue, weight gain, constipation, and bradycardia—strongly point toward a hypometabolic state. The physical examination finding of a delayed relaxation phase in the deep tendon reflexes (Woltman sign) is highly specific for severe hypothyroidism. Hypothyroidism frequently causes a secondary myopathy characterized by elevated CK levels and proximal weakness.

Step-by-Step Solution

1
Analyze the musculoskeletal and laboratory findings.
The patient has progressive proximal muscle weakness, myalgias, and a significantly elevated creatine kinase (CK) level.
This establishes the presence of a primary myopathy with muscle breakdown, requiring a broad differential including inflammatory, toxic/drug-induced, and endocrine etiologies.
2
Evaluate the timeline and medication history to assess for drug-induced causes.
The patient takes rosuvastatin, but has tolerated it for 4 years. The recent addition of azithromycin does not create a significant pharmacokinetic interaction because azithromycin lacks strong CYP3A4 inhibition, and rosuvastatin is not heavily CYP3A4-dependent.
This makes a sudden, drug-interaction-induced statin myotoxicity highly unlikely.
3
Synthesize the systemic physical examination and vital sign abnormalities.
The patient exhibits bradycardia (HR 56/min), weight gain, constipation, and deep tendon reflexes with a delayed relaxation phase (Woltman sign).
These are classic, definitive systemic signs of a hypometabolic state, specifically identifying hypothyroidism as the unifying cause of the myopathy and elevated CK.

Key Concept

Formulating an accurate differential diagnosis for myopathy requires synthesizing systemic physical exam findings (like delayed reflex relaxation and bradycardia) to distinguish endocrine etiologies (hypothyroidism) from toxic/pharmacologic or inflammatory causes.
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Formulating a Differential Diagnosis

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