Can methimazole (antithyroid medication) cause leg weakness or propylthiouracil (PTU) (thyroid inhibitor) cause skin breakouts?

Antithyroid Drug Side Effects: Methimazole and Propylthiouracil

Direct Answer

Neither leg weakness nor skin breakouts are characteristic or commonly reported adverse effects of methimazole or propylthiouracil based on current clinical evidence. However, PTU can cause skin rashes (pruritus and rash are well-documented), while methimazole has been rarely associated with myositis that could theoretically present with muscle weakness 1, 2, 3.

Methimazole and Leg Weakness

Methimazole does not typically cause leg weakness as a recognized adverse effect. The established side effects of methimazole include:

• Common adverse effects: Dose-dependent hypothyroidism, pruritus, and rash 1
• Rare but serious effects: Agranulocytosis (0.11% of exposed patients), hepatotoxicity (0.03%), aplastic anemia, and arthralgias (1-5% of patients) 1, 4, 5
• Very rare musculoskeletal effects: Methimazole-induced myositis has been reported in isolated case reports, which could theoretically manifest as muscle weakness, but this is an exceptionally rare occurrence occurring independently of lupus-like syndrome or ANCA-associated vasculitis 3

Important caveat: If a patient on methimazole develops leg weakness, consider:

• Uncontrolled hyperthyroidism itself (thyrotoxic myopathy presents with proximal muscle weakness) 3
• Rare methimazole-induced myositis (would typically be accompanied by myalgia, elevated creatine kinase, and eosinophilia) 3
• Other unrelated causes of weakness

Propylthiouracil (PTU) and Skin Breakouts

Yes, PTU can cause skin breakouts—this is a well-documented adverse effect. PTU-associated dermatologic reactions include:

• Common skin reactions: Pruritus and rash are recognized adverse effects of PTU 1, 2
• Management approach: When rash or itching develops with PTU, switching to methimazole is one treatment option (though cross-reactivity between the two drugs can occur in some cases) 1, 2
• Serious dermatologic manifestations: PTU can rarely cause ANCA-positive vasculitis with cutaneous involvement, though this typically occurs only after long-term exposure (ROR 29.84 times higher for PTU than methimazole) 1, 5

Comparative Safety Profile

Both antithyroid drugs share similar common adverse effects, but differ in their serious complications:

• Agranulocytosis: More common with PTU (0.27%) than methimazole (0.11%), typically occurring within the first 3 months of treatment 4, 5
• Hepatotoxicity: PTU carries higher risk of severe, even lethal liver injury (particularly in children and adolescents), while methimazole has lower hepatotoxicity risk 1, 4
• Skin reactions: Both drugs cause pruritus and rash, with potential cross-reactivity when switching between them 1, 2
• ANCA-associated vasculitis: Strongly associated with PTU (29.84-fold higher ROR) compared to methimazole 5

Clinical Monitoring Recommendations

Patients on either antithyroid drug should be counseled to immediately seek medical attention if they develop:

• Fever, sore throat, or malaise (potential agranulocytosis) 6, 1
• Abdominal complaints or jaundice (potential hepatotoxicity) 1
• New rash or skin lesions (dermatologic reactions) 1
• Arthralgias (may herald more serious immunologic complications and warrant drug discontinuation) 1

Routine monitoring should include:

• Thyroid function testing every 2-4 weeks initially, then every trimester once stable 6
• Baseline and periodic liver function tests, especially with PTU 1
• Clinical surveillance for the adverse effects listed above 6, 1