In a 35‑year‑old woman with new‑onset fatigue, generalized weakness and fluctuating ptosis over a few days, and a history of Hashimoto’s thyroiditis, what is the most likely diagnosis and how should it be managed in a primary‑care setting?

Myasthenia Gravis: Diagnosis and Primary Care Management

Most Likely Diagnosis

This patient most likely has myasthenia gravis (MG), an autoimmune neuromuscular junction disorder that commonly presents with fluctuating ptosis and generalized weakness, and is strongly associated with other autoimmune conditions like Hashimoto's thyroiditis. 1

The clinical presentation is classic for MG:

• Ptosis developing over days is often the first symptom, characteristically worsening with fatigue and prolonged upgaze 1
• Generalized fatigue and weakness that fluctuates and worsens with activity is the hallmark of neuromuscular junction pathology 1
• Hashimoto's thyroiditis history is significant, as MG frequently co-occurs with other autoimmune diseases including thyroid disease 1
• Stable vitals argue against acute thyroid storm or myxedema coma from her known thyroid condition 2

Critical Initial Assessment in Primary Care

Before proceeding with diagnostic workup, immediately assess for respiratory involvement—this is life-threatening and the most critical pitfall to avoid. 1, 3

Red Flag Screening (Perform Immediately):

• Ask about dysphagia and aspiration risk—severe dysphagia signals impending myasthenic crisis 1
• Assess respiratory function: Ask about shortness of breath with exertion, difficulty taking deep breaths, or orthopnea 1
• Check for bulbar symptoms: Slurred speech (dysarthria), difficulty chewing, nasal voice 1
• Examine neck strength: Ask patient to lift head from supine position—neck drop indicates generalized disease requiring urgent referral 3

If any respiratory symptoms are present, this requires same-day emergency referral or ED evaluation for pulmonary function testing (vital capacity, negative inspiratory force). 3

Diagnostic Workup in Primary Care

First-Line Serologic Testing:

Order acetylcholine receptor (AChR) antibody testing—this is the gold standard serological test with 80-88% sensitivity for generalized MG and 98-100% specificity. 4

• AChR antibodies are present in nearly all patients with generalized MG 1
• If negative, approximately one-third of seronegative patients will have muscle-specific kinase (anti-MuSK) antibodies 5, 4
• Lipoprotein-related protein 4 (LRP4) antibodies should also be tested in seronegative cases 5

Bedside Clinical Tests:

Perform the ice pack test: Apply ice pack over closed eyes for 2 minutes—improvement in ptosis is highly specific for MG 4, 3

Assess for fatigability: Have patient maintain prolonged upgaze for 60 seconds and look for worsening ptosis or Cogan lid-twitch sign 1, 3

Additional Testing:

• Thyroid function tests (TSH, free T4): Rule out hypothyroidism from Hashimoto's as contributing factor, though her stable vitals make acute thyroid dysfunction less likely 2
• CPK and aldolase: Should be normal in MG; elevation suggests concurrent myositis (which can co-occur, especially with immune checkpoint inhibitor exposure) 1

Immediate Referrals Required

Refer urgently to neurology for same-week evaluation—early recognition and treatment prevent progression to respiratory failure. 1

Order chest CT to screen for thymoma once diagnosis is suspected—present in 10-15% of MG patients and requires different management including possible thymectomy. 1, 4

Initial Treatment Approach

While Awaiting Neurology Consultation:

Do NOT initiate treatment in primary care—management requires neurologist expertise for proper medication selection and dosing. 5

However, you should:

• Educate patient about fluctuating symptoms and importance of rest 1
• Provide medication safety counseling: Avoid beta-blockers, IV magnesium, fluoroquinolones, aminoglycosides, and macrolide antibiotics—these can precipitate myasthenic crisis 1
• Instruct patient to seek emergency care immediately if they develop difficulty swallowing, breathing problems, or severe weakness 1

Expected Neurologist Management:

Once diagnosis is confirmed, neurologist will typically initiate:

• Pyridostigmine bromide (oral, 2-4 times daily) as first-line treatment, though only 50% of patients with ocular symptoms respond 5
• Corticosteroids show positive response in 66-85% of patients 5
• Immunosuppressive therapy (azathioprine or other agents) may be needed 5
• Thymectomy is indicated if thymoma is present and may reduce symptoms substantially 5

Key Clinical Pitfalls to Avoid

Never assume symptoms are solely from thyroid disease—while Hashimoto's can cause fatigue, it does not cause ptosis or fluctuating weakness. 6, 7

Pupils should be normal in MG—if pupils are affected, consider third nerve palsy or other diagnoses instead. 1

Do not delay referral waiting for antibody results—clinical suspicion alone warrants urgent neurology evaluation given risk of progression. 1

Failure to recognize early respiratory involvement can be fatal—all grades of MG warrant thorough evaluation for potential respiratory compromise. 1

Screen for concurrent myocarditis or myositis if patient has elevated CPK or any cardiac symptoms—obtain troponin, ECG, and consider echocardiography. 1