What is the next step in managing a patient with hyperthyroidism on 50mg of propylthiouracil (PTU) who presents with tiredness, hypotension, and bradycardia, despite normal Thyroid-Stimulating Hormone (TSH) and free triiodothyronine (FT3) levels?

Immediate Discontinuation of Propylthiouracil and Evaluation for Drug-Induced Hypothyroidism

Stop propylthiouracil immediately and check free T4 levels, as the patient's symptoms of tiredness, hypotension, and bradycardia strongly suggest iatrogenic hypothyroidism despite normal TSH and FT3, which can occur when PTU overdoses the thyroid or causes direct cardiac/systemic toxicity. 1

Critical Assessment of Current Clinical Picture

This presentation is highly concerning for PTU-induced complications affecting multiple organ systems:

• Tiredness combined with hypotension and bradycardia are classic signs of hypothyroidism, even when TSH has not yet risen due to the lag time in pituitary response 2
• PTU can cause direct hepatotoxicity presenting as tiredness, which the FDA specifically warns about as an early symptom requiring immediate drug discontinuation 1
• The cardiovascular manifestations (hypotension and bradycardia) are opposite to what hyperthyroidism causes, indicating the patient has been rendered functionally hypothyroid 2

Immediate Diagnostic Steps Required

Obtain the following labs urgently:

• Free T4 level - TSH lags behind actual thyroid status by weeks, and normal TSH with normal FT3 does not exclude hypothyroidism if free T4 is low 2
• Comprehensive metabolic panel with liver function tests (ALT, AST, bilirubin, alkaline phosphatase) - PTU causes hepatotoxicity in up to 0.1-0.5% of patients, with tiredness as an early warning sign 1
• Complete blood count with differential - to rule out agranulocytosis, another serious PTU complication that presents with tiredness and malaise 2, 1
• Morning cortisol level - hypotension and tiredness could indicate adrenal insufficiency, which must be ruled out before any thyroid hormone adjustment 3

Why Normal TSH and FT3 Don't Exclude the Problem

The normal TSH is misleading in this acute setting:

• TSH takes 6-8 weeks to equilibrate after changes in thyroid hormone levels, so it reflects the patient's status from weeks ago, not their current state 3
• PTU inhibits peripheral conversion of T4 to T3, which can maintain normal or even elevated T3 levels while T4 drops dangerously low 4, 5
• Some patients paradoxically maintain normal T3 despite low T4 on PTU due to increased thyroid deiodinase activity, making T3 an unreliable marker 4

Immediate Management Algorithm

Follow this sequence:

1. Discontinue PTU immediately - do not wait for lab confirmation given the concerning clinical presentation 1

2. If free T4 comes back low (below reference range):

   • Start levothyroxine 25-50 mcg daily if patient is elderly or has cardiac disease 3
   • Start levothyroxine 1.6 mcg/kg/day if patient is young and healthy 3
   • Critical: Rule out adrenal insufficiency FIRST - if morning cortisol is low, start hydrocortisone before levothyroxine to avoid precipitating adrenal crisis 3, 1

3. If liver enzymes are elevated (ALT/AST >3x upper limit of normal):

   • This represents PTU-induced hepatotoxicity requiring permanent discontinuation 1, 6
   • Switch to methimazole only after liver function normalizes, or consider radioactive iodine or surgery 2, 1
   • Monitor liver function weekly until normalized 1, 6

4. If white blood cell count is low (<1,500 neutrophils):

   • This represents agranulocytosis requiring immediate hospitalization 2, 1
   • Never restart PTU - switch to alternative therapy 2

Alternative Antithyroid Management

Once PTU is discontinued, consider these options:

• Methimazole 10-20 mg daily - safer alternative with lower risk of hepatotoxicity, though contraindicated in first trimester pregnancy 2, 1
• Beta-blocker therapy (propranolol 10-40 mg three times daily) - to control cardiovascular symptoms while awaiting definitive therapy 2
• Radioactive iodine ablation - definitive treatment if patient is not pregnant and has no contraindications 2
• Thyroidectomy - reserved for patients who cannot tolerate medical therapy or have failed other treatments 2

Critical Pitfalls to Avoid

• Never continue PTU when tiredness develops - this is the FDA's primary warning sign for hepatotoxicity that can progress to liver failure and death 1
• Never assume normal TSH means adequate thyroid function in a patient on antithyroid drugs - TSH lags clinical status by weeks 3
• Never restart PTU after hepatotoxicity or agranulocytosis - these are absolute contraindications to rechallenge 1
• Never start levothyroxine before ruling out adrenal insufficiency - this can precipitate life-threatening adrenal crisis 3, 1

Monitoring After PTU Discontinuation

Recheck thyroid function and liver enzymes in 2 weeks:

• If hypothyroid, titrate levothyroxine to achieve TSH 0.5-4.5 mIU/L 3
• If still hyperthyroid after PTU washout, initiate methimazole or definitive therapy 2
• Monitor liver function until completely normalized if hepatotoxicity was present 1, 6