What is the next step in workup for a patient with elevated Thyroid-Stimulating Hormone (TSH) to diagnose hypothyroidism?

Workup for Elevated TSH to Diagnose Hypothyroidism

When a patient presents with elevated TSH, you should measure free T4 to distinguish between subclinical hypothyroidism (normal free T4) and overt hypothyroidism (low free T4). 1

Initial Diagnostic Testing

• Confirm elevated TSH with repeat testing after 3-6 weeks, as 30-60% of high TSH levels normalize on repeat testing 1
• Measure both TSH and free T4 to establish the diagnosis and determine severity 1, 2
• Consider testing for anti-TPO antibodies to identify autoimmune thyroiditis as the cause, which helps predict risk of progression to overt hypothyroidism 1, 3
• If TSH is undetectable and free T4 is normal, obtain a T3 level to evaluate for T3 toxicosis 4, 2
• Low TSH with low free T4 suggests central hypothyroidism, which requires evaluation for pituitary or hypothalamic disease 1, 5

Management Based on TSH Levels

For TSH >10 mIU/L:

• Initiate levothyroxine therapy regardless of symptoms 1, 6
• This level carries a higher risk of progression to overt hypothyroidism (approximately 5% per year) 1, 6
• Treatment prevents complications of hypothyroidism in patients who progress 1

For TSH 4.5-10 mIU/L with normal free T4:

• Consider treatment for symptomatic patients 1, 6
• Consider treatment for patients with infertility, goiter, or positive anti-TPO antibodies 6
• Monitor thyroid function every 6-12 months in asymptomatic patients without treatment 1, 5
• Always treat pregnant women or those planning pregnancy 1, 5, 6

Levothyroxine Dosing Guidelines

• For patients <70 years without cardiac disease or multiple comorbidities: 1.6 mcg/kg/day 4, 1
• For patients >70 years or with cardiac disease/multiple comorbidities: Start with 25-50 mcg/day and titrate gradually 4, 1
• Target TSH within the reference range (0.5-2.0 mIU/L) for primary hypothyroidism 1, 6
• Monitor TSH every 6-8 weeks while titrating hormone replacement 4, 1
• Once adequately treated, repeat testing every 6-12 months or if symptoms change 4, 1

Common Pitfalls to Avoid

• Failing to confirm elevated TSH with repeat testing before initiating treatment 1
• Undertreatment leading to persistent hypothyroid symptoms and adverse effects on cardiovascular function, lipid metabolism, and quality of life 1
• Overtreatment resulting in iatrogenic hyperthyroidism, which increases risk for osteoporosis, fractures, abnormal cardiac output, and ventricular hypertrophy 1
• Failing to recognize transient hypothyroidism, which may lead to unnecessary lifelong treatment 1
• Starting thyroid hormone replacement before ruling out adrenal insufficiency in patients with suspected central hypothyroidism 1, 6
• Adjusting doses too frequently before reaching steady state (should wait 6-8 weeks between adjustments) 1

Special Considerations

• In pregnancy: More aggressive normalization of TSH is warranted due to risks of adverse pregnancy outcomes 1, 6
• In elderly patients: Consider age-specific reference ranges and more conservative treatment approaches 1, 7
• In patients with cardiac disease: Use smaller dose increments (12.5 mcg) to avoid potential cardiac complications 1
• In patients with persistent symptoms despite normalized TSH: Consider checking free T4 to help interpret ongoing abnormal TSH levels, as TSH may take longer to normalize 4, 1