What are the diagnostic steps for hypothyroidism?

Diagnosing Hypothyroidism

The diagnosis of hypothyroidism requires measuring TSH and free T4 levels, with a high TSH and normal or low free T4 confirming the diagnosis. 1

Diagnostic Algorithm

Step 1: Laboratory Testing

• Initial test: Measure serum TSH
• Follow-up test: Measure free T4 (FT4)
• If TSH is elevated and FT4 is normal or low, repeat both tests in 2 weeks to 3 months to confirm the diagnosis 2

Step 2: Interpretation of Results

• Overt hypothyroidism: Elevated TSH + Low free T4
• Subclinical hypothyroidism: Elevated TSH + Normal free T4 1

Step 3: Additional Testing (When Indicated)

• Anti-thyroid peroxidase (anti-TPO) antibodies may be considered to identify autoimmune etiology, though evidence is insufficient to recommend routine measurement 2
• TRH stimulation test may be used to differentiate between pituitary and hypothalamic causes in suspected central hypothyroidism 3

Important Clinical Considerations

Diagnostic Pitfalls

• A single abnormal TSH value is insufficient for diagnosis; serial measurements are essential 2
• TSH levels can vary by up to 50% on a day-to-day basis 2
• Physical examination alone has poor diagnostic accuracy for hypothyroidism (positive likelihood ratios range from 1.0 to 3.88) 4
• TSH secretion varies among different populations based on age, race/ethnicity, and sex 2
• TSH can be affected by:
  • Acute illness (often suppressed)
  • Medications (iodine, dopamine, glucocorticoids, octreotide, bexarotene)
  • Pregnancy (especially first trimester)
  • Other conditions (adrenal insufficiency, anorexia nervosa, pituitary disorders) 2

Classification of Hypothyroidism

• Primary hypothyroidism (most common): Thyroid gland failure
  • Clinical: Elevated TSH + Low free T4
  • Subclinical: Elevated TSH + Normal free T4
• Secondary (central) hypothyroidism: Pituitary or hypothalamic failure
  • Low/normal TSH + Low free T4 3, 1

Common Causes of Hypothyroidism

• Chronic autoimmune thyroiditis (Hashimoto's) - most common cause
• Radioiodine treatment
• Thyroidectomy
• Iodine deficiency or excess
• Medications (amiodarone, lithium, tyrosine kinase inhibitors) 3

Monitoring Considerations

• For primary hypothyroidism: Monitor TSH levels
• For central hypothyroidism: Monitor free T4 and T3 concentrations (TSH cannot be used) 5
• TSH and free T4 should be monitored every 6-8 weeks during treatment adjustments 1

Clinical Implications

• Untreated hypothyroidism can lead to serious complications including myxedema coma, cardiovascular disease, and increased mortality 1
• In pregnancy, untreated hypothyroidism increases risk of preeclampsia, preterm delivery, and miscarriage 1
• Subclinical hypothyroidism may progress to overt hypothyroidism at a rate of 2.6-4.3% per year 2

Remember that while physical examination findings (coarse skin, puffy face, slow movements, bradycardia, pretibial edema, delayed ankle reflexes) may suggest hypothyroidism, they cannot reliably confirm or rule out the diagnosis without laboratory testing 4.