What is the diagnostic test for hypothyroidism?

Diagnostic Testing for Hypothyroidism

Measure serum TSH as the initial and most sensitive test for diagnosing hypothyroidism, followed by free T4 measurement when TSH is elevated to distinguish between subclinical and overt disease. 1, 2

Initial Diagnostic Approach

First-Line Testing

• TSH is the primary screening test with 98% sensitivity and 92% specificity for detecting thyroid dysfunction when clinical suspicion exists 1
• Measure free T4 when TSH is abnormal to differentiate between:
  • Subclinical hypothyroidism: elevated TSH with normal free T4 3, 1
  • Overt hypothyroidism: elevated TSH with low free T4 3, 2

Critical Testing Considerations

• Never rely on a single TSH value - TSH levels vary by up to 50% day-to-day and 40% at the same time of day 3, 1
• Obtain serial TSH measurements over 3-6 months to confirm persistent abnormality before establishing a definitive diagnosis 1
• Normal TSH reference range is typically 0.4-4.5 mIU/L, though this varies by laboratory and is not based on clinical outcomes 3, 1

Additional Diagnostic Testing

Antibody Testing

• Measure anti-TPO and anti-thyroglobulin antibodies when hypothyroidism is confirmed to identify Hashimoto's thyroiditis, which causes up to 85% of primary hypothyroidism in iodine-sufficient areas 1, 2
• In children with type 1 diabetes, measure thyroid antibodies shortly after diabetes diagnosis 1

Special Populations

• In pregnancy: measure both TSH and free T4 when hypothyroidism is suspected 3, 1
• In older adults (>80 years): recognize that 12% have TSH >4.5 mIU/L without thyroid disease, making standard reference ranges potentially inappropriate 3, 1

Important Confounding Factors to Exclude

Before confirming hypothyroidism, rule out these causes of falsely elevated TSH 3, 1:

• Recent levothyroxine dose adjustments (not at steady state)
• Recovery from acute illness or hospitalization
• Recovery from destructive thyroiditis (subacute or postpartum)
• Untreated primary adrenal insufficiency
• Medications: iodine, dopamine, glucocorticoids, octreotide, bexarotene
• Pregnancy (especially first trimester)
• Heterophilic antibodies causing assay interference

Central Hypothyroidism Exception

• When central (secondary) hypothyroidism is suspected, TSH may be low, normal, or mildly elevated with low free T4 3
• Monitor with free T4 and T3 levels rather than TSH in confirmed central hypothyroidism 4
• Consider morning ACTH and cortisol testing to evaluate for concurrent hypopituitarism 3

Common Diagnostic Pitfalls

• Avoid screening asymptomatic low-risk individuals - the prevalence of overt hypothyroidism is only 0.3% in the general population, leading to overdiagnosis and unnecessary treatment 1, 2
• Target testing to high-risk patients: those with type 1 diabetes, autoimmune diseases, prior thyroid surgery/radiation, family history, or immune checkpoint inhibitor therapy 3, 2
• Recognize that symptoms are non-specific - fatigue, weight gain, and cognitive issues occur in 23-83% of hypothyroid patients but are common in the general population, making clinical diagnosis unreliable without biochemical confirmation 2, 5