What is the initial test to diagnose hypothyroidism?

Diagnosing Hypothyroidism

The initial test to diagnose hypothyroidism is a thyroid-stimulating hormone (TSH) test, which has high sensitivity (98%) and specificity (92%) for detecting thyroid dysfunction. 1

Diagnostic Algorithm

1. First-line testing:

   • Measure serum TSH level
   • If TSH is elevated (>6.5 mU/L), proceed to step 2
   • Normal TSH (within reference range) generally rules out primary hypothyroidism

2. Second-line testing:

   • Measure free T4 (thyroxine) level
   • Interpretation:
     • Elevated TSH + Low free T4 = Overt (primary) hypothyroidism
     • Elevated TSH + Normal free T4 = Subclinical hypothyroidism 1, 2

3. Additional testing (when indicated):

   • Measure T3 (triiodothyronine) if TSH is undetectable and free T4 is normal 3
   • Consider thyroid autoantibodies (anti-TPO, anti-thyroglobulin) to confirm autoimmune etiology (Hashimoto's thyroiditis) 2

Interpretation of Results

Condition	TSH	Free T4	Diagnosis
Subclinical Hypothyroidism	Elevated	Normal	Mild hypothyroidism
Overt Hypothyroidism	Elevated	Low	Severe hypothyroidism
Subclinical Hyperthyroidism	Low	Normal	Mild hyperthyroidism
Overt Hyperthyroidism	Low	Elevated	Severe hyperthyroidism

1

Clinical Context

• Hypothyroidism affects up to 5% of the general population, with another estimated 5% being undiagnosed 4
• Hashimoto's thyroiditis (autoimmune) is the cause of primary hypothyroidism in up to 85% of patients in iodine-sufficient areas 2
• Common symptoms include fatigue (68-83%), weight gain (24-59%), cognitive issues (45-48%), and menstrual irregularities (23%) 2

Important Considerations and Pitfalls

• Timing of testing: TSH exhibits diurnal variation; morning samples are preferred 5
• Biotin interference: Supplements containing biotin can interfere with assay results, causing either under or overestimation 1
• Population factors: Age, sex, ethnicity, iodine status, and pregnancy can affect TSH reference ranges 6, 5
• Medication effects: Certain medications (amiodarone, lithium, immune checkpoint inhibitors) can cause hypothyroidism 2, 6
• Central hypothyroidism: In suspected pituitary/hypothalamic dysfunction, TSH may be inappropriately normal or low; free T4 is the primary diagnostic test 3
• Non-specific symptoms: Symptoms of hypothyroidism are often non-specific, making biochemical confirmation essential 6

Monitoring Treatment

• After initiating levothyroxine, monitor TSH every 6-8 weeks until stable 2
• Once stable, monitor TSH annually to avoid overtreatment or undertreatment 2
• For central hypothyroidism, monitor free T4 and T3 concentrations rather than TSH 3

High-Risk Groups for Targeted Testing

• Women over 50 years with general symptoms
• Postpartum women
• Pregnant women and women planning pregnancy
• Patients with Down syndrome
• Individuals with high levels of radiation exposure (>20 mGy)
• Patients with type 1 diabetes 1, 2

Note that screening for hypothyroidism is not recommended for asymptomatic individuals in the general population 2.