What is the diagnostic plan for hypothyroidism?

Diagnostic Plan for Hypothyroidism

The diagnostic plan for hypothyroidism should begin with measuring thyroid-stimulating hormone (TSH) as the initial test, followed by free T4 measurement if TSH is elevated to differentiate between subclinical and overt hypothyroidism. 1, 2

Initial Diagnostic Testing

• Measure TSH as the first-line test for suspected hypothyroidism 1, 3
• If TSH is elevated, measure free T4 to differentiate between subclinical hypothyroidism (normal free T4) and overt hypothyroidism (low free T4) 1, 2
• Repeat abnormal results in 2 weeks to 3 months before initiating treatment to confirm diagnosis and avoid overdiagnosis 1, 2
• Morning testing is preferred for more accurate results, especially when assessing adrenal function simultaneously 1

Interpretation of Results

• Overt primary hypothyroidism: elevated TSH with low free T4 4
• Subclinical hypothyroidism: elevated TSH (4.5-10 mIU/L) with normal free T4 1, 2
• Central hypothyroidism: low or inappropriately normal TSH with low free T4 2

Additional Testing to Consider

• Anti-thyroid peroxidase (anti-TPO) antibodies to identify autoimmune etiology (Hashimoto's thyroiditis), which predicts a higher risk of developing overt hypothyroidism (4.3% per year vs 2.6% per year in antibody-negative individuals) 1, 2
• Lipid profile testing, as hypothyroidism can affect cholesterol levels 1, 2
• If TSH is undetectable and free T4 is normal, obtain a triiodothyronine (T3) level 3

Special Considerations

• Imaging studies (thyroid ultrasound, CT, MRI, or radionuclide scans) are not indicated for the initial workup of hypothyroidism 1
• Targeted testing is recommended for high-risk individuals, such as patients with type 1 diabetes 1, 4
• For monitoring treatment adequacy in primary hypothyroidism, TSH is the most important parameter 3
• For central hypothyroidism, free T4 and T3 concentrations should be used for monitoring instead of TSH 3

Common Pitfalls to Avoid

• Relying solely on physical examination for diagnosis: No single physical sign or combination of signs can reliably diagnose hypothyroidism (positive likelihood ratios range from 1.0 to 3.88) 5
• Misdiagnosing subclinical hypothyroidism: Not all patients with TSH between 4.5-10 mIU/L require treatment, especially if asymptomatic 6, 2
• Failing to recognize euthyroid sick syndrome: Thyroid function tests may be misleading if performed during acute illness, ketosis, or significant weight loss 1
• Initiating thyroid hormone replacement before ruling out adrenal insufficiency, which can precipitate an adrenal crisis 2
• Overdiagnosis: Many persons labeled with hypothyroidism spontaneously revert to a euthyroid state over time (37% in one study) 6

Diagnostic Algorithm

1. Measure TSH in patients with symptoms suggestive of hypothyroidism or those at high risk 1, 4
2. If TSH is normal, hypothyroidism is unlikely 3
3. If TSH is elevated, measure free T4 1, 2
4. If TSH is elevated and free T4 is low, diagnose overt hypothyroidism 4
5. If TSH is elevated and free T4 is normal, diagnose subclinical hypothyroidism 1, 2
6. Confirm abnormal results with repeat testing in 2-3 months before initiating treatment 1, 2
7. Consider testing for anti-TPO antibodies to determine etiology and risk of progression 1, 2