What are the steps for diagnosing and treating hypothyroidism (underactive thyroid) using thyroid-stimulating hormone (TSH) and free thyroxine (FT4) tests?

Diagnosing and Treating Hypothyroidism Using TSH and FT4 Tests

The initial diagnostic step for suspected hypothyroidism is measuring thyroid-stimulating hormone (TSH), followed by free thyroxine (FT4) if TSH is abnormal, with treatment initiated using levothyroxine at appropriate dosages based on patient characteristics. 1, 2

Diagnostic Algorithm

Step 1: Initial Laboratory Testing

• Measure TSH as the preferred first-line test for suspected primary hypothyroidism 2
• If TSH is abnormal, proceed with free T4 measurement to further narrow the diagnosis 2
• If TSH is undetectable and free T4 is normal, obtain a triiodothyronine (T3) level 2

Step 2: Interpretation of Results

• Primary hypothyroidism: Elevated TSH with low free T4
• Subclinical hypothyroidism: Elevated TSH with normal free T4
• Central hypothyroidism: Low or normal TSH with low free T4 (requires different monitoring approach) 2

Step 3: Additional Testing Considerations

• Consider testing for thyroid peroxidase (TPO) antibodies, as they are more predictive than antithyroglobulin antibodies for future thyroid dysfunction 1
• Annual thyroid function testing (TSH and free T4) is recommended for patients with positive TPO antibodies and normal thyroid function 1

Treatment Protocol

Initiating Levothyroxine Therapy

For non-pregnant adults:

• Patients under 70 without cardiac disease:

  • Starting dose: 1.6 mcg/kg/day
  • Target TSH range: 0.5-2.0 mIU/L 1

• Elderly patients or those with cardiac conditions:

  • Starting dose: 25-50 mcg/day
  • Target TSH range: 1.0-4.0 mIU/L 1

For special populations:

• Pregnant women:

  • Pre-existing hypothyroidism: May need dose increase during pregnancy
  • New onset hypothyroidism (TSH ≥10 IU/L): 1.6 mcg/kg/day
  • New onset hypothyroidism (TSH <10 IU/L): 1.0 mcg/kg/day
  • Target: Maintain TSH in trimester-specific reference range 3

• Pediatric patients at risk for cardiac failure:

  • Start at lower dosage and increase every 4-6 weeks based on clinical and laboratory response 3

• Pediatric patients at risk for hyperactivity:

  • Start at one-fourth the recommended full replacement dosage
  • Increase weekly by one-fourth until full recommended dosage is reached 3

Monitoring Therapy

For adults:

• Monitor TSH 6-8 weeks after any dosage change
• Once stable, evaluate clinical and biochemical response every 6-12 months 3
• For primary hypothyroidism, TSH is the most important parameter to monitor 2

For pregnant patients:

• Measure serum TSH and free T4 at minimum during each trimester
• Monitor TSH every 4 weeks until stable dose is reached
• Reduce to pre-pregnancy levels immediately after delivery
• Monitor serum TSH 4-8 weeks postpartum 3

For pediatric patients:

• Monitor TSH and total or free T4 at 2 and 4 weeks after treatment initiation
• Monitor 2 weeks after any dosage change
• Then every 3-12 months after dosage stabilization until growth is completed 3

Important Clinical Considerations

Medication Administration

• Take levothyroxine on an empty stomach, 30-60 minutes before breakfast
• Avoid taking within 4 hours of calcium supplements, iron, or antacids
• Maintain consistent brand of levothyroxine to avoid fluctuations in bioavailability 1

Special Monitoring Situations

• Central hypothyroidism: Cannot use TSH for monitoring; use free T4 and T3 concentrations instead 2
• Metabolic instability: Thyroid function tests may be misleading; repeat after achieving metabolic stability 1
• Drug interactions: Monitor for interactions between treatments for other conditions and thyroid medication 1

Transient Thyroid Dysfunction

• Some cases of subclinical hypothyroidism resolve spontaneously (37% in one study) 1
• For patients with mild TSH elevation (≤6.9 mIU/L), consider repeating TSH after six months before initiating treatment 4
• For females with TSH above 6.9 mIU/L, particularly with FT3 and FT4 in the lower half of reference range, consider trial of levothyroxine as they are more likely to develop overt hypothyroidism 4

Pitfalls to Avoid

• Avoid routine thyroid function screening in asymptomatic individuals due to lack of demonstrated benefit and potential harm from overdiagnosis 5
• Be aware that TSH levels naturally increase with age, potentially leading to overdiagnosis in elderly patients 1
• Poor compliance, abnormal values, or persistent symptoms despite adequate replacement dose may necessitate more frequent monitoring 3
• First-line combined TSH and FT4 testing has a low positive predictive value (2-4%) for central hypothyroidism 6