What is the initial internal workup and treatment for a patient with suspected hypothyroidism (underactive thyroid gland)?

Initial Workup for Suspected Hypothyroidism

Measure serum TSH as the first-line test, followed by free T4 if TSH is elevated, to distinguish between subclinical and overt hypothyroidism. 1, 2

Diagnostic Testing Algorithm

First-Line Laboratory Tests

• TSH is the most sensitive initial test with sensitivity above 98% and specificity greater than 92% for detecting thyroid dysfunction 1, 2
• If TSH is elevated, measure free T4 immediately to distinguish between:
  • Subclinical hypothyroidism: elevated TSH with normal free T4 1, 2
  • Overt hypothyroidism: elevated TSH with low free T4 1, 3

Confirmation Testing

• Repeat TSH and free T4 after 3-6 weeks if initially elevated, as 30-60% of elevated TSH levels normalize spontaneously 1, 2
• Do not initiate treatment based on a single elevated TSH value without confirmation 1

Additional Diagnostic Tests

• Measure anti-TPO antibodies to identify autoimmune etiology (Hashimoto's thyroiditis), which predicts higher progression risk to overt hypothyroidism (4.3% per year vs 2.6% in antibody-negative patients) 1, 2
• Avoid imaging studies (ultrasound, CT, MRI, radioiodine uptake scans) in the workup of primary hypothyroidism, as they do not help differentiate among causes 2

Treatment Initiation Based on TSH Levels

TSH >10 mIU/L with Normal or Low Free T4

• Initiate levothyroxine therapy immediately regardless of symptoms, as this level carries approximately 5% annual risk of progression to overt hypothyroidism 1, 4, 5
• Treatment may improve symptoms and lower LDL cholesterol 1

TSH 4.5-10 mIU/L with Normal Free T4 (Subclinical Hypothyroidism)

• Do not routinely treat, but monitor TSH every 6-12 months 1, 5
• Consider treatment in specific situations:
  • Symptomatic patients with fatigue, weight gain, cold intolerance, or constipation 1
  • Positive anti-TPO antibodies (higher progression risk) 1, 2
  • Women planning pregnancy or currently pregnant 1
  • Patients with goiter or infertility 4

Overt Hypothyroidism (Low Free T4)

• Start levothyroxine without delay to prevent cardiovascular dysfunction, adverse lipid profiles, and quality of life deterioration 1, 3

Levothyroxine Dosing Guidelines

Standard Dosing for Adults

• For patients <70 years without cardiac disease: start with full replacement dose of approximately 1.6 mcg/kg/day 1, 6, 7
• For patients >70 years or with cardiac disease/multiple comorbidities: start with lower dose of 25-50 mcg/day and titrate gradually 1, 6

Special Populations

• Pregnant women with pre-existing hypothyroidism: increase levothyroxine dose by 25-50% immediately upon pregnancy confirmation, as requirements increase during early pregnancy 1, 6
• New onset hypothyroidism in pregnancy with TSH ≥10 mIU/L: start 1.6 mcg/kg/day 6
• New onset hypothyroidism in pregnancy with TSH <10 mIU/L: start 1.0 mcg/kg/day 6

Monitoring Protocol

During Dose Titration

• Recheck TSH and free T4 every 6-8 weeks after initiating therapy or changing dose 1, 6, 3
• Target TSH range: 0.5-4.5 mIU/L with normal free T4 1, 5
• Adjust levothyroxine dose by 12.5-25 mcg increments based on patient characteristics 1

After Stabilization

• Monitor TSH annually once stable dose is achieved and TSH is within target range 1, 6
• Recheck sooner if symptoms change 1

Critical Safety Considerations

Before Starting Levothyroxine

• Rule out concurrent adrenal insufficiency, especially in suspected central hypothyroidism, as starting thyroid hormone before corticosteroids can precipitate life-threatening adrenal crisis 1, 2, 4
• In central hypothyroidism, always start physiologic dose steroids 1 week prior to thyroid hormone replacement 1

Avoiding Overtreatment

• Approximately 25% of patients on levothyroxine are unintentionally maintained on doses sufficient to fully suppress TSH, increasing risks for atrial fibrillation, osteoporosis, fractures, and cardiac complications 1, 4
• Overtreatment occurs in 14-21% of treated patients 1
• TSH suppression (<0.1 mIU/L) significantly increases risk for atrial fibrillation (especially in elderly), osteoporosis, fractures, and cardiovascular mortality 1

Central Hypothyroidism Considerations

• If low free T4 with normal or low TSH, suspect central (secondary) hypothyroidism from pituitary or hypothalamic dysfunction 2, 8
• Obtain morning pituitary hormone panel and MRI of sella with pituitary cuts 2
• Evaluate and treat adrenal insufficiency BEFORE starting thyroid hormone to avoid adrenal crisis 2
• Monitor with free T4 levels (not TSH), maintaining free T4 in upper half of normal range 6, 4

Common Pitfalls to Avoid

• Never treat based on single elevated TSH without confirmation, as transient elevations are common 1, 2
• Never start thyroid hormone before ruling out adrenal insufficiency in suspected central hypothyroidism 1, 2
• Avoid excessive dose increases that could lead to iatrogenic hyperthyroidism 1
• Do not use imaging studies for routine primary hypothyroidism workup 2
• Consider recent iodine exposure (CT contrast) which can transiently affect thyroid function tests 1