What are the initial steps for diagnosing and managing hypothyroidism (underactive thyroid) through blood work, including Thyroid-Stimulating Hormone (TSH) test and Free Thyroxine (FT4) test?

Diagnosing and Managing Hypothyroidism Through Blood Work

The initial diagnostic workup for hypothyroidism should include both Thyroid-Stimulating Hormone (TSH) and Free Thyroxine (FT4) measurements, as this combination provides the most accurate assessment of thyroid function and helps distinguish between primary and central hypothyroidism. 1

Initial Diagnostic Testing

• First-line tests:

  • TSH measurement (essential)
  • FT4 measurement (from the same sample)
  • Consider anti-thyroid peroxidase antibodies (TPO-Ab) for suspected autoimmune thyroiditis

• Interpretation of results:

  • Primary hypothyroidism: Elevated TSH with low FT4, or TSH >10 with normal FT4
  • Central (secondary) hypothyroidism: Low FT4 with normal or low TSH
  • Subclinical hypothyroidism: Elevated TSH with normal FT4

Diagnostic Algorithm

1. TSH and FT4 testing:

   • If TSH is elevated and FT4 is low → Primary hypothyroidism (most common)
   • If TSH is elevated (>10 mIU/L) and FT4 is normal → Subclinical hypothyroidism
   • If TSH is low/normal and FT4 is low → Central hypothyroidism (rare)
   • If TSH and FT4 are normal → No thyroid dysfunction

2. Additional testing considerations:

   • Morning cortisol measurement if central hypothyroidism is suspected
   • Thyroid antibodies (TPO-Ab) to confirm autoimmune thyroiditis (Hashimoto's)
   • Repeat testing in 4-6 weeks if results are borderline

Management Based on Test Results

Primary Hypothyroidism (Elevated TSH, Low FT4)

• Treatment: Levothyroxine 0.5-1.5 μg/kg daily (start at lower doses in elderly or those with cardiac history) 2, 1
• Goal: Normalize TSH within reference range
• Monitoring: Check TSH and FT4 every 4-6 weeks while titrating dose, then every 6-12 months once stable

Subclinical Hypothyroidism (Elevated TSH, Normal FT4)

• TSH 4.5-10 mIU/L and asymptomatic:
  • Continue monitoring TSH and FT4 every 4-6 weeks 2
  • Consider treatment if patient develops symptoms
• TSH >10 mIU/L or symptomatic:
  • Initiate levothyroxine therapy 2, 1
  • Monitor TSH every 6-8 weeks while titrating dose

Central Hypothyroidism (Low/Normal TSH, Low FT4)

• Treatment: Levothyroxine therapy with dose titration based on FT4 levels (not TSH)
• Important: Evaluate pituitary function and consider cortisol replacement before starting levothyroxine

Special Considerations

• Elderly patients or those with cardiac disease:

  • Start with lower levothyroxine doses (25-50 mcg daily)
  • Gradually increase to avoid exacerbating cardiac symptoms 1

• Severe hypothyroidism:

  • Consider hospital admission for myxedema (bradycardia, hypothermia, altered mental status)
  • Endocrinology consultation for IV levothyroxine dosing 2
  • If uncertain whether primary or central, give hydrocortisone before thyroid hormone

• Monitoring frequency:

  • During initial treatment: Every 4-6 weeks
  • Once stable: Every 6-12 months or with change in symptoms 2, 1

Common Pitfalls to Avoid

1. Relying on TSH alone: While TSH is sensitive for primary hypothyroidism, it can miss central hypothyroidism. Testing both TSH and FT4 provides more complete assessment. 1, 3

2. Overlooking subclinical hypothyroidism: TSH >10 mIU/L even with normal FT4 often warrants treatment, especially in symptomatic patients. 2, 4

3. Failure to recognize central hypothyroidism: Low FT4 with normal/low TSH requires evaluation for pituitary dysfunction. 2

4. Starting full replacement doses in high-risk patients: Elderly or cardiac patients need gradual dose titration to avoid complications. 2, 1

5. Inadequate monitoring: Regular TSH and FT4 testing is essential during dose adjustment and periodically thereafter. 2, 1

By following this systematic approach to blood work for hypothyroidism, clinicians can accurately diagnose the condition, determine its severity and type, and initiate appropriate management to improve patient outcomes.