What to do if Thyroid Stimulating Hormone (TSH) is normal and free Thyroxine (T4) is low?

Management of Normal TSH with Low Free T4

For patients with normal TSH and low free T4, initiate levothyroxine therapy to restore free T4 to normal range, as this pattern suggests central hypothyroidism requiring hormone replacement. 1

Diagnostic Approach

When encountering this thyroid function pattern:

1. Confirm the diagnosis:

   • Repeat thyroid function tests to verify the pattern of normal TSH with low free T4
   • This pattern is characteristic of central (secondary) hypothyroidism, which originates from pituitary or hypothalamic dysfunction 1, 2

2. Additional testing to consider:

   • Evaluate pituitary function with morning cortisol, prolactin, LH/FSH, IGF-1
   • Consider pituitary imaging (MRI) to rule out pituitary adenoma or other structural lesions
   • Check for symptoms of other pituitary hormone deficiencies

Treatment Recommendations

Levothyroxine Therapy

• Initiation dose:

  • Start with 1.6 mcg/kg/day for patients under 70 years without cardiac disease 1
  • Use lower doses (25-50 mcg/day) for elderly patients or those with cardiac conditions 1, 3

• Monitoring and dose adjustment:

  • Unlike primary hypothyroidism, TSH cannot be used to monitor therapy in central hypothyroidism
  • Target free T4 levels in the upper half of the normal reference range 2, 4
  • Monitor free T3 levels to ensure they remain within normal range 2, 4
  • Assess clinical response and biochemical markers of thyroid hormone action 2

• Follow-up timing:

  • Check thyroid function tests 6-8 weeks after initiating therapy or changing dose 5
  • Once stable, annual monitoring is usually sufficient 5

Important Clinical Considerations

• Pitfalls to avoid:

  • Do not rely on TSH for dose adjustment in central hypothyroidism, as it remains inappropriately normal despite low free T4 2, 4
  • Avoid overtreatment, as excessive levothyroxine can increase risk of atrial fibrillation and osteoporosis, particularly in elderly patients 1
  • Watch for signs of adrenal insufficiency that may be unmasked by thyroid hormone replacement

• Special situations:

  • In patients with multiple pituitary hormone deficiencies, always treat adrenal insufficiency before initiating thyroid hormone replacement
  • Patients with cardiac disease require more cautious dosing and monitoring 1

• Bioequivalence concerns:

  • Be aware that bioequivalence may differ among generic and brand-name levothyroxine preparations 5
  • Consider maintaining patients on the same preparation to avoid fluctuations in hormone levels

Central hypothyroidism can be challenging to manage as it requires careful monitoring of free T4 and clinical parameters rather than relying on TSH. The goal is to restore physiologic thyroid hormone levels while avoiding both under- and over-replacement.