What is the treatment for central hypothyroidism?

Treatment of Central Hypothyroidism

Levothyroxine (T4) is the treatment of choice for central hypothyroidism, with dosing based on free T4 levels rather than TSH, targeting the upper half of the normal reference range. 1, 2

Diagnosis and Pathophysiology

Central hypothyroidism (CH) is a rare form of hypothyroidism caused by insufficient stimulation of a normal thyroid gland due to either:

• Secondary hypothyroidism (pituitary defect)
• Tertiary hypothyroidism (hypothalamic defect) 2

Unlike primary hypothyroidism, central hypothyroidism presents with:

• Low or inappropriately normal TSH levels
• Low free T4 (FT4) levels 2, 3

Key Diagnostic Considerations

• TSH cannot be used to monitor treatment as it may be normal, low, or even elevated in central hypothyroidism 3
• Free T4 is the best indicator for diagnosis, though it may remain in the low-normal range in some patients, especially those with childhood-onset disease 3
• Always evaluate for other pituitary hormone deficiencies, particularly adrenal insufficiency, which should be treated before starting thyroid replacement 4

Treatment Protocol

Initial Therapy

• Starting dose:
  • Adults under 70 without cardiac disease: 1.6 mcg/kg/day 1
  • Elderly patients or those with cardiac conditions: 25-50 mcg/day 1
  • Consider starting at lower doses (12.5-50 mcg/day) in patients over 60 or with known/suspected heart disease 5

Critical Consideration

• When multiple pituitary hormones are deficient, hydrocortisone must be started before thyroid hormone replacement to prevent precipitating an adrenal crisis 4

Monitoring and Dose Adjustment

• Monitor free T4 levels (not TSH) to guide therapy 2
• Target free T4 in the upper half of the normal reference range 3
• Check thyroid function 4-6 weeks after starting therapy and adjust dose accordingly 1
• Once stable, monitor every 6-12 months or if symptoms change 1

Special Considerations

1. Pregnancy:

   • Increase weekly dosage by 30% (take one extra dose twice weekly)
   • Monitor monthly and adjust as needed 1, 6

2. Concomitant Hormone Replacement:

   • Patients on GH therapy (males) or estrogen therapy (females) typically require higher levothyroxine doses 3
   • Adjust dose based on free T4 levels

3. Elderly Patients:

   • Use lower initial doses (25-50 mcg/day)
   • Target TSH range for elderly is 1.0-4.0 mIU/L (though TSH is not the primary monitoring parameter in central hypothyroidism) 1
   • Avoid overtreatment which increases risk of atrial fibrillation and osteoporosis 1

Alternative Therapies

While combination therapy with T3 (liothyronine) is sometimes considered for primary hypothyroidism patients with persistent symptoms despite normal TSH levels, there is insufficient evidence to recommend this approach specifically for central hypothyroidism 7, 5.

Treatment Outcomes

With appropriate levothyroxine replacement:

• Most patients achieve normal free T4 levels (94% in one study)
• Normal free T3 levels may be achieved in only about half of patients (49%) 3
• Adequacy of therapy is best reflected by upper normal free T4 and low-normal free T3 levels 3

Common Pitfalls to Avoid

1. Using TSH to monitor therapy - Unlike primary hypothyroidism, TSH is unreliable in central hypothyroidism and should not guide treatment decisions 2, 3

2. Failure to evaluate for other pituitary hormone deficiencies - Central hypothyroidism often occurs with other pituitary hormone deficiencies that require treatment 8

3. Starting thyroid hormone before treating adrenal insufficiency - This can precipitate an adrenal crisis due to increased cortisol metabolism 4

4. Inadequate dose adjustments - Patients on other hormone replacements (GH, estrogen) typically need higher levothyroxine doses 3

5. Overlooking central hypothyroidism - The condition may be missed because TSH is often normal and free T4 may be in the low-normal range 3