Central Hypothyroidism: Diagnosis and Management
This patient has central hypothyroidism (secondary or tertiary hypothyroidism), not primary hypothyroidism, and requires immediate evaluation for concurrent pituitary hormone deficiencies—particularly adrenal insufficiency—before initiating thyroid hormone replacement. 1
Understanding the Lab Pattern
The combination of low T4 (4.7 ug/dL) with inappropriately low/normal TSH (0.183 u[IU]/mL) indicates a pituitary or hypothalamic problem, not a thyroid gland problem. 1 In primary hypothyroidism, the TSH would be elevated in response to low thyroid hormone levels. 2 This patient's TSH is suppressed when it should be markedly elevated, pointing to central hypothyroidism where the pituitary fails to produce adequate TSH. 1
Critical First Step: Rule Out Adrenal Insufficiency
Before starting any thyroid hormone replacement, you must evaluate for and treat adrenal insufficiency to avoid precipitating adrenal crisis. 1, 3, 4 This is non-negotiable because:
- More than 75% of central hypothyroidism patients have concurrent pituitary hormone deficiencies, most commonly adrenal insufficiency 1
- Starting thyroid hormone in the presence of untreated adrenal insufficiency can trigger life-threatening adrenal crisis 1, 3
- Steroids must always be initiated before thyroid hormone replacement in patients with both conditions 1, 3
Immediate Diagnostic Workup
Obtain morning hormone levels (ideally between 8-9 AM): 1
- ACTH and cortisol
- FSH and LH
- Gonadal hormones (testosterone in men, estradiol in women)
- Repeat TSH and free T4 for confirmation
- Prolactin
Order MRI of the sella with dedicated pituitary cuts to evaluate for: 1
- Pituitary enlargement
- Stalk thickening
- Suprasellar convexity
- Heterogeneous enhancement
- Mass lesions
Diagnostic Confirmation Criteria
Central hypothyroidism is confirmed by either: 1
- At least one pituitary hormone deficiency (TSH or ACTH) combined with MRI abnormality, OR
- At least two pituitary hormone deficiencies with headache and symptoms
Clinical History to Obtain
Specifically ask about: 1
- Headache (present in 85% of cases)
- Fatigue (present in 66% of cases)
- Visual changes
- History of pituitary disease, brain tumor, or head trauma
- Recent use of immune checkpoint inhibitors (ipilimumab, nivolumab)—these cause hypophysitis in up to 17% of cases
- Symptoms of other hormone deficiencies (low libido, amenorrhea, erectile dysfunction)
Treatment Approach
If Adrenal Insufficiency is Present:
- Start glucocorticoid replacement FIRST (typically hydrocortisone 15-25 mg daily in divided doses) 1, 3
- Wait until steroid replacement is stable
- Then initiate levothyroxine
Levothyroxine Dosing:
- Start with standard replacement doses (1.6 mcg/kg/day for most adults) 4
- Monitor using free T4 levels, NOT TSH 1, 2
- TSH cannot be used to guide treatment in central hypothyroidism because the pituitary response is impaired 1, 2
Treatment Target:
Maintain free T4 levels in the upper half of the normal range for age 1, 2 This differs from primary hypothyroidism where TSH normalization is the goal.
Monitoring Strategy
- Check free T4 (and free T3 if available) 6-8 weeks after starting therapy or dose changes 4, 2
- Adjust levothyroxine dose based on free T4 level and clinical symptoms 1
- Both adrenal insufficiency and hypothyroidism typically require lifelong hormonal replacement 1
- Monitor for symptoms of under-replacement: persistent cold intolerance, dry skin, hair loss, constipation, depression 3
Common Pitfalls to Avoid
- Never use TSH to monitor treatment in central hypothyroidism—it will remain low regardless of adequate replacement 1, 2
- Never start thyroid hormone before ruling out and treating adrenal insufficiency 1, 3, 4
- Don't assume normal free T4 rules out hypothyroidism in this context—the total T4 is clearly low and the free T4 index is at the lower end of normal 1
- Consider endocrinology consultation for complex cases, especially when managing multiple pituitary hormone deficiencies 3