What is Central Hypothyroidism
Central hypothyroidism is a form of hypothyroidism caused by insufficient stimulation of an otherwise normal thyroid gland due to inadequate TSH secretion from the pituitary (secondary) or hypothalamic dysfunction (tertiary). 1, 2
Pathophysiology
Central hypothyroidism results from defects at the hypothalamic-pituitary level rather than the thyroid gland itself. 2 The condition can arise from:
- Pituitary disorders (secondary hypothyroidism) - most commonly pituitary macroadenomas, pituitary surgery, or post-irradiation 3
- Hypothalamic disorders (tertiary hypothyroidism) - affecting TRH secretion 4
- Combined hypothalamic-pituitary dysfunction - which occurs most frequently 1
In the context of immune checkpoint inhibitor therapy, central hypothyroidism most commonly results from acute hypophysitis, occurring in >90% of patients with this complication. 5
Key Diagnostic Features
The hallmark laboratory finding is low free T4 with low or inappropriately normal TSH levels - this distinguishes it from primary hypothyroidism where TSH is elevated. 5
Critical Diagnostic Pitfalls:
- TSH can remain within the normal reference range despite significant hypothyroidism, making the "TSH-reflex strategy" (checking only TSH) inadequate for diagnosis 5, 2
- Both TSH and free T4 must be measured together when hypothyroidism is suspected clinically 5
- The thyroid hormone deficiency is typically less severe than in primary hypothyroidism 1
Epidemiology
Central hypothyroidism is approximately 1,000-fold rarer than primary hypothyroidism, with an estimated prevalence of 1 in 80,000 to 1 in 120,000. 1, 3
Clinical Presentation
The clinical manifestations are usually milder and more nonspecific than primary hypothyroidism. 2 Common symptoms include:
- Fatigue (most common) 3
- Peripheral edema 3
- Headache (particularly when associated with hypophysitis) 5
Central hypothyroidism frequently coexists with other pituitary hormone deficiencies, particularly central adrenal insufficiency (occurring together in >75% of hypophysitis cases). 5
Critical Management Consideration
When both central hypothyroidism and adrenal insufficiency are present, corticosteroids must always be initiated before thyroid hormone replacement to prevent precipitating an adrenal crisis. 5 Starting levothyroxine first increases cortisol metabolism and can trigger life-threatening adrenal crisis. 5