Immediate Evaluation for Central Hypothyroidism and Adrenal Insufficiency Required
Your patient's TSH of 0.140 with T4 of 0.99 indicates central hypothyroidism—a pituitary or hypothalamic disorder—and you must immediately check morning cortisol and ACTH before starting any thyroid hormone replacement, as initiating levothyroxine without first treating concurrent adrenal insufficiency can precipitate life-threatening adrenal crisis. 1
Critical Diagnostic Pattern
This combination of low TSH with low T4 definitively indicates central hypothyroidism rather than primary thyroid disease, requiring urgent evaluation for hypophysitis or other pituitary pathology 1. The pattern represents pituitary failure to produce adequate TSH despite low thyroid hormone levels 2.
Immediate Diagnostic Workup
Before any treatment:
- Morning (9 AM) ACTH and cortisol levels or 1 mcg cosyntropin stimulation test to rule out adrenal insufficiency 1
- MRI of the sella with pituitary cuts to evaluate for hypophysitis, pituitary enlargement, stalk thickening, or suprasellar convexity 1
- FSH, LH, and gonadal hormones to assess for panhypopituitarism 1
- Free T4 by equilibrium dialysis for more accurate measurement 1
Central adrenal insufficiency coexists with central hypothyroidism in >75% of hypophysitis cases 1. If both conditions are confirmed, corticosteroids must be started several days before initiating levothyroxine to prevent adrenal crisis 1, 3.
Clinical Context Matters
If Patient is on Immunotherapy
- Hypophysitis occurs in 1-16% of patients on anti-CTLA4 therapy and 8% on combination immunotherapy (ipilimumab plus nivolumab) 2
- The falling TSH with normal or lowered T4 across two measurements suggests pituitary dysfunction requiring weekly cortisol measurements 2
- Headache occurs in 85% and fatigue in 66% of hypophysitis cases 1
If Not on Immunotherapy
Other causes of central hypothyroidism include pituitary tumors, Sheehan syndrome, traumatic brain injury, or infiltrative diseases requiring MRI evaluation 1.
Treatment Protocol Once Adrenal Status Confirmed
Levothyroxine Dosing for Central Hypothyroidism
Initial dosing:
- Age <70 without cardiac disease: Start 1.6 mcg/kg/day 1
- Age >70 or with cardiac disease: Start 25-50 mcg/day with gradual titration, monitoring for cardiac arrhythmias 1
Dose adjustments:
- Increase in 12.5-25 mcg increments based on free T4 levels (NOT TSH) 1
- Wait 6-8 weeks between adjustments 1
Monitoring Strategy
TSH cannot guide therapy in central hypothyroidism 1, 4, 5. Instead:
- Target free T4 in the upper half of normal range (approximately 14-19 pmol/L) 1, 4, 5
- Recheck free T4 6-8 weeks after dose adjustment 1
- Once stable, monitor free T4 every 6-12 months 1
- Annual monitoring of other pituitary hormones may be warranted 1
Critical Pitfalls to Avoid
Never start levothyroxine before ruling out and treating adrenal insufficiency—this is the most dangerous error and can be fatal 1, 3
Do not use TSH to guide therapy—TSH remains low regardless of adequate replacement in central hypothyroidism 1, 4
Avoid under-replacement—38.9% of pituitary patients on levothyroxine have free T4 ≤13 pmol/l compared to only 9.5-13.4% of primary hypothyroidism patients, indicating systematic under-treatment 4
Do not assume isolated thyroid dysfunction—panhypopituitarism occurs in approximately 50% of hypophysitis cases 1