A 52-year-old woman with primary hypothyroidism presents with fatigue and weight gain. Her TSH is 45 mIU/L and free T4 is 0.6 ng/dL. Which single feature best distinguishes primary hypothyroidism from secondary (central) hypothyroidism?

Explanation

## Distinguishing Primary from Central Hypothyroidism ### TSH-Free T4 Relationship **Key Point:** The TSH level is the single best discriminator between primary and central (secondary/tertiary) hypothyroidism. In primary hypothyroidism, the failing thyroid gland cannot produce adequate T4, so the pituitary responds by increasing TSH via negative feedback loss. In central hypothyroidism, the pituitary or hypothalamus is dysfunctional, so TSH production itself is impaired. ### Comparison Table | Feature | Primary Hypothyroidism | Secondary Hypothyroidism | Tertiary Hypothyroidism | | --- | --- | --- | --- | | **Free T4** | Low | Low | Low | | **TSH** | **Elevated (>10 mIU/L)** | **Low or normal** | **Low or normal** | | **TRH stimulation test** | TSH rises (intact axis) | TSH does not rise | TSH may rise (slow) | | **Cause** | Thyroid gland failure | Pituitary disease | Hypothalamic disease | **High-Yield:** In primary hypothyroidism, the TSH is markedly elevated (often >20 mIU/L) because the pituitary is intact and "trying" to stimulate a failing gland. This is the hallmark finding. ### Clinical Pearl When you see **low free T4 + elevated TSH**, think primary hypothyroidism immediately. This pattern reflects an intact hypothalamic-pituitary-thyroid (HPT) axis with peripheral gland failure. Conversely, low T4 with low or normal TSH indicates central disease (pituitary or hypothalamic pathology). ### Mnemonic **"Primary = TSH UP, Secondary = TSH DOWN"** — In primary disease, the intact pituitary compensates by raising TSH; in central disease, the pituitary itself is broken, so TSH stays low despite low T4.