All of the following statements regarding thyroid hormone synthesis and secretion are correct EXCEPT:

Explanation

## Analysis of Thyroid Hormone Synthesis and Secretion ### Correct Statements (Options 0, 1, 2) **Option 0 — Thyroid Peroxidase (TPO) Function:** **Key Point:** TPO is the rate-limiting enzyme in thyroid hormone synthesis. It catalyzes two critical reactions: - Iodination of tyrosine residues to form monoiodotyrosine (MIT) and diiodotyrosine (DIT) - Coupling of iodotyrosines to form T3 (MIT + DIT) and T4 (DIT + DIT) This statement is **correct**. **Option 1 — Peripheral Conversion of T4 to T3:** **High-Yield:** Approximately 80% of circulating T3 is produced from T4 in peripheral tissues, not in the thyroid itself. Type 1 deiodinase (D1) is the major source in liver and kidney. Type 2 deiodinase (D2) operates in brain, pituitary, and brown adipose tissue and is important for local T3 production. This statement is **correct**. **Option 2 — Thyroglobulin Synthesis and Storage:** **Key Point:** Thyroglobulin is a large glycoprotein synthesized in the rough ER, transported to the Golgi, and secreted into the follicular lumen where it accumulates as colloid. Upon TSH stimulation, follicular cells endocytose colloid, and lysosomal proteases cleave thyroglobulin to release free T3 and T4 into the bloodstream. This statement is **correct**. ### Incorrect Statement (Option 3) — THE ANSWER **Option 3 — TSH and NIS Activation:** **Warning:** This is a common misconception. TSH does NOT directly activate NIS. Instead: 1. TSH binds to the TSH receptor (TSHR) on the basolateral membrane of thyroid follicular cells 2. This activates a cAMP-dependent signaling cascade 3. The cascade upregulates NIS expression at the apical membrane (facing the colloid) 4. **Crucially:** NIS is located on the **basolateral membrane** (blood side), NOT the apical membrane 5. Iodide is actively transported from blood into the follicular cell via NIS on the basolateral membrane 6. Iodide then moves to the apical membrane via pendrin (chloride-iodide antiporter) or other transporters The statement incorrectly places NIS on the apical membrane and oversimplifies the mechanism as "direct activation." This statement is **incorrect**. ### Summary Table | Component | Correct Function | Location/Mechanism | |-----------|------------------|--------------------| | TPO | Iodination + coupling of iodotyrosines | Apical membrane/colloid interface | | D1 Deiodinase | T4 → T3 conversion (80% of circulating T3) | Liver, kidney | | Thyroglobulin | Storage form of T3/T4 in colloid | Follicular lumen | | NIS | Iodide uptake from blood | **Basolateral membrane** (NOT apical) | | TSH | Upregulates NIS via cAMP cascade (indirect) | Acts on basolateral TSHR | **Clinical Pearl:** Mutations in NIS cause congenital iodide transport defect, leading to hypothyroidism despite normal thyroid structure. This demonstrates that NIS function is essential for iodide entry into the thyroid. [cite:Guyton and Hall 14e Ch 76]