Iodide is accumulated in salivary gland , placenta , choroid plexus and mammary gland too . But they do not form thyroid hormones . Why ?
These tissues accumulate iodide via the same sodium-iodide symporter (NIS) as the thyroid, but they lack the key enzymatic machinery needed to organify iodide into thyroid hormones - specifically thyroid peroxidase (TPO) and thyroglobulin. Without TPO to oxidize iodide and incorporate it into tyrosine residues on thyroglobulin, no MIT/DIT or T3/T4 can be formed. The iodide simply accumulates and is then secreted unchanged.
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Why Non-Thyroidal Tissues Cannot Make Thyroid Hormones Despite Concentrating Iodide
The Shared Step: NIS-Mediated Iodide Uptake
The sodium-iodide symporter (NIS) is expressed not only in thyrocytes but also in:
- Salivary glands
- Gastric mucosa
- Placenta
- Choroid plexus
- Mammary glands
- Ciliary body of the eye
All these tissues use NIS to transport iodide against a concentration gradient (co-transporting 2 Na+ ions per I- ion). However, as Ganong's Review of Medical Physiology states directly:
"The salivary glands, the gastric mucosa, the placenta, the ciliary body of the eye, the choroid plexus, the mammary glands... also express NIS and can transport iodide against a concentration gradient, but the transporter in these tissues is not affected by TSH."
- Ganong's Review of Medical Physiology, 26e
The Missing Steps: Why They Cannot Organify Iodide
Thyroid hormone synthesis requires a highly specific, multi-step process that goes far beyond just accumulating iodide. Non-thyroidal tissues are missing every one of these downstream steps:
Thyroid hormone biosynthesis - Ganong's Review of Medical Physiology, 26e
Step 1 - Oxidation of Iodide (requires Thyroid Peroxidase)
In the thyroid, iodide (I-) is oxidized to active iodine (I+, or iodonium ion) at the apical border of thyrocytes. This reaction is catalyzed by thyroid peroxidase (TPO), a membrane-bound heme-enzyme. Non-thyroidal tissues do not express TPO, so iodide cannot be activated.
"The oxidation of iodide to its active form is accomplished by thyroid peroxidase."
- Goodman & Gilman's Pharmacological Basis of Therapeutics
Step 2 - Organification (requires Thyroglobulin)
Activated iodine is then incorporated into tyrosine residues of thyroglobulin - a large glycoprotein (660 kDa, 123 tyrosine residues) that is synthesized exclusively by thyrocytes and secreted into the colloid. This process, called organification, produces monoiodotyrosine (MIT) and diiodotyrosine (DIT).
Non-thyroidal tissues do not synthesize thyroglobulin, so there is no scaffold on which iodination can occur.
Step 3 - Coupling Reaction (again requires TPO)
TPO then catalyzes an oxidative coupling of two iodotyrosine residues still attached to thyroglobulin:
- DIT + DIT → T4 (thyroxine) + alanine
- MIT + DIT → T3 + alanine
Without TPO, this coupling step also cannot happen.
Step 4 - Proteolysis and Secretion
Finally, thyrocytes endocytose colloid and lysosomal proteases hydrolyze thyroglobulin to release free T3 and T4 into the circulation. Non-thyroidal tissues lack this entire secretory machinery.
Summary Table
| Step | Enzyme/Molecule Required | Present in Thyroid? | Present in Salivary/Mammary/Placenta/Choroid Plexus? |
|---|---|---|---|
| Iodide uptake | NIS | Yes | Yes - but NOT TSH-regulated |
| Iodide oxidation | Thyroid Peroxidase (TPO) | Yes | No |
| Iodination scaffold | Thyroglobulin | Yes | No |
| Coupling of MIT/DIT | Thyroid Peroxidase (TPO) | Yes | No |
| Hormone release | Lysosomal proteases on Tg | Yes | No |
Why Do These Tissues Concentrate Iodide at All?
The physiological significance of extrathyroidal iodide accumulation is not fully understood. Proposed roles include:
- Mammary glands: Secreting iodide into breast milk to supply the neonatal thyroid with iodine (especially important since the neonatal gut also expresses NIS)
- Placenta: Facilitating iodide transfer to the fetus
- Salivary/gastric: Recycling iodide back into the gut for reabsorption (enterosalivary circulation of iodide)
- Choroid plexus: Possibly regulating CSF iodide levels
A clinically useful consequence: because NIS is expressed in many cancers derived from these tissues (e.g., breast cancer, thyroid cancer metastases), radioiodine (I-131) can be used for diagnostic imaging or ablation of NIS-expressing tumors.
In short: NIS is the transport mechanism - a "door" that lets iodide in. But making thyroid hormones also requires the "factory machinery" inside the cell: TPO to activate and organify the iodide, and thyroglobulin to serve as the protein backbone. Non-thyroidal tissues have the door but completely lack the factory.
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