Full mechanism, in text

Raw material for thyroid hormone

1 · Dietary iodide enters blood

Iodine comes almost exclusively from food, is absorbed as iodide in the stomach and upper small intestine, and 70-80% of the body store sits in the thyroid.Iodine comes almost exclusively from food — kelp, nori, sea fish, and shellfish are natural rich sources, and iodized salt is the mandatory tool in most countries. Food iodine is mostly absorbed as iodide (I⁻) in the stomach and upper small intestine, and nearly all of it reaches the blood.

We need 150 µg/day (220 µg in pregnancy, 290 µg during lactation). The whole body holds only ~15-20 mg of iodine, of which 70-80% is concentrated in the thyroid — the rest is scattered in the breast, salivary glands, and gastric mucosa.

This is the starting point for "why the thyroid is so special": it is the only gland in the body that actively concentrates iodine, and the first organ that iodine deficiency harms.

2 · NIS pumps iodide into thyrocyte

NIS on thyroid follicular cells uses the Na⁺ electrochemical gradient to pump blood iodide into the cell against its gradient, to 20-40 times plasma levels.On the basolateral membrane of thyroid follicular cells sits a molecular pump called NIS (sodium-iodide symporter) — each cycle imports 2 Na⁺ + 1 I⁻, using the Na⁺ electrochemical gradient to pump blood iodide into the cell against its concentration gradient.

Result: intracellular I⁻ in the follicular cell is 20-40× plasma.

Key: NIS is not picky — nitrate, perchlorate and thiocyanate (found in cigarette smoke) all compete with I⁻ at the NIS transport site. By the mechanism, this competition matters more when iodine intake is already low.

The same principle is used in reverse: after a nuclear accident, potassium iodide (KI) tablets flood NIS with stable iodine, so radioactive ¹³¹I is not pumped into the thyroid.

3 · TPO iodinates thyroglobulin

uses H₂O₂ to oxidize I⁻ into reactive iodine and attach it to tyrosines on thyroglobulin (Tg), making MIT and DIT.After I⁻ enters the cell, it heads for the follicular lumen — a cavity filled with thyroglobulin (Tg) colloid. Tg is a giant protein carrying over a hundred tyrosine (Tyr) residues, some of which get loaded with iodine.

The key enzyme is (thyroid peroxidase) — using H₂O₂ as cofactor, it:
· Oxidizes I⁻ to I⁺/I• (reactive iodine).
· Couples reactive iodine to the phenyl ring of Tyr on Tg.

One Tyr + one iodine → MIT (monoiodotyrosine).
One Tyr + two iodines → DIT (diiodotyrosine).

Clinical: TPO is the most common autoimmune target in hypothyroidism — anti-TPO antibody positivity is the hallmark of Hashimoto's thyroiditis. The hyperthyroidism drug methimazole is also a TPO inhibitor.

4 · Coupling yields T4 / T3, secreted

then couples two iodinated Tyr residues into or ; about 80% of what the thyroid secretes is T4, which peripheral deiodinases convert to the active T3. has a second job: coupling two iodinated Tyr residues on the same Tg:

· DIT + DIT → (tetraiodothyronine / thyroxine — the main product).
· MIT + DIT → (triiodothyronine — the true active hormone).

The thyroid secretes mostly T4 (about 80%) + a little T3. T4 is the "storage form," T3 is what actually works — T4 is converted to T3 in peripheral tissues (liver, kidney, muscle) by 5'-deiodinase, which clips off one iodine.

T3 enters the nucleus, binds the TR receptor, and regulates a large set of genes: basal metabolic rate, heart rate, bowel motility, bone turnover, brain development, thermogenesis. This is why people with hypothyroidism feel cold, become constipated, have a slow heart rate, and feel sluggish — almost every metabolic pathway is simultaneously dialed down.

Iodine deficiency in pregnancy causes irreversible fetal cognitive impairment (cretinism) — Pregnancy totals: US 220 µg/day, WHO target 250 µg/day; the ATA 150 µg/day is a supplemental amount in the prenatal, not a total.

Full mechanism, in text

1 · Dietary iodide enters blood

2 · NIS pumps iodide into thyrocyte

3 · TPO iodinates thyroglobulin

4 · Coupling yields T4 / T3, secreted

Iodine · Thyroid hormone synthesis

Full mechanism, in text

1 · Dietary iodide enters blood

2 · NIS pumps iodide into thyrocyte

3 · TPO iodinates thyroglobulin

4 · Coupling yields T4 / T3, secreted

Iodine · Thyroid hormone synthesis