Thyroid

The thyroid is a butterfly-shaped gland sitting in front of the trachea just below the larynx. It weighs about 20-30 g in adults and pulls iodine out of the bloodstream to make two hormones — T4 and T3 — that tell virtually every cell in the body how fast to metabolize. When it runs slow, so do you. When it runs fast, you cook yourself.

At a glance

What it does

Sets metabolic rate. Thyroid hormone increases basal oxygen consumption, heat production, cardiac output, GI motility, bone turnover, and CNS activity. It is permissive for growth hormone action in children and required for normal neurological development in utero and infancy — which is why congenital hypothyroidism is screened for at birth and treated immediately.

T4 (thyroxine) is the prohormone. Most of it is converted in peripheral tissues to T3 (triiodothyronine), which is the biologically active form that binds nuclear receptors. The thyroid itself makes the two in roughly a 14:1 ratio; the rest of the T3 comes from deiodinase enzymes in liver, kidney, muscle, and brain.

Calcitonin is a secondary output from parafollicular C cells and lowers calcium modestly — pharmacologically interesting but physiologically minor in adults.

How it works

Iodine is trapped from blood by the sodium-iodide symporter on the basolateral membrane of thyroid follicular cells. It is oxidized and attached to tyrosine residues on a giant storage protein called thyroglobulin, sitting in the colloid-filled follicle lumen. Two iodinated tyrosines are coupled to make T4 or T3, still bound to thyroglobulin. When TSH signals release, the cell endocytoses chunks of colloid, proteolytically cleaves out the hormones, and secretes them.

TSH from the anterior pituitary drives the whole operation. TRH from the hypothalamus drives TSH. Thyroid hormones feed back to suppress both, producing the classic three-tier loop. This is why TSH is the best single lab test for thyroid function in most settings — high TSH means the pituitary is shouting at an underperforming gland; low TSH usually means the gland is making too much and suppressing its own signal.

Most circulating T4 and T3 are bound to thyroxine-binding globulin, transthyretin, and albumin. Only the free fraction is active. This matters because anything that changes binding protein levels (estrogen, pregnancy, nephrotic syndrome) changes total T4 without changing what actually hits tissue.

When it goes wrong

Hypothyroidism is common, especially in women over 40 — global prevalence around 5% overt plus another 5-10% subclinical. Hashimoto's thyroiditis is the leading cause in iodine-sufficient countries, a slow autoimmune destruction with TPO and thyroglobulin antibodies. Symptoms drift in over years: fatigue, weight gain, cold intolerance, constipation, dry skin, menstrual changes, slowed thought. Treatment is levothyroxine — synthetic T4, taken daily, dose titrated to TSH.

Hyperthyroidism is less common but more dramatic. Graves' disease is the main cause — autoimmune antibodies stimulate the TSH receptor directly, so the gland runs wild independent of pituitary control. Symptoms: heat intolerance, weight loss despite appetite, tachycardia, tremor, anxiety, loose stools, sometimes proptosis (Graves' ophthalmopathy). Treatment options are antithyroid drugs, radioactive iodine ablation, or surgery, each with trade-offs.

Thyroid cancer is mostly indolent — papillary and follicular types have excellent prognosis with surgery. Medullary and anaplastic types are rarer and nastier. The epidemic of "thyroid cancer" incidence over the past 30 years is largely overdiagnosis of small papillary cancers that would never have caused symptoms.

Subclinical hypothyroidism — mildly elevated TSH with normal free T4 — is genuinely contested. Large trials in older adults with TSH in the 4-10 range have shown limited benefit from levothyroxine treatment on symptoms or hard endpoints. "Thyroid fatigue" as a catch-all diagnosis is frequently oversold by functional medicine practices, and many patients with vague fatigue and normal labs get put on thyroid hormone they do not need.

Interactions

Iodine deficiency causes hypothyroidism and goiter. Excess iodine can trigger or worsen thyroid disease (Wolff-Chaikoff and Jod-Basedow phenomena). Selenium is a cofactor for deiodinase enzymes; severe selenium deficiency impairs T4-to-T3 conversion. Amiodarone (a cardiac drug with massive iodine content) can cause both hypo- and hyperthyroidism.

Cortisol suppresses TSH and blunts T4-to-T3 conversion — this is part of the "euthyroid sick syndrome" seen in acute illness and severe stress, and it is a reason not to diagnose thyroid disease from labs drawn during critical illness. Estrogen raises TBG, raising total but not free T4; a woman starting estrogen therapy may need higher levothyroxine doses to keep free T4 steady.

Honest take

Sources

• Jonklaas et al., Thyroid — ATA guidelines for hypothyroidism treatment.
• Ross et al., Thyroid — ATA guidelines for hyperthyroidism and thyrotoxicosis.
• Stott et al., NEJM (2017) — TRUST trial on levothyroxine in older adults with subclinical hypothyroidism.