Thyroid hormones

Biosynthesis and Mechanism of Action

The functional unit of the thyroid gland is the follicle, an epithelial-lined cavity filled with colloid. The colloid contains thyroglobulin (a large glycoprotein containing about 115 tyrosine residues).

Stages of hormone biosynthesis:

1. Iodine capture: iodine molecules are actively transported from the blood through the epithelial basal membrane and reach the apical membrane via transcytosis.
2. Oxidation: the enzyme thyroperoxidase oxidizes iodine, after which it enters the follicular lumen.
3. Iodination: iodine attaches to tyrosine within the thyroglobulin molecule. Attachment at position 3 yields monoiodotyrosine, and subsequent iodination at position 5 yields diiodotyrosine.
4. Condensation: molecules combine into dimers. Diiodotyrosine + monoiodotyrosine form triiodothyronine ($T_3$). Two diiodotyrosines form thyroxine ($T_4$).

For release into the bloodstream, iodinated thyroglobulin is recaptured into the cells via endocytosis, where it undergoes lysosomal degradation. The liberated $T_3$ and $T_4$ are secreted into the capillary network.

At the molecular level, $T_4$ is converted in the cytoplasm of target cells into the more potent $T_3$. The hormone stimulates intracellular receptors, activating mRNA transcription and enhancing protein synthesis.

Effects on Metabolism and Target Organs

Thyroid hormones stimulate all types of basal metabolism (protein, lipid, carbohydrate). They increase tissue oxygen demand and produce a thermogenic effect (raising body temperature, particularly in response to cooling). The main target organs are the heart, liver, kidneys, and skeletal muscles.

• Cardiac effects: hormones enhance cardiac contractility (positive inotropic effect), increase heart rate (positive chronotropic effect), and elevate cardiac output.
• Growth and development: in pediatrics, these hormones are critical for normal development. They act directly on tissues and potentiate the effects of growth hormone (somatotropin).
• Musculoskeletal system: ensure normal osteogenesis and increase tissue sensitivity to parathyroid hormone and calcitonin.

Thyroid function is regulated by the hypothalamic-pituitary system. The hypothalamus secretes thyrotropin-releasing hormone, which stimulates the production of thyroid-stimulating hormone (TSH) by the pituitary gland. TSH stimulates the thyroid gland. When hormone levels are excessively high, negative feedback is triggered, suppressing TSH secretion (with $T_3$ doing this more potently than $T_4$).

Pathologies: Hypothyroidism, Hyperthyroidism, and Goiter

Thyroid dysfunction leads to severe metabolic shifts:

• Hypofunction (hypothyroidism): manifests as myxedema in adults; leads to cretinism (delayed mental and physical development) in children.
• Hyperfunction (hyperthyroidism): a classic example is Graves' disease (basedowification).

Goiter (struma) is classified separately as an enlargement of the gland. It can be toxic (presenting with symptoms of hyperthyroidism) or simple (non-toxic).

The most common cause of simple goiter is dietary iodine deficiency. The pathogenesis relies on a feedback mechanism: inadequate dietary iodine reduces hormone synthesis. Lower blood levels of these hormones activate the hypothalamic-pituitary system. Upregulated TSH production continuously stimulates the thyroid gland, causing hypertrophy. A paradox arises: the gland is enlarged, but hormone levels do not increase because there is no substrate (iodine) for their synthesis.

Pharmacology: Medications for Hypothyroidism

Replacement therapy for hypothyroidism utilizes thyroid hormone preparations, inorganic iodine, or combinations thereof.

Liothyronine (Liothyroninum) is a synthetic analogue of $T_3$.

• Pharmacokinetics: 95% absorbed, rapid onset of action. The latent period is 4–8 hours, with peak effect at 2–3 days. The half-life is 2.5 days.
• Indications: myxedema, cretinism, endemic and sporadic goiter, thyroid cancer, hypothyroid obesity.
• Side effects: tachycardia, arrhythmias, angina pectoris, headache, suppression of TSH secretion.
• Contraindications: thyrotoxicosis, coronary artery disease (angina), Addison's disease, diabetes mellitus.

Levothyroxine sodium (Levothyroxinum natrium) is a synthetic analogue of $T_4$. It is weaker and slower in action (onset in 3–4 days, maximum in 10–15 days). Its primary advantage is a less pronounced arrhythmogenic effect.

Also used:

• Thyreotom (Thyreotom): a combination drug (40 mcg levothyroxine + 10 mcg liothyronine).
• Thyreoidinum (Thyreoidinum): an animal-derived preparation (from slaughterhouse cattle glands). Contains levorotatory isomers of $T_3$ and $T_4$. Acts similarly to liothyronine, but 3–5 times less potent.

Briefly: answers to topical questions

Class and exam questions

What else to study on this topic

• Lysosomal degradation of thyroglobulin during hormone release into the blood.
• Interaction of thyroid hormones with insulin, glucagon, and catecholamines.
• Use of thyroid hormone preparations in oncology (thyroid cancer).
• Diagnostic suppression tests using liothyronine.
• Antithyroid drugs (thioamides) for the treatment of hyperthyroidism.

Other topics in the section "Hormone preparations, their synthetic substitutes, and antagonists"

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