Thyroid Hormones Overview

Thyroid Hormone Overview

• Thyroid hormone is crucial for metabolic processes.
• The thyroid gland produces T4, T3, and rT3 hormones that regulate basal metabolic rate (BMR).

Thyroid Hormone Structure and Function

• 3,5,3',5'-tetraiodothyronine (L-thyroxine/L-T4) and 3,5,3'-triiodothyronine (L-triiodothyronine/L-T3) are critical thyroid hormones, with T4 being produced in greater amounts. T3 has higher potency than T4.

• A small percentage of produced hormone is reversed T3 (rT3) which is inactive.

• T4 is converted to T3 by a "deiodinase" enzyme in peripheral tissues.

• T3 binds to T3 receptors (TRα and TRẞ) within the cell nucleus. This binding regulates mRNA synthesis and protein synthesis.

• Calcitonin, secreted by parafollicular cells, is also a thyroid hormone.

Thyroid Gland Structure

• Thyroid follicles contain colloid.
• Colloid is a glycoprotein.
• Follicular cells secrete thyroid hormones.
• Parafollicular cells secrete calcitonin.

Thyroid Gland Products Synthesis

• Thyroglobulin (TG/TRG), synthesized by thyroid epithelial cells, is secreted into the follicle lumen. TG comprises 134 tyrosines.

• Iodide (I⁻) is avidly absorbed from blood via sodium-iodide symporter.

• Iodide travels to the colloid along with thyroglobulin.

• Thyroid peroxidase catalyzes the iodination and coupling sequential reactions to create thyroid hormones.

• Thyroid epithelial cells ingest colloid via endocytosis and fuse with lysosomes that contain enzymes for thyroglobulin digestion.

• Free thyroid hormones diffuse into the blood and bind to carrier proteins (TBG, transthyretin, albumin).

Iodine Distribution and Turnover

• Approximately 400 µg of iodine is consumed and excreted daily.

• Adults require 150 µg iodine a day.

• For pregnant women, it is 200 µg.

• The thyroid gland stores a substantial amount of iodine (7500 µg) as iodothyronines, with 70-80 µg released daily.

• The high iodine storage supports body against deficiencies for extended periods.

Thyroid Hormone Receptors

• Thyroid hormones act as heterodimers with Retinoic Acid X receptor (RXR).

• TR-RXR complexes bind to Thyroid Response Elements (TREs) on the target genes.

• In the absence of TH, TR-RXR represses gene transcription through recruitment of a corepressor complex (containing histone deacetylase (HDAC)).

• When TH is present, corepressor complexes are released and coactivator complexes (including histone acetyltransferase (HAT)) are recruited. HAT complexes promote transcription by increasing histone acetylation.

Physiological Effects of Thyroid Hormones

• Thyroid hormones regulate cellular differentiation and development, mainly in the nervous system.
• Thyroid hormones control the metabolism of carbohydrates, lipids, and proteins. These actions are interconnected across the body.

Physiological Effects on Metabolism and Growth

• Thyroid hormones enhance basal metabolic rate (BMR), increase oxygen consumption, and boost heat production.

• During development and growth, thyroid hormones stimulate neural growth and central nervous system maturation.

• Adequate thyroid hormones after birth are necessary for subsequent mental and physical development.

Physiological Effects on Cardiovascular System

• Thyroid hormones modify Ca2+ channels in the sarcoplasmic reticulum and enhance adrenoceptor sensitivity by noradrenaline.
• Thyroid hormones accelerate metabolic responses to starvation, as well as to autonomic nervous system signals.

Effects on the Nervous System

• Thyroid hormones enhance wakefulness, alertness and responsiveness to stimuli.

Thyroid Hormone Secretion Regulation

• TRH (thyrotropic releasing hormone) from the hypothalamus stimulates the anterior pituitary to release TSH (thyroid stimulating hormone).

• TSH subsequently stimulates the thyroid gland to produce T3 and T4. Circulating T3 and T4 levels regulate the negative feedback loop governing TRH and TSH.

• Factors such as low BMR, cold, trauma, and stress can increase TRH and TSH release.

• Estrogens and glucocorticoids impact thyroid hormone regulation.

Abnormalities of Thyroid Function

• Hyperthyroidism can occur due to autoimmune disease (Graves' disease), benign thyroid tumor, or excessive TSH secretion.
• Hypothyroidism symptoms involve autoimmune disease (Hashimoto's disease) and/or hypothalamic /pituitary dysfunction.

Goitre

• An enlarged thyroid gland, often caused by iodine deficiency, can result in hypothyroidism or hyperthyroidism.
• Grave's disease or excess TSH from the pituitary can also cause goitre.

Hyperthyroidism - Graves Disease

• Characteristic of Graves' disease is weight loss despite increased food intake. (increased BMR and increased heat production).
• Other symptoms: increased heart rate, difficulty swallowing/breathing, exophthalmos, and periorbital edema.
• Diagnosis via elevated serum free/total T3/T4 and low serum TSH levels.
• The disease is primarily caused by autoantibodies (thyroid stimulating immunoglobulin (TSI)) stimulating the thyroid gland.
• The disorder is considered secondary endocrine, as the problem is pituitary suppression by T3/T4.

Treatment of Hyperthyroidism

• Surgery: Removal of the gland is an option, especially if the gland is enlarged or malignant.

• Drugs:

• Thioureylenes (propylthiouracil, carbimazole, methimazole): Inhibit thyroid hormone synthesis; they initially decrease thyroid hormone synthesis immediately, but effects can take weeks due to existing gland hormone stores.

• Iodine-containing preparations (radioiodine): Radioactive iodine is ingested to target the thyroid gland and destroy it, a more permanent solution. A risk is causing hypothyroidism or thyroid damage.

• ADRENORECEPTOR antagonists: Used to counteract the overactive sympathetic nervous system (e.g. Propranolol) , managing symptoms like increased heart rate and arrhythmias.

Treatment of Hypothyroidism

• Replacement therapy: Synthetic T4 (levothyroxine) or T3 is used.
• Synthetic hormones restore healthy hormone levels.

MCT8 Mutations

• MCT8 defects severely hinder the delivery of T3 to the brain.
• This results in specific types of neurodevelopmental disorders in males, and milder thyroid phenotypes in females.

This quiz provides an in-depth overview of thyroid hormones, including their structure, function, and the role of the thyroid gland in metabolic processes. Test your knowledge on the different types of thyroid hormones, their interactions, and how they regulate various body functions.