Thyroid Gland Overview and Hormones

Thyroid Gland

• Butterfly-shaped endocrine gland located at the front of the neck.
• Controls the body's metabolism (how the body uses energy).

Thyroid Hormones

• Secretes two primary hormones:
  • Thyroxin (T4) and Tri-iodothyronine (T3).
  • Thyrocalcitonin

Synthesis, Storage, and Release of Thyroid Hormones (T3 and T4)

• Hypothalamus secretes thyrotropin-releasing hormone (TRH).
• TRH stimulates the anterior pituitary gland to release thyroid-stimulating hormone (TSH).
• TSH binds to receptors on the thyroid cell, activating adenyl cyclase, which increases cAMP levels.
• This leads to increased size, vasculature, and function of the thyroid gland.
• The thyroid gland actively traps and concentrates iodide (iodide trapping), facilitated by TSH and ATP.
• Approximately 50% of circulating iodide is trapped by the thyroid gland, with the rest excreted in urine.
• Active iodide trapping can be inhibited by:
  • Monovalent chemical groups like perchlorate, nitrates, and thiocyanate.
  • Anaerobic conditions that deplete ATP.
  • Digitalis, which antagonizes the ATPase enzyme, thereby impacting ATP utilization.

Iodide Metabolism

• Conversion of iodide to active elementary iodine by thyroid peroxidase (TPO).
• Organification of iodine involves iodine combining with thyroglobulin to form mono-iodotyrosine (MIT) and di-iodotyrosine (DIT).
• Coupling of MIT and DIT yields tri-iodothyronine (T3) and tetra-iodothyronine (T4).
• MIT and DIT are retained within the cell and de-iodinated by thyroid de-iodinase enzyme, releasing elemental iodine for further iodination of tyrosine.
• Lack of thyroid de-iodinase enzyme reduces iodine availability, leading to hypothyroidism.
• Release of T3 and T4 after secretion is regulated by TSH.

Pharmacokinetics of Thyroid Hormones

• Oral absorption is irregular, with better absorption when taken before meals on an empty stomach.
• Distributed throughout the body.
• Circulating T3 and T4 are primarily protein-bound, mainly to thyroxin-binding globulin.
• T4: 99.9% is bound, 0.1% is free and active.
• T3: 99.6% is bound, 0.4% is free and active.
• Aspirin displaces T3 and T4 from plasma protein binding sites, leading to increased free form.
• Loss of plasma proteins reduces binding sites for T3 and T4, increasing the free form.
• Estrogens increase binding of T3 and T4, leading to decreased free form.

Fate of Thyroid Hormones

• Major portion undergoes hepatic conjugation with glucuronic acid, leading to excretion in the bile, then into the intestine (majority excreted in stool).
• The remaining portion is deconjugated in the intestine and reabsorbed into the liver (entero-hepatic circulation).
• In the kidney (primarily) and liver, they undergo oxidative deamination and transamination:
  • T3 to tri-iodo-thyro-acetic acid
  • T4 to tetra-iodo-thyro-acetic acid
• These metabolites are excreted in the urine.
• T4 is also acted upon by tissue de-iodinase, leading to de-iodination into T3 (four times more than T4).

Pharmacodynamics of Thyroid Hormones: Actions and Toxicity

• Calorigenic effect: Increased basal metabolic rate leading to hyperpyrexia (elevated body temperature), warmth, flushing, and heat intolerance.
• Sympathetic activity: Resulting in anxiety, skeletal muscle tremors, and sweating.
• Cardiovascular System (CVS): Direct action on blood vessels and heart, causing vasodilatation (widening of blood vessels) and tachycardia (fast heart rate).
• Kidney: Diuretic action.
• Gastrointestinal Tract (G.I.T): Increased motility leading to diarrhea and malabsorption, increased appetite (but weight loss due to increased metabolic rate).

Preparations of Thyroid Hormones

• Levothyroxine sodium (L-T4): 100 micrograms/day, available as tablets or powder for injection after reconstitution.
• Liothyronine sodium (T3): 25 micrograms/day, stronger than T4 (four times more T3), quicker onset, but shorter duration.
• Liotrix: T4 + T3 in a 4:1 ratio (physiological).

Therapeutic Uses of Thyroid Hormones

• Replacement therapy in hypothyroidism: Hypothyroidism in adults (myxedema) - levothyroxine sodium is used; start with 50 micrograms/day for two weeks, 100 micrograms/day for two weeks, then 150 micrograms/day for life.
• Hypothyroidism in children (cretinism) - early treatment results in better outcomes; use levothyroxine sodium, adjusting the dose based on the child's age.
• Simple non-toxic goiter: Often caused by decreased thyroid hormones leading to increased TSH, resulting in thyroid enlargement.
• Hypercholesterolemia: D-thyroxin is used in euthyroid (normal thyroid function) or cardiac patients; levothyroxine is used in hypothyroid patients as part of replacement therapy.
• Gynaecological disorders: Amenorrhea (absence of menstruation) and recurrent abortions.

Antithyroid Drugs

• Thioamides: Decrease organification, resulting in decreased synthesis of thyroid hormones.
• Ionic inhibitors (e.g., Potassium perchlorate): Decrease iodide trapping, reducing the synthesis of T3 and T4.
• Iodide therapy (e.g., Lugol’s iodine): Reduces the effects of TSH on the thyroid gland and inhibits the release of T3 and T4.
• Radioactive 131-Iodine: Emits beta rays that destroy thyroid tissue.
• Beta-blockers (e.g., Propranolol).
• Surgical: Subtotal thyroidectomy.

Thioamides (Thiouracils and Thioureas)

• Propylthiouracil: 100mg three times daily until symptom control, then 50mg once daily orally.
• Methimazole: 10mg three times daily until symptom control, then 5mg once daily orally.
• Carbimazole: Similar to methimazole.

Mechanism of Action of Thioamides

• Inhibit organification of iodide, leading to decreased synthesis of thyroid hormones.
• Inhibit peroxidase enzyme, reducing the conversion of iodide to active elementary iodine.
• Inhibit the incorporation of iodine into thyroglobulin, hindering the formation of MIT and DIT.
• Inhibit the coupling of MIT and DIT, decreasing the synthesis of T3 and T4.

Therapeutic Uses of Thioamides

• Drugs of choice for mild hyperthyroidism.
• Temporary control of moderate and severe hyperthyroidism until preparation for subtotal thyroidectomy.

Side Effects and Toxicity of Thioamides

• Agranulocytosis (severe decrease in white blood cells).
• Hypersensitivity reactions (e.g., skin rash, gastrointestinal upsets).
• Increased size and vasculature of the thyroid gland.
• Exophthalmos (bulging eyes).
• Cretinism if given during pregnancy or lactation.
• Loss or depigmentation of hair.
• Liver and kidney damage.
• Joint pains.

Potassium Perchlorate

• Mechanism of action: Ionic inhibitor that competes with iodine for uptake and storage by the thyroid gland, leading to decreased synthesis of thyroid hormones.
• Effects:
  • Inhibits thyroid function after a latent period of one to two weeks until depletion of stored colloid.
  • Increases size and vascularity of the thyroid gland due to increased TSH.
  • Exophthalmos.

Therapeutic Uses of Potassium Perchlorate

• Similar to Thioamides; used as an alternative for patients allergic to thioamides.

Side Effects of Potassium Perchlorate

• Similar to Thioamides
• Fetal aplastic anemia.

Iodide Therapy

• Preparations:
  • Lugol’s iodine (5% iodine in 10% potassium iodide): 0.3ml three times daily orally.
  • Potassium iodide: 60mg three times daily orally.

Actions of Iodides

• Antithyroid effect:
  • Attenuates the effect of TSH on the thyroid gland.
  • Decreases size and vascularity of the thyroid gland.
  • Decreases endocytosis of thyroglobulin, leading to colloid accumulation in the follicle lumen.
  • Decreases proteolysis of thyroglobulin.
  • Decreases the release of T3 and T4.
• Saline expectorant: Sodium and potassium iodide absorbed from the stomach and intestine are secreted by all exocrine glands, causing irritation. They increase conjunctival, lacrimal, salivary, and bronchial secretions. Iodine directly liquefies tenacious sputum.

Uses of Iodides

• Chronic bronchitis.
• Pre-operative preparation (7-10 days) before subtotal thyroidectomy.
• Hyperthyroid crisis.

Side Effects of Iodides

• Allergic reactions.
• Iodism: Headache, conjunctivitis (inflammation of the conjunctiva), rhinitis (inflammation of the nasal mucous membrane), sialadenitis (inflammation of the salivary glands), and gastritis (inflammation of the stomach lining).

Radioactive Iodine-131

• Radioactive iodine-131 is trapped by the thyroid.

• Within the thyroid gland, radioactive iodine converts to radioactive T3 and T4 and is stored in colloid.

• Radioactive iodine emits two types of rays:

  • Iodine-131 (large dose): Emits beta-rays (destructive and low penetration).
  • Iodine-132 (small dose): Emits gamma-rays (non-destructive and high penetration).

• Note: The half-life of iodine-131 is 8 days; it is used for therapy. The half-life of iodine-132 is 2 hours; it is used for diagnosis.

Therapeutic Uses of Radioactive Iodine-131

• Moderate and severe hyperthyroidism in:
  • Elderly patients.
  • Cardiac patients.
  • Patients with recurrence after surgery.
  • Patients who have failed anti-thyroid drug therapy.
• The effect of treatment with radioactive iodine appears after 2-3 months, during which the patient is temporarily managed with anti-thyroid drugs plus beta-blockers.
• Cancer of the thyroid.
• Thyroid function test (small dose of iodine-132 is used, and gamma-rays are measured).

Side Effects of Radioactive Iodine-131

• Pain and congestion at the site of the thyroid.
• Hypothyroidism.

Contraindications for Radioactive Iodine-131 Therapy

• Children (risk of hypothyroidism and malignancy).
• Pregnancy (potential damage to fetal thyroid).

Beta-Blockers

• Example: Propranolol (oral and intravenous).

Advantages of Beta-Blockers

• Protects the heart from tachycardia, angina, and arrhythmia associated with hyperthyroidism.
• Reduces tremor.
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This quiz covers the basics of the thyroid gland, its functions, and the hormones it produces. Learn about the synthesis, storage, and release mechanisms of Thyroxin (T4) and Tri-iodothyronine (T3). Test your knowledge on how the body regulates metabolism through this essential endocrine gland.