Thyroid Hormone Synthesis and Function

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Questions and Answers

Which of the following describes the mechanism of action of the thioamides for the management of hyperthyroidism?

Block uptake of iodine by the follicular cells

Inhibit proteolysis of thyroglobulin

Block the peroxidase-catalyzed reactions (correct)

Block coupling of iodotyrosines (correct)

What is the role of beta-blockers in the management of thyrotoxicosis?

Beta-blockers enhance the uptake of iodide in the thyroid gland

Beta-blockers can inhibit the peroxidase-catalyzed reaction in the synthesis of thyroid hormones

Beta-blockers may inhibit the peripheral conversion of T4 to T3

Beta-blockers control the sympathetic symptoms of hyperthyroidism (correct)

Which process follows iodide uptake in the synthesis of thyroid hormones?

Peroxidation of iodide to form iodine (correct)

Acting upon thyroglobulin for proteolysis

Release of hormones into the bloodstream

Coupling of iodotyrosines to form T3 and T4

Which of the following hormones is produced from the coupling of DIT and MIT?

Triiodothyronine (T3) Signup and view all the answers

What is one of the functions of thyroid hormones?

Enhance β-adrenergic effects Signup and view all the answers

What is the most common cause of hypothyroidism in iodine-sufficient regions?

Hashimoto's Thyroiditis Signup and view all the answers

Which of the following is a manifestation of hyperthyroidism?

Heat intolerance Signup and view all the answers

In the context of thyroid function, which laboratory findings indicate hyperthyroidism?

↓ TSH, ↑ T3 & T4 Signup and view all the answers

What is the primary mechanism of action of Thioamides like Methimazole?

Inhibit thyroid peroxidase (TPO) Signup and view all the answers

Which disorder is characterized by hypothyroidism starting at birth, leading to severe mental retardation?

Cretinism Signup and view all the answers

Which thyroid preparation is considered the drug of choice for thyroid hormone replacement?

Levothyroxine (T4) Signup and view all the answers

What is the role of beta-blockers in thyroid storm management?

Block beta adrenoreceptors Signup and view all the answers

What defines a thyroid storm?

Severe and rapid worsening of hyperthyroidism symptoms Signup and view all the answers

Which of the following symptoms is NOT typically associated with hypothyroidism?

Heat intolerance Signup and view all the answers

What is the mechanism of action of radioactive iodine (I 131)?

Radioactive destruction of thyroid tissue Signup and view all the answers

What is a common toxicity associated with thioamide antithyroid agents?

Agranulocytosis Signup and view all the answers

Which of the following thyroid preparations carries a higher risk of cardiotoxicity?

Liothyronine (T3) Signup and view all the answers

What physiological response is primary for β 1 receptors in the heart?

Increases basal metabolic rate Signup and view all the answers

Study Notes

Thyroid Hormone

Thyroid hormone is essential for normal growth, development, and metabolism.
Synthesis, storage, and release of thyroid hormone are regulated by the hypothalamus and pituitary gland.
The thyroid gland is composed of spherical structures called thyroid follicles.
Thyroid follicles are lined by follicular epithelial cells which produce and store colloid, a protein called thyroglobulin, in the follicular lumen.

Synthesis of Thyroid Hormone:

Iodide uptake: Thyroid gland cells take up iodide from blood.
Peroxidation of iodide to iodine: Iodide is oxidized to iodine by thyroid peroxidase.
Organification of iodine: Iodine is attached to tyrosyl residues on the thyroglobulin molecule.
Coupling reaction: Monoiodotyrosine (MIT) and Diiodotyrosine (DIT) are coupled to produce two hormones:
- T4 (thyroxine): DIT + DIT
- T3 (triiodothyronine): DIT + MIT
Proteolysis: Thyroglobulin is broken down releasing T3 and T4.
Peripheral conversion of T4 to T3: T4 is converted to T3 in the peripheral tissues.

Function of Thyroid Hormone

Brain maturation.
Bone growth (synergism with growth hormone).
Β-adrenergic effects: (β1 receptors in the heart)
Increased basal metabolic rate.
Blood sugar regulation.
Breakdown of lipids.
Stimulates surfactant synthesis in infants.

Disorders of Thyroid Function

Hypothyroidism:
- Most common disorder of thyroid function.
- Characterized by increased TSH and decreased T3 and T4.
- Hashimoto's Thyroiditis:
  - Most common cause of hypothyroidism in iodine-sufficient regions.
  - Autoimmune disorder with antithyroid peroxidase (antimicrosomal) and antithyroglobulin antibodies.
- Cretinism:
  - Hypothyroidism that begins at birth resulting in developmental abnormalities and severe mental retardation.
- Myxedema:
  - Severe hypothyroidism.
Hyperthyroidism:
- Characterized by decreased TSH and increased T3 and T4.
- Grave's Disease:
  - Most common form of hyperthyroidism.
  - Autoimmune disorder with TSH receptor stimulating antibodies.
  - Presents with the typical manifestations of hyperthyroidism and can also cause Grave's ophthalmology, characterized by eye bulging.
- Thyroid Storm:
  - Sudden acute exacerbation of all the symptoms of hyperthyroidism, presenting as a life-threatening syndrome.

Comparison of Hypothyroidism and Hyperthyroidism

Metabolic:
- Hypothyroidism: Cold intolerance, decreased sweating, weight gain, decreased basal metabolic rate.
- Hyperthyroidism: Heat intolerance, increased sweating, weight loss, increased basal metabolic rate.
Skin/Hair:
- Hypothyroidism: Dry, cool skin, puffy face and generalized nonpitting edema, coarse hair.
- Hyperthyroidism: Moist, warm skin, fine hair, onycholysis (nail separation).
Ocular:
- Hypothyroidism: Periorbital edema.
- Hyperthyroidism: Ophthalmology seen in Grave's disease.
Gastrointestinal:
- Hypothyroidism: Constipation, decreased appetite.
- Hyperthyroidism: Hyperdefecation (increased motility), increased appetite.
Musculoskeletal:
- Hypothyroidism: Muscle fatigue, carpal tunnel syndrome, decreased deep tendon reflex.
- Hyperthyroidism: Muscle fatigue, osteoporosis, increased deep tendon reflex, fine tremors.
Reproductive:
- Hypothyroidism: Decreased libido, infertility, increased gonadal steroid metabolism.
- Hyperthyroidism: Decreased libido, infertility, decreased gonadal steroid metabolism.
Cardiovascular:
- Hypothyroidism: Bradycardia (slow heart rate).
- Hyperthyroidism: Tachycardia (fast heart rate), arrhythmia, palpitations.
Labs:
- Hypothyroidism: Increased TSH, decreased free T3/T4.
- Hyperthyroidism: Decreased TSH, increased free T3/T4.

Thyroid Preparations

Dessicated Thyroid:
- Mixture of levothyroxine and liothyronine (2-5:1 ratio).
- Less preferred treatment option.
Levothyroxine (T4):
- Preferred treatment for thyroid replacement and suppression.
- Stable, uniform content, low cost, lack of allergic foreign protein, longer half-life.
- Peripherally converted to T3.
Liothyronine (T3):
- 3-4 times more potent than T4.
- Requires multiple doses and is difficult to monitor.
- Greater risk for cardiotoxicity.

Antithyroid Agents

Thioamides:
- Methimazole (MMI):
  - 10 times more potent than PTU.
  - Used for children and adults.
- Propylthiouracil (PTU):
  - Preferred agent for pregnant women.
- Mechanism of Action:
  - Inhibit the thyroid peroxidase (TPO) enzyme.
  - Inhibit coupling and organification of iodine.
  - Inhibit peripheral conversion of T4 to T3.
- Uses: Manage hyperthyroidism.
- Toxicity:
  - Gastrointestinal distress, rash.
  - Agranulocytosis (severe decrease in white blood cells).
  - Aplasia cutis congenita (birth defect characterized by missing skin).
Anion Inhibitors:
- Perchlorate (ClO4-), Pertechnetate (TcO4-), Thiocyanate (SCN-).
- Mechanism of Action: Block iodide transport mechanism.
- Uses: Manage iodide-induced hyperthyroidism, such as that caused by amiodarone.
Iodides:
- Lugol Solution, Potassium Iodide (KI).
- Mechanism of Action:
  - Inhibit organification and hormone release.
  - Decrease the size and vascularity of the thyroid gland.
- Uses: Manage hyperthyroidism and thyroid storm.
- Used to prepare patients for surgical thyroidectomy.
- Toxicity:
  - Iodism (symptoms include acneiform rash, swollen salivary glands, and mucosal ulceration).
Radioactive Iodine (I131):
- Mechanism of Action: Radioactive destruction of thyroid parenchyma.
- Uses: Manage hyperthyroidism.
- Toxicity: Sore throat, Sialitis (inflammation of salivary glands), Hypothyroidism.
Beta-Blockers:
- Metoprolol, Atenolol, Propranolol.
- Mechanism of Action:
  - Block beta-adrenoreceptors.
  - Propranolol also inhibits peripheral conversion of T4 to T3.
- Uses:
  - Manage thyroid storm.
  - Used as an adjunct therapy to control tachycardia, hypertension, and arrhythmia in patients with hyperthyroidism.

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Description

This quiz covers the critical roles of thyroid hormones in growth, metabolism, and development. Learn about the synthesis, storage, and release of thyroid hormones, including the detailed biochemical processes involved. Test your understanding of how iodide is utilized and the production of T3 and T4 hormones.