UPSC MainsMEDICAL-SCIENCE-PAPER-I20188 Marks
Q11.

Role of iodine in synthesis and function of thyroid hormone. What is Graves Disease?

How to Approach

This question requires a two-part answer. First, detail the role of iodine in thyroid hormone synthesis and function, covering the biochemical steps involved. Second, explain Graves’ disease – its pathophysiology, clinical features, and underlying mechanisms. Structure the answer by first addressing iodine’s role, then dedicating a separate section to Graves’ disease. Use diagrams or flowcharts where appropriate to illustrate the hormone synthesis pathway. Focus on the physiological and pathological aspects relevant to medical science.

Model Answer

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Introduction

The thyroid gland, a vital component of the endocrine system, produces thyroid hormones – thyroxine (T4) and triiodothyronine (T3) – crucial for regulating metabolism, growth, and development. These hormones are synthesized using iodine, making it an essential micronutrient. Disruptions in thyroid hormone production, whether due to iodine deficiency or autoimmune conditions like Graves’ disease, can lead to significant health consequences. Graves’ disease, discovered by Robert Graves in 1835, is an autoimmune disorder characterized by hyperthyroidism and often, ophthalmopathy.

Role of Iodine in Thyroid Hormone Synthesis and Function

Iodine is an indispensable component of thyroid hormones. The synthesis of thyroid hormones is a multi-step process:

  • Iodide Trapping: The thyroid follicular cells actively transport iodide (I-) from the bloodstream into the follicular lumen against a concentration gradient. This is mediated by the Sodium-Iodide Symporter (NIS).
  • Iodide Oxidation: Within the follicular lumen, iodide is oxidized to iodine (I2) by the enzyme thyroid peroxidase (TPO). Hydrogen peroxide (H2O2) is required for this reaction.
  • Organification: Iodine is then attached to tyrosine residues within thyroglobulin, a large protein synthesized in the follicular cells. This process, also catalyzed by TPO, forms monoiodotyrosine (MIT) and diiodotyrosine (DIT).
  • Coupling: MIT and DIT molecules are coupled together to form T3 (MIT + DIT) and T4 (DIT + DIT).
  • Endocytosis & Hormone Release: The follicular cells endocytose the thyroglobulin, and lysosomes break down the thyroglobulin, releasing T3 and T4 into the bloodstream.

Functions of Thyroid Hormones (T3 & T4):

  • Metabolic Regulation: Increase basal metabolic rate, oxygen consumption, and heat production.
  • Growth and Development: Essential for normal brain development, skeletal growth, and reproductive function.
  • Cardiovascular Effects: Increase heart rate, contractility, and cardiac output.
  • Neurological Effects: Affect mood, cognitive function, and reflexes.

T4 is the major hormone produced by the thyroid, but T3 is the more biologically active form. T4 is converted to T3 in peripheral tissues by deiodinase enzymes.

Graves’ Disease

Graves’ disease is an autoimmune disorder characterized by hyperthyroidism caused by antibodies that stimulate the thyroid-stimulating hormone (TSH) receptor. These antibodies, known as thyroid-stimulating immunoglobulins (TSIs), mimic the action of TSH, leading to excessive thyroid hormone production.

Pathophysiology

The exact cause of Graves’ disease is unknown, but it is believed to be a combination of genetic predisposition and environmental factors. TSIs bind to the TSH receptor on thyroid follicular cells, activating the receptor and causing increased synthesis and release of T3 and T4. This leads to a positive feedback loop, further exacerbating hyperthyroidism.

Clinical Features

  • Hyperthyroidism Symptoms: Weight loss, increased appetite, heat intolerance, sweating, anxiety, irritability, palpitations, and fatigue.
  • Goiter: Enlargement of the thyroid gland.
  • Graves’ Ophthalmopathy: Characterized by proptosis (bulging eyes), periorbital edema, and diplopia (double vision). This is caused by inflammation and accumulation of glycosaminoglycans in the orbital tissues.
  • Graves’ Dermopathy (Pretibial Myxedema): Thickening and discoloration of the skin, typically on the shins.

Diagnosis

  • Thyroid Function Tests: Elevated T3 and T4 levels, suppressed TSH levels.
  • TSH Receptor Antibodies: Presence of TSIs in the blood.
  • Radioactive Iodine Uptake Scan: Shows increased uptake of iodine by the thyroid gland.

Treatment

  • Antithyroid Drugs: Methimazole and propylthiouracil inhibit thyroid hormone synthesis.
  • Radioactive Iodine Therapy: Destroys thyroid cells, reducing hormone production.
  • Surgery (Thyroidectomy): Removal of the thyroid gland.
  • Beta-blockers: Used to manage symptoms like palpitations and anxiety.

Conclusion

Iodine plays a critical and non-negotiable role in the synthesis of thyroid hormones, which are essential for numerous physiological processes. Graves’ disease, a complex autoimmune condition, disrupts this delicate hormonal balance, leading to hyperthyroidism and a range of associated symptoms. Understanding the pathophysiology and clinical manifestations of Graves’ disease is crucial for effective diagnosis and management, ultimately improving patient outcomes. Continued research into the genetic and environmental factors contributing to this disease is vital for developing more targeted therapies.

Answer Length

This is a comprehensive model answer for learning purposes and may exceed the word limit. In the exam, always adhere to the prescribed word count.

Additional Resources

Key Definitions

Thyroglobulin
A large glycoprotein synthesized in the thyroid follicular cells that serves as a scaffold for the attachment of iodine and the formation of thyroid hormones.
TSI (Thyroid-Stimulating Immunoglobulin)
Antibodies produced in Graves’ disease that bind to and activate the TSH receptor, leading to excessive thyroid hormone production.

Key Statistics

Globally, an estimated 7.5% of the population has some form of thyroid disease, with Graves’ disease accounting for a significant proportion of hyperthyroidism cases.

Source: World Thyroid Organization (as of knowledge cutoff 2023)

Graves’ disease is approximately 7-8 times more common in women than in men.

Source: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) (as of knowledge cutoff 2023)

Examples

Hashimoto's Thyroiditis vs. Graves' Disease

Both are autoimmune thyroid diseases, but Hashimoto's causes hypothyroidism (underactive thyroid) due to antibody-mediated destruction of thyroid cells, while Graves' disease causes hyperthyroidism due to antibody stimulation of the TSH receptor.

Frequently Asked Questions

What is the role of selenium in thyroid hormone metabolism?

Selenium is a cofactor for deiodinase enzymes, which convert T4 to the more active T3. Selenium deficiency can impair thyroid hormone metabolism.

Topics Covered

PhysiologyEndocrinologyThyroid HormoneIodine MetabolismAutoimmune Diseases