Lecture on Hypothyroidism and Thyroid Hormone Replacement

Introduction to Hypothyroidism

• Hypothyroidism: Condition with insufficient thyroid hormones.
• Thyroid Hormones: Triiodothyronine (T3) and Thyroxine (T4).
  • Produced by the thyroid gland in the neck.
  • Essential for metabolism and physiological effects.

Thyroid Gland Structure and Hormone Synthesis

• Thyroid Gland: Located anterior in the neck, consists of two lobes.
• Thyrocytes: Line the follicles within the gland.
• Colloid: Central lumen with thyroglobulin, precursor to thyroid hormones.

Steps of Hormone Synthesis

1. Iodide Trapping: Uptake of iodide ions into follicular cells.
2. Oxidation and Iodination: Conversion of iodide to iodine, attachment to tyrosine residues (MIT and DIT).
3. Coupling: MIT and DIT couple to form T3, two DITs form T4.

Regulation of Thyroid Hormone Production

• Controlled by the Hypothalamus-Pituitary Axis.
  • TRH from hypothalamus stimulates TSH release from the pituitary.
  • TSH: Stimulates T3 and T4 production.
  • Free vs. Bound Hormones: Only free hormones are active.

Types of Hypothyroidism

1. Primary Hypothyroidism: Problem in the thyroid gland (e.g., iodine deficiency, Hashimoto's).
2. Secondary Hypothyroidism: Insufficient TSH production (e.g., pituitary tumor).
3. Tertiary Hypothyroidism: Insufficient TRH production by the hypothalamus.
4. Congenital Hypothyroidism: Present at birth, underdeveloped gland or ineffective hormone production.

Symptoms of Hypothyroidism

• Cold intolerance, dry skin, weight gain, constipation.
• Mental symptoms: Lethargy, fatigue.
• In infants: Delayed development.
• Myxedema Coma: Acute decrease in T3/T4, medical emergency.

Treatment for Hypothyroidism

• Iodine Deficiency: Provide iodine-rich foods.
• Thyroid Replacement Therapy: Synthetic hormones.
  • Lyothyronine (T3): Potent, short-acting, emergency use.
  • Levothyroxine (T4): Long-acting, choice for chronic therapy.

Considerations

• Pregnancy: Increase Levothyroxine dose due to high estrogen levels.
• Cardiovascular Sensitivity: Start with lower doses in sensitive individuals.

Drug Interactions

• Decreased Absorption: Iron, calcium, PPIs, etc. require higher Levothyroxine doses.
• Increased Metabolism: Rifampin, phenytoin, etc.
• Binding Globulin Effects: Estrogens, androgens affect free T4 levels.
• Propranolol: Reduces T4 to T3 conversion.

Additional Uses of Thyroid Hormones

• TSH Suppressive Therapy: Reduce TSH-sensitive growth (e.g., nodules, cancer).

Contraindications

• Adrenal Insufficiency: Must address before thyroid treatment.
• Long-term Risks: Osteoporosis, worsened glycemic control.

Alternative Preparations

• Liatrix: Synthetic T4 and T3 mixture.
• Desiccated Thyroid: Natural T3 and T4 from pigs, less reliable.

Recap

• Address iodine deficiency with diet.
• Use synthetic hormones for gland or pituitary issues.
• Levothyroxine: Long-term treatment.
• Lyothyronine: Rapid treatment in emergencies.
• Non-synthetic hormone replacement less reliable.