Overview
This lecture covers hypothyroidism, its pathophysiology, causes, clinical features, and approaches to treatment with synthetic and non-synthetic thyroid hormone replacement therapies.
Basics of Hypothyroidism and Thyroid Hormones
- Hypothyroidism is a condition with insufficient thyroid hormone production (T3 and T4).
- Thyroid hormones are produced in the thyroid gland, which consists of follicles lined by follicular cells.
- Synthesis involves iodide uptake, oxidation (via TPO), iodination, and coupling to make T3 (active) and T4 (less active).
- T4 is produced in greater amounts but T3 is more potent.
Regulation and Function of Thyroid Hormones
- The hypothalamus releases TRH, which stimulates the pituitary to release TSH.
- TSH stimulates the thyroid to produce and release T3 and T4.
- Most thyroid hormones are transported bound to TBG; only free hormones are active.
- T3 acts on nuclear receptors to regulate metabolism, sympathetic activity, GI motility, and fetal development.
Types and Causes of Hypothyroidism
- Primary: due to thyroid gland dysfunction (e.g., Hashimoto’s, iodine deficiency, post-thyroidectomy).
- Secondary: due to insufficient TSH (e.g., pituitary tumors).
- Tertiary: due to insufficient TRH from the hypothalamus.
- Congenital: present at birth, from gland dysgenesis or defective hormone synthesis.
Clinical Features and Emergencies
- Symptoms: cold/dry skin, cold intolerance, hair loss, weight gain, constipation, lethargy, delayed development in children.
- Myxedema coma: acute, life-threatening hypothyroid state in the elderly after stress.
Treatment Approaches
- Iodine deficiency: treat with iodine-rich foods.
- Synthetic thyroid hormone replacement is main therapy for most types:
- Levothyroxine (T4 analog): long-acting, standard for chronic therapy and pregnancy.
- Lyothyronine (T3 analog): short-acting, used in emergencies (myxedema coma).
- Dose adjustments needed in pregnancy (increase dose), and in elderly or those with heart issues (start low).
- Non-synthetic therapies include liatrix (synthetic T4/T3 mix) and desiccated thyroid (porcine-derived, variable potency).
Drug Interactions and Contraindications
- Drugs reducing levothyroxine absorption: iron, calcium, PPIs, sucralfate, bile acid binders.
- Drugs increasing metabolism: rifampin, phenytoin, carbamazepine.
- Drugs altering TBG levels: estrogens (increase, need higher dose), androgens/glucocorticoids (decrease, need lower dose).
- Propranolol decreases T4→T3 conversion; may require higher levothyroxine doses.
- Contraindication: uncorrected adrenal insufficiency (risk of adrenal crisis).
Special Therapeutic Uses and Risks
- TSH-suppressive therapy: used in thyroid cancer and nodules to prevent growth/recurrence.
- Long-term thyroid hormone use increases osteoporosis and may worsen diabetes control.
- Thyroid hormones should not be used solely for weight loss.
Key Terms & Definitions
- Hypothyroidism — insufficient production of thyroid hormones.
- T3 (Triiodothyronine) — active thyroid hormone.
- T4 (Thyroxine) — less active, longer half-life thyroid hormone.
- TSH — Thyroid Stimulating Hormone, stimulates thyroid hormone synthesis.
- TRH — Thyrotropin-Releasing Hormone, stimulates TSH release.
- TPO — Thyroid Peroxidase, enzyme for hormone synthesis.
- Levothyroxine — synthetic T4, standard hypothyroidism therapy.
- Lyothyronine — synthetic T3, used in hypothyroid emergencies.
- TBG (Thyroxine-Binding Globulin) — blood protein that binds thyroid hormones.
Action Items / Next Steps
- Review the synthesis and regulation of thyroid hormones.
- Know the differences between primary, secondary, tertiary, and congenital hypothyroidism.
- Memorize main drug interactions affecting thyroid therapy.
- Read more on Hashimoto’s thyroiditis and myxedema coma for clinical significance.
- Practice adjusting levothyroxine dosing in different patient scenarios.