Study Notes on Thyroid Pharmacology and Disorders

Quiz Preparation and Class Instructions

  • All belongings must be placed at the front of the room before beginning.
  • No cell phones or technology allowed during the quiz/exam.

Course Overview

  • Lecture focused on the pharmacology of medications used in thyroid disorders: hyperthyroidism and hypothyroidism.
  • Handouts and self-study materials available for review prior to the quiz.
  • Summary of lecture will be posted post-class to assist with studying.
  • Emphasis placed on understanding rather than memorizing all slides for the quiz and exam.
  • All quiz questions sourced from NAPLEX verbatim.

Physiology of the Thyroid Gland

Hormones Produced

  • Thyroid Hormones: Specifically, thyroxine (T4) and triiodothyronine (T3)
      - Calcitonin: Secretion from a different cell type in the thyroid, involved in calcium regulation and osteoporosis treatment, but not classified as a thyroid hormone.

Synthesis of Thyroid Hormones

  • Iodine Uptake: First step; iodine taken from blood via sodium-iodine symporter (NIS), against a concentration gradient using secondary active transport.
      - Rapid process: When injecting radio-labeled iodine, uptake occurs within seconds.
  • Iodine Organification: Conversion of iodine to incorporate it into tyrosine residues in thyroglobulin (Tg) by thyroperoxidase (TPO).
      - Catalyzed by TPO using hydrogen peroxide.
      - Stores thyroid hormones for extended periods in the thyroid gland, unlike adrenal hormones that are synthesized and released on-demand.
  • Conversion of T4 to T3:
      - T4 (inactive/storage form) is converted to T3 (active form) in peripheral tissues.
      - T3 is 3-5 times more biologically active than T4.

Role in Metabolism and Effects

  • Both hormones essential for growth, development, and energy metabolism.
  • Hormone Binding: Over 99% of T4 and T3 are bound to plasma proteins (primarily thyroxine-binding globulin, TBG).
  • Plasma Levels:
      - T4 typically higher in binding than T3, affecting biological activity.
Physiological Effects of Thyroid Hormones
  • Metabolism: Increase in mitochondrial metabolism, respiratory enzymes, oxygen consumption, protein synthesis, and thermogenesis via uncoupling proteins in brown fat.
  • Cardiovascular Effects: Increased cardiac output, heart rate, blood pressure, and ventilation rates.
  • Growth and Development: Essential for physical and mental development, including linear bone growth and neurogenesis up to six months postpartum.

Pathophysiology of Thyroid Disorders

Hyperthyroidism

  • Autoimmune component: Graves' disease as a common cause characterized by exophthalmos due to activating antibodies against the TSH receptor.
  • Medications such as amiodarone can induce hyperthyroidism or hypothyroidism, depending on patient iodine status.

Hypothyroidism

  • Commonly due to Hashimoto's thyroiditis, an autoimmune hypothyroid condition.
  • Various medications and external factors causing secondary hypothyroidism discussed.

Pharmacology of Thyroid Medications

Synthetic T3 and T4

  • Levothyroxine: Synthetic T4, commonly used for hypothyroidism.
  • Liothyronine: Synthetic T3, used primarily in emergencies like myxedema coma.
  • Administration Tips:
      - Levothyroxine should be taken on an empty stomach for better absorption and consistent hormone levels.

Antithyroid Medications

  • Thionamides: Methimazole and Propylthiouracil (PTU), used to reduce thyroid function in hyperthyroidism.
      - Mechanism: Inhibition of TPO blocking the synthesis of T3 and T4.
      - Propylthiouracil also inhibits the conversion of T4 to T3, making it act faster in emergencies.
      - Adverse effects include agranulocytosis, rashes, and drug-induced lupus syndrome.

Radioiodine Treatment

  • Used for: Treatment of thyroid tumors by destroying thyroid tissue with radioactive iodine (I-131); leads to eventual hypothyroidism requiring hormonal replacement.

Beta Blockers

  • Propranolol: Used in hyperthyroidism to alleviate cardiovascular symptoms; inhibits conversion of T4 to T3.
      - Cautions: May cause asthma exacerbations in asthmatic patients due to non-selective blocking of beta receptors.
  • Alternatives: Beta-1 selective blockers like metoprolol for patients with asthma or diabetes.

Thyroid Eye Disease (TED)

  • Treatment: Antithyroid drugs & beta blockers do not help TED.
      - Preferred treatments include glucocorticoids and monoclonal antibodies like Teprotumumab to target the IGF-1 receptor.

Summary Notes for Examination

  • Focus on the pharmacology of thionamides (methimazole and PTU), synthetic thyroid hormones (T4 and T3), and beta-blockers in relation to thyroid disorders.
  • Understand the synthesis and physiological effect of thyroid hormones and the importance of iodine in thyroid function.
  • Familiarity with common pathologies like Hashimoto's (hypothyroidism) and Graves' disease (hyperthyroidism).
  • Keep in mind the significance of clinical effects for both physiological and pharmacotherapy approaches to treatment.