Treatment of Thyroid Disorders

Treatment of Thyroid Disorders

Introduction

  • Course: Pharmacology 3B (Session 2024-25)

  • Topic: Treatment of Thyroid Disorders

  • Professor: Prof. Simon Kennedy

Intended Learning Outcomes (ILOs)

  • Describe the anatomy and physiology of the thyroid gland and regulation of hormones it secretes.

  • Explain actions and mechanisms of actions of thyroid hormones.

  • Discuss dysfunctions of the thyroid gland and thyroid hormone action along with abnormalities from over and underactivity.

  • Outline the clinical treatment of thyroid hormone dysfunction.

Thyroid Gland Anatomy

  • Location: Set beneath the larynx and in front of the trachea.

  • Structure: Composed of two lobes (right and left) and is involved in hormone production, storage, and release.

Functions of the Thyroid Gland

  • Produces and secretes hormones: thyroxine (T4), triiodothyronine (T3), and calcitonin.

  • Maintains:

  • Metabolic stability

  • Body temperature regulation

  • Growth and development

  • Energy use

Thyroid Hormone Synthesis and Regulation

  • Main Hormones:

  • T4 (Thyroxine): Predominantly secreted; less potent.

  • T3 (Triiodothyronine): More active form, derived from T4 by conversion in target tissues.

  • Functional Unit: Follicle/acinus with a cavity filled with colloid containing thyroglobulin, which is iodinated to form thyroid hormones.

  • Production Steps:

  • Iodide uptake into the follicular lumen.

  • Incorporation into thyroglobulin via thyroperoxidase enzyme.

  • Hormones processed from endocytosed thyroglobulin.

Regulation of Thyroid Function

  • Hypothalamus-Pituitary-Thyroid Axis:

  • TRH (Thyrotropin-releasing hormone) from hypothalamus stimulates TSH (Thyroid-stimulating hormone) secretion from the anterior pituitary.

  • TSH regulates:

    • Iodide uptake

    • Thyroglobulin synthesis and secretion

    • Thyroid hormone secretion (T3/T4)

    • Blood flow through thyroid gland.

Actions of Thyroid Hormones

  • Metabolism:

  • Increase in metabolism of carbohydrates, fats, and proteins in most tissues.

  • Work synergistically with insulin, glucagon, etc.

  • Enhance oxygen consumption and basal metabolic rate.

  • Growth and Development:

  • Directly affect cell growth; important for CNS maturation.

  • Act through nuclear receptors to regulate gene transcription.

Abnormalities of Thyroid Function

Hyperthyroidism

  • Symptoms: Excessive hormone activity, increased metabolic rate, weight loss, nervousness, heat sensitivity.

  • Diseases:

  • Graves’ disease: Autoimmune disorder causing overproduction of thyroid hormone.

  • Manifestations include:

    • Ophthalmopathy

    • Dermopathy

    • Acropachy (distal phalangeal changes).

Hypothyroidism (Myxoedema)

  • Symptoms: Low metabolic rate, lethargy, cold sensitivity, weight gain, skin thickening.

  • Consequences in Children: Can lead to cretinism.

Clinical Presentation

  • Graves' Disease Features:

  • Ophthalmopathy, dermopathy, acropachy.

  • Signs of Hypothyroidism:

  • Coarse features, periorbital edema, thin eyebrows, and dull visage.

Diagnosis and Monitoring

  • TSH levels indicate thyroid function:

  • Elevated TSH indicates hypothyroidism.

  • Reduced TSH may indicate hyperthyroidism.

  • TPO (Thyroid peroxidase antibodies) can indicate autoimmune thyroid issues.

Treatment Approaches

Hyperthyroidism

  • Radioiodine Therapy:

  • Administered orally; selectively taken by thyroid; leads to cell damage and eventual hypothyroidism.

  • Thioureylenes (e.g., Carbimazole, Propylthiouracil):

  • Reduce hormone synthesis; inhibit thyroperoxidase.

  • High-Dose Iodine:

  • Transiently reduces thyroid hormone secretion.

Hypothyroidism

  • Levothyroxine:

  • Standard treatment for hypothyroidism; mimics endogenous T4.

  • Liothyronine:

  • Treatment of choice for urgent cases like myxoedema coma.

Critical Situations

  • Myxoedema Coma:

  • End-stage hypothyroidism; symptoms include hypothermia and altered consciousness.

  • Treatment involves IV thyroxine and support.

  • Thyroid Storm:

  • Severe thyrotoxicosis; presents with fever, tachycardia, and confusion.

  • Life-threatening, requires prompt intervention.

Conclusion

  • Effective management of thyroid disorders involves understanding thyroid anatomy, hormone actions, and potential dysfunctions, alongside appropriate treatment approaches based on patient-specific needs and conditions.

Note: Further reading can be found in Rang and Dales Pharmacology, 9th Edition, Chapter 35.