Week 1 Thyroid Structure, Function, and Testing Guide

CHE2 Week 1: Blackboard Collaborate Review

  • Key Concepts:

    • Hypothalamus

    • Thyrotropin-releasing hormone (TRH)

    • Pituitary gland

    • Thyroid-stimulating hormone (TSH)

    • Thyroid gland

    • Thyroid hormones: Thyroxine (T4) & Triiodothyronine (T3)

    • Peripheral tissues

Thyroid Structure & Function

Basic Structure

  • Description:

    • The thyroid is a butterfly-shaped organ located in the neck, centered near the trachea, consist of two connected lobes.

  • Location details:

    • The position is marked by an oblique line on the thyroid cartilage associated with the larynx.

    • The right thyroid gland and left thyroid gland are positioned adjacent to the trachea.

    • Other anatomical landmarks include the hyoid bone, thyroid notch, laryngeal prominence, cricothyroid ligament, and the arch of cricoid.

  • Functions:

    • Regulates metabolism, growth, and development.

    • Enhances catecholamine effects.

Thyroid Follicles

  • Definition:

    • The basic structural unit of the thyroid, known as a follicle.

  • Components:

    • Each follicle consists of a single circle of thyroid follicular cells surrounding a lumen.

    • The lumen is filled with colloid, a proteinaceous fluid where thyroid hormone precursors (such as thyroglobulin) are stored.

Thyroid Hormone Production Pathway

  • Process Description:

    1. Iodination: The process of attaching iodine to tyrosine residues in thyroglobulin.

    2. Oxidation & Endocytosis:

    • Follicular cells absorb iodinated thyroglobulin through endocytosis.

    1. Proteolysis & Exocytosis:

    • Thyroglobulin is cleaved to release T4 and T3.

      • Final Products:

    • Thyroxine (T4) and Triiodothyronine (T3).

Thyroid Regulation and Feedback Mechanisms

Normal Regulation of Thyroid Hormones

  • Key Players:

    • Hypothalamus releases TRH (Thyrotropin-releasing hormone).

    • This stimulates the anterior pituitary gland to produce TSH (Thyroid-stimulating hormone).

    • TSH acts on the thyroid gland to synthesize T4 and T3.

  • Feedback Loop:

    • Increased levels of T4 and T3 provide negative feedback to reduce TRH and TSH release.

Physiologic or Emotional Stress Effects

  • Effects of Stress:

    • Stress can impact thyroid hormone levels and metabolism, which can alter TRH and TSH production.

    • Iodine regulation can be influenced, leading to conditions such as the Jod-Basedow effect (hyperthyroid response to increased iodine) or Wolff-Chaikoff effect (i.e., decreased synthesis of T4 and T3).

Thyroid Clinical Significance

Hypothyroidism Symptoms:

  • Clinical Manifestations include:

    • Hair loss

    • Apathy, lethargy

    • Dry skin, muscle aches

    • Weakness, constipation

    • Cold intolerance, bradycardia

    • Changes in menstrual cycle, including amenorrhea

    • Weight gain, subnormal body temperature

    • Thickening of skin and cardiac complications

Hyperthyroidism Symptoms:

  • Clinical Manifestations include:

    • Intolerance to heat, increased appetite, weight loss, muscle wasting

    • Tremors, anxiety, diarrhea

    • Goiter (enlarged thyroid), bulging eyes, facial flushing

    • Tachycardia, breast enlargement, systolic blood pressure changes

Thyroid Conditions: Primary vs Secondary

Condition

TSH

T4

Normal

Normal

Normal

Hyperthyroidism

Low (Primary) / High (Secondary)

High

Hypothyroidism

High (Primary) / Low (Secondary)

Low

Thyroid Testing

Thyroid Function Tests

  • Key Tests:

    • Measurement of TSH, free T4 (fT4), and total T3 levels.

  • Clinical Interpretations:

    • Elevated TSH with decreased fT4 indicates primary hypothyroidism.

    • Low TSH and elevated fT4 indicate hyperthyroidism.

    • Normal fT4 with high TSH suggests subclinical hypothyroidism.

Euthyroid Sick Syndrome

  • Description:

    • Occurs during non-thyroidal illnesses (NTI) where thyroid function tests are abnormal despite no dysfunction in the thyroid or pituitary.

    • After recovery from NTI, thyroid tests normalize.

  • Associated Conditions:

    • GI disorders, pulmonary disease, renal disease, metabolic disorders, myocardial infarction, cancer, starvation, sepsis, burns, trauma, surgery, and cardiovascular disease.

Thyroid Testing - Clinical Significance

Evaluation of Hyperthyroidism

  • Interpreting Results:

    • Low TSH coupled with elevated fT4 indicates primary hyperthyroidism.

    • If TRAb test is positive, it suggests Graves' disease.

  • Testing Methodologies:

    • TRH stimulation tests can help differentiate types of hypothyroidism.

Thyroid Autoantibodies Testing

  • Types of Autoantibodies:

    • Thyrotropin receptor antibodies (TRAb)

    • Thyroid-stimulating immunoglobulin (TSI)

    • Thyroid-stimulating blocking antibodies (TSHBAb)

    • Antibodies to thyroperoxidase (TPO) and thyroglobulin.

  • Clinical Implications:

    • Useful in confirming diagnoses and monitoring autoimmune thyroid disease responses.

Reverse T3 (rT3)

  • Definition:

    • Reverse T3 is an inactive metabolite derived from T4 deiodination.

  • Clinical Relevance:

    • Often elevated during NTI where total T3 is commonly low.

Summary of Testing Procedures

  1. Evaluate: Measure TSH and T4 levels carefully to diagnose.

  2. Follow-Up Tests: For abnormal results, measure antibodies, repeat tests, or consider advanced functional evaluations (e.g. TRH stimulation) as clinically indicated.

  3. Recommendations: Monitor autoantibodies and conducting annual follow-ups in patients under T4 treatment.

Important Resources and References

  • Longo DL, Fauci AS, Kasper DL, Hauser SL, Jameson JL, Loscalzo

  • Harrison's Principles of Internal Medicine, 18th Edition.

  • www.accessmedicine.com