Thyroid Disorders: Biochemical Investigations

• The document provides information about the biochemical investigation of thyroid disorders, including thyroid function tests, pathophysiology, and future trends in diagnostics.
• The content is presented by Dr. Yusuff J.O. from the Department of Chemical Pathology and Immunology at the University of Ilorin.

Introduction to Thyroid Disorders

• The thyroid gland, located in the neck, is a butterfly-shaped organ.
• The thyroid gland produces thyroid hormones T3 and T4.
• Thyroid hormones are responsible for regulating metabolism, growth, and development.
• Common thyroid disorders include:
  • Hypothyroidism, or underactive thyroid, an example being Hashimoto's thyroiditis.
  • Hyperthyroidism, or overactive thyroid, exemplified by Graves' disease.
  • Goiter, which is the enlargement of the thyroid gland.
  • Thyroid nodules, referring to abnormal growths in the thyroid.
  • Thyroid cancer, or malignant tumors of the thyroid.

Thyroid Hormones and their Functions

• Thyroxine (T4) is produced in larger quantities and is converted to T3 in tissues.
• Triiodothyronine (T3) is the biologically active form of thyroid hormone.
• Thyroid-Stimulating Hormone (TSH) is secreted by the pituitary gland and regulates T3 and T4 production.
• The Hypothalamic-Pituitary-Thyroid Axis involves:
  • The hypothalamus releasing Thyrotropin-Releasing Hormone (TRH).
  • TRH stimulating the pituitary gland to release TSH.
  • TSH stimulating the thyroid to produce T3 and T4.

Thyroid Function Tests (TFTs)

• TSH is the most sensitive marker for thyroid function.
• Free T4 measures unbound, biologically active T4.
• Free T3 measures unbound, biologically active T3.
• Total T4 and Total T3 measure both bound and unbound hormone levels.
• Indications for testing include:
  • Symptoms of hypothyroidism like fatigue, weight gain, and cold intolerance.
  • Symptoms of hyperthyroidism like weight loss, heat intolerance, and palpitations.
  • Screening in high-risk populations such as pregnant women and the elderly.

Pathophysiology - Hypofunctioning

• Hypofunctioning of the thyroid leads to a slowing of metabolic processes.
• Possible causes of hypofunctioning include:
  • Auto-immune destruction of the gland, such as in Hashimoto's thyroiditis.
  • Inflammatory processes like De Quavain's thyroiditis.
  • Nutritional deficiencies such as iodine deficiency.
  • Congenital hormone synthesis issues leading to congenital hypothyroidism, like Pendred syndrome.
  • Exposure to radiation or surgeries.

Pathophysiology - Hyperfunctioning

• Hyperfunctioning leads to increased basal metabolic rates.
• Possible causes of hyperfunctioning include:
  • Auto-immune diseases like Graves disease.
  • Nutritional factors like Jods-Basedow's disease.
  • Toxic causes like multinodular or Plummer's disease.

Signs and Symptoms to Request Thyroid Tests

• High suspicion of thyroid disease is indicated by:
  • Goiter.
  • Delayed reflexes, which suggests Hypothyroidism
  • Thyroid bruit, Lid lag, and Proptosis, which suggests Hyperthyroidism
• Intermediate suspicion is indicated by:
  • Fatigue.
  • Weight gain or difficulty losing weight, cold intolerance, dry/rough/pale skin, constipation, Family history and hoarseness, which suggests Hypothyroidism.
  • Weight loss despite increased appetite, heat intolerance/sweating, fine tremor, family history, increased bowel movements, fast heart rate/palpitations or staring gaze, which suggest Hyperthyroidism
• Low suspicion, non-specific symptoms include:
  • Coarse, dry hair, hair loss, muscle cramps/aches, depression, irritability, memory loss, abnormal menstrual cycles, and decreased libido, which suggests Hypothyroidism
  • Nervousness, insomnia, breathlessness, light or absent periods, weight loss, muscle weakness, warm moist skin or hair loss, which suggests Hyperthyroidism

Thyroid Function Tests (TFTS) - Reference Intervals

• TSH normal range is 0.4–4.0 mIU/L.
• Free T4 normal range is 0.8–1.8 ng/dL.
• Free T3 normal range is 2.3 – 4.2 pg/mL.

Interpretation of Thyroid Function Tests

• Primary Hypothyroidism is indicated by high TSH and low Free T4.
• Primary Hyperthyroidism is indicated by low TSH, high Free T4 and Free T3.
• Subclinical Hypothyroidism: High TSH, normal Free T4.
• Subclinical Hyperthyroidism: Low TSH, normal Free T4.

Hypothyroidism Biochemical Investigation

• Hypothyroidism causes include autoimmune disorders like Hashimoto's thyroiditis, iodine deficiency, and medications like lithium and amiodarone.
• Biochemical Findings: Elevated TSH and Low Free T4.
• Additional Tests: Anti-TPO antibodies for autoimmune hypothyroidism.

Hyperthyroidism Biochemical Investigation

• Hyperthyroidism causes include Graves' disease (autoimmune), toxic nodular goiter, and thyroiditis, like postpartum thyroiditis.
• Biochemical Findings: Suppressed TSH, and Elevated Free T4 and Free T3.
• Additional Tests: TSH Receptor Antibodies (TRAb) for Graves' disease.

Thyroid Antibodies in Autoimmune Disorders

• Anti-Thyroid Peroxidase (TPO) Antibodies are present in Hashimoto's thyroiditis.
• Anti-Thyroglobulin (Tg) Antibodies are present in Hashimoto's thyroiditis.
• TSH Receptor Antibodies (TRAb) are present in Graves' disease.

Imaging in Thyroid Disorders

• Ultrasound evaluates thyroid size, nodules, and structure.
• Radioactive Iodine Uptake (RAIU) assesses thyroid function, especially in hyperthyroidism.
• Thyroid Scan differentiates between Graves' disease and toxic nodular goiter.

Case Study

• A 45-year-old female presents with fatigue, weight gain, and cold intolerance
• Her biochemical findings are TSH = 12 mIU/L (high), Free T4 = 0.6 ng/dL (low).
• The diagnosis is primary hypothyroidism due to Hashimoto’s thyroiditis.
• Management involves Levothyroxine replacement therapy.

Challenges in Thyroid Testing

• Interferences from heterophilic antibodies, which can cause false results.
• Biotin supplements can affect immunoassays.
• Non-Thyroidal Illness (Euthyroid Sick Syndrome) causes Abnormal TFTs in critically ill patients.

Future Trends in Thyroid Diagnostics

• Molecular Testing: Genetic markers for thyroid cancer (e.g., BRAF mutation).
• Point-of-Care Testing: Rapid TFTs for faster diagnosis.
• Artificial Intelligence (AI): Improved interpretation of imaging and lab results.

Conclusion

• Accurate interpretation of TFTs requires understanding of the hypothalamic-pituitary-thyroid axis.
• Challenges like interferences and non-thyroidal illness must be considered.