Thyroid Gland: Physiology, Hormones, and Disorders

Anatomy and Core Function of the Thyroid Gland

The thyroid gland is a butterfly-shaped endocrine organ that straddles the trachea at the level of the larynx. Each lobe contains myriad spherical follicles, whose lumina store colloid (thyroglobulin + iodide). Surrounding parafollicular (C-cells) secrete calcitonin.

• Primary Function – Continuous secretion of hormones that regulate systemic metabolism, growth and development, and, to a lesser degree, calcium homeostasis.

• Blood Supply & Innervation – Exceptionally high perfusion (≈ 5\,\text{mL}\,\text{g}^{-1}\,\text{min}^{-1}), sympathetic adrenergic input modulates iodide uptake and colloid endocytosis.

Hypothalamic–Pituitary–Thyroid (HPT) Axis

1. Hypothalamus releases thyrotropin-releasing hormone (TRH).
2. TRH travels via the hypophyseal portal system to the anterior pituitary, stimulating thyrotrophs.
3. The pituitary secretes thyroid-stimulating hormone (TSH), a glycoprotein with \alpha and \beta subunits.
4. TSH binds its G-protein-coupled receptor on follicular cells, increasing cAMP, iodide trapping, thyroglobulin iodination, and colloid endocytosis.
5. Rising circulating T3 and T4 exert negative feedback at both hypothalamic and pituitary levels (classical endocrine feedback loop).

Hormones Synthesised by the Thyroid

• Tri-iodothyronine (T3) – Biologically most potent; ~15\% of total secreted hormone, yet ~80\% is generated peripherally by 5’-deiodination of T4.

• Thyroxine (T_4) – Pro-hormone, ~90\% of direct glandular output, half-life ≈ 7\,\text{days}.

• Calcitonin – Peptide hormone that lowers plasma calcium by inhibiting osteoclastic resorption; its physiologic importance in adults is limited compared with parathyroid hormone (PTH).

Cellular and Systemic Actions of Thyroid Hormones

1. Genomic Actions – T3 binds nuclear thyroid-hormone receptors (TR\alpha1, TR\beta_1/2) → hormone–receptor complex interacts with thyroid-response elements, modulating transcription.

2. Thermogenesis & Basal Metabolic Rate (BMR) – Up-regulates Na⁺/K⁺-ATPase and mitochondrial UCP-2; every 1 log unit rise in T_3 can elevate BMR by 10–20\%.

3. Carbohydrate & Lipid Metabolism – Enhances intestinal glucose absorption, hepatic gluconeogenesis, lipolysis, and LDL-receptor expression → net ↓ serum LDL.

4. Growth & Development – Synergises with GH for longitudinal bone growth; essential for myelination and neuronal maturation in utero and infancy (cretinism results from deficiency).

5. Cardiovascular Effects – ↑ β-adrenergic receptor density → positive chronotropic and inotropic actions; ↓ systemic vascular resistance through vasodilation.

6. Other Systems – Accelerates GI motility, modulates menstrual cyclicity, and influences mood and cognition (hyper → anxiety/insomnia; hypo → depression, cognitive dulling).

Thyroid Disorders: Definitions

• Hyperthyroidism / Thyrotoxicosis – Clinical state caused by excess free T4, T3, or both. Common etiologies include Graves’ disease (TSH-receptor-stimulating antibodies), toxic multinodular goitre, and iatrogenic overdose.

• Hypothyroidism – Deficiency of thyroid hormone action. Primary (thyroidal) causes dominate: Hashimoto thyroiditis (anti-TPO antibodies), post-ablative or congenital dysgenesis. Central (secondary or tertiary) forms are rare.

Key Signs and Symptoms

Laboratory Profiles

1. Primary Hyperthyroidism
   • ↓ TSH (often < 0.01\,\text{mU\,L}^{-1}).
   • ↑ Free T4 and/or T3.
   • Possible positive TSH-receptor antibodies (TRAb) in Graves’.

2. Primary Hypothyroidism
   • ↑ TSH (compensatory, > 4.0\,\text{mU\,L}^{-1}).
   • ↓ Free T_4.
   • Anti-thyroid peroxidase (anti-TPO) and anti-thyroglobulin antibodies often elevated.

3. Central (Secondary/Tertiary) Disorders – Inappropriate low-normal or low TSH with parallel low T_4.

4. Adjunctive Tests – Radioactive iodine uptake scan, ultrasonography, ESR/CRP for sub-acute thyroiditis, lipid panels (hypo ↑ LDL, ↑ triglycerides).

Ethical, Philosophical & Practical Considerations

• Screening in Pregnancy – Maternal hypothyroxinaemia jeopardises fetal neurodevelopment; routine TSH checks remain debated (autonomy vs. beneficence).

• Radioiodine Ablation – Balances curative intent with lifelong hormone replacement; raises questions of patient education and informed consent.

• Over-the-Counter Supplements – Unregulated ‘thyroid boosters’ can precipitate thyrotoxicosis, underscoring the duty of clinicians to counsel on evidence-based therapies.

Conclusion

The thyroid gland integrates hypothalamic and pituitary signals to fine-tune systemic metabolism. Its principal hormones—T3, T4, and calcitonin—exert wide-ranging genomic and non-genomic effects from thermogenesis to neurodevelopment. Dysregulation presents as hyper- or hypothyroidism, each with distinctive clinical spectra and laboratory fingerprints. Mastery of hormone synthesis, feedback, symptomatology and lab interpretation enables accurate diagnosis and optimised management of these prevalent endocrine disorders.

References

Guyton, A. C., & Hall, J. E. (2021). Textbook of Medical Physiology (14th ed.). Elsevier.

(All in-text factual statements derive from the above source unless otherwise indicated.)