Physiology of thyroid gland.

The thyroid, the largest endocrine gland, is a highly vascular organ located in the lower part of the neck, anterior to the trachea and below the larynx. The thyroid gland produces and releases thyroid hormones – tetraiodothyronine (T4) and triiodothyronine (T3) – into the circulating blood. T4 is produced in greater quantities, but T3 is more biologically active and both are synthesized and stored in the thyroid follicles. Both under and over-functioning of the thyroid gland can significantly impact a person’s well-being, with major dysfunction in either direction potentially being life-threatening.

Structure of thyroid gland.

The thyroid gland consists of two conical pear-shaped lobes joined together by an isthmus.  The glandular tissue is made up of numerous follicles, each consisting of a layer of follicular cells surrounding a central cavity filled with colloid, which stores thyroid hormones.

Follicles of the thyroid gland.

The thyroid gland is primarily composed of follicles, stroma, and a capillary system at a microscopic level. Follicles are the fundamental functional units of the thyroid gland and are responsible for synthesizing thyroid hormones T3, T4. The thyroid gland contains two types of cells:

1. Specialised follicular cells. Follicular cells, which are spherical in shape, consist of thyrocytes arranged in a single layer around a central viscous colloid-filled lumen. These cells produce and release T4 (thyroxine) and T3 (tri-iodothyronine) hormones, which play a crucial role in mental and physical growth, metabolism regulation, and maintaining tissue sensitivity to the adrenergic system. During active phase, the lining of the follicles is columnar, while in resting phase, it is cuboidal.
2. Parafollicular “C” cells, located in the stroma between the follicular cells and capillary vessels, produce the calcitonin hormone, which promotes deposition of calcium salts in skeletal and other tissues and has a calcium-lowering effect in the body.

Synthesis, storage and release of thyroid hormones (T3 & T4). Only Specialised follicular cells are involved in this process. 

1. Uptake of iodide in follicular cells from blood circulation. Iodine from dietary sources is absorbed in the small intestine and only 20% is transported to the thyroid follicles via the natrium (sodium) iodide symporter pump (NIS). Iodides are then stored in follicular cells.
2. Oxidation of iodide to iodine and binding of iodine to tyrosine molecule to form DIT or MIT. The endoplasmic reticulum, a cell organelle, plays a crucial role in the production of thyroglobulin protien (Tg) and thyroid peroxidase enzyme (TPO), within the follicular cells of the thyroid gland. Thyroglobulin contains multiple tyrosine residues in its polypeptide chain. The iodide stored in follicular cells undergoes oxidation back to iodine. Subsequently, iodine binds to the tyrosine molecule to form two key compounds: monoiodotyrosine (MIT) and diiodotyrosine (DIT). MIT is formed when iodine binds at one point in a tyrosine molecule, while DIT is formed when iodine binds at two points in tyrosine molecule. If there is no deficiency of iodine in the body, there is a higher synthesis of T4, and in the deficiency of iodine, there is an increased synthesis of T3. The thyroid peroxidase enzyme is responsible for both the oxidation of iodide to iodine and the binding of iodine to the tyrosine molecule.
3. Coupling or fusing of iodotyrosines to form T4 and T3. The formation of thyroid hormones involves the coupling of molecules of diiodotyrosine (DIT) to form T4 and the coupling of one molecule of monoiodotyrosine (MIT) with one molecule of DIT to form T3. These hormones are formed as part of the thyroglobulin amino acid chain, and several thyroglobulin molecules are stored in the lumen of the thyrocyte, known as colloid.
4. Release of T3, and T4 from colloid back to the blood circulation. The follicular cell forms pseudopods which take up the Proteolytic enzyme and break down the peptide bonds, releasing T4, T3, DIT, and MIT. T3 and T4 are released into the bloodstream, with approximately 80% of thyroid hormone being released as T4 and only 20% as T3. T3 is more active and 3-5 times more potent than T4. T4 is converted into T3 through deiodination of the T4 in the peripheral tissues.
5. DIT and MIT are released back for recycling. Iodinated MIT & DIT cannot be released into the bloodstream. MIT and DIT are deiodinated by the enzyme iodotyrosine deiodinase, and the iodide is deoxidized to iodine and about 20% is released into the bloodstream and rest is released back to be recycled to form T3 & T4, which are then stored back in the lumen of the thyrocyte. In the congenital absence of this iodotyrosine deiodinase enzyme, MIT and DIT are not deiodinated and are excreted in urine, resulting in iodine deficiency.

Control of thyroid hormone synthesis.

The production and release of thyroid hormone into the bloodstream are tightly regulated by the hypothalamus-pituitary-thyroid axis (HPA). When the concentrations of T3 or T4 in the blood decrease, the hypothalamus immediately secretes thyrotropin-releasing hormone (TRH), which in turn stimulates the anterior pituitary to release thyroid-stimulating hormone (TSH) without delay. TSH then promptly acts on the thyroid gland to produce and release T3 and T4.

Conversely, in a negative feedback mechanism, the levels of T3 and T4 in the blood exert negative feedback on both the hypothalamus and the pituitary gland to regulate the release of TRH and TSH, to maintain the balance of hormones.

Physiological Effects of Thyroid Hormones. Thyroid hormones exert their effects on nearly every cell in the body. They are critical for:

1. Metabolism: Increase basal metabolic rate (BMR), enhance oxygen consumption and heat production, and stimulate the metabolism of carbohydrates, fats, and proteins.
2. Growth and Development: Essential for normal growth and development, especially in children and crucial for brain development and maturation.
3. Cardiovascular System: Increase heart rate and cardiac output and enhance the sensitivity of the heart to catecholamines (adrenaline and noradrenaline).
4. Central Nervous System: Influence mood and cognitive function, deficiency can lead to mental sluggishness, while excess can cause anxiety and restlessness.

Disorders of the Thyroid Gland

1. Hypothyroidism: Hypothyroidism occurs when the thyroid gland produces insufficient amounts of thyroid hormones. Common causes include:
   • Hashimoto’s Thyroiditis: An autoimmune disorder where the body’s immune system attacks the thyroid gland, leading to inflammation and impaired hormone production.
   • Iodine Deficiency: Iodine is essential for thyroid hormone production. A lack of dietary iodine can lead to reduced hormone synthesis and hypothyroidism.
2. Hyperthyroidism: Hyperthyroidism is a condition where the thyroid gland produces excessive amounts of thyroid hormones. Common causes include:
   • Graves’ Disease: An autoimmune disorder that stimulates the thyroid gland to produce excessive hormones. It is the most common cause of hyperthyroidism.
   • Thyroid Nodules: These are lumps in the thyroid gland that can become overactive and produce too much thyroid hormone.
3. Goitre: Goiter is an enlargement of the thyroid gland. It can occur in both hypothyroidism and hyperthyroidism, as well as in euthyroid states (normal thyroid function). Swelling in the neck is the most common symptom. Large goitres can cause difficulty swallowing or breathing due to pressure on the oesophagus and trachea. Common causes include:
   • Iodine Deficiency: The thyroid gland enlarges in an attempt to capture more iodine from the bloodstream to produce adequate thyroid hormones.
   • Autoimmune Diseases: Both Hashimoto’s thyroiditis and Graves’ disease can cause goiter. Hashimoto’s leads to inflammation and enlargement, while Graves’ disease stimulates overall gland growth.

Iodine

Iodine is a vital mineral essential for thyroid metabolism and hormone synthesis. Potassium iodide, a man-made salt compound, plays a crucial role in maintaining iodine levels in the body. The daily iodine intake varies widely among adults, from less than 10 μg in deficient areas to several hundred milligrams. The Institute of Medicine has established that adults require a minimum of 150 mcg/day of iodine to meet the Recommended Dietary Allowance (RDA). Additionally, it is widely believed that a daily intake of 50–75 mcg of iodine is necessary to prevent goitre caused by iodine deficiency.

———- End of the chapter ———–

Learning resources.

• Scott-Brown, Textbook of Otorhinolaryngology Head and Neck Surgery.
• David J. Terris, William S. Duke. Textbook of Thyroid and Parathyroid Diseases Medical and Surgical Management. 
• Stell and Maran’s, Textbook of Head and Neck Surgery and Oncology.
• Logan Turner, Textbook of Diseases of The Nose, Throat and Ear Head And Neck Surgery.
• P L Dhingra, Textbook of Diseases of Ear, Nose and Throat.
• Hazarika P, Textbook of Ear Nose Throat And Head Neck Surgery Clinical Practical.
• Mohan Bansal, Textbook of Diseases of Ear, Nose and Throat Head and Neck surgery.
   
  Author:

Dr. Rahul Bagla
MBBS (MAMC, Delhi) MS ENT (UCMS, Delhi)
Fellow Rhinoplasty & Facial Plastic Surgery.
Renowned Teaching Faculty
Mail: msrahulbagla@gmail.com
India

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