Thyroid Gland

This gland is an endocrine gland that produces hormones and regulates many body functions. It's located in the lower front of the neck, below the larynx (Adam's apple), and in front of the trachea. The thyroid is shaped like a butterfly, with two lobes on either side of the windpipe and a thin piece of tissue called the isthmus connecting them. 

1.0Introduction

• The thyroid gland comprises two lobes on either side of the trachea. 
• Both lobes are interconnected with a thin flap of connective tissue called isthmus (non-glandular part). 
• Origin: Endodermal 
• Position: Located in the neck between the trachea and larynx. 
• Structure: 'H' shape, Largest Endocrine gland. 

2.0Structure of Thyroid Gland 

• The butterfly-shaped thyroid gland is located against and around the front of the larynx (behind the thyroid cartilage) and trachea, composed of two pear-shaped right and left lateral lobes, one on either side of the trachea. 
• The right lobe (lobus dexter) is often larger than the left (lobus sinister) and is connected by an isthmus. Thyroid cartilage lies just above the gland and behind Adam's apple. 
• Each lobe of the thyroid gland measures 50-60 mm in length. The superior poles of the lobes reach up to the thyroid cartilage, while the lower poles extend laterally at the level of the fourth to sixth tracheal rings. 
• Four parathyroid glands, two on each side, lie on each side at the back of the thyroid lobes. It is a highly vascularized gland and receives 80–120 mL of blood per minute. 
• Each thyroid lobe is supplied by a superior and an inferior thyroid artery and drained by three veins 

1. superior thyroid veins - drain superior poles 

2. middle thyroid veins - drain lateral parts 

3. inferior thyroid veins - drain inferior poles

3.0Internal structure of Thyroid Gland 

• Spherical colloid-filled follicles of variable size are the characteristic identification feature of the thyroid gland. Follicles (100 to 300 micrometres in diameter) are structural and functional thyroid gland units lined by follicular cells, also known as principal cells. 
• Follicular cells rest on a basement membrane and are responsible for thyroid hormone secretion (T3 and T4). 
• They synthesize, release, and store their product in the lumen of follicles as acidophilic colloids. When stimulated by thyroid-stimulating hormone (TSH) from the anterior pituitary, they secrete the thyroid hormone into the bloodstream. Follicular cells usually are cuboidal in shape but become columnar when stimulated and squamous when inactive. 
• In addition to follicular cells, the gland also contains large, pale-staining interfollicular cells, parafollicular cells, or C cells located within the follicular epithelium as single cells or as cell clusters adjacent to the follicles. 
• They synthesize and secrete the hormone calcitonin/thyrocalcitonin, which is responsible for calcium metabolism & homeostasis in the body. 

4.0Thyroid Hormone

• The thyroid gland synthesizes primarily two iodine-containing hormones, thyroxine (T4) and triiodothyronine (T3), along with calcitonin, a peptide hormone. Although the T4 and T3 hormones have the same qualitative functions, they differ in rapidity and intensity of action. 
• T3 is the active hormone three to four times more potent than thyroxine. Besides its high metabolic effect, only 7% of the total hormone is secreted as T3 and the remaining 93% as T4 because the latter has a longer half-life. 
• Contrary to the high level of T4 in the blood, almost all of it is converted to T3 before acting on the genes of target cells by removing one iodide because intracellular receptors for thyroid hormone have very high affinity for T3. Therefore, T3 is the functional form of thyroid hormone in the cells and is also produced by the deiodination of T4 in the liver, kidney, brain, and pituitary. 

Regulation of Thyroid Hormone

• It is important to keep the right amount of thyroid hormone in the blood to maintain normal metabolic activity levels. This regulation is achieved by thyroid-stimulating hormone (TSH) released by the anterior pituitary in response to TRH from the hypothalamus. 
• Low blood levels of T3 and T4 or low metabolic rates stimulate the release of TRH and TSH. TSH stimulates the follicular cells by binding to TSH receptors.

Function of Thyroid Hormone

• The thyroid hormones (T3 and T4) have a wide range of effects on the human body and are required for the homeostasis of all the cells. 
• Thyroid hormones target virtually all the tissues of the body, and broadly, they have two major functions: 

1. an increase in overall metabolic rate 

2. stimulate growth and development

Effect of thyroid hormone on growth and development

• Proper development during the gestational period is a critical determinant in the overall growth of an individual. 
• Thyroid hormones play a crucial role in early development, particularly in promoting the growth of the brain and central nervous system. If congenital hypothyroidism or chronic hypothyroidism goes untreated during fetal development, infancy, or childhood, it can result in severe intellectual disabilities and incomplete physical growth.
• Also, together with human growth hormone, insulin, and other growth factors, thyroid hormones accelerate body growth, particularly the development of the nervous and skeletal systems throughout life.

Metabolic effects of thyroid hormones

Synthesis of Sodium-potassium pumps/calorigenic effect:

Function of Calcitonin:

• Copp and Cheney purified calcitonin in 1962. It is a 32-amino-acid polypeptide with a molecular weight of 3700 Dalton and a disulfide bridge between residues 1 and 7. Parafollicular cells synthesize calcitonin in response to high blood calcium levels. 
• Calcitonin lowers blood calcium levels by inhibiting the number and activity of osteoclasts, the bone resorption cells. 
• It also inhibits the reabsorption of calcium and phosphate ions in the renal tubules, increasing excretion through urine. 
• Calcium production and release of calcitonin are completely independent of the pituitary gland and depend only on the calcium level in the blood.

5.0Disorders associated with thyroid gland functioning 

• Endocrine disorders associated with the thyroid gland have a high prevalence in India, especially in females. 
• Thyroid diseases are broadly divided into two classes:  Hypothyroidism (hyposecretion of TH) and Hyperthyroidism (hypersecretion of TH) 

Hypothyroidism 

• Hypothyroidism in fetal life, infants and children is known as cretinism, causing mental retardation and stunted growth. 
• At birth, the child with congenital hypothyroidism is normal because it was supplied with some (but usually not enough) maternal thyroid hormone. Still, after birth, the baby becomes sluggish, showing symptoms of retarded growth. 
• Oral thyroid hormone treatment is prescribed soon after birth and continues for life.
• Hypothyroidism in adults results in a severe condition with an almost total lack of thyroid hormone function, known as myxedema. 
• Myxedema is characterized by oedema, i.e., the accumulation of immobile interstitial fluid (hyaluronic acid and chondroitin sulfate bound with protein from excessive tissue gel), causing the facial tissue to swell and puffy. Oral thyroid hormone therapy helps reduce the symptoms. 

Causes of Hypothyroidism

Primary Causes of Hypothyroidism:

• Hashimoto's Disease – Autoimmune disease against the thyroid gland leads to ―autoimmune thyroiditis, which means thyroid inflammation. Thyroid-attacking antibodies, including thyroid peroxidase antibodies (TPO) and thyroglobulin antibodies (TgAb), are synthesized by the body's immune system and attack the thyroid gland. Progressive deterioration leads to gland fibrosis and low thyroid hormone secretion. Increased risk of thyroid nodules, goitre (an enlarged thyroid), and thyroid cancer are associated with the disease.
• Endemic colloid thyroid goitre - Iodine deficiency is frequently linked to the enlargement of the thyroid gland and is a common cause of endemic colloid thyroid goitre. When iodine intake is insufficient, it hampers hormone synthesis, resulting in low levels of circulating thyroid hormones. This triggers a negative feedback mechanism, leading to increased production of TRH by the hypothalamus and TSH by the pituitary gland.

Secondary Causes of Hypothyroidism:

Defect in the functioning/communications of the pituitary gland and the hypothalamus leading to deficient secretion of TSH and TRH respectively. 

Symptoms of Hypothyroidism 

Hyperthyroidism

• Hyperthyroidism or thyrotoxicosis is caused by elevated levels of thyroid hormones and reflected by hyperactivity of the thyroid gland caused by Graves’ disease, toxic adenoma, multinodular goiter, or thyroiditis. 
• Graves' Disease - The disease is seven to ten times more common in females than in males before age 40. It is an autoimmune disorder where the body produces antibodies that mimic the action of thyroid-stimulating hormone (TSH). These antibodies are known as thyroid-stimulating immunoglobulin (TSI). TSI continually stimulates the thyroid gland hypertrophy and produces thyroid hormones. Increased thyroid hormone negative feedback suppresses the level of TSH. Therefore, Graves' disease is characterized by elevated levels of T3 and T4 with low TSH. Hypertrophy of the gland leads to the development of goitre. 
• Thyroid Adenoma - Thyroid adenoma (tumor) develops in the thyroid tissue and secretes large quantities of thyroid hormone by suppressing the secretory function of the gland because increased thyroid hormone from the adenoma inhibit the production of TSH pituitary gland.  Toxic Multinodular Goiter - Functional multiple nodules develop and produce elevated levels of thyroid hormone and hypertrophy of the gland.  Thyroiditis - Inflammation of thyroid gland leads to thyroiditis and is caused by antibodies attacking thyroid gland.

Symptoms of Hyperthyroidism