Al-Mustaqbal College University

Department of Pathological Analysis Techniques

Physiology Of Thyroid Gland

Introduction

The thyroid gland is located in front of the larynx on either side and anterior to the
trachea and is shaped like a butterfly, and it is responsible for the formation and
secretion of the thyroid hormones as well as iodine homeostasis within the human
body. The thyroid produces approximately inactive thyroid hormone, or thyroxine
(T4) and active thyroid hormone, or triiodothyronine (T3). Inactive thyroid hormone
is converted peripherally to either activated thyroid hormone or an alternative
inactive thyroid hormone (1).

The thyroid gland is composed of thyroid follicles that synthesize and store thyroid
hormone. The epithelial cells referred to as follicular cells or thyrocytes surround
the colloid in the lumen. The ultimo-branchial cells or neural cells accompanying
them are the origins of the C-cells in the thyroid gland, which secrete the hormone
calcitonin (2).

The hypothalamus releases thyroid-releasing hormone (TRH), which stimulates

thyrotrophs of the anterior pituitary to secrete thyroid-stimulating hormone (TSH).
The anterior pituitary releases TSH and stimulates the thyroid follicular cells to
release thyroxine, T4 and triiodothyronine, or T3 (3).

T3 is responsible for affecting many organs and tissues throughout the body, which
can effect of increasing metabolic rate and protein synthesis. Parafollicular cells, or
C cells, are responsible for the production and secretion of calcitonin. Calcitonin
opposes parathyroid hormone to decrease blood calcium levels and maintain calcium
homeostasis (4).
Development of thyroid gland

The thyroid diverticulum first forms at the end of the fourth week of development
as a solid, proliferating mass of endoderm at the foramen cecum on what will become
the tongue. This mass of endoderm migrates down through the developing neck via
the thyroglossal duct toward its eventual home just inferior to the cricoid cartilage.
In normal development, the thyroglossal duct deteriorates by the end of the fifth
week. The only remaining aspect of the thyroid’s embryonal development will be
the foramen cecum at the base of the developed tongue. The isolated thyroid gland
develops two distinct lobes connected by an isthmus of tissue by this time and
continues to descend and reaches its final destination by the end of the seventh week
of development. Cells from the ultimobranchial bodies invade the developing
thyroid and form the parafollicular cells, or C cells, which will produce calcitonin.
The connective tissue of the thyroid gland forms from invading neural crest cells (5).

The thyroid hormone

The thyroid hormone is well known for controlling metabolism, growth, and many
other body functions. The thyroid gland, anterior pituitary gland, and hypothalamus
comprise a self-regulatory circuit called the hypothalamic-pituitary-thyroid axis.
The main hormones produced by the thyroid gland are thyroxine or
tetraiodothyronine (T4) and triiodothyronine (T3). Thyrotropin-releasing hormone
(TRH) from hypothalamus, thyroid-stimulating hormone (TSH) from the anterior
pituitary gland, and T4 work in synchronous harmony to maintain a proper feedback
mechanism and homeostasis (6)

Thyroid hormone also plays a role in reproductive health and other endocrine organ
function. It allows for the regulation of normal reproductive function in both men
and women by regulating both the ovulatory cycle and spermatogenesis. Thyroid
hormone also regulates pituitary function; growth hormone production and release
are stimulated by thyroid hormone while inhibiting prolactin production and release.
Additionally, renal clearance of many substances, including some medications, can
be increased due to activated thyroid hormone stimulation of renal blood flow and
glomerular filtration rate (7).

Iodine is an essential trace element absorbed in the small intestine. It is an integral

part of T3 and T4. Sources of iodine include iodized table salt, seafood, seaweed,
and vegetables. Decreased iodine intake can cause iodine deficiency and decreased
thyroid hormone synthesis. Iodine deficiency can cause cretinism, goiter, myxedema
coma, and hypothyroidism (8).

FIGURE 1.Overview of sites of thyroid hormone regulation of metabolism.

Mechanism of thyroid gland

The thyroid gland is responsible for the production of iodothyronines, of which there
are three. The primary secretory product is inactive thyroxine, or T4, which is a
prohormone of triiodothyronine, or T3. T4 is converted to T3 peripherally by type 1
deiodinase in tissues with high blood flow, such as the liver and kidneys. In the brain,
T4 is converted to active T3 by type 2 deiodinase produced by glial cells. The third
iodothyronine is called reverse T3, or rT3. rT3 is inactive and forms by type 3
deiodinase activity on T4 (9).

These iodothyronines are composed of thyroglobulin and iodine. Thyroglobulin is

formed from amino acids in a basal to apical fashion within the thyroid cells
themselves. Thyroglobulin is then secreted into the follicular lumen, where it is
enzymatically combined with iodine to form iodinated thyroglobulin. Endosomes
containing this iodinated thyroglobulin then fuse with lysosomes, which
enzymatically release the thyroglobulin from the resultant thyroid hormone. The
thyroid hormones are next released from the cell while the remaining thyroglobulin
is deiodinated and recycled for further use (10).

Pathophysiology of thyroid gland

Hypothyroidism (myxoedema) is a common endocrine disorder resulting from

deficiency production of thyroid hormone. or, more rarely, from their impaired
activity at tissue level leads to inadequate production of thyroid hormones and a
slowing of metabolism, deepens the voice, cold intolerance and weight gain due to
decreased basal metabolic rate and thermogenesis, depression, fatigue, decreased
peripheral reflexes, and constipation, due to decreased stimulation of the central and
peripheral nervous system. Many other consequences of hypothyroidism can
manifest secondary to the lack of activated thyroid hormone on various tissues and
organs of the body (11)

Hyperthyroidism (thyrotoxicosis) is an endocrine disorder with excess thyroid

hormone production of any cause and therefore includes hyperthyroidism. Signs and
symptoms vary between people and may include speeding up of metabolism, weight
loss, temperature elevation, nervousness and irritability, but under activity of the
thyroid gland (12).

In Graves disease, an autoimmune condition where the TSH-receptor becomes

activated by an auto-antibody, additional pathophysiology of orbitopathy can be
present. The TSH-receptor antibody also activates T cells and causes fibroblast
proliferation and accumulation of glycosaminoglycans in the extraocular muscles
and retroocular connective tissue leading to proptosis. Hashimoto thyroiditis is a
primary cause of hypothyroidism, which is associated with HLA-DR5. The presence
of anti-thyroglobulin and thyroid peroxidase antibodies suggest Hashimoto
thyroiditis (13).

Organ Systems Involved

The thyroid gland affects almost every organ system of the body. It affects the
cardiovascular system by regulating the cardiac output, stroke volume, heart rate,
and contractility of the heart. The defects in the thyroid mechanism can affect the
nervous system, presenting as numbness, tingling, pain, or burning in the affected
parts of the body. Hypothyroidism can also cause depression in patients. It is also
involved with the gastrointestinal motility. Thyroid gland disorders would affect the
reproduction system with women suffering from irregularities in their menstrual
cycles and problems when trying to conceive (14).
References:

1- Ilse, T. (2011). Clinical review: hyper- and hypothyroidism. evidence-based

Pharmacy Practice. S Afr. Pharm. J.,78(6), 10–14.
2- Gupta V,Lee M, Central hypothyroidism. Indian journal of endocrinology and
metabolism. 2011 Jul [PubMed PMID: 21966662]
3- Mariotti S,Beck-Peccoz P, Physiology of the Hypothalamic-Pituitary-Thyroid
Axis null. 2000 [PubMed PMID: 25905193]
4- Maradonna F, Carnevali O. Lipid Metabolism Alteration by Endocrine
Disruptors in Animal Models: An Overview. Front Endocrinol
(Lausanne). 2018;9:654. [PMC free article] [PubMed] [Reference list]
5- Coste AH, Lofgren DH, Shermetaro C. StatPearls [Internet]. StatPearls
Publishing; Treasure Island (FL): Feb 11, 2020. Branchial Cleft Cys.
6- Núñez A, Bedregal P, Becerra C, Grob L F. [Neurodevelopmental assessment
of patients with congenital hypothyroidism]. Rev Med Chil. 2017
Dec;145(12):1579-1587. [PubMed]
7- Yasoda A. [Secondary osteoporosis. Hyperthyroidism.] Clin
Calcium. 2018;28(12):1619-1625. [PubMed] [Reference list]
8- Sorisky A. Subclinical Hypothyroidism - What is Responsible for its
Association with Cardiovascular Disease? Eur Endocrinol. 2016
Aug;12(2):96-98. [PMC free article] [PubMed]
9- Khakisahneh S, Zhang XY, Nouri Z, Hao SY, Chi QS, Wang DH. Thyroid
hormones mediate metabolic rate and oxidative, anti-oxidative balance at
different temperatures in Mongolian gerbils (Meriones unguiculatus). Comp.
Biochem. Physiol. C Toxicol. Pharmacol. 2019 Feb;216:101-109. [PubMed]
10- Cioffi F, Gentile A, Silvestri E, Goglia F, Lombardi A. Effect of
Iodothyronines on Thermogenesis: Focus on Brown Adipose Tissue. Front
Endocrinol (Lausanne). 2018;9:254. [PMC free article] [PubMed]
11- Merson J. Hypothyroidism. JAAPA. 2018 Dec;31(12):43-
44. [PubMed]
12- Davis JR, Dackiw AP, Holt SA, Nwariaku FE, Oltmann SC. Rapid
Relief: Thyroidectomy is a Quicker Cure than Radioactive Iodine Ablation
(RAI) in Patients with Hyperthyroidism. World J Surg. 2019 Mar;43(3):812-
817. [PubMed]
13- Mincer DL, Jialal I. StatPearls [Internet]. StatPearls Publishing;
Treasure Island (FL): Feb 23, 2020. Hashimoto Thyroiditis. [PubMed]
14- Chattergoon NN, Thyroid hormone signaling and consequences for
cardiac development. The Journal of endocrinology. 2019 Jul 1 [PubMed
PMID: 31117055]