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Endocrine System 3: Thyroid and Parathyroid Glands Copyright EMAP Publishing 2021 This article is not for distribution except for journal club use Clinical Practice Keywords Thyroid/Parathyroid/ Endocrine system/Hormones Systems of life This article has been Endocrine system double-blind peer reviewed In this article... ● How thyroid hormones T3 and T4 act to regulate cellular metabolism ● Clinical features of hypothyroidism and hyperthyroidism ● The role of the thyroid and parathyroid glands in maintaining calcium homeostasis Endocrine system 3: thyroid and parathyroid glands Key points Authors John Knight is associate professor in biomedical science; Maria Andrade is The thyroid is in the honorary associate professor in biomedical science; Zubeyde Bayram-Weston is neck, just below the senior lecturer in biomedical science; all at College of Human and Health Sciences, Adam’s apple, and Swansea University. contains four tiny, independently Abstract The endocrine system comprises glands and tissues that produce hormones functioning, to regulate and coordinate vital bodily functions. This article, the third in an eight-part parathyroid glands series on the endocrine system, examines the anatomy and physiology of the thyroid and parathyroid glands, and the pathophysiology associated with some common Thyroid follicular thyroid diseases. cells secrete iodine-rich Citation Knight J et al (2021) Endocrine system 3: thyroid and parathyroid glands. hormones, T3 and Nursing Times [online]; 117: 7, 46-50. T4, which help regulate metabolism his eight-part series on the endo- the adult thyroid gland varies between 15g Release of T3 and crine system opened with an and 30g, and each of the major lobes is T4 is modulated by overview of endocrine glands and around 4cm long and 2cm wide (Benvenga hypothalamus and Tthe role of hormones as chemical et al, 2018; Dorion, 2017). Embedded in the pituitary gland signals that help maintain the homeostatic posterior portion of the thyroid are four hormones balance that is essential to health; the tiny parathyroid glands, which function remaining articles each explore different independently of the thyroid (Fig 1). Hypothyroidism and major endocrine glands and tissues. The hyperthyroidism are second article in the series focused on the Histology common thyroid hypothalamus and pituitary gland. In this The thyroid contains two major popula- disorders, often third article, we explore the anatomy and tions of endocrine cells: treatable with drugs physiology of the thyroid and parathyroid ● Follicular cells – each major lobe of the or radioactive iodine glands, as well as the pathophysiology of thyroid consists of smaller lobules that therapy some common thyroid diseases. are composed of sac-like follicles (Fig 2). The walls of each follicle primarily Calcitonin produced Thyroid gland consist of cube-shaped cells. These by the thyroid works Anatomy synthesise and secrete iodine-rich antagonistically with The thyroid is a bi-lobed gland, often hormones that regulate metabolism; parathyroid described as resembling a butterfly or bow ● Parafollicular cells – these are found in hormone to maintain tie. It is positioned in the neck, between the much smaller numbers, interspersed calcium homeostasis C5 and T1 vertebrae, just below the thyroid between the thyroid follicles, and cartilage (Adam’s apple) of the larynx. It synthesise calcitonin, a hormone that consists of two major lobes (right and left), helps maintain calcium homeostasis. which are connected by a smaller piece of tissue called the isthmus; around half of Thyroid hormones: T3 and T4 individuals also possess an additional third The follicular cells of the thyroid produce lobe, usually triangular shaped and known two iodine-containing hormones, called as the pyramidal lobe (Fig 1). The weight of T3 and T4 (also known as thyroxine). Each Nursing Times [online] July 2021 / Vol 117 Issue 7 46 www.nursingtimes.net Copyright EMAP Publishing 2021 This article is not for distribution except for journal club use Clinical Practice Systems of life Fig 1. Thyroid and parathyroid glands smaller amounts present in potato skins, watercress, kale, green beans, cranberries, strawberries and most types of nut. Many Anterior view Posterior view people supplement their iodine intake with combined multivitamin and mineral Hyoid bone preparations or iodised table salt. The cur- rent recommended daily intake (reference Epiglottis intake) of iodine for adults is 140-150µg, Right lobe Thyroid cartilage rising to 200µg in women who are preg- of larynx Superior parathyroid nant or breastfeeding (Bit.ly/NHSIodine; Pyramidal lobe gland Bit.ly/BDAIodine). Thyroid Around 90% of dietary iodine is rapidly gland Isthmus Inferior absorbed in the stomach and duodenum parathyroid before circulating in the blood (Leung et al, Left lobe gland 2010). The majority of plasma iodine is Trachea taken up by the thyroid gland and any excess is eliminated efficiently by the kid- neys. The follicular cells of the thyroid are equipped with transporter proteins in their Fig 2. Follicular and parafolicular cells of the thyroid gland cell membranes; these facilitate rapid uptake of iodine, which is then joined to a large protein called thyroglobulin. This Follicle iodised thyroglobulin is stored and con- centrated in the centre of the thyroid folli- cles, where it forms the major component of a homogenous suspension called colloid Follicular cell (Fig 2). Thyroglobulin is rich in the amino acid Parafollicular cell tyrosine, which provides the substrate for (C cell) the biosynthesis of thyroid hormones T3 Colloid and T4. These thyroid hormones are com- posed of two molecules of tyrosine linked Blood capillary together, containing three (T3) or four (T4) atoms of iodine (Fig 3). When T3 and T4 are Red blood cell required, small droplets of iodised thy- roglobulin are taken back into the follicular cells from the central colloid. The thyroglob- Fig 3. Structure of tyrosine, T3 and T4 ulin is digested by intracellular enzymes to release individual molecules of T3 and T4 H H (Benvenga et al, 2018; Leung et al, 2010). Like all endocrine glands, the thyroid is H O O I I I highly vascularised and T3 and T4 are O released directly into the blood. Propor- tionally, the thyroid gland releases approx- O O imately 80% T4 and 20% T3, although it is I I I I estimated that T3 has around four times HHC the potency of T4 (Sargis, 2019). Both hor- HOOC C NH2 mones have very low solubility in the HHC HHC H aqueous environment of the plasma so are HOOC C NH2 HOOC C NH2 transported around the body bound to H H plasma proteins. These include: ● Albumin (the most abundant plasma Tyrosine Triiodothyronine (T3) Tetraiodothyronine (T4) protein); ● Transthyretin; ● Thyroxine-binding globulin (TBG). molecule of T3 (triiodothyronine) has and shellfish, are particularly rich sources Each of these three plasma proteins is three atoms of iodine, while each molecule of this trace mineral. Smaller amounts are synthesised by the liver, with TBG having of T4 (tetraiodothyronine) has four iodine also found in eggs, red meats, poultry and the highest binding affinity (Chakravarthy atoms. To ensure normal biosynthesis of dairy products, including, milk, yoghurt and Ejaz, 2020). T3 and T4 are bound to T3 and T4, it is essential to maintain an and cheeses. For vegetarians and vegans, their plasma protein vehicles but cannot adequate intake of iodine in the diet. various forms of kelp (seaweed) offer an exert any biological effects; however, small JENNIFER N.R. SMITH Seafood, including most types of fish incredibly rich source of iodine, with amounts of T3 and T4 detach and, once Nursing Times [online] July 2021 / Vol 117 Issue 7 47 www.nursingtimes.net Copyright EMAP Publishing 2021 This article is not for distribution except for journal club use Clinical Practice Systems of life free, are able to exert their effects. The hypothalamus continually monitors production of autoantibodies that bind to Free T3 and T4 cross into their target the concentration of T3 and T4 circulating the follicular components of the thyroid cells and bind to thyroid hormone recep- in the plasma. When levels of T3 and T4 gland, which are progressively destroyed by tors (THRs) located in the cell nucleus. decrease, the hypothalamus synthesises the patient’s own immune system. The con- Both hormones can bind to THRs, but T3 and releases thyrotropin-releasing hor- dition is associated with varying degrees of binds with a much greater affinity than T4. mone (TRH). TRH is a small peptide that inflammation of the thyroid, while loss of Many of the target cells have enzymes, binds to receptors in the anterior pituitary, follicular cells results in reduced secretion called deiodinases, which rapidly remove initiating the secretion of thyroid stimu- of T3 and T4, and a reduced metabolic rate an atom of iodine from the T4 molecules, lating hormone (TSH). TSH (another pep- (Machala et al, 2019). thereby generating greater amounts of the tide hormone) circulates in the blood before Blood tests usually reveal significantly more-potent T3 (Shahid et al, 2020). binding to its complementary receptors on elevated levels of TSH in patients with the follicular cells of the thyroid gland, Hashimoto’s thyroiditis (Chaker et al, Biological effects of T3 and T4 which then release T3 and T4 (Fig 4). 2017). This is because the low circulating Virtually all human cells and tissues have The HPT axis is fine-tuned via continual levels of T3 and T4 are detected by the THRs and can respond to free T3 and T4, negative feedback. Increased levels of T3 hypothalamus, which releases TRH, initi- which play an essential role in regulating and T4 circulating in the plasma are ating the release of TSH from the anterior cellular metabolism. detected by the hypothalamus, reducing pituitary. Ageing is often linked to an To release the energy needed to drive the the secretion of TRH. This reduces the increase in circulating autoantibodies that biochemical processes necessary to sustain release of TSH by the anterior pituitary react with the follicular cells of the thyroid life, cells need to use simple food-derived gland, thereby reducing the release of T3 gland (Calsolaro et al, 2019); this may par- molecules, such as sugars and fats.
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