PHYSIOLOGY OF THYROID GLAND Dr. Shaikh Mujeeb Ahmed Assistant Professor AlMaarefa College ENDO BLOCK 412

Objectives The student should be able to: Describe the distribution of iodine in the body, dietary requirements for iodine and thyroid uptake of iodine. Identify the structure and formula for thyroxine (T4) and triiodothyronine (T3). Know the basic steps involved in the biosynthesis of T3 and T4. Identify the bound forms and quantities of T3 and T4 in circulation. Relate the plasma half-life of thyroid hormones to their biological effects. Describe the effects of TSH on thyroid activity. Describe the relationship of TSH, and TRH to T4 secretion. Know the physiological effects of thyroid hormone. Indicate the relative activities of T4 and T3. Describe the etiology, symptoms and treatment of thyrotoxicosis and hypothyroidism.

Physiologic Anatomy of the Thyroid Gland located immediately below the larynx on each side of and anterior to the trachea one of the largest of the endocrine glands secretes two major hormones, thyroxine and triiodothyronine, commonly called T 4 and T 3, respectively

Anatomy of thyroid gland The gland is composed of – large numbers of closed follicles (100 to 300 micrometers in diameter) – filled with a secretory substance called colloid and – lined with cuboidal epithelial cells that secrete into the interior of the follicles. – The major constituent of colloid is the large glycoprotein thyroglobulin, which contains the thyroid hormones within its molecule.

Fig. 19-1b, p. 692

Interspersed in the interstitial spaces between the follicles is another secretory cell type, the C cells, which secrete the peptide hormone calcitonin.

IMPORTANT  Thyroid gland maintains the level of metabolism in the tissues that is optimal for their normal functioning  Thyroid hormone stimulate the O2 consumption of most of the cells in the body  Help to regulate the lipid & carbohydrate metabolism & are necessary for normal growth & maturation Thyroid gland is not essential for life but its absence causes – Mental & Physical slowing – Poor resistance to cold – In children mental retardation & dwarfism

Unique features of thyroid hormone synthesis Thyroid hormone contain large amount of iodine Synthesis of thyroid hormone is partly intracellular & partly extra cellular & is stored in follicular lumen. T4 is major secretary product of thyroid gland but it is not the most active form.

Iodine requirement Iodine is essential for synthesis of thyroid hormone About 1 mg/week iodine is required to prevent iodine deficiency Minimum daily iodine intake is 150 µg in adults Normal plasma iodine level is 0.3 µg/dl

Thyroid hormones two iodine-containing hormones derived from the amino acid tyrosine: Tetraiodothyronine (T 4, or thyroxine) and Tri-iodothyronine (T 3 ). The prefixes tetra and tri and the subscripts 4 and 3 denote the number of iodine atoms incorporated into each of these hormones.

Steps in the synthesis of thyroid hormones Iodide Pump (Iodide Trapping) TSH stimulates and hypophysectomy greatly diminishes the activity of the iodide pump in thyroid cells. Oxidation of the Iodide Ion. This oxidation of iodine is promoted by the enzyme thyroperoxidase (TPO).

Steps in the synthesis of thyroid hormones Iodination of Tyrosine and Formation of the Thyroid Hormones— “Organification” of Thyroglobulin. Attachment of one iodine to tyrosine yields monoiodotyrosine (MIT) Attachment of two iodines to tyrosine yields di- iodotyrosine (DIT). Coupling of one MIT (with one iodide) and one DIT (with two iodides) yields tri-iodothyronine, or T3

Steps in the synthesis of thyroid hormones Coupling of two DITs (each bearing two iodide atoms) yields tetraiodothyronine (T4, or thyroxine). Thyroid hormones remain stored in this form in the colloid until they are split off and secreted To secrete thyroid hormone, the follicular cells phagocytize thyroglobulin-laden colloid.

Storage of Thyroglobulin The thyroid gland is unusual among the endocrine glands in its ability to store large amounts of hormone. Stimulation of thyroid cells by TSH – Iodinated thyroglobulin is taken back into follicular cells – Lysosomal enzyme digest thyroglobulin – Release T 4 & T 3 in circulation – Leftover MIT & DIT are deiodinated.

In circulation most of T 3 & T 4 is bound to thyroxine binding globulin (TGB). – In hepatic failure TGB level decreases – decrease in total thyroid hormone level. – In pregnancy TGB level increases – increase in total thyroid hormone level. In peripheral tissues T 4 is converted to T 3 or to rT 3 – T 3 is biologically more active than T 4. – rT 3 is inactive.

Synthesis, storage, and secretion of thyroid hormone

Chemical structure of thyroid hormone

Metabolism of Thyroxine by Deiodination in Peripheral Tissues OHO II C HNH 2 COOHC H H II T4T4T4T4 OHO II C HNH 2 COOHC HH I T3 OHO II C HNH 2 COOHC HH I RT 3 5’/3’-deiodinase 5/3-deiodinase

Thyroxin and its precursors: Structure & Synthesis

Regulation of thyroid hormone secretion

Actions of thyroid hormone Thyroid hormone is the main determinant of the basal metabolic rate and exerts other effects as well. Effect on metabolic rate and heat production – increases the body’s overall basal metabolic rate – Regulates the body’s rate of O 2 consumption and energy expenditure –its calorigenic (“heat-producing”)

Basal metabolic rate (BMR)  Na + - K + ATPase.  O 2 consumption  heat production  BMR

EFFECT ON INTERMEDIARY METABOLISM Overall metabolism is increased Glucose absorption from GIT is increased  Glycogenolysis, gluconeogenesis & glucose oxidation  lipolysis  protein synthesis & catabolism (overall catabolic effect)

Growth Attainment of adult stature Acts synergistically with growth hormone & somatomedins to promote bone formation Stimulate bone maturation

Central nervous system Perinatal period – Maturation of the CNS is absolutely dependent on thyroid hormone – Thyroid hormone deficiency causes irreversible mental retardation Adulthood – Hperthyroidism causes hyperexcitability and irritability – Hypothyroidism causes decrease mental capacity & impaired memory

Autonomic nervous system Has same actions as sympathetic stimulation Up regulate β1 adrenergic receptors in the heart.

Cardiovascular and Respiratory system Increase cardiac output – Increase heart rate – Increased stroke volume Increased ventilation

Effects of thyroid hormone summary Effect on metabolic rate and heat production Sympathomimetic effect Effect on cardiovascular system Effect on growth and nervous system

References  Human physiology, Lauralee Sherwood, seventh edition.  Text book physiology by Guyton &Hall,11 th edition.  Text book of physiology by Linda.S.Costanzo third edition 32