«Named after the thyroid cartilage (Greek: Shield-shaped) The Thyroid Gland Vercelloni 1711: “a bag of worms” whose eggs pass into the esophagus ...»
Ass Professor of Endocrine And Bariatric Surgery
Mansoura Faculty Of Medicine
Mansoura - Egypt
The Thyroid Gland
Named after the thyroid
The Thyroid Gland
Vercelloni 1711: “a bag of worms” whose eggs
pass into the esophagus for digestive purposes
Parry 1825: “a vascular shunt” to cushion the
brain from sudden increases in blood flow
Medial portion of thyroid gland
Arises frome the endodermal tissue of the base of tongue posteriorly, the foramen cecum - lack of migration results in a retrolingual mass Attached to tongue by the thyroglossal duct - lack of atrophy after thyroid descent results in midline cyst formation (thyroglossal duct cyst) Descent occurs about fifth week of fetal life - remnants may persist along track of descent Lateral lobes of thyroid gland Derived from a portion of ultimobranchial body, part of the fifth branchial pouch from which C cells are also derived (calcitonin secreting cells) Lingual Thyroid (failure of descent) Verification that lingual mass is thyroid by its ability to trap I123 Lingual thyroid Chin marker Significance: May be only thyroid tissue in body (~70% of time), removal resulting in hypothyroidism; treatment consists of TSH suppression to shrink size Anatomy, physiology and pathology of the thyroid gland Anatomy Thyroid Anatomy Brownish-red and soft during life Usually weighs about 25g (larger in women) Surrounded by a thin, fibrous capsule of connective tissue External to this is a “false capsule” formed by pretracheal fascia Right and left lobes United by a narrow isthmus, which extends across the trachea anterior to second and third tracheal cartilages In some people a third “pyramidal lobe” exists, ascending from the isthmus towards hyoid bone Position and relations Clasps anterior and lateral surface of pharynx, larynx, oesophagus and trachea “like a shield” Lies deep to sternothyroid and sternohyoid muscles Parathyroid glands usually lie between posterior border of thyroid gland and its sheath (usually 2 on each side of the thyroid), often just lateral to anastomosis between vessel joining superior and inferior thyroid arteries Internal jugular vein and common carotid artery lie postero-lateral to thyroid Positionand relations Recurrent laryngeal nerve is an important structure lying between trachea and thyroid – may be injured during thyroid surgery → ipsilateral VC paralysis, hoarse voice Each lobe – pear-shaped and ~5cm long – extends inferiorly on each side of trachea (and oesophagus), often to level of 6th tracheal cartilage Attached to arch of cricoid cartilage and to oblique line of thyroid cartilage – moves up and down with swallowing and oscillates during speaking Arterial supply highly vascular main supply from superior and inferior thyroid arteries – lie between capsule and pretracheal fascia (false capsule) all thyroid arteries anastomose with one another on and in the substance of the thyroid, but little anastomosis across the median plane (except for branches of superior thyroid artery) Arterial supply superior thyroid artery – first branch of ECA – descends to superior pole of gland, pierces pretracheal fascia then divides into 2-3 branches inferior thyroid artery – branch of thyro-cervical trunk – runs superomedially posterior to carotid sheath – reaches posterior aspect of gland – divides into several branches which pierce pretracheal fascia to supply inferior pole of thyroid gland – intimate relationship with recurrent laryngeal nerve – in ~10% of people the thyroid ima artery arises from aorta, brachiocephalic trunk or ICA, ascends anterior to trachea to supply the isthmus Venous drainage usually 3 pairs of veins drain venous plexus on anterior surface of thyroid – superior thyroid veins drain superior poles – middle thyroid veins drain lateral parts
• superior and middle thyroid veins empty into internal jugular veins – inferior thyroid veins drain inferior poles
• empty into brachio-cephalic veins
• often unite to form a single vein that drains into one or other brachio-cephalic vein Lymphatic drainage lymphatics run in the interlobular connective tissue, often around arteries communicate with a capsular network of lymph vessels pass to prelaryngeal LN’s → pretracheal and paratracheal LN’s lateral lymphatic vessels along superior thyroid veins pass to deep cervical LN’s some drainage directly into brachio-cephalic LN’s or directly into thoracic duct Lymph nodes of the neck Innervation nerves derived from superior, middle and inferior cervical sympathetic ganglia – reach thyroid through cardiac and laryngeal branches of vagus nerve which accompany arterial supply postganglionic fibres and vasomotor – indirect action on thyroid by regulating blood vessels Histology The thyroid gland is composed of 2 lobes connected by an isthmus.
The thyroid gland is subdivided by capsular septa into lobules containing follicles.
These septa also serve as conduits for blood vessels, lymphatic vessels, & nerves Thyroid Follicles Thyroid follicles are spherical structures filled with colloid, a viscous gel consisting mostly of iodinated thyroglobulin.
Thyroid follicles are enveloped by a layer of epithelial cells, called follicular cells, which in turn are surrounded by parafollicular cells. These 2 parenchymal cell types rest on a basal lamina, which separates them from the abundant network of fenestrated capillaries in the connective tissue.
Function. Thyroid follciles synthesize & store thyroid hormones.
Follicular Cells Follicular cells are normally cuboidal in shape but become columnar when stimulated & squamous when inactive.
Follicular cells contain many small apical vesicles, involved in transport & release of thyroglobulin & into the colloid.
Follicles: the Functional Units of the Thyroid Gland Follicles Are the Sites Where Key Thyroid
• Thyroglobulin (Tg)
• Thyroxine (T4)
• Triiodotyrosine (T3) Follicular Cells Synthesis & release of the thyroid hormones throxine (T4) & triiodothyronine (T3) Thyroglobulin is synthesized like other secretory proteins.
Circulating iodide is actively transported into the cytosol, where a thyroid peroxidase oxidizes it & iodinates tyrosine residues on the thyroglobulin molecule; iodination occurs mostly at the apical plasma membrane.
A rearrangement of the iodinated tyrosine residues of thyroglobulin in the colloid produces the iodothyronines T4 & T3.
Follicular Cells Binding of thyroid-stimulating hormone to receptors on the basal surface stimulates follicular cells to become columnar & to form apical pseudopods, which engulf colloid by endocytosis.
After the colloid droplets fuse with lysosomes, controlled hydrolysis of iodinated thyroglobulin liberates T3 & T4 into the cytosol.
These hormones move basally & are released basally into the bloodstream & lymphatic vessels.
These processes are promoted by TSH, which binds to G-protein-linked receptors on the basal surface of follicular cells.
Parafollicular Cells Parafollicular cells are also called clear (C) cells because they stain less intensely than thyroid follicular cells.
They synthesize & release calcitonin, a polypeptide hormone, in response to high blood calcium levels.
Thyroid Physiology The Thyroid Produces and Secretes 2 Metabolic Hormones
• Two principal hormones – Thyroxine (T4 ) and triiodothyronine (T3)
• Required for homeostasis of all cells
• Influence cell differentiation, growth, and metabolism
• Considered the major metabolic hormones because they target virtually every tissue TRH Produced by Hypothalamus Release is pulsatile, circadian Downregulated by T3 Travels through portal venous system to adenohypophysis Stimulates TSH formation Thyroid-Stimulating Hormone (TSH)
• Upregulated by TRH
• Downregulated by T4, T3
• Travels through portal venous system to cavernous sinus, body.
• Stimulates several processes – Iodine uptake – Colloid endocytosis – Growth of thyroid gland
• Produced by Adenohypophysis Thyrotrophs Hypothalamic-Pituitary-Thyroid Axis Negative Feedback Mechanism Biosynthesis of T4 and T3 The process includes
• Dietary iodine (I) ingestion
• Active transport and uptake of iodide (I-) by thyroid gland
• Oxidation of I- and iodination of thyroglobulin (Tg) tyrosine residues
• Coupling of iodotyrosine residues (MIT and DIT) to form T4 and T3
• Proteolysis of Tg with release of T4 and T3 into the circulation Iodine Sources
• Available through certain foods (eg, seafood, bread, dairy products), iodized salt, or dietary supplements, as a trace mineral
• The recommended minimum intake is 150 µg/day Active Transport and I- Uptake by the Thyroid
• Dietary iodine reaches the circulation as iodide anion (I-) The thyroid gland transports I- to the • sites of hormone synthesis I- accumulation in the thyroid is an • active transport process that is stimulated by TSH Oxidation of I- and Iodination of Thyroglobulin (Tg) Tyrosyl Residues
• I- must be oxidized to be able to iodinate tyrosyl residues of Tg
• Iodination of the tyrosyl residues then forms monoiodotyrosine (MIT) and diiodotyrosine (DIT), which are then coupled to form either T3 or T4
• Both reactions are catalyzed by TPO Thyroperoxidase (TPO)
• TPO catalyzes the oxidation steps involved in I- activation, iodination of Tg tyrosyl residues, and coupling of iodotyrosyl residues
• TPO has binding sites for I- and tyrosine
• TPO uses H2O2 as the oxidant to activate I- to hypoiodate (OI-), the iodinating species Proteolysis of Tg With Release of T4 and T3
• T4 and T3 are synthesized and stored within the Tg molecule
• Proteolysis is an essential step for releasing the hormones
• To liberate T4 and T3, Tg is resorbed into the follicular cells in the form of colloid droplets, which fuse with lysosomes to form phagolysosomes
• Tg is then hydrolyzed to T4 and T3, which are then secreted into the circulation Conversion of T4 to T3 in Peripheral Tissues Production of T4 and T3
• T4 is the primary secretory product of the thyroid gland, which is the only source of T4
• The thyroid secretes approximately 70-90 µg of T4 per day
• T3 is derived from 2 processes – The total daily production rate of T3 is about 15-30 µg – About 80% of circulating T3 comes from deiodination of T4 in peripheral tissues – About 20% comes from direct thyroid secretion T4: A Prohormone for T3
• T4 is biologically inactive in target tissues until converted to T3 – Activation occurs with 5' iodination of the outer ring of T4
• T3 then becomes the biologically active hormone responsible for the majority of thyroid hormone effects Sites of T4 Conversion
• The liver is the major extrathyroidal T4 conversion site for production of T3
• Some T4 to T3 conversion also occurs in the kidney and other tissues T4 Disposition
• Normal disposition of T4 – About 41% is converted to T3 – 38% is converted to reverse T3 (rT3), which is metabolically inactive – 21% is metabolized via other pathways, such as conjugation in the liver and excretion in the bile
• Normal circulating concentrations – T4 4.5-11 µg/dL – T3 60-180 ng/dL (~100-fold less than T4) Hormonal Transport Carriers for Circulating Thyroid Hormones
• More than 99% of circulating T4 and T3 is bound to plasma carrier proteins – Thyroxine-binding globulin (TBG), binds about 75% – Transthyretin (TTR), also called thyroxine-binding prealbumin (TBPA), binds about 10%-15% – Albumin binds about 7% – High-density lipoproteins (HDL), binds about 3%
• Carrier proteins can be affected by physiologic changes, drugs, and disease Free Hormone Concept
• Only unbound (free) hormone has metabolic activity and physiologic effects – Free hormone is a tiny percentage of total hormone in plasma (about 0.03% T4; 0.3% T3)
• Total hormone concentration – Normally is kept proportional to the concentration of carrier proteins – Is kept appropriate to maintain a constant free hormone level Changes in TBG Concentration Determine Binding and Influence T4 and T3 Levels
• Increased TBG – Total serum T4 and T3 levels increase – Free T4 (FT4), and free T3 (FT3) concentrations remain unchanged
• Decreased TBG – Total serum T4 and T3 levels decrease – FT4 and FT3 levels remain unchanged Drugs and Conditions That Increase Serum T4 and T3 Levels by Increasing TBG
• Drugs that decrease • Conditions that decrease serum T4 and T3 serum T4 and T3 – Glucocorticoids – Genetic factors – Androgens – Acute and chronic illness – L-Asparaginase – Salicylates – Mefenamic acid – Antiseizure medications, eg, phenytoin, carbamazepine – Furosemide Wolff-Chaikoff Effect Increasing doses of Iincrease hormone synthesis initially Higher doses cause cessation of hormone formation.
This effect is countered by the Iodide leak from normal thyroid tissue.
Patients with autoimmune thyroiditis may fail to adapt and become hypothyroid.
Jod-Basedow Effect Opposite of the Wolff-Chaikoff effect Excessive iodine loads induce hyperthyroidism Observed in hyperthyroid disease processes – Graves’ disease – Toxic multinodular goiter – Toxic adenoma This effect may lead to symptomatic thyrotoxicosis in patients who receive large iodine doses from – Dietary changes – Contrast administration – Iodine containing medication (Amiodarone) Perchlorate ClO4- ion inhibits the Na+ / I- transport protein.
Normal individuals show no leak of I123 after ClO4due to organification of Ito MIT / DIT Patients with organification defects show loss of RAIU.
Used in diagnosis of Pendred syndrome Thyroid Hormone Action Thyroid Hormone Plays a Major Role in Growth and Development
• Thyroid hormone initiates or sustains differentiation and growth – Stimulates formation of proteins, which exert trophic effects on tissues – Is essential for normal brain development