Endocrine System - PDF

 Introduction  Endocrine glands 1. Pituitary 2. Pineal 3. Adrenal 4. Thyroid 5. parathyroid 6. Endocrine pancreas  Together the nervous & endocrine systems coordinate functions of all body systems 1. The nervous system controls body actions through nerve impulses ( rapid responses ) EX. c...

 Introduction  Endocrine glands 1. Pituitary 2. Pineal 3. Adrenal 4. Thyroid 5. parathyroid 6. Endocrine pancreas  Together the nervous & endocrine systems coordinate functions of all body systems 1. The nervous system controls body actions through nerve impulses ( rapid responses ) EX. causes muscles to contract or glands to secrete 2. The endocrine system controls body activities by releasing hormones ( slow & diffused effect) EX. altering metabolism, regulating growth & development, and influencing reproductive processes   Ductless glands that produce & release hormones into the extracellular space through diffusion  The hormones have different pathways to exert their action The hormones may:  Enter the blood stream to reach their target organs (endocrine)  Or may affect nearby cells (paracrine )  Or acts on the same cell that produced it (autocrine) Endocrine Endocrine glands Release Hormones Paracrine Autocrine   Cells must have specific membrane or intracellular receptors to which hormones can bind  Are chemical signals that are secreted by the endocrine cells to regulate the metabolic functions of other cells ( target cells )  Amino acid based : EX. Thyroid & adrenomedullary hormones  Protein & peptide : EX. all other hormones  Steroids derived from cholesterol EX. Sex hormones ( testosterone, progesterone, estrogen) & adrenocortical hormones * Endocrine glands derived from mesoderm produce steroid hormones; those derived from ectoderm or endoderm produce amines, peptides, or protein hormones  Water-soluble hormones (all amino acid-based hormones except thyroid hormone) exert their effects by activating plasma membrane receptors, intracellular second messenger is released  Lipid-soluble hormones (steroids and thyroid hormone) diffuse into the cell, bind to intracellular receptors, migrate to the nucleus, and alter the gene expression  Most hormone synthesis and release is regulated through negative feedback mechanisms  Endocrine gland stimuli may be humoral, neural, or hormonal  The major endocrine glands  Pituitary gland  Pineal body  Thyroid gland  Parathyroid gland  Adrenal gland  Endocrine component of Glands endocrine tissue constitutes only part of the parenchyma of the organ  Pancreas & kidneys  ovaries & testes  Diffuse Neuroendocrine cells Small groups or individual endocrine cells found in a variety of other organs, e.g. GIT & kidneys  Capsule Stroma Septa Histological Reticular organization fibers Cells of the Parenchyma gland  Endocrine cells are all specialized for secretion  Their specific appearance depends on the nature of the secretory product & on the cellular machinery need to manufacture and store that product (peptide or steroid)  Endocrine cells are commonly arranged into cords or groups  The cells are closely associated with fenestrated capillaries  The hypothalamus is the major integrating link between the nervous and endocrine systems  It oversees many internal body conditions  It receives nervous stimuli from receptors throughout the body  the hypothalamus stimulates cellular activity in various parts of the body by directing and regulating the release of hormones from the pituitary gland Hypophysis (under growth) Location: in the sella turcica of the sphinoid bone in the base of the skull  It has 2 subdivisions, which develop from different embryologic sources (dual origin): 1. Adenohypophysis develops from an evagination (out pocketing) of the oral ectoderm (Rathke's pouch) of the roof of the primitive mouth or stomodium 2. Neurohypophysis develops from neural ectoderm as a down growth of the floor of diencephalon 1. Anterior pituitary (adenohypophysis) : Consists of : 1. Pars distalis (or the anterior lobe) 2. Pars tuberalis 3. Pars intermedia 2. Posterior pituitary (neurohypophysis) : Consists of : 1. Pars nervosa 2. Infundibulum with its stalk attached to the hypothalamus at the median eminence  two groups of vessels coming off the internal carotid artery 1. The superior hypophyseal arteries supply the median eminence and the infundibular stalk 2. The inferior hypophyseal arteries provide blood mainly for the neurohypophysis, with a small supply to the stalk  The superior hypophyseal arteries form a primary capillary network irrigating the stalk and median eminence  The capillaries then rejoin to form venules that branch again as a larger secondary capillary network in the adenohypophysis (pars distalis ) 1. Vascular connection : with the anterior pituitary  Occurs through releasing & inhibiting hormones produced by neurons of the hypothalamus ( neurosecretory cells of dorsal medial, ventral medial & infundibular nuclei)  These hormones released into the primary plexus and transported through hypophyseal portal veins to the secondary plexus that supplies the anterior pituitary 2. Neural connection with the posterior pituitary  occurs through hormones produced by the cell bodies of the neurosecretory cells ( Supraoptic & paraventricular nuclei )  These hormones are packaged in vesicles & transported through the axon (hypothalamo- hypophyseal tract), and stored in the axon terminals that lie in the posterior pituitary  Develops from Rathke's pouch, a diverticulum of the oral ectoderm  The adenohypophysis consists of: 1. Pars distalis 2. Pars intermedia 3. Pars tuberalis  accounts for 75% of the adenohypophysis  covered by a thin fibrous capsule  The main components are: 1. Cords (groups)of epithelial cells 2. Fenestrated sinusoidal capillaries 3. Fibroblasts which produce reticular fibers for support Based on staining affinity the cells are 2 groups: 1. Chromophils 2. Chromophobes  Represents 48% of the cells in pars distalis Are secretory cells in which hormone is stored in cytoplasmic granules Larger & more dense stained cytoplasm Are of 2 groups according to their affinity to acidic or basic dyes: 1. Acidophils : smaller , 37%, granules stain orange-red with eosin 2. Basophils : larger , 11%, granules stain blue with basic dyes  Acidophils Basophils  Subtypes of basophilic & acidophilic cells are Somatotropic Thryrotropic identified by transmission EM or by immunohistochemistry and are named for Mamotropic Gonadotropic their specific hormones or target cells Corticotropic Somatotrophs Secrete STH somatotropin(or growth hormone GH) Increase cellular metabolic rates Target all body tissues (bone, muscles, liver & adipose ) Mamotrophs Secrete prolactin Stimulate breast development & milk secretion Thryrotrophs Secrete TSH(Thyroid stimulating hormone) Gonadotrophs Secrete FSH (Follicle-stimulating hormone)stimulate growth of ovarian follicles in females & spermatogenesis in males LH (luteinizing hormone OR interstitial cell- stimulating hormone (ICSH); Leydig cells in male & corpus luteum in female Corticotrophs Secrete ACTH (Adrenal corticotropin ) lipotrophin (lipid metabolism)  Hormones & their target tissues(cells)  *Most of hormones secreted by hypothalamus and anterior pituitary are tropic hormones *Tropic hormones are the hormones that act on other endocrine glands (as their target) to control the release of their hormones  Over production :  In childhood ; before puberty leads to gigantism (overgrowth of all bones)  After puberty leads to acromegally ( over growth of terminal portions of bones )  Difficient production : Leads to dwarfism  Stain weakly  Few or no secretory granules  Represent a heterogeneous group, including stem & undifferentiated progenitor cells & any degranulated cells present  Controlled primarily by hormones produced by specialized neurons in hypothalamic nuclei  Most of these hormones are hypothalamic- releasing hormones (five hormones, one for each subtype of secretory cells )  Two are hypothalamic-inhibiting hormones for acidophilic cells ( somatotrophs & mamotrophs )  Negative feedback by hormones from the target organs on secretion of the relevant hypothalamic factors & on hormone secretion by the relevant pituitary cells  Is a funnel-shaped region surrounding the infundibulum  Most of the cells are basophilic gonadotropic cells that secrete follicle-stimulating hormone (FSH) and luteinizing hormone (LH)  Is highly vascularized by arteries and the hypophyseal portal system  lies between the pars distalis & the pars nervosa and contains colloid-filled cysts that are remnants of Rathke's pouch  Function of this region in adults is not clear, but in the fetus the basophils produce melanocyte-stimulating hormones (MSH) important for melanocyte activity  Consists of : 1. Pars nervosa 2. Infundibular stalk  Unlike the pars disalis, it does not contain secretory cells  It is composed of neural tissue  It consists of: 1. Unmylinated axons 2. Herring bodies 3. Pituicytes 4. Fenestrated capillaries 1. Unmylinated axons of the hypothalamo-hypophyseal tract  The cell bodies of these fibers present in the nuclei in the hypothalamus that produce neurosecretions 2. Neurosecretory bodies or Herring bodies  Distended axon terminals or axonal dilations containing accumulations of neurosecretion( vasopressin (ADH)& oxytocin ){ membrane-enclosed granules with either oxytocin or vasopressin bound to carrier proteins called neurophysin I and II respectively }  Visible in the light microscope as faintly eosinophilic structures  3. Pituicytes :  Are not secretory cells  Highly branched glia cells support the axons  Pituicytes contain lipid droplets, lipochrome pigment, and intermediate filaments  numerous cytoplasmic processes that contact and form gap junctions with each other  In addition to their support function they may have trophic function  Vasopressin & oxytocin  Are peptide hormones  Secreted by nuclei in hypothalamus & stored as Herring bodies (axonal dilations )in pars nervosa  Vasopressin (ADH ) is secreted by cell bodies of neurons located mainly in the supraoptic nucleus of the hypothalamus  Oxytocin is secreted by cell bodies of neurons located mostly in the paraventricular nucleus of the hypothalamus   Released in response to increased tonicity of the blood, recognized by osmoreceptor cells in the hypothalamus The main effect of ADH is to increase the permeability of the collecting ducts of the kidney to water ( more water is absorbed instead of being eliminated in the urine Thus, ADH helps to regulate the osmotic balance of body fluids  The secretion of oxytocin is stimulated by breast- feeding via sensory tracts that act on the hypothalamus in a neurohormonal reflex called the milk-ejection reflex  Oxytocin stimulates contraction of the myoepithelial cells around the alveoli & ducts of the mammary glands during nursing  & contraction of uterine smooth muscle during childbirth  Overproduction of ADH (Vasopressin) causes excessive water retention  Underproduction causes Diabetes insipidus – characterizes by polyuria ( excessive production of very diluted urine & excessive thirst )  Location: found in the posterior of the third ventricle, attached to the brain by a short stalk  Origin: develops with the brain from neuroectoderm in the roof of the diencephalon  Shape: cone or pine -shaped  It is covered by the pia mater, which sends septa of connective tissue into the gland 1. Pinealocytes are the secretory cells  Have slightly basophilic cytoplasm  Secretory vesicles, many mitochondria & long cytoplasmic processes  Produce melatonin, ( derived from serotonin ) a low molecular-weight tryptophan derivative  Melatonin is secreted at night & serotonin is secreted at day time  enter the pineal gland along the septa  associated indirectly with photoreceptive neurons in the retinas and running to the pinealocytes to stimulate melatonin release in periods of darkness  Most closely resemble astrocytes  They have elongated nuclei more heavily stained than those of pinealocytes  long cytoplasmic processes  Found in perivascular areas & between the groups of pinealocytes  Pineal astrocytes represent only about 5% of the cells in the gland  A characteristic feature (excellent land marker in radiological & computer-assisted tomography ) of the pineal gland  Variously sized concretions of calcium & magnesium salts  Form by precipitation around extracellular protein deposits  Appear during childhood and gradually increase in number & size with age  Have no apparent effect on the gland's function (unknown function)  stimulated by darkness & inhibited by daylight  Induces rhythmic changes or circadian rhythm (24- hours biological cycle, day/night) in the activity of the hypothalamus & pituitary gland (stimulates secretion of growth hormone & inhibits the release of gonadotropin)  Melatonin delays development of gonads till puberty (delays onset of puberty) suppress gonadotrophic hormones  Pineal distruction in males result in precocious puberty  Melatonin induces the feeling of sleepiness  It acts as antioxidant  The gland Some times referred to as endocrine clock  Location : Paired organ near the superior poles of the kidneys embedded in adipose tissue  Shape: flattened structures with a half-moon shape  The right is pyramid- shaped and sits directly on top of the right kidney  The left is more crescent-shaped and lies along the medial border of the left kidney from the hilus to its superior pole  Covered by a dense CT capsule that sends thin septa to the interior of the gland as trabeculae  Stroma of rich network of reticular fibers that support the secretory cells  The gland consists of two histologically & functionally different regions 1. Adrenal cortex: a yellowish peripheral layer 2. Adrenal medulla: a reddish-brown central layer  The adrenal cortex & adrenal medulla can be considered two organs with distinct origins, functions, & morphologic characteristics that become united during embryonic development  The cortex arises from mesoderm  The medulla consists of cells derived from the neural crest, from which sympathetic ganglion cells also originate  Accounts for 80%-90% of the gland Contains cells that synthesize & secrete several steroid hormones without storing them (no secretory granules) Cells of the adrenal cortex have characteristic features of steroid-secreting cells Central nuclei & acidophilic cytoplasm Rich in lipid droplets Abundant smooth ER which contain the enzymes for cholesterol synthesis Abundant mitochondria with tubular cristae Three classes : 1. Mineralocorticoids 2. Glucocorticoids 3. Androgens All are synthesized from cholesterol, the major component of low-density lipoprotein Hormone is synthesized by enzymes of SER & mitochondria As low-molecular-weight, lipid-soluble molecules, steroids diffuse freely through the plasma membrane and do not require exocytosis to be released from the cells  The cords of cortical cells are arranged differently and are specialized to produce different classes of steroid hormones The cortex is subdivided histologically into three concentric zones named, from the capsule inward 1. Zona glomerulosa 2. Zona fasciculata 3. Zona reticularis  The outer small zone Immediately inside the connective tissue capsule Forms 15% of the cortex  The cells are columnar or pyramidal The cells are arranged in spherical or arched cords The cells are surrounded by fenestrated capillaries  Secrete mineralocorticocoids The principal product is aldosterone ( the major regulator of salt & water balance, which acts to stimulate Na+ reabsorption & water in the distal convoluted tubules ) It also increase Na+ reabsorption by intestine Decrease Na+ & increase K+ content of sweat & saliva Aldosterone secretion is stimulated by angiotensin II and also by an increase in plasma K+ & decrease Na+ concentrations, but only weakly by ACTH  The intermediate layer of cells in the suprarenal cortex The largest layer of the cortex, accounts for up to 80% of the cortex  Polyhedral cells larger than the cells of the zona glomerulosa Arranged in radial columns, one to two layers thick Stain lightly acidophilic Sinusoidal capillaries between the columns of the cells Many lipid droplets (appear vacuolated and are called spongiocytes)  Cells of this zone secrete glucocorticoids, especially cortisol & small amount of androgens Glucocorticoids function in the control of carbohydrate, fat, and protein metabolism Cortisol has anti-inflammatory effect & suppress the immune response Secretion of glucocorticoids is controlled by ACTH from the anterior pituitary & negative feedback Stimulated also by stress & catecholamines  The innermost layer of the suprarenal cortex constituting about 7% of the cortex  Darkly staining acidophilic cells The cells are arranged in anastomosing cords The cells are similar to the spongiocytes of the zona fasciculata but are smaller The cells contain fewer lipid droplets & more lipofuscin pigment Several cells near the suprarenal medulla are dark with electron-dense cytoplasm and pyknotic nuclei, which suggests that this zone contains degenerating parenchymal cells  Cells of the zona reticularis also produce cortisol, but primarily secrete the weak androgen dehydroepiandrosterone (DHEA) which is converted to testosterone in several other tissues Secretion by these cells is stimulated by ACTH & is under feedback regulation with the pituitary and hypothalamus At this age, a layer of fetal or provisional cortex, comprising 80% of the total gland The fetal cortex is thick & contain cells that secret sulfated DHEA under the control of the fetal pituitary DEHA converted in the placenta to active estrogens (and androgens), which mostly enter the maternal circulation After birth, the provisional cortex undergoes involution while the permanent cortex organizes the three layers (zones) Hyperfunction:  Cushing's syndrome: Increase production of glucocorticoids Cause: most often (90%) due to a pituitary adenoma that results in excessive production of ACTH  Conn's syndrome: increase production of aldosterone Cause: adenoma or hyperplasia Signs: hypertension &muscle weakness ( loss of k+ )  Excessive production of adrenal androgens:  in boys: precocious puberty  in girls: hirsutism (abnormal hair growth) & virilization (muscle bulk, body hair & deep voice) Hypofunction: Addison disease: Cause: destruction of the adrenal cortex & failure of secretion of both glucocorticoids & mineralocorticoids  Capsular arteries Cortical arterioles Medullary arterioles branch into medullary capillary network  Adrenal medulla is more vascular & have dual blood supply : 1. Arterial blood from medullary capillary 2. Blood of cortical capillaries carrying cortical hormones composed of : Chromaffin cells (pheochrome) : large, pale-staining polyhedral cells arranged in cords or clumps Few parasympathetic ganglion cells A profuse supply of sinusoidal capillaries between adjacent cords ( more vascular ) Chromaffin reaction : The granules take yellowish brown color when treated with chromic acid or chromium salts  Origin of medullary cells Chromaffin cells, arise from neural crest cells, as do the postganglionic neurons of sympathetic & parasympathetic ganglia. Chromaffin cells can be considered modified sympathetic postganglionic neurons, lacking axons & dendrites and specialized as secretory cells Unlike cells of the cortex, medullary chromaffin cells contain many electron-dense granules for hormone storage & secretion These granules contain catecholamines: epinephrine or norepinephrine About 80% of the catecholamines secreted from the adrenal medulla is epinephrine The granules of epinephrine-secreting cells are less electron-dense & smaller than those of norepinephrine-secreting cells Catecholamine, together with Ca2+ and ATP, are bound in a granular storage complex with proteins called chromogranins Medullary chromaffin cells are innervated by cholinergic endings of preganglionic sympathetic neurons, from which impulses trigger hormone release by exocytosis Catecholamines derived from tyrosine  Medullary hormones deals with physical & emotional stress Get the body ready to fight or flight The fight-or-flight response : produce vasoconstriction, increased blood pressure, changes in heart rate, and metabolic effects such as elevated blood glucose  Adrenal medulla disorders  Pheochromocytoma: a tumor of its cells that causes hyperglycemia & transient elevations of blood pressure  Composed of spherical aggregates of cells, known as islets of Langerhans, that are scattered among the exocrine acini  There are more than 1 million islets in the human pancreas, concentrated mainly at the tail  Very thin capsule of reticular fibers surrounds each islet  Origin: endodermal (epithelial cells )  Each islet consists of polygonal or rounded cells  Smaller & more lightly stained than the surrounding acinar cells  Arranged in cords that are separated by a network of fenestrated capillaries  Autonomic nerve fibers contact some of the endocrine cells and the blood vessels  By Routine stains or trichrome islet cells are acidophilic or basophilic with fine cytoplasmic granules  4 types of cells on the bases of : 1. immunohistochemical staining 2. Size, electron density & distribution of their secretory granules 1. Alpha (α) or A cells , 20% , secrete glucagon and are usually located near the periphery of islets, stained pink with Gomori stain their granules have homogenous electron dense core & lower density peripheral zone 2. Beta (β)or B cells, 70%, produce insulin, are located centrally in islets, smaller & most numerous cell type, stains blue with Gomori their granules contain one or more dense crystals in a low density matrix 3. Delta (δ)or D cells, 5-10% secreting somatostatin, are scattered and much less abundant Their granules are larger & less electron dense 4. F or PP cells , less than 5% secrete pancreatic polypeptide, more common in islets located within the head of the pancreas Their granules are small with variable density are all polypeptides Both insulin & glucagon are important in the regulation of carbohydrate, protein and lipid metabolism  Insulin is an anabolic hormone, it increases the storage of glucose, fatty acids and amino acids in cells and tissues (acts to lower blood sugar)  Glucagon is a catabolic hormone, it mobilizes glucose, fatty acids and amino acids from stores into the blood (acts to raise blood sugar) Sympathetic fibers during stressful situations, emergencies, and exercise increase glucagon release and inhibit insulin release parasympathetic fibers during restful times and during the digestion of a meal stimulate the release of insulin  Stimuli for insulin release primarily is high blood glucose levels  Glucagon is released in response to low blood glucose levels  Cell Quantity Hormone Hormone function type Alpha 20% glucagon Increases blood glucose level (α Cells) Beta 70% insulin Decreases blood glucose level (β cells ) Delta 5-10% somatostatin Paracrine: inhibits hormone release (δ cells ) from endocrine pancreas & enzymes from exocrine pancreas Endocrine: inhibits release of GH & TSH in anterior pituitary & HCl secretion by gastric parietal cells F cells rare Pancreatic Stimulates activity of gastric chief (PPcells) polypeptide cells; inhibits bile secretion, pancreatic enzyme & bicarbonate secretion & intestinal motility  Insulin-dependent or type 1 diabetes usually affects persons younger than 20 years of age Results from partial or total autoimmune destruction of beta cells & subsequent lack of insulin (insulin insufficiency)  Insulin-independent diabetes or type 2 diabetes usually affects persons older than 40 years of age results from a failure of cells to respond to insulin (insulin resistance ) , and is frequently associated with obesity Location: in the cervical region anterior to the larynx, consists of two lobes united by an isthmus It is surrounded by dense, irregular collagenous CT capsule subdivide the gland into lobules parathyroid glands embedded within the capsule, on the posterior aspect of the gland  The thyroid originates from two main structures: the primitive pharynx near the base of the future tongue ( main bulk of the gland ) begins as epithelial diverticulum growing down from the endodermal lining of the foregut  & from the neural crest ( parafollicular cells )  It originates from between the first and second pharyngeal pouches  It is mainly endodermal in origin The thyroid follicle is the structural and functional unit of the thyroid gland (20-30 million) The wall of the follicle is formed of: 1. Follicular cells = 98% 2. Parafollicular = 2% The cells are resting on a basement membrane Central lumen filled with acidophilic, gelatinous substance ( colloid )  Single layer Cuboidal basophilic, central nucleus Exhibit characters of protein secreting cells Apical secretory granules Abundant lysosomes Surface microvilli Follicular cells range in shape from squamous to low columnar and the follicles are quite variable in diameter The size & cellular features of thyroid follicles vary with their functional activity  Active glands have more follicles of low columnar epithelium  Glands with mostly squamous follicular cells are considered hypoactive  Follicular cells produce the thyroid hormones (T3 & T4)  Found inside the basal lamina of the follicular epithelium or as isolated clusters between follicles Derived from neural crest cells Usually larger than follicular cells Less intensely stained They have a smaller amount of rough ER, large Golgi complexes, and numerous small granules containing polypeptide hormone colloid Thyroid is the only endocrine gland whose secretory product is stored in great quantity & accumulated as a colloid within the follicles  Synthesize & secrete hormone calcitonin ( lower blood Ca2+ level ) by inhibiting bone resorption by osteoclasts (decreases osteoclast activity) & increases loss of Ca++ in urine  Calcitonin secretion is triggered by elevated blood Ca2+ levels  It is a glycoprotein of high molecular mass thyroglobulin the precursor for the active thyroid hormones  hormones T4 and T3 are stored in the colloid, which is bound to thyroglobulin  When the hormones are to be released, the hormone-bound thyroglobulin is endocytosed and the hormones are cleaved from it by lysosomal proteases Regulated by: 1. The iodide levels in the follicular cell 2. The binding of TSH to TSH receptors of the follicular cells This process involves the following steps: TSH is secreted by basophilic cells of pars distalis (anterior pituitary)  Under stimulation of TSH  Synthesized in RER & transported to Golgi to form secretory vesicles  Released into the lumen  By the Na/I symporter in the basolateral cell membrane of follicular cells  Oxidation of iodide to active iodine by membrane-bound thyroid peroxidase at the luminal cell surface  Transported to the lumen to iodinate the tyrosine residues of stored thyroglobulin  This result in formation of mono & di- iodinated thyrosine which are conjugated (coupling )to form T3 & T4  In response to TSH follicular cells take up the colloid by endocytosis  Digestion & hydrolysis of thyroglobulin by lysosomal enzymes  Transported to the cytosol as T1,T2, T3 & T4  T1& T2 remain in the cytoplasm & broken into iodine & thyrosine to be reused  T3 & T4 secreted through the basolateral membrane into the blood capillaries  T4 ( thyroxin )is the more abundant compound, constituting 90% of the circulating thyroid hormone  It is a prohormone and a reservoir for active T3  but T3 is 2-10 folds more active (potent) than T4  The half-life of T3 is 1.5 days in comparison with a week for T4  Most of the thyroid hormone circulating in the blood is bound to transport proteins Thyroid hormones are important for growth, for cell differentiation, and for the control of the basal metabolic rate and oxygen consumption in cells throughout the body. Thyroid hormones affect protein, lipid, and carbohydrate metabolism 1. TSH from anterior pituitary stimulates synthesis & release of the hormones  TSH also Increases the activity & height of the epithelium  TSH receptors at the base of follicular cells 2. Negative feed back 3. Iodine level Thyroid hormone act through intracellular receptors Iodine dificiency Goiter Enlargement of the thyroid gland due to iodine deficiency which result in accumulation of non- iodinated thyroglobulin in the lumen & enlargement of thyroid Goiters are endemic in some regions of the world, where dietary iodide is scarce Hypothyrodisim Leads to cretinism in infants (congenital or iodine lack ) Autoimmune diseases of the thyroid, such as Hashimoto disease, may impair its function, with consequent hypothyroidism (fatigue, weight gain, pale or puffy face, feeling cold, joint and muscle pain) Hyperthyrodisim Cause Graves' disease an autoimmune disease in which anti-TSH receptor antibodies bind to TSH receptors on the thyroid and stimulate continuous thyroid hormone release , bulging of the eyes (exophthalmos)may occur  Usually 4 in number, are located on the posterior surface of the thyroid gland  one parathyroid gland is located on both poles (superior and inferior) of the right and left lobes of the thyroid gland  Usually embedded in the larger gland's capsule  Derived from the pharyngeal pouches—the superior glands from the fourth pouch and the inferior glands from the third pouch  Capsule , septa & clusters of secretory cells  With increasing age many secretory cells are replaced with adipocytes, which may constitute more than 50% of the gland in older people  The parenchyma of the parathyroid glands is composed of two cell types:  Chief cells  Oxyphil cells  polygonal cells with round nuclei and pale- staining, slightly acidophilic cytoplasm  The cytoplasm is filled with secretory granules containing the polypeptide parathyroid hormone or parathormone (PTH), a major regulator of blood calcium levels  The main target cell is osteoblast which release osteoclast stimulating factor which increases the number & activity of osteoclasts  Parathyroid hormone also indirectly increases the absorption of Ca2+ from the gastrointestinal tract by stimulating the PTH synthesis increases of vitamin the number and D, which is necessary for this absorption activity of osteoclasts, increases Ca and Mg +2 +2 reabsorption from distal tubules and inhibits the reabsorption of HPO4-2 so more is secreted in the urine, and promotes activation of vit D, which increases the absorption of Ca+2, Mg+2 from the GIT Parathyroid hormone ( secreted by chief cells of parathyroid ) & calcitonin ( secreted by parafollicular cells of thyroid ) have opposing effects & constitute a dual mechanism to regulate blood levels of Ca2  Less numerous, larger  Stain more deeply with eosin than chief cells  Oxyphils appear in groups & as isolated cells  They have more abundant mitochondria than do chief cells, but their Golgi apparatus is small and there is little RER  Glycogen in their cytoplasm  Probably represent inactive phase of chief cells  Appear around puberty and increase in number  Unknown function  Hyperparathyroidism: concentrations of blood phosphate are decreased & concentrations of blood Ca2+ are increased Loss of bone minerals & deposits of calcium in organs, such as kidneys & arteries Osteitis fibrosa cystica: Bones are less stress-resistant and prone to fractures  Hypoparathyroidism: concentrations of blood phosphate are increased & concentrations of blood Ca2+ are decreased The bones become denser and more mineralized Causes spastic contractions of the skeletal muscles and generalized convulsions ( spasm ) called tetany Patients with hypoparathyroidism are treated with calcium salts and vitamin D to promote Ca2+ uptake in the gut Good luck