Pathophysiology of the thyroid, parathyroid and sexual glands

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Prepared by MD, PhD Marta R. Gerasymchuk, pathophysiology department, Ivano-Frankivsk National Medical University

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  • Thyroid and parathyroid glands. Note their relationship to each other and to the larynx (voice box) and trachea.
  • The thyroid gland The thyroid gland maintains the metabolic level of almost all cells in the body by producing, in its follicular cells, two thyroid hormones: triiodothyronine (T3), and tetraiodothyronine (T4) or thyroxine . Iodine (I2) has an atomic weight of 127 and a molecular weight of 254; T4 has a molecular weight of 777 Daltons of which 508 is iodide. Thyroid hormones are essential for normal neural development, linear bone growth, and proper sexual maturation . Parafollicular cells called C-cells are located close to the follicular cells. C-cells produce the polypeptide hormone, calcitonin .
  • Calcitonin is produced by the parafollicular C-cells of the thyroid. The hormone inhibits bone resorption by blocking the parathyroid hormone (PTH)-receptors on the osteoclasts. Calcitonin is important in bone remodelling and in treatment of osteoporosis. Thyroid releasing hormone (TRH) is released from the hypothalamus and reaches the adenohypophysis via the portal system. Here, the thyrotropic cells are stimulated to produce TSH. ·  Thyroid stimulating hormone (TSH) is released from the thyrotropic cells of the adenohypophysis to the systemic blood by which it travels to the thyroid gland.
  • Actions of Thyroid Hormone All the major organs in the body are affected by altered levels of thyroid hormone. Thyroid hormone has two major functions: it increases metabolism and protein synthesis, and it is necessary for growth and development in children, including mental development and attainment of sexual maturity. Metabolic Rate. Thyroid hormone increases the metabolism of all body tissues except the retina, spleen, testes, and lungs. The basal metabolic rate can increase by 60% to 100% above normal when large amounts of T4 are present. As a result of this higher metabolism, the rate of glucose, fat, and protein use increases. Lipids are mobilized from adipose tissue, and the catabolism of cholesterol by the liver is increased. Blood levels of cholesterol are decreased in hyperthyroidism and increased in hypothyroidism. Muscle proteins are broken down and used as fuel, probably accounting for some of the muscle fatigue that occurs with hyperthyroidism. The absorption of glucose from the gastrointestinal tract is increased. Because vitamins are essential parts of metabolic enzymes and coenzymes, an increase in the metabolic rate “speeds up” the use of vitamins and tends to cause vitamin deficiency. Cardiovascular Function. Cardiovascular and respiratory functions are strongly affected by thyroid function. With an increase in metabolism, there is an increase in oxygen consumption and production of metabolic end-products, with an accompanying increase in vasodilatation. Blood flow to the skin, in particular, is augmented as a means of dissipating the body heat that results from the higher metabolism. Blood volume, cardiac output, and ventilation all are increased as a means of maintaining blood flow and oxygen delivery to body tissues. Heart rate and cardiac contractility are enhanced as a means of maintaining the needed cardiac output. However, blood pressure is likely to change little because the increase in vasodilatation tends to offset the increase in cardiac output. Gastrointestinal Function. Thyroid hormone enhances gastrointestinal function, causing an increase in motility and production of gastrointestinal secretions that often results in diarrhea. An increase in appetite and food intake accompanies the higher metabolic rate that occurs with increased thyroid hormone levels. At the same time, weight loss occurs because of the increased use of calories. Neuromuscular Effects. Thyroid hormone has marked effects on neural control of muscle function and tone. Slight elevations in hormone levels cause skeletal muscles to react more vigorously, and a drop in hormone levels causes muscles to react more sluggishly. In the hyperthyroid state, a fine muscle tremor is present. The cause of this tremor is unknown, but it may represent an increased sensitivity of the neural synapses in the spinal cord that control muscle tone. In the infant, thyroid hormone is necessary for normal brain development. The hormone enhances cerebration; in the hyperthyroid state, it causes extreme nervousness, anxiety, and difficulty in sleeping. Evidence suggests a strong interaction between thyroid hormone and the sympathetic nervous system. Many of the signs and symptoms of hyperthyroidism suggest overactivity of the sympathetic division of the autonomic nervous system, such as tachycardia, palpitations, and sweating. Tremor, restlessness, anxiety, and diarrhea also may reflect autonomic nervous system imbalances. Drugs that block sympathetic activity have proved to be valuable adjuncts in the treatment of hyperthyroidism because of their ability to relieve some of these undesirable symptoms.
  • Thyroid hormones are synthesised in adults as long as the dietary iodine (I2) supersedes 75  g daily . This is an adequate supply to prevent goitre formation. The daily ingestion of iodide is 400-500  g daily in many areas and the same amount is excreted in the urine in a steady state. The synthesis in the thyroid gland takes place in the following way: A . Dietary iodine (I2) is reduced to iodide (I-) in the stomach and gut is rapidly absorbed and circulates as iodide (slide picture). The production and secretion of thyroid hormones. B . Follicular cells in the thyroid gland possess an active iodide trap that requires and concentrates iodide from the circulating blood. Iodide is transported into the cell against an electrochemical gradient (more than 50 mV) by a Na+-I--symport. The iodide pump is linked to a Na+-K+-pump, which requires energy in the form of oxidative phosphorylation (ATP) and is inhibited by ouabain. The thyroid absorption of iodide is also inhibited by negative ions (such as perchlorate, pertechnetate, thiocyanate and nitrate), because they compete with the iodide at the trap. In the follicular cell, iodide passes down its electrochemical gradient through the apical membrane and into the follicular colloid. Iodide is instantly oxidised – with hydrogen peroxide as oxidant - by a thyroid peroxidase to atomic or molecular iodine (I0 or I2) at the colloid surface of the apical membrane. Thiouracil and sulfonamides block this peroxidase. C . The rough endoplasmic reticulum synthesises a large storage molecule called thyroglobulin . This compound is build up by a long peptide chain with tyrosine units and a carbohydrate unit completed by the Golgi apparatus. Iodide-free thyroglobulin is transported in vesicles to the apical membrane, where they fuse with the membrane and finally release thyroglobulin at the apical membrane. D . At the apical membrane the oxidised iodide is attached to the tyrosine units (L-tyrosine) in thyroglobulin at one or two positions, forming the hormone precursors mono-iodotyrosine (MIT), and di-iodotyrosine (DIT), respectively. This and the following reactions are dependent on thyroid peroxidase in the presence of hydrogen peroxide -both located at the apical membrane. As MIT couples to DIT it produces tri-iodothyronine (3,5,3`-T3), whereas two DIT molecules form tetra-iodothyronine (T4), or thyroxine . These two molecules are the two thyroid hormones. Small amounts of the inactive reverse T3 (3,3`,5`- T3) is also synthesised. E . Each thyroglobulin molecule contains up to 4 residues of T4 and zero to one T3. Thyroglobulin is retrieved back into the follicular cell as colloid droplets by pinocytosis . Pseudopods engulf a pocket of colloid. These colloid droplets pass towards the basal membrane and fuse with lysosomes forming phagolysosomes. F . Lysosomal exopeptidases break the binding between thyroglobulin and T4 (or T3). Large quantities of T4 are released to the capillary blood. Only minor quantities of T3 are secreted from the thyroid gland. G . The proteolysis of thyroglobulin also releases MIT and DIT. These molecules are deiodinated by the enzyme deiodinase, whereby iodide can be reused into T4 or T3. Normally, only few intact thyroglobulin molecules leave the follicular cells. H . TSH stimulates almost all processes involved in thyroid hormone synthesis and secretion.
  • http://www.1cro.com/medicalphysiology/chapter28/kap28.htm
  • http://www.1cro.com/medicalphysiology/chapter28/kap28.htm
  • Metabolism of thyroid hormones In the blood we have only small amounts of thyroxine-binding globulin (TBG; approximately 10 mg per l), but the affinity for T4 is high. The total T4 is 10-7 mol per l equal to 77.7  g per l of blood serum, because 777 g of T4 equals one mol. out of the total. Approximately 70% of T4 and T3 binds to TBG, and the rest to thyroxine-binding albumin (TBA) and to transthyrenin . Oestrogens stimulate the synthesis of TBG. The T3 hormone is elimina­ted quickly (half-life: 24 hours), because it has the lowest degree of protein binding. The thyroxine (T4) molecule has a biological half-life of 7 days, almost equal to the physical half-life of the radioactive isotope 131I (8 days). T4 is likely to be a prohormone, which is deiodinised by monodeiodinase to the more potent T3 just before it is used in the cells. Thus T3 is probably the final active hormone, although it is present only in a very low concentration (10-9 mol per l). Most of the daily T4 released from the thyroid gland undergoes deiodination, with subsequent deamination and decarboxylation. Some of the hormone molecules are coupled to sulphate and glucuronic acid in the liver and are excreted in the bile. In the intestine most of the coupled molecules are hydrolysed, and the hormones are reabsorbed by the blood, whereby they reach hepar again (the enterohepatic circuit ).
  • Thyrotoxicosis Hypermetabolic state caused by elevated circulating levels of free T3 and T4 Most common causes Diffuse hyperplasia of the thyroid associated with Graves disease (85% of cases) Hyperfunctional multinodular goiter Hyperfunctional adenoma of the thyroid Thyroid storm Abrupt onset of hyperthyroidism Occurs most commonly in patients with Graves disease – acute elevation of catecholamine levels A medical emergency Untreated patients die of cardiac arrhythmias Apathetic hyperthyroidism Thyrotoxicosis occuring in the elderly
  • In Graves' Disease a patient produces autoantibodies that bind to the receptors for thyroid-stimulating hormone (TSH). TSH is produced by the pituitary gland and the receptors for TSH are present on thyroid cells. Binding of these autoantibodies mimics the normal action of TSH which is to stimulate the production of two thyroid hormones, thyroxine and triiodothyronine. However, the autoantibodies are not under a negative feedback control system and therefore lead to overproduction of the thyroid hormones. For this reason these autoantibodies have been termed long-acting thyroid-stimulating (LATS) antibodies . Overproduction of thyroid hormones leads to many metabolic problems.
  • ouabain - a poisonous white crystalline glycoside extracted from certain trees and used as a heart stimulant and, by some African tribes, on poison darts. Formula: C29H44O12.8H2O
  • http://www.micronutrient.org/Francais/view.asp?id=38&x=656
  • http://medicalshow.blogspot.com/2012/05/clinical-picture-mnemonics-of-cretinism.html
  • http://medicalshow.blogspot.com/2012/05/clinical-picture-mnemonics-of-cretinism.html
  • Decreased Iodine leads to decreased thyroid hormone, which leads to increased TSH which leads to increased growth of follicles. That’s how an iodine deficiency leads to a goiter. The probability of having a goiter is DIRECTLY proportional to how far you live from the ocean.
  • Many vegetables are goiterogens, fruits are NOT. Which one is NOT a goiterogen?
  • Most goiters worldwide are due to iodine deficiency. Why? Ans: The thyroid enlarges to try to trap more iodine, when serum levels are low. This is a adaptive response.
  • MALE REPRODUCTIVE SYSTEM ■ The male genitourinary system functions in both urine elimination and reproduction. ■ The testes function in both production of male germ cells (spermatogenesis) and secretion of the male sex hormone, testosterone. ■ The ductile system (epididymides, vas deferens, and ejaculatory ducts) transports and stores sperm and assists in their maturation, and the accessory glands (seminal vesicles, prostate gland, and bulbourethral glands) prepare the sperm for ejaculation. ■ Sperm production requires temperatures that are 2° to 3°C below body temperature. The position of the testes in the scrotum and the unique blood flowcooling mechanisms provide this environment. ■ The urethra, which is enclosed in the penis, is the terminal portion of the male genitourinary system. Because it conveys both urine and semen, it serves both urinary and reproductive functions.
  • Pathophysiology of the thyroid, parathyroid and sexual glands

    1. 1. Pathophysiology of thyroid,Pathophysiology of thyroid,parathyroid and sexualparathyroid and sexualglands.glands.By MD, PhD, Marta R. GerasymchukBy MD, PhD, Marta R. Gerasymchuk,Pathophysiology departmentPathophysiology departmentIvano-Frankivsk National MedicalIvano-Frankivsk National MedicalUniversityUniversity
    2. 2. CONTENTCONTENT1.1. Pathology of thyroid gland. Hypothyroidism: etiology,Pathology of thyroid gland. Hypothyroidism: etiology,pathogenesis, mechanisms of development of mainpathogenesis, mechanisms of development of mainmanifestations.manifestations.2.2. Radiation damage of thyroid gland, endemic goiter,Radiation damage of thyroid gland, endemic goiter,Hashimoto’s autoimmune thyroiditis.Hashimoto’s autoimmune thyroiditis.3.3. Hyperthyroidism. Diffuse toxic goiter, role of immuneHyperthyroidism. Diffuse toxic goiter, role of immunemechanisms in its development. Pathogenesis of mainmechanisms in its development. Pathogenesis of mainmanifestations of hyperthyroidism.manifestations of hyperthyroidism.4.4. Pathology of parathyroid glands. Hypo- andPathology of parathyroid glands. Hypo- andhyperparathyroidism.hyperparathyroidism.5.5. Pathology of sexual glands. Male hypo- andPathology of sexual glands. Male hypo- andhypergonadism, etiology and pathogenesis.hypergonadism, etiology and pathogenesis.Eunochoidism.Eunochoidism.6.6. Female hypo- and hypergonadism. Disorder of sexualFemale hypo- and hypergonadism. Disorder of sexualdifferentiation and development.differentiation and development.Disorders of cyclic functions of female organism; disordersDisorders of cyclic functions of female organism; disordersof pregnancy, delivery and lactation caused by hormones.of pregnancy, delivery and lactation caused by hormones.7.7. Extragenital manifestations of sexual gland dysfunction.Extragenital manifestations of sexual gland dysfunction.Disorder of endocrine function of placenta.Disorder of endocrine function of placenta.
    3. 3. Actuality of the lectureActuality of the lectureThe diseases in the basis of which is the disturbance of the endocrine glandsThe diseases in the basis of which is the disturbance of the endocrine glandsfunctions are widely spread in all the world. On data the WHO, on a planet is notfunctions are widely spread in all the world. On data the WHO, on a planet is notless then 200 millions people suffer by diffuse toxic goiter. Except sporadicless then 200 millions people suffer by diffuse toxic goiter. Except sporadiccases ofcases of thyreotoxicosisthyreotoxicosis andand myxedemamyxedema, which meet everywhere, on territory, which meet everywhere, on territoryof a number of the states there are regions, where the people are sick ofof a number of the states there are regions, where the people are sick ofendemic goiter, frequently with manifestations hypo- and hyperfunction of thyroidendemic goiter, frequently with manifestations hypo- and hyperfunction of thyroidgland. In our district such region is the Carpathians. Recently thegland. In our district such region is the Carpathians. Recently the diseases ofdiseases ofthyroid glandthyroid gland show the tendency to increase. This is promoted by such factors:show the tendency to increase. This is promoted by such factors:inadequate receipt of iodium into the organism, radiation (scaning, radiotherapy,inadequate receipt of iodium into the organism, radiation (scaning, radiotherapy,external sources), medical drugs, biphenols, which are used in agricultures,external sources), medical drugs, biphenols, which are used in agricultures,features of nutrition, activity of the person in conditions of high and lowfeatures of nutrition, activity of the person in conditions of high and lowtemperature. The amount of persons with the disturbanced function of thyroidtemperature. The amount of persons with the disturbanced function of thyroidgland hardly increased after Chornobel catastroph.gland hardly increased after Chornobel catastroph.TheThe diseases of parathyreoiddiseases of parathyreoid glands meet not so often. Because of largeglands meet not so often. Because of largenumber and deleted accommodation of the glands of disease and the casualnumber and deleted accommodation of the glands of disease and the casualdamages seldom lead them to destruction of such amount of parathyreoiddamages seldom lead them to destruction of such amount of parathyreoidtissues to cause it insufficiency. More often hypofunction of this organ meets intissues to cause it insufficiency. More often hypofunction of this organ meets inthe patients, which the taken place as a result of operating interference on thethe patients, which the taken place as a result of operating interference on thethyroid gland the destruction of glands. The second form of parathyreoidthyroid gland the destruction of glands. The second form of parathyreoidinsufficiency is ideopatic. This state, it is a result of autoimune response, whichinsufficiency is ideopatic. This state, it is a result of autoimune response, whichare arisen on base of an inflammation, infection, destructive processes in gland.are arisen on base of an inflammation, infection, destructive processes in gland.Hyperfunction of parathyroid glands is observed in many states, which areHyperfunction of parathyroid glands is observed in many states, which areaccompanied by calcium loss (osteomalation, rachitic, renal insufficiency,accompanied by calcium loss (osteomalation, rachitic, renal insufficiency,multiple myeloma,osteoporosis), and also as primary disease due to themultiple myeloma,osteoporosis), and also as primary disease due to theadenoma of one or several endocrine bodies.adenoma of one or several endocrine bodies.
    4. 4. Thyroid GlandThyroid Gland
    5. 5. The thyroid gland and thefollicular structure
    6. 6. Chemistry of thyroid hormoneChemistry of thyroid hormoneproductionproduction
    7. 7. Hormones of the Thyroid GlandHormones of the Thyroid Gland• Thyroxine (T4)• Principle hormone• Increases energy and protein metabolismrate• Triiodothyronine (T3)• Increases energy and protein metabolismrate• Calcitonin• Regulates calcium metabolism• Works with parathyroid hormone andvitamin D
    8. 8. Thyroid hormones are synthesised in adults as long as the dietary iodine (I2) supersedes 75 µg daily. This is anadequate supply to prevent goiter formation. The daily ingestion of iodide is 400-500 µg daily in many areasand the same amount is excreted in the urine in a steady state.
    9. 9. The synthesis in the thyroid gland takesThe synthesis in the thyroid gland takesplace in the following way:place in the following way: AA.. Dietary iodineDietary iodine (I(I22)) is reduced tois reduced to iodideiodide (I-)(I-) in the stomach and gut isin the stomach and gut israpidly absorbed and circulates as iodide.rapidly absorbed and circulates as iodide. BB.. Follicular cellsFollicular cells in the thyroid gland possess an activein the thyroid gland possess an active iodide trapiodide trap thatthatrequires and concentrates iodide from the circulating blood.requires and concentrates iodide from the circulating blood. IodideIodide isistransported into the cell against an electrochemical gradient (more thantransported into the cell against an electrochemical gradient (more than50 mV) by a Na+50 mV) by a Na+--I-I---symport. The iodide pump is linked to asymport. The iodide pump is linked to a Na+Na+--K+K+--pump,pump, which requires energy in the form of oxidative phosphorylationwhich requires energy in the form of oxidative phosphorylation(ATP) and is inhibited by ouabain. The(ATP) and is inhibited by ouabain. The thyroid absorption of iodidethyroid absorption of iodide isisalso inhibited by negative ions (such asalso inhibited by negative ions (such as perchlorate, pertechnetate,perchlorate, pertechnetate,thiocyanate and nitratethiocyanate and nitrate), because they compete with the iodide at the), because they compete with the iodide at thetrap.trap. In the follicular cellIn the follicular cell, iodide passes down its electrochemical, iodide passes down its electrochemicalgradient through the apical membrane and into the follicular colloid.gradient through the apical membrane and into the follicular colloid.Iodide is instantly oxidised – with hydrogen peroxide as oxidant - by aIodide is instantly oxidised – with hydrogen peroxide as oxidant - by athyroid peroxidasethyroid peroxidase to atomic or molecular iodine (Ito atomic or molecular iodine (I00 or Ior I22) at the colloid) at the colloidsurface of the apical membrane. Thiouracil and sulfonamides block thissurface of the apical membrane. Thiouracil and sulfonamides block thisperoxidase.peroxidase. CC. The. The rough endoplasmic reticulumrough endoplasmic reticulum synthesises a large storagesynthesises a large storagemolecule calledmolecule called thyroglobulinthyroglobulin. This compound is build up by a long. This compound is build up by a longpeptide chain with tyrosine units and a carbohydrate unit completed bypeptide chain with tyrosine units and a carbohydrate unit completed bythe Golgi apparatus. Iodide-free thyroglobulin is transported inthe Golgi apparatus. Iodide-free thyroglobulin is transported in vesiclesvesiclesto the apical membrane, where they fuse with the membrane and finallyto the apical membrane, where they fuse with the membrane and finallyrelease thyroglobulin at the apical membrane.release thyroglobulin at the apical membrane.
    10. 10. The synthesis in the thyroid gland takesThe synthesis in the thyroid gland takesplace in the following way:place in the following way: DD.. At the apical membraneAt the apical membrane thethe oxidised iodideoxidised iodide is attached to the tyrosineis attached to the tyrosineunits (L-tyrosine)units (L-tyrosine) in thyroglobulinin thyroglobulin at one or two positions, forming theat one or two positions, forming thehormone precursorshormone precursors mono-iodotyrosinemono-iodotyrosine (MIT)(MIT), and, and di-iodotyrosinedi-iodotyrosine (DIT),(DIT),respectively. This and the following reactions are dependent onrespectively. This and the following reactions are dependent on thyroidthyroidperoxidaseperoxidase in the presence of hydrogen peroxide -both located at the apicalin the presence of hydrogen peroxide -both located at the apicalmembrane. Asmembrane. As MIT couples to DIT it producesMIT couples to DIT it produces tri-iodothyroninetri-iodothyronine (3,5,3`-T3),(3,5,3`-T3),whereaswhereas two DIT moleculestwo DIT molecules formform tetra-iodothyroninetetra-iodothyronine (T4),(T4), oror thyroxinethyroxine..These two molecules are the two thyroid hormones. Small amounts of theThese two molecules are the two thyroid hormones. Small amounts of theinactiveinactive reversereverse T3 (3,3`,5`- T3) is also synthesised.T3 (3,3`,5`- T3) is also synthesised. EE.. Each thyroglobulin moleculeEach thyroglobulin molecule contains up to 4 residues of T4contains up to 4 residues of T4 and zero toand zero toone T3.one T3. Thyroglobulin is retrieved backThyroglobulin is retrieved back into the follicular cell asinto the follicular cell as colloidcolloiddropletsdroplets byby pinocytosispinocytosis. Pseudopods engulf a pocket of colloid. These. Pseudopods engulf a pocket of colloid. Thesecolloid droplets pass towards the basal membrane and fuse withcolloid droplets pass towards the basal membrane and fuse with lysosomeslysosomesformingforming phagolysosomes.phagolysosomes. FF.. Lysosomal exopeptidasesLysosomal exopeptidases break the binding between thyroglobulin andbreak the binding between thyroglobulin andT4T4 (or T3). Large quantities of T4 are released to the capillary blood. Only(or T3). Large quantities of T4 are released to the capillary blood. Onlyminor quantities of T3 are secreted from the thyroid gland.minor quantities of T3 are secreted from the thyroid gland. GG. The. The proteolysis of thyroglobulinproteolysis of thyroglobulin also releases MIT and DIT. Thesealso releases MIT and DIT. Thesemolecules are deiodinated by the enzyme deiodinase, whereby iodide canmolecules are deiodinated by the enzyme deiodinase, whereby iodide canbe reused into T4 or T3.be reused into T4 or T3. Normally, only few intact thyroglobulin moleculesNormally, only few intact thyroglobulin moleculesleave the follicular cellsleave the follicular cells.. HH.. TSHTSH stimulatesstimulates almost all processes involved inalmost all processes involved in thyroid hormonethyroid hormonesynthesis and secretionsynthesis and secretion..
    11. 11. The hypothalamic-pituitary-thyroid feedback system, which regulates thebody levels of thyroid hormone.
    12. 12. Control of thyroid gland activityControl of thyroid gland activity TheThe hypothalamic-pituitary-thyroid axishypothalamic-pituitary-thyroid axis controls the thyroidcontrols the thyroidgland function and growth.gland function and growth. a.a. The production and release of thyroid hormone is controlledThe production and release of thyroid hormone is controlledbyby thyroid-releasing hormonethyroid-releasing hormone (TRH)(TRH) from the hypothalamus.from the hypothalamus. TRHTRH reaches thereaches the anterior pituitaryanterior pituitary via the portal system, wherevia the portal system, wherethe thyrotropic cells are stimulated to producethe thyrotropic cells are stimulated to produce thyroid-thyroid-stimulating hormonestimulating hormone (TSH) or(TSH) or thyrotropinthyrotropin.. TSHTSH is theis the only known regulatoronly known regulator of thyroid hormone secretionof thyroid hormone secretionin humans.in humans. TSHTSH is released to the systemic blood, by which itis released to the systemic blood, by which ittravels to the thyroid gland. Here,travels to the thyroid gland. Here, TSHTSH stimulates the uptakestimulates the uptakeof iodide, and all other processes that promoteof iodide, and all other processes that promote formation andformation andrelease of T4 (and T3).release of T4 (and T3). TSHTSH activatesactivates adenylcyclaseadenylcyclase bound to the cell membranes ofbound to the cell membranes ofthe follicular cells andthe follicular cells and increases their cAMPincreases their cAMP.. T3T3 has a stronghas a strong inhibitoryinhibitory effecteffect onon TRHTRH secretion, as well assecretion, as well ason theon the expression of the gene for the TRH precursor.expression of the gene for the TRH precursor.
    13. 13. Control of thyroid gland activityControl of thyroid gland activity• bb.. Almost allAlmost all circulatingcirculating T3T3 is derived from T4is derived from T4.. TSHTSH also stimulates thealso stimulates theconversion of T4conversion of T4 to the moreto the more biologically activebiologically active T3T3..• Most of theMost of the circulating thyroid hormonescirculating thyroid hormones areare bound to plasma proteinsbound to plasma proteins,,whereby the hormone is protected during transport. There is anwhereby the hormone is protected during transport. There is anequilibrium between the pool of protein-bound thyroid hormone andequilibrium between the pool of protein-bound thyroid hormone andthe free, biologically active forms (T3 and T4) that can enter the bodythe free, biologically active forms (T3 and T4) that can enter the bodycells.cells.• Thyroid hormonesThyroid hormones areare lipid-solublelipid-soluble and they canand they can easily crosseasily cross the cellularthe cellularmembrane by diffusionmembrane by diffusion..• cc.. Inside the cell,Inside the cell, T3T3 binds tobinds to nuclear receptorsnuclear receptors and stimulates cellularand stimulates cellularmetabolism andmetabolism and increasesincreases metabolic ratemetabolic rate..• dd.. The concentrations ofThe concentrations of T3T3 andand T4T4 in the blood arein the blood are recordedrecorded bybypituitary and hypothalamic receptorspituitary and hypothalamic receptors..• ThisThis negative feedback systemnegative feedback system keeps the blood concentrations within normalkeeps the blood concentrations within normallimits, and there is only alimits, and there is only a minimalminimal nocturnalnocturnal increase in TSH secretionincrease in TSH secretionand T4 releaseand T4 release..
    14. 14. The hypothalamic-pituitary-thyroid axis controls the thyroid glandfunction and growth.
    15. 15. Actions of thyroid hormonesActions of thyroid hormones Thyroid hormones are lipid-soluble and pass through cellmembranes easily. T3 binds to specific nuclear receptorproteins with an affinity that is tenfold greater than the affinity for T4. Theinformation alters DNA transcription into mRNA, and the information iseventually translated into many effector proteins. One type of thyroidreceptor protein is bound to thyroid regulatory elements in target cellgenes. Important cellular constituents are stimulated by T3: The mitochondria,the Na+-K+-pump, myosin ATPase, adrenergic b-receptors, manyenzyme systems and proteins for growth and maturation including CNSdevelopment. Thyroid hormones stimulate oxygen consumption in almost all cells. Thyroid hormones stimulate the rate of:1) hepatic glucose output and peripheral glucose utilisation;2) hepatic metabolism of fatty acids, cholesterol and triglycerides;3) the synthesis of important proteins (the Na+-K+-pump, respiratoryenzymes, erythropoietin, b-adrenergic receptors, sex hormones, growthfactors etc);4) the absorption of carbohydrates in the intestine and the gut excretion ofcholesterol;5) the modulation of reproductive function.
    16. 16. Actions of thyroid hormonesActions of thyroid hormones The many rate-stimulating effects are summarized in an overall increaseThe many rate-stimulating effects are summarized in an overall increaseinin oxygen consumptionoxygen consumption. This slow - but long lasting -. This slow - but long lasting - calorigeniccalorigenic andandthermogenicthermogenic effect is confined to theeffect is confined to the mitochondriamitochondria.. TheThe thyroid hormones and the catecholaminesthyroid hormones and the catecholamines work togetherwork together ininmetabolic acceleration.metabolic acceleration. Thyroid hormonesThyroid hormones increase cardiac rate and output as well asincrease cardiac rate and output as well asventilationventilation.. TheThe high basal metabolic rate raiseshigh basal metabolic rate raises thethe core and shell temperaturecore and shell temperature, so, sothat thethat the peripheral vessels dilatateperipheral vessels dilatate. This. This vasodilatation forces thevasodilatation forces thecardiac output to increasecardiac output to increase. A. A circulatory shock developscirculatory shock develops,, if the rise inif the rise incardiac output is insufficient to match the vasodilatationcardiac output is insufficient to match the vasodilatation - socalled- socalled highhighoutput failureoutput failure.. A human body overloaded with thyroid hormones for a prolongedA human body overloaded with thyroid hormones for a prolongedperiod (period (hyperthyroidismhyperthyroidism) will suffer from) will suffer from muscle atrophia, bonemuscle atrophia, bonedestruction and hunger damagedestruction and hunger damage, due to, due to increased catabolism of cellularincreased catabolism of cellularproteins and fatproteins and fat. Eventually. Eventually hypothyroidismhypothyroidism may develop due tomay develop due tosuppression.suppression.
    17. 17. CalcitoninCalcitonin is produced by the parafollicular C-cells of the thyroid.is produced by the parafollicular C-cells of the thyroid. CalcitoninCalcitonin inhibits bone resorptioninhibits bone resorption by blocking theby blocking the parathyroidparathyroidhormone (PTH)-receptorshormone (PTH)-receptors on the osteoclasts. The result is anon the osteoclasts. The result is anextremely effective lowering of plasma-extremely effective lowering of plasma-[[CaCa22++]] andand--[[phosphatephosphate]]. Calcitonin is important in bone remodelling and in. Calcitonin is important in bone remodelling and intreatment oftreatment of osteoporosisosteoporosis.. CalcitoninCalcitonin is a single-chain peptide with a disulphide ring,is a single-chain peptide with a disulphide ring,containingcontaining 32 amino acids32 amino acids. Calcitonin. Calcitonin is secretedis secreted from thefrom thethyroid glandthyroid gland in response to hypercalcaemiain response to hypercalcaemia and itand it acts to loweracts to lowerplasma [Caplasma [Ca22+],+], as opposed to the effect of PTH.as opposed to the effect of PTH. Administration of calcitoninAdministration of calcitonin leads to a rapid fall in plasmaleads to a rapid fall in plasma[Ca[Ca22+].+]. CalcitoninCalcitonin is theis the physiologic antagonistphysiologic antagonist to PTHto PTH andandinhibits Cainhibits Ca22+ -liberation from bone+ -liberation from bone (ie,(ie, inhibits both osteolysisinhibits both osteolysisby osteocytes and bone resorption by osteoclastsby osteocytes and bone resorption by osteoclasts). But). Butcalcitonincalcitonin reduces plasma phosphate just as PTHreduces plasma phosphate just as PTH.. CalcitoninCalcitonin probablyprobably inhibits reabsorption of phosphateinhibits reabsorption of phosphate in thein thedistal tubules of the kidney, but calcitonin alsodistal tubules of the kidney, but calcitonin also inhibits the renalinhibits the renalreabsorp­tion of Careabsorp­tion of Ca22+, Na+ and Mg+, Na+ and Mg22+.+. Calcitonin mayCalcitonin may inhibit gutinhibit gutabsorption of Caabsorption of Ca22++ andand promote phosphate entrance into bonepromote phosphate entrance into boneand cause important bone remodelling.and cause important bone remodelling.
    18. 18.  Calcitonin deficiencyCalcitonin deficiency does not leaddoes not lead toto hypercalcaemiahypercalcaemia, and, andexcessexcess calcitonin from tumours does not lead tocalcitonin from tumours does not lead tohypocalcaemiahypocalcaemia. Therefore, most effects of calcitonin are. Therefore, most effects of calcitonin areevidently offset by appropriate regulation through the actions ofevidently offset by appropriate regulation through the actions ofPTHPTH andand vitamin Dvitamin D.. CalcitoninCalcitonin in plasma declines with age andin plasma declines with age and is lower in womenis lower in womenthan in menthan in men. Low levels of calcitonin are involved in accelerated. Low levels of calcitonin are involved in acceleratedbone loss with age and after menopause (bone loss with age and after menopause (osteoporosisosteoporosis).). CalcitoninCalcitonin protects theprotects the female skeletonfemale skeleton from thefrom the drain of Cadrain of Ca22++during pregnancy and lactation.during pregnancy and lactation. CalcitoninCalcitonin is ais aneurotransmitterneurotransmitter ininthe hypothalamusthe hypothalamusand in other CNSand in other CNSlocations.locations. CalcitoninCalcitonin isisadministered toadministered topostmenopausalpostmenopausalfemalesfemales in attempt toin attempt topreventpreventosteoporosis.osteoporosis.
    19. 19. Disorders of the Thyroid GlandDisorders of the Thyroid Gland• GoiterGoiter is enlargement of thyroid glandis enlargement of thyroid gland• Simple goiterSimple goiter• Adenomatous or nodular goiterAdenomatous or nodular goiter• HypothyroidismHypothyroidism• Infantile hypothyroidism (cretinism)Infantile hypothyroidism (cretinism)• MyxedemaMyxedema• HyperthyroidismHyperthyroidism• Graves diseaseGraves disease• Thyroid stormThyroid storm• ThyroiditisThyroiditis• Hashimoto diseaseHashimoto diseaseHypothyroidism (Hashimoto’sdisease, Goiter) andHyperthyroidism (Graves’ disease)
    20. 20. HyperthyroidismHyperthyroidism TheThe classical hyperthyroidismclassical hyperthyroidism or thyrotoxicosis (Graves thyroiditis, Basedowsor thyrotoxicosis (Graves thyroiditis, Basedowsdisease) is a condition characterized by an abnormal rise in basaldisease) is a condition characterized by an abnormal rise in basalmetabolic rate, struma and eye signs (thyroid eye disease). The eyes ofmetabolic rate, struma and eye signs (thyroid eye disease). The eyes ofthe patient typically bulge (ie,the patient typically bulge (ie, exophtalmusexophtalmus). Patients with). Patients with thyrotoxicosisthyrotoxicosis havehaveoverwhelmingly high metabolic rates.overwhelmingly high metabolic rates. Neuromuscular systemNeuromuscular system Tremors, hyperactivity, emotional lability, anxiety, inability toTremors, hyperactivity, emotional lability, anxiety, inability toconcentrate, insomniaconcentrate, insomnia Thyroid myopathy – proximal muscle weakness with decrease muscleThyroid myopathy – proximal muscle weakness with decrease musclemassmass Ocular changesOcular changes Wide, staring gaze and lid lagWide, staring gaze and lid lag Thyroid ophthalmopathyThyroid ophthalmopathy Gastrointestinal systemGastrointestinal system Hypermotility, malabsorption, and diarrheaHypermotility, malabsorption, and diarrhea Skeletal systemSkeletal system Stimulates bone resorption (inc. porosity of cortical bone andStimulates bone resorption (inc. porosity of cortical bone andreduced volume of trabecular bone)reduced volume of trabecular bone) Osteoporosis and increased risk of fracturesOsteoporosis and increased risk of fractures
    21. 21. Graves DiseaseGraves Disease The disease is named for Robert Graves who inThe disease is named for Robert Graves who in1835 first identified the association of goiter,1835 first identified the association of goiter,palpitations, and exophthalmos.palpitations, and exophthalmos. Most common cause of endogenousMost common cause of endogenoushyperthyroidismhyperthyroidism Triad:Triad:– HyperthyroidismHyperthyroidism– Infiltrative ophthalmopathy with resultantInfiltrative ophthalmopathy with resultantexophthalmosexophthalmos– Localized, infiltrative dermopathy (pretibialLocalized, infiltrative dermopathy (pretibialmyxedema)myxedema)
    22. 22. HyperthyroidismHyperthyroidism ((Graves DiseaseGraves Disease)) Thyroid eye diseaseThyroid eye disease (with exophtalmus) is not confined(with exophtalmus) is not confinedto Graves’s hyperthyroidism only. Some exophtalmusto Graves’s hyperthyroidism only. Some exophtalmuspatients are euthyroid or hypothyroid.patients are euthyroid or hypothyroid. Common to all types of thyroid eye diseases areCommon to all types of thyroid eye diseases arespecific antibodiesspecific antibodies that cause inflammation of thethat cause inflammation of the retro-retro-orbital tissueorbital tissue withwith swellingswelling of theof the extraocular eyeextraocular eyemusclesmuscles, so, so they cannot move the eyes normallythey cannot move the eyes normally.. ProptosisProptosis andand lid lagslid lags areare typical signstypical signs, and, andconjunctivitis and scarsconjunctivitis and scars on the cornea follow due to lackon the cornea follow due to lackof protective cover.of protective cover. TheThe oedematous retro-orbital tissueoedematous retro-orbital tissue may force the eyemay force the eyeballs forward and press on the optic nerveballs forward and press on the optic nerve to such anto such anextent that vision is impaired or blindnessextent that vision is impaired or blindness results.results. The best treatment is to normalise the accompanyingThe best treatment is to normalise the accompanyingthyrotoxicosis. Other therapeutic measures arethyrotoxicosis. Other therapeutic measures arepalliative.palliative.
    23. 23. Lid lag in Graves disease
    24. 24. HyperthyroidismHyperthyroidism ((Graves DiseaseGraves Disease))TSH receptor antibodyTSH receptor antibody ((IgG antibodiesIgG antibodies) release causes Graves’s disease) release causes Graves’s diseasefrom activated B-cellsfrom activated B-cells. A genetic deficiency is involved, which is shown by. A genetic deficiency is involved, which is shown bythe 50% concordance in monozygotic twins.the 50% concordance in monozygotic twins. Trigger mechanismsTrigger mechanisms arearepresumed to be bacterial or viral infections producingpresumed to be bacterial or viral infections producing autoimmuneautoimmunephenomenaphenomena in genetically deficient individuals.in genetically deficient individuals.The autoimmune system can produce the following autoantibodies:The autoimmune system can produce the following autoantibodies:1.1. TSH-receptor antibodiesTSH-receptor antibodies to theto the TSHTSHreceptors (antigens)receptors (antigens) on theon the surface ofsurface ofthe thyroid follicular cellsthe thyroid follicular cells, which they, which theystimulate just like TSH itself,stimulate just like TSH itself, causingcausingthyroid hypersecretionthyroid hypersecretion. These. These IgGIgGantibodiesantibodies are also termedare also termed long-long-acting thyroid stimulatoracting thyroid stimulator..2.2. Specific autoantibodiesSpecific autoantibodies causingcausingretro-orbital inflammation and thyroidretro-orbital inflammation and thyroideye diseaseeye disease..3.3. ThyroglobinThyroglobin antibodiesantibodies against theagainst thestorage molecule, thyroglobin.storage molecule, thyroglobin.4.4. Microsomal antibodiesMicrosomal antibodies againstagainstthyroid peroxidasethyroid peroxidase..TheseThese autoantibodiesautoantibodies can be found incan be found inthe plasma of most cases of Grave’sthe plasma of most cases of Grave’sdisease.disease.
    25. 25.  The increasedThe increased metabolic ratemetabolic rate andand sympatho-adrenergic activitysympatho-adrenergic activity dominatedominatethe patient.the patient. The patient isThe patient is anxious with warm and sweaty skin,anxious with warm and sweaty skin, tachycardia,tachycardia, palpitations,palpitations, fine finger tremor,fine finger tremor, pretibial myxoedema (ie, accumulation of mucopolysaccharides).pretibial myxoedema (ie, accumulation of mucopolysaccharides). Typically is aTypically is a symmetrical, warm pulsating goitresymmetrical, warm pulsating goitre. Lean hyperthyroid. Lean hyperthyroidfemales - like female distance runners - havefemales - like female distance runners - have small fat storessmall fat stores andand greatlygreatlyreduced menstrual bleedingsreduced menstrual bleedings ((oligomenorrhoeaoligomenorrhoea) or even) or even amenorrhoeaamenorrhoea.. TheThe high T3high T3 levellevel increases the density ofincreases the density of ββ-adrenergic receptors-adrenergic receptors on theon themyocardial cellsmyocardial cells. The. The cardiac output is highcardiac output is high even at rest andeven at rest and arrhythmiasarrhythmiasare frequentare frequent (eg, atrial fibrillation).(eg, atrial fibrillation). Elderly patientsElderly patients may present with anmay present with an apathetic hyperthyroidismapathetic hyperthyroidism,, wherewhere theytheycomplain of tiredness and somnolencecomplain of tiredness and somnolence. Measurement of serum TSH with. Measurement of serum TSH withT3/T4 reveals that the diagnosisT3/T4 reveals that the diagnosis is not hypo- butis not hypo- but hyperthyroidismhyperthyroidism..Erroneous treatment with thyroid hormoneErroneous treatment with thyroid hormone can kill the patientcan kill the patient by causingby causingvasodilatation andvasodilatation and cardiac output failurecardiac output failure.. A suppressed serum TSH confirms the diagnosis of hyperthyroidism, andA suppressed serum TSH confirms the diagnosis of hyperthyroidism, andthe serum T3 or T4 is raised.the serum T3 or T4 is raised.The pathogenesis of Graves disease, and theThe pathogenesis of Graves disease, and theclinical manifestations of Graves’s disease.clinical manifestations of Graves’s disease.
    26. 26. The pathogenesis of Graves disease, andThe pathogenesis of Graves disease, andthe clinical manifestations of Graves’sthe clinical manifestations of Graves’sdisease.disease.► Several drugs are used in the treatment of hyperthyroidism.Several drugs are used in the treatment of hyperthyroidism.► CarbimazoleCarbimazole andand methimazolemethimazole inhibit the production of thyroid hormoneinhibit the production of thyroid hormoneandand have immuno-suppressive actionshave immuno-suppressive actions..► Monovalent anions andMonovalent anions and ouabainouabain inhibitinhibit the iodide trap.the iodide trap.► ThiocarbamideThiocarbamide inhibitsinhibits the iodination of tyrosyl residues.the iodination of tyrosyl residues.► SulphonamidesSulphonamides inhibitinhibit thyroid peroxidase, which oxidises iodide to iodine.thyroid peroxidase, which oxidises iodide to iodine.► Large doses of iodideLarge doses of iodide inhibitinhibit the TSH-receptors on the thyroid gland.the TSH-receptors on the thyroid gland.► TheThe high activity of the sympatho-adrenergichigh activity of the sympatho-adrenergic system issystem is inhibited byinhibited by ββ--blockersblockers, preferably, preferably with central sedative effectswith central sedative effects..► Subtotal thyroidectomySubtotal thyroidectomy is used to treat patients with a large goiter, oris used to treat patients with a large goiter, orpatients with severe side effects to drug therapy.patients with severe side effects to drug therapy.► Radioactive iodineRadioactive iodine is stored in the gland and destroys the follicle cells.is stored in the gland and destroys the follicle cells.This therapy is complicated, and some patients develop hypothyroidism.This therapy is complicated, and some patients develop hypothyroidism.
    27. 27. Toxic goiterToxic goiter andand toxic solitary adenomatoxic solitary adenoma(Plummers disease) are cases of(Plummers disease) are cases of secondarysecondaryhyperthyroidismhyperthyroidism just as inflammation injust as inflammation inacute thyroiditisacute thyroiditis andand chronic thyroiditis.chronic thyroiditis.The cells secrete thyroid hormone withoutThe cells secrete thyroid hormone withoutinhibition from the hypothalamo-pituitaryinhibition from the hypothalamo-pituitaryaxis.axis.Thyroid scintigraphies.Thyroid scintigraphies. A. Graves’ Disease. Diffuse thyroid uptake.A. Graves’ Disease. Diffuse thyroid uptake.B. Plummer’s Disease. Nodular uptake on left thyoid lobeB. Plummer’s Disease. Nodular uptake on left thyoid lobewith suppression of the gland.with suppression of the gland.
    28. 28. Hypothyroidism Primary hypothyroidism is an abnormally low activity of thethyroid gland with low circulating thyroid hormone levelscaused by thyroid disease. Secondary hypothyroidism results from hypothalamic-pituitarydisease. Primary hypothyroidism is caused by microsomalautoantibodies precipitated in the glandular tissue. Lymphoidinfiltration of the thyroid may eventually lead to atrophy withabnormally low production of T4. Another clinical form startsout as Hashimotos thyroiditis, often with hyperthyroidism andgoiter. Following atrophy caused by microsomal autoantibodies, thecondition ends as hypothyroidism, or the patient is euthyroid.
    29. 29. • When hypothyroidismhypothyroidism is congenital both physical and mentaldevelopment is impaired and cretinism is the result. Also iodidedeficiency in childhood may also result in a cretincretin or a mentallyretarded hypothyroid dwarf.• Myxoedema in the adult is severe thyroid gland hypothyroidism witha puffy swollen face due to a hard, non-pitting oedema (calledmyxoedema or tortoise skin). The skin is dry and cold; there isbradycardia, often cardiomegaly (ie, myxoedema heart), hair loss,constipation, muscle weakness and anovulatory cycles in females.• A high TSH level and a low total or free T4 in plasma confirms thediagnosis primary hypothyroidism. Thyroid autoantibodies areusually demonstrable in the plasma. Hypercholesterolaemia andincreased concentrations of liver and muscle enzymes (aspartatetransferase, creatine kinase) in the plasma is typical.• As stated thyroid gland high TSH characterises hypothyroidism. Atest dose of TSH to a patient with thyroid hypothyroidism will notstimulate the thyroid gland.• A test dose of TRH (Thyroid releasing hormone) will result in anincreased TSH response in thyroid gland hypothyroidism anddecrease in hyperthyroidism. This is due to the negative feedback ofthyroid hormones on the hypophysis.• Hypothyroid females often have excessive and frequent menstrualbleedings (menorrhagia and polymenorrhoea). Hypothyroid patientsexhibit slow cardiac activity.
    30. 30.  Secondary hypothyroidismSecondary hypothyroidism is causedis causedby reduced TSH (by reduced TSH (Thyroid stimulatingThyroid stimulatinghormonehormone) drive due to pituitary or) drive due to pituitary orhypothalamic insufficiency. A testhypothalamic insufficiency. A testdose of TRH (dose of TRH (Thyroid releasingThyroid releasinghormonehormone) to a myxoedema patient) to a myxoedema patientwith hypothalamic or pituitarywith hypothalamic or pituitaryinsufficiency will result in a normalinsufficiency will result in a normalTSH response.TSH response. Replacement is given to theReplacement is given to thehypothyroid patient withhypothyroid patient withapproximately 100approximately 100 µµg T4 daily for theg T4 daily for therest of the patients life.rest of the patients life.
    31. 31. HYPO-THYROIDISMHYPO-THYROIDISM CretinismCretinism• Severe retardationSevere retardation• CNS/Musc-skelCNS/Musc-skel• Short statureShort stature• Protruding tongueProtruding tongue• Umbilical herniaUmbilical hernia• Maternal iodine defic.Maternal iodine defic. Myxedema (coma)Myxedema (coma)• SluggishnessSluggishness• Cold skinCold skinStructural or functionalStructural or functionalderangement that interfere withderangement that interfere withthe production of adequatethe production of adequatelevels of thyroid hormonelevels of thyroid hormonePrimary, secondary, or tertiaryPrimary, secondary, or tertiary
    32. 32. CretinismCretinismHypothyroidism that occurs in infancyHypothyroidism that occurs in infancyor early childhoodor early childhoodImpaired development of the skeletalImpaired development of the skeletalsystem and CNSsystem and CNSManifests asManifests as severe mentalsevere mentalretardationretardation, short stature, coarse facial, short stature, coarse facialfeatures, protruding tongue andfeatures, protruding tongue andumbilical herniaumbilical herniaCretinism, also known asNeonatal hypothyroidismis decreased thyroid hormone production in a newborn.
    33. 33. CretinismCretinismThis 1 year old babyThis 1 year old babywas diagnosed withwas diagnosed withCretinism.The thyroidCretinism.The thyroidprofile showed aprofile showed ahypothyroid picture.hypothyroid picture.Replacement therapyReplacement therapyhas been started.has been started.These four brothers work at a saltfactory in Pakistan. Two of them sufferfrom cretinism, caused by iodinedeficiency. All the brothers ensurethey use iodized salt in theirhouseholds to prevent cretinism in thenext generation and give their childrenthe iodine they need for intellectualdevelopment. HH → Hypotonia → 1→ Hypotonia → 1YY → Yellow (icterus >3) →1→ Yellow (icterus >3) →1PP → Pallor, cold, hypothermia →1→ Pallor, cold, hypothermia →1OO → Open post. fontanel →1→ Open post. fontanel →1TT → Tongue enlarged →1→ Tongue enlarged →1HH → Umbilical hernia →2→ Umbilical hernia →2YY → absent Y (female) →1→ absent Y (female) →1RR → Rough dry skin →1→ Rough dry skin →1OO → Edematous typical face →2→ Edematous typical face →2I.DI.D.→ Inactive defecation → 2.→ Inactive defecation → 2Birth weightBirth weight > 3.5 kg →1> 3.5 kg →1Post.maturePost.mature > 40w →1> 40w →1Total = 15.Total = 15.If score > 5If score > 5 suggest hypothyroidism,suggest hypothyroidism,must investigate.must investigate.APGAR score of early suspicion of hypothyroidism
    34. 34. Simple Mnemonics for ClinicalSimple Mnemonics for Clinicalpicture of cretinismpicture of cretinismat birth & early neonatal :1- Feeding difficulty, choking & anorexia2- Constipation, abdomenal distention,umbilical hernia, delayed passage ofmeconium3- Heavy birth weight (Over weight).4- Hypothermia, cold skin.5- Open posterior fontanel.6- Less activity, always sleep, little cryhoarse voice.7- Prolonged physiological jaundice.8- Bradycardia: ↓ HR (Slow Pulse) .9- Apneic attacks: ↓ Respiratory rate.10- X- Ray knee: absent ossific centersat birth of the lower end of the femur.
    35. 35. TypicalTypicalSymptomsSymptoms& Signs:& Signs:• 3- Skin:Pale yellow skin(carotenemia). & Dry,rough, cold.• 4- Abdomen:Potts belly abdomen. &Umbilical hernia.• 5- C.V.S: Bradycardia.•  Haemic murmur.•  Cardiomegally → CHF.• 6- C.N.S:Hypotonia• Hyporeflexia,• apathy.• A- Delayed growth & development andmetal retardation.Delayed motor mile stones.• Delayed social development.• Growth retardation & short stature .• B- Characteristic features:1- Head:Face → coarse puffy face.• Skull → delayed closure of fontanels(anterior).• Hair → coarse dry hair, low hair line.• Eyes → hypertdorism, puffy eye lids,scanty hair of brows.•  Nose → depressed nasal bridge.•  Tongue → macroglossia, thick lips.•  Teeth → delayed eruption, tendency todecay.• 2- Neck:short & webbed. & thyroid maypalpable.
    36. 36. MyxedemaMyxedema Hypothyroidism developing in the older child orHypothyroidism developing in the older child oradultadult Gull diseaseGull disease Characterized by slowing of physical and mentalCharacterized by slowing of physical and mentalactivityactivity Accumulation of matrix substancesAccumulation of matrix substances((glycosaminoglycans and hyaluronic acidglycosaminoglycans and hyaluronic acid) in the) in theskin, subcutaneous tissues, and visceral sitesskin, subcutaneous tissues, and visceral sites edemaedema, broadening and coarsening of facial, broadening and coarsening of facialfeatures, enlargement of the tongue, andfeatures, enlargement of the tongue, anddeepening of the voicedeepening of the voice Measurement of serumMeasurement of serum TSH levelTSH level is the mostis the mostsensitivesensitive screening testscreening test
    37. 37. PrimaryPrimaryhypotyrioidismhypotyrioidismMyxedemaMyxedema
    38. 38. Myxedematous Coma.Myxedematous Coma.• Myxedematous comaMyxedematous coma is a lifethreatening,is a lifethreatening, end-stage expression ofend-stage expression ofhypothyroidismhypothyroidism..• It is characterized by coma,It is characterized by coma, hypothermia, cardiovascular collapse,hypothermia, cardiovascular collapse,hypoventilation, and severe metabolic disorders that includehypoventilation, and severe metabolic disorders that includehyponatremia, hypoglycemia, and lactic acidosishyponatremia, hypoglycemia, and lactic acidosis. It occurs most often in. It occurs most often inelderly women who have chronic hypothyroidism from a spectrum ofelderly women who have chronic hypothyroidism from a spectrum ofcauses. It occurs morecauses. It occurs more frequently in the winter monthsfrequently in the winter months, which suggests, which suggeststhat cold exposure may be a precipitating factor. Thethat cold exposure may be a precipitating factor. The severelyseverelyhypothyroid person ishypothyroid person is unable to metabolizeunable to metabolize sedatives, analgesics, andsedatives, analgesics, andanesthetic drugs, and buildup of these agents may precipitate comaanesthetic drugs, and buildup of these agents may precipitate coma..• TreatmentTreatment includes aggressive management of precipitating factors;includes aggressive management of precipitating factors;supportive therapy such as management of cardiorespiratory status,supportive therapy such as management of cardiorespiratory status,hyponatremia, and hypoglycemia; and thyroid replacement therapy.hyponatremia, and hypoglycemia; and thyroid replacement therapy.PreventionPrevention is preferable to treatment and entailsis preferable to treatment and entails special attention tospecial attention tohigh-risk populationshigh-risk populations, such as, such as women with a history of Hashimoto’swomen with a history of Hashimoto’sthyroiditisthyroiditis. These persons should be informed about the signs and. These persons should be informed about the signs andsymptoms of severe hypothyroidism and the need for early medicalsymptoms of severe hypothyroidism and the need for early medicaltreatment.treatment.
    39. 39. Diffuse and Multinodular GoitersDiffuse and Multinodular Goiters• Reflect impaired synthesis of thyroid hormonesReflect impaired synthesis of thyroid hormones• Diffuse nontoxic (simple) goiterDiffuse nontoxic (simple) goiter– Diffusely involves the entire gland without producingDiffusely involves the entire gland without producingnodularitynodularity– Enlarged follicles are filled with colloid = colloid goiterEnlarged follicles are filled with colloid = colloid goiter• Multinodular goiterMultinodular goiter– Irregular enlargement of the glandIrregular enlargement of the gland– Produce the most extreme enlargement and are moreProduce the most extreme enlargement and are moremistaken for neoplastic involvement than any othermistaken for neoplastic involvement than any otherform of thyroid diseaseform of thyroid disease
    40. 40. GOITERGOITER • ENLARGEMENT OF THE THYROID GLAND.ENLARGEMENT OF THE THYROID GLAND.TYPES:TYPES:TOXIC NODULARTOXIC NODULAR• COMMON IN ELDERLYCOMMON IN ELDERLY• FROM LONG STANDING SIMPLE GOITERFROM LONG STANDING SIMPLE GOITER• NODULESNODULES– FUNCTIONING TISSUEFUNCTIONING TISSUE– SECRETES THYROXINE AUTONOMOUSLY FROMSECRETES THYROXINE AUTONOMOUSLY FROMTSHTSH• NONTOXICNONTOXICSIMPLE/ COLLOID/ EUTHYROID)SIMPLE/ COLLOID/ EUTHYROID)CAUSE :CAUSE :• IODINE DEFICIENCYIODINE DEFICIENCY• INTAKE OF GOITROGENIC SUBSTANCES/INTAKE OF GOITROGENIC SUBSTANCES/DRUGS:DRUGS:– CASSAVA,CASSAVA,– CABBAGE,CABBAGE,– CAULIFLOWER,CAULIFLOWER,– CARROTSCARROTS– RADDISHRADDISH– TURNIPSTURNIPS– RED SKIN OF PEANUTSRED SKIN OF PEANUTS– IODINEIODINE– COBALTCOBALT
    41. 41. Many vegetables are goiterogens, fruits are NOT. Which one is NOT a goiterogen?Many vegetables are goiterogens, fruits are NOT. Which one is NOT a goiterogen?
    42. 42. NON-TOXIC GOITERNON-TOXIC GOITERIMPAIRED THYROID HORMONE SYNTHESISIMPAIRED THYROID HORMONE SYNTHESISSERUM THYROXINESERUM THYROXINEPITUITARY SECRETE TSHPITUITARY SECRETE TSHTHYROID GLAND ENLARGESTHYROID GLAND ENLARGESTO COMPENSATE FOR THE REDUCED LEVEL OF THYROXINETO COMPENSATE FOR THE REDUCED LEVEL OF THYROXINEIODINE DEFICIENCY ORIODINE DEFICIENCY ORINTAKE OF GOITROGENIC SUBSTANCESINTAKE OF GOITROGENIC SUBSTANCES
    43. 43. GOITER
    44. 44. MultinodularMultinodulargoitergoiter
    45. 45. Hashimoto ThyroiditisHashimoto Thyroiditis Chronic lymphocytic thyroiditisChronic lymphocytic thyroiditis Struma lymphomatosaStruma lymphomatosa Most common cause ofMost common cause ofhypothyroidism in areas of thehypothyroidism in areas of theworld where iodine levels areworld where iodine levels aresufficientsufficient Pathogenesis:Pathogenesis: CD8+ cytotoxic T-cell mediatedCD8+ cytotoxic T-cell mediatedcell deathcell death Cytokine mediated cell deathCytokine mediated cell death Binding of anti-thyroid Ab’sBinding of anti-thyroid Ab’s ADCCADCC Anti-TSH receptor Ab’s,Anti-TSH receptor Ab’s,antithyroglobulin, antithyroidantithyroglobulin, antithyroidperoxidase Ab’speroxidase Ab’sA woman presenting with an enlargedthyroid who has Hashimotos thyroiditis
    46. 46. Hashimoto’s thyroiditisHashimoto’s thyroiditis isis the most common form ofthe most common form ofthyroiditis. It is athyroiditis. It is a form ofform of autoimmuneautoimmune thyroditisthyroditis; more; morecommon incommon in women and in late middle agewomen and in late middle age. Thyroid. Thyroidperoxidase (TPO) antibodies are usually present in thisperoxidase (TPO) antibodies are usually present in thiscondition, often in very high levels. It may be associatedcondition, often in very high levels. It may be associatedwith other endocrine organ deficiencies such aswith other endocrine organ deficiencies such as diabetesdiabetesmellitus or Addisons disease.mellitus or Addisons disease.Hashimoto’s thyroiditisHashimoto’s thyroiditis also occurs more commonly inalso occurs more commonly inpatients with Down’s and Turner’s syndromes.patients with Down’s and Turner’s syndromes.It produces atrophic changes with regeneration. This canIt produces atrophic changes with regeneration. This canlead to a goitelead to a goiterr forming. Patients withforming. Patients with Hashimoto’s thyroiditisHashimoto’s thyroiditisare usuallyare usually hypothyroid or euthyroidhypothyroid or euthyroid. However, they may. However, they mayhave an initial thyrotoxic phase at presentation.have an initial thyrotoxic phase at presentation.SpecificSpecific helper-T lymphocyteshelper-T lymphocytes are activated in this conditionare activated in this conditionwhich results in anwhich results in an immune response directed against theimmune response directed against thethyroid cellthyroid cell. This activation may be triggered by a viral. This activation may be triggered by a viralinfection.infection.Although thyroid lymphoma is rare, the risk of thyroidAlthough thyroid lymphoma is rare, the risk of thyroidlymphoma is increased 60-fold in patients with Hashimoto’slymphoma is increased 60-fold in patients with Hashimoto’sthyroiditis. Patients presenting with a new thyroid lumpthyroiditis. Patients presenting with a new thyroid lumpshould undergo fine-needle aspiration biopsy.should undergo fine-needle aspiration biopsy.
    47. 47. Riedel ThyroiditisRiedel Thyroiditis Rare disorder of unknown etiologyRare disorder of unknown etiology Extensive fibrosis involving theExtensive fibrosis involving thethyroid and contiguous neck structuresthyroid and contiguous neck structures Hard and fixed thyroid massHard and fixed thyroid mass Riedels thyroiditis is classified as rare. Most patients remainRiedels thyroiditis is classified as rare. Most patients remaineuthyroideuthyroid, but approximately 30% of patients become, but approximately 30% of patients becomehypothyroidhypothyroid and very few patients areand very few patients are hyperthyroidhyperthyroid. It is most. It is mostseen in womenseen in women.. RRiedel’s thyroiditisiedel’s thyroiditis is a very rare chronic inflammatory disorderis a very rare chronic inflammatory disorderthat leads tothat leads to progressive fibrosisprogressive fibrosis of the thyroid gland ofof the thyroid gland ofunknown cause. It is often associated with otherunknown cause. It is often associated with otherfibroproliferative disorders (e.g. mediastinal andfibroproliferative disorders (e.g. mediastinal andretroperitoneal fibrosis, sclerosing cholangitis). Patientsretroperitoneal fibrosis, sclerosing cholangitis). Patientspresent with a rock-hard, fixed and painless goitepresent with a rock-hard, fixed and painless goiter.r.
    48. 48. Manifestations of Hypothyroid andManifestations of Hypothyroid andHyperthyroid StatesHyperthyroid StatesLevel of Organization Hypothyroidism HyperthyroidismBasal metabolic rate Decreased IncreasedSensitivity tocatecholaminesDecreased IncreasedGeneral featuresMyxedematous featuresDeep voiceImpaired growth (child)ExophthalmosLid lagDecreased blinkingBlood cholesterol levels Increased DecreasedGeneral behaviorMental retardation (infant)Mental and physical sluggishnessSomnolenceRestlessness, irritability, anxietyHyperkinesisWakefulnessCardiovascular functionDecreased cardiac outputBradycardiaIncreased cardiac outputTachycardia and palpitationsGastrointestinal functionConstipationDecreased appetiteDiarrheaIncreased appetiteRespiratory function Hypoventilation DyspneaMuscle tone and reflexesDecreased Increased, with tremor and fibrillatorytwitchingTemperature tolerance Cold intolerance Heat intoleranceSkin and hairDecreased sweatingCoarse and dry skin and hairIncreased sweatingThin and silky skin and hair
    49. 49. The Parathyroid GlandsThe Parathyroid GlandsFour glandsFour glands in posterior capsule of thyroid• Secrete parathyroid hormoneparathyroid hormone (PTH)• Works with calcitonin to regulate calciumregulate calciummetabolismmetabolism• If this gland is notworking properly,your nerves andmuscles will notfunction properlyeither due tocalcium deficiency.
    50. 50. Parathyroid glandsParathyroid glands
    51. 51. Parathyroid HormoneParathyroid Hormone1. Parathyroid hormone (PTH) increases bloodcalcium ion concentration and decreases phosphateion concentration.2. PTH stimulates bone resorption by osteoclasts,which releases calcium into the blood.3. PTH also influences the kidneys to conservecalcium and causes increased absorption of calciumin the intestines.4. A negative feedback mechanism involving bloodcalcium levels regulates release of PTH.CalcitoninCalcitonin and PTHPTH exert opposite effects inregulating calcium ion levels in the blood.
    52. 52. Calcium MetabolismCalcium MetabolismCalcium balance requiresCalcium balance requires• Calcitriol (dihydroxycholecalciferol)Calcitriol (dihydroxycholecalciferol)• Produced by modifying vitamin D in liver then inProduced by modifying vitamin D in liver then inkidneykidney• Parathyroid hormoneParathyroid hormone• CalcitoninCalcitoninDisorders of the Parathyroid GlandsDisorders of the Parathyroid Glands• Tetany• Inadequate production of parathyroid hormone(PTH)• Fragile bones and kidney stones• Excess production of parathyroid hormone(PTH)
    53. 53. HYPOPARATHYROIDISMHYPOPARATHYROIDISM Surgically inducedSurgically induced Congenital absenceCongenital absence Familial hypothyroidismFamilial hypothyroidism Associated with chronic mucocutaneousAssociated with chronic mucocutaneouscandidiasis and primary adrenal insufficiencycandidiasis and primary adrenal insufficiency Known asKnown as autoimmune polyendocrineautoimmune polyendocrinesyndrome type Isyndrome type I (APS I)(APS I) Mutations in theMutations in the autoimmune regulatorautoimmune regulator(AIRE) gene(AIRE) gene Idiopathic hypothyroidismIdiopathic hypothyroidism
    54. 54. HYPOPARATHYROIDISMHYPOPARATHYROIDISM• Clinical presentationsClinical presentations• Tetany – neuromuscular irritability• Mental status changes emotionalinstability, anxiety, and depression,confusional states, hallucinations andpsychosis• Intracranial manifestations – calcificationof the basal ganglia, parkinson-likemovement disorders, increase ICP(intracranial pressure)• Ocular disease – cataract formation• CV manifestations prolongation of QTinterval• Dental abnormalities – dental hypoplasia,failure of dental eruption, defective
    55. 55. HYPERPARATHYROIDISMHYPERPARATHYROIDISM INCREASED PTH PRODUCTIONINCREASED PTH PRODUCTION HYPERCALCEMIAHYPERCALCEMIA HYPOPHOSPHATEMIAHYPOPHOSPHATEMIA PRIMARY –PRIMARY – TUMOR ORTUMOR ORHYPERPLASIA OF THE PARATHYROIDHYPERPLASIA OF THE PARATHYROIDGLANDGLAND SECONDARY –SECONDARY – COMPENSATORYCOMPENSATORYOVERSECRETION OF PTH IN RESPONSEOVERSECRETION OF PTH IN RESPONSETO HYPOCALCEMIA FROM:TO HYPOCALCEMIA FROM: CHRONIC RENAL DSECHRONIC RENAL DSE RICKETSRICKETS MALABSORPTION SYNDROMEMALABSORPTION SYNDROME OSTEOMALACIAOSTEOMALACIA
    56. 56. HYPERPARATHYROIDISMHYPERPARATHYROIDISMS/SX:S/SX:BONE PAIN : ESP. THE BACK,BONE PAIN : ESP. THE BACK,PATHOLOGIC FRUCTURESPATHOLOGIC FRUCTURES TUBULAR CALCIUMTUBULAR CALCIUMDEPOSITS - KIDNEY STONES,DEPOSITS - KIDNEY STONES,RENAL COLIC, POLYURIA,RENAL COLIC, POLYURIA,POLYDIPSIAPOLYDIPSIA MUSCLE WEAKNESSMUSCLE WEAKNESS PERSONALITY CX,PERSONALITY CX,DEPRESSIONDEPRESSION CARDIAC ARRHYTHMIAS,CARDIAC ARRHYTHMIAS,HPNHPNXRAY:XRAY: BONEBONEDEMINERALIZATIONDEMINERALIZATION
    57. 57. PseudohypoparathyroidismPseudohypoparathyroidism End-organ unresponsiveness to PTHEnd-organ unresponsiveness to PTH Serum PTH levels are normal or elevatedSerum PTH levels are normal or elevated Pseudohypoparathyroidism Type IAPseudohypoparathyroidism Type IA Associated with multihormone resistance (PTH, TSH, &Associated with multihormone resistance (PTH, TSH, &FSH/LH) and Albright hereditary osteodystrophy (AHO)FSH/LH) and Albright hereditary osteodystrophy (AHO) Short stature, obesity, short metacarpal and metatarsalShort stature, obesity, short metacarpal and metatarsalbones, and variable mental deficitsbones, and variable mental deficits Hypocalcemia, hyperphosphatemia, and elevatedHypocalcemia, hyperphosphatemia, and elevatedcirculating PTHcirculating PTH TSH resistance is mild; LH/FSH resistance manifests asTSH resistance is mild; LH/FSH resistance manifests ashypogonadotrophic hypogonadism in femaleshypogonadotrophic hypogonadism in females Mutation is inherited on the maternal alleleMutation is inherited on the maternal allele PseudopseudohypoparathyroidismPseudopseudohypoparathyroidismMutation is inherited on the paternal alleleMutation is inherited on the paternal alleleCharacterized by AHO withoutCharacterized by AHO withoutaccompanying multihormonal resistanceaccompanying multihormonal resistanceNormal serum calcium, phosphate, and PTHNormal serum calcium, phosphate, and PTH
    58. 58. PHYSIOLOGIC BASIS OF MALE REPRODUCTIVEPHYSIOLOGIC BASIS OF MALE REPRODUCTIVEFUNCTION AND THEIR DISORDERSFUNCTION AND THEIR DISORDERSThe male sex hormones are calledThe male sex hormones are called androgensandrogens.. TheThetestes secrete several male sex hormones,testes secrete several male sex hormones,includingincluding testosterone,testosterone, dihydrotestosteronedihydrotestosterone, and, andandrostenedioneandrostenedione..TestosteroneTestosterone, which is the most abundant of, which is the most abundant ofthese hormones, is considered the main testicularthese hormones, is considered the main testicularhormone. Thehormone. The adrenal cortex also producesadrenal cortex also producesandrogensandrogens, although in much smaller quantities, although in much smaller quantities(<5% of the total male androgens) than those(<5% of the total male androgens) than thoseproduced in the testes. Theproduced in the testes. The testes also secretetestes also secretesmall quantities of estradiol and estronesmall quantities of estradiol and estrone. The. Themale sex hormones are calledmale sex hormones are called androgensandrogens..All or almost all of the actions of testosterone and other androgensAll or almost all of the actions of testosterone and other androgensresult fromresult from increased protein synthesis in target tissuesincreased protein synthesis in target tissues.. Androgens functionAndrogens functionasas anabolic agentsanabolic agents in males and femalesin males and females to promote metabolism andto promote metabolism andmusculoskeletal growthmusculoskeletal growth.. TestosteroneTestosterone and theand the androgensandrogens have a great effecthave a great effecton the developmenton the development of increasing musculature during puberty, withof increasing musculature during puberty, with boysboysaveraging approximately 50% more of an increase inaveraging approximately 50% more of an increase in muscle mass than domuscle mass than dogirlsgirls..
    59. 59. Male InfertilityMale Infertility InfertilityInfertility is defined as the inability of a couple to achieve pregnancy despiteis defined as the inability of a couple to achieve pregnancy despiteunprotected intercourse for a period ofunprotected intercourse for a period of more than 12 monthsmore than 12 months. About. About 15%15% of allof allcouplescouples are infertileare infertile and it is estimated that a male factor plays a role in aboutand it is estimated that a male factor plays a role in abouthalf of the cases. In spite of this, the evaluation of the male partner is oftenhalf of the cases. In spite of this, the evaluation of the male partner is oftenneglected, mainly because of the high pregnancy rates that can be achieved byneglected, mainly because of the high pregnancy rates that can be achieved byassisted reproductive techniques (ART). This practice is unfortunate since maleassisted reproductive techniques (ART). This practice is unfortunate since maleinfertility can often be cured, sparing the female partner the extensive treatmentinfertility can often be cured, sparing the female partner the extensive treatmentand cost of ART. Furthermore, evidence suggests that ART procedures can beand cost of ART. Furthermore, evidence suggests that ART procedures can beassociated with increased risks for both mother and child. Finally, neglecting toassociated with increased risks for both mother and child. Finally, neglecting toexamine the infertile man properly risks overlooking serious conditions such asexamine the infertile man properly risks overlooking serious conditions such astesticular cancer that may coexist with infertility.testicular cancer that may coexist with infertility. For conception to occur, the following conditions must be met:For conception to occur, the following conditions must be met: (1) The testes must have normal spermatogenesis;(1) The testes must have normal spermatogenesis; (2) the spermatozoa must complete their maturation;(2) the spermatozoa must complete their maturation; (3) the ducts for sperm transport must be patent;(3) the ducts for sperm transport must be patent; (4) the prostate and seminal vesicles must supply adequate amounts of(4) the prostate and seminal vesicles must supply adequate amounts ofseminal fluid;seminal fluid; (5) the coital technique must enable the male partner to deposit his semen(5) the coital technique must enable the male partner to deposit his semennear the females cervix;near the females cervix; (6) the spermatozoa must be able to penetrate the cervical mucus and(6) the spermatozoa must be able to penetrate the cervical mucus andreach the uterine tubes;reach the uterine tubes; (7) the spermatozoa must undergo capacitation and the acrosome(7) the spermatozoa must undergo capacitation and the acrosomereaction, fuse with the oolemma, and be incorporated into the ooplasm.reaction, fuse with the oolemma, and be incorporated into the ooplasm.Any defect in this pathway can result in infertility.Any defect in this pathway can result in infertility.
    60. 60. Causes of Testicular AtrophyCauses of Testicular Atrophy TraumaTrauma Testicular torsionTesticular torsion HypopituitarismHypopituitarism CryptorchidismCryptorchidism Klinefelters syndrome (47,XXY)Klinefelters syndrome (47,XXY) Alcoholism and cirrhosisInfection (eg, mumpsAlcoholism and cirrhosisInfection (eg, mumpsorchitis, gonococcal epididymitis)orchitis, gonococcal epididymitis) Malnutrition and cachexiaMalnutrition and cachexia RadiationRadiation Obstruction to outflow of semenObstruction to outflow of semen AgingDrugs (eg, estrogen therapy for prostaticAgingDrugs (eg, estrogen therapy for prostaticcancer)cancer)
    61. 61. Cigarette smokingCigarette smoking Cigarette smokingCigarette smoking has been associated with an overall reduction inhas been associated with an overall reduction insemen quality, andsemen quality, and specifically aspecifically a reduction in sperm countreduction in sperm count andand motilitymotilityand anand an increase in abnormal formsincrease in abnormal forms.. Cigarette smoking can also causeCigarette smoking can also cause damage to sperm DNAdamage to sperm DNA. A meta-. A meta-analysis of 21 studies of the effect of cigarette smoking on semenanalysis of 21 studies of the effect of cigarette smoking on semenquality revealed thatquality revealed that smoking lowered sperm concentration by 13–smoking lowered sperm concentration by 13–17%17% in 7 studies and no effect in 14 studies. However, it remainsin 7 studies and no effect in 14 studies. However, it remainscontroversial whether smokingcontroversial whether smoking actually decreases male fertility ratesactually decreases male fertility rates.. Also controversial is whether second-hand smoke from a male partnerAlso controversial is whether second-hand smoke from a male partnercan affect female fertility. There is, however, some evidence thatcan affect female fertility. There is, however, some evidence thatmaternal smoking may be related to decreased sperm counts in thematernal smoking may be related to decreased sperm counts in theoffspring. Finally, the risk of developing erectile dysfunction is almostoffspring. Finally, the risk of developing erectile dysfunction is almostdoubled for smokers compared to nonsmokers, and this can limit maledoubled for smokers compared to nonsmokers, and this can limit malefertility.fertility. Testicular temperaturesTesticular temperatures are approximatelyare approximately 2 °C below core body2 °C below core bodytemperature and spermatogenesis is dependent on this coolertemperature and spermatogenesis is dependent on this coolertemperaturetemperature.. Factors such as clothing, lifestyle, season, and fever canFactors such as clothing, lifestyle, season, and fever cancause increases in scrotal temperature.cause increases in scrotal temperature. Increases in scrotal temperature reduce sperm quantity and qualityIncreases in scrotal temperature reduce sperm quantity and quality..
    62. 62. Semen Analysis: Normal Values andSemen Analysis: Normal Values andDefinitions.Definitions.Characteristic Reference StandardEjaculate volume > 2 mLpH 7.2–7.8Sperm concentration 20 million/mLSperm count 40 million/mLSperm motility 50% with normal motilitySperm morphology 15%1–30% with normal formsTerm Definition Normospermia Normal ejaculate (as defined by reference standardsabove)Oligozoospermia Sperm concentration < 20 million/mLAsthenozoospermia < 50% of spermatozoa with forward progression of< 25% with rapid progressionAzoospermia No spermatozoa in ejaculate
    63. 63. STRUCTURE AND FUNCTION OF THE FEMALESTRUCTURE AND FUNCTION OF THE FEMALEREPRODUCTIVE SYSTEMREPRODUCTIVE SYSTEM► Ovarian hormonesOvarian hormones are secretedare secretedin a cyclic pattern as a result ofin a cyclic pattern as a result ofthe interaction between thethe interaction between thehypothalamic gonadotrophichypothalamic gonadotrophicreleasing hormone (GnRH)releasing hormone (GnRH) andandthethe pituitary gonadotropicpituitary gonadotropichormoneshormones,, follicle stimulatingfollicle stimulatinghormonehormone (FSH), and(FSH), and luteinizingluteinizinghormonehormone (LH). The secretion of(LH). The secretion ofLH and FSH is stimulated byLH and FSH is stimulated byGnRH from the hypothalamus.GnRH from the hypothalamus.► The female genitourinary system consists of the external and internalThe female genitourinary system consists of the external and internalgenital organs. The external sex organs of the female are referred to asgenital organs. The external sex organs of the female are referred to asthe genitalia or vulva. The internal genital organs include the vagina,the genitalia or vulva. The internal genital organs include the vagina,uterus, uterine tubes, and ovaries. These organs are largely locateduterus, uterine tubes, and ovaries. These organs are largely locatedwithin the pelvic cavitywithin the pelvic cavity
    64. 64. Hypothalamic-pituitary feedback control ofHypothalamic-pituitary feedback control ofestrogen and progesterone levels in the female.estrogen and progesterone levels in the female.The dashed line represents negative feedback.The dashed line represents negative feedback.
    65. 65. Actions of EstrogensActions of EstrogensGeneral Function Specific ActionsGrowth andGrowth anddevelopmentdevelopment• Reproductive organs• SkeletonStimulate development of vagina, uterus, and fallopian tubes inutero and of secondary sex characteristics during pubertyAccelerate growth of long bones and closure of epiphyses atpubertyReproductive processesReproductive processesOvulationFertilizationImplantation• Vagina• Cervix• BreastsPromote growth of ovarian folliclesAlter the cervical secretions to favor survival and transport ofspermPromote motility of sperm within the fallopian tubes bydecreasing mucus viscosityPromote development of endometrial lining in the event ofpregnancyProliferate and cornify vaginal mucosaIncrease mucus consistencyStimulate stromal development and ductal growthGeneral metabolicGeneral metaboliceffectseffectsBone resorptionPlasma proteinsLipoproteinsDecrease rate of bone resorptionIncrease production of thyroid and other binding globulinsIncrease high-density and slightly decrease low-densitylipoproteins
    66. 66. Dysfunctional MenstrualDysfunctional MenstrualCyclesCycles Normal menstrual function results fromNormal menstrual function results frominteractions among the central nervous system,interactions among the central nervous system,hypothalamus, anterior pituitary, ovaries, andhypothalamus, anterior pituitary, ovaries, andassociated target tissues.associated target tissues. Although each part of the system is essential toAlthough each part of the system is essential tonormal function, the ovaries are primarilynormal function, the ovaries are primarilyresponsible for controlling the cyclic changesresponsible for controlling the cyclic changesand the length of the menstrual cycle.and the length of the menstrual cycle. In most women in the middle reproductiveIn most women in the middle reproductiveyears, menstrual bleeding occurs every 25 toyears, menstrual bleeding occurs every 25 to35 days, with a median length of 28 days.35 days, with a median length of 28 days.
    67. 67. Symptoms of PremenstrualSymptoms of PremenstrualSyndrome (PMS) by SystemSyndrome (PMS) by SystemBody System SymptomsCerebralCerebralIrritability, anxiety, nervousness, fatigue, andexhaustion; increased physical and mentalactivity; lability; crying spells; depressions;inability to concentrateGastrointestinalGastrointestinalCraving for sweets or salts, lower abdominal pain,bloating, nausea, vomiting, diarrhea,constipationVascularVascular Headache, edema, weakness, or faintingReproductiveReproductiveSwelling and tenderness of the breasts, pelviccongestion, ovarian pain, altered libidoNeuromuscularNeuromuscularTrembling of the extremities, changes incoordination, clumsiness, backache, leg achesGeneralGeneral Weight gain, insomnia, dizziness, acne
    68. 68. Literature:Literature:1.1. General and clinical pathophysiology / Edited by Anatoliy V. Kubyshkin – Vinnytsia: NovaGeneral and clinical pathophysiology / Edited by Anatoliy V. Kubyshkin – Vinnytsia: NovaKnuha Publishers – 2011. – P. 612–Knuha Publishers – 2011. – P. 612–627627..2.2. Russell JRussell J.. GreeneGreene.. Pathology and Therapeutics for Pharmacists. A basis for clinicalPathology and Therapeutics for Pharmacists. A basis for clinicalpharmacy practicepharmacy practice // Russell JRussell J.. Greene, Norman DGreene, Norman D.. Harris // Published by theHarris // Published by thePharmaceutical Press An imprint of RPS Publishing 1 Lambeth High Street, London SE1Pharmaceutical Press An imprint of RPS Publishing 1 Lambeth High Street, London SE17JN, UK 100 South Atkinson Road, Suite 200, Greyslake, IL 60030-7820,7JN, UK 100 South Atkinson Road, Suite 200, Greyslake, IL 60030-7820, 3rd edition,3rd edition,USAUSA. – 2008. – Chapter 9. – P. 630–644.. – 2008. – Chapter 9. – P. 630–644.3.3. Essentials of Pathophysiology: Concepts of Altered Health States (Lippincott Williams &Essentials of Pathophysiology: Concepts of Altered Health States (Lippincott Williams &Wilkins), Trade paperback (2003)Wilkins), Trade paperback (2003) // Carol Mattson Porth, Kathryn J. Gaspard. –Carol Mattson Porth, Kathryn J. Gaspard. – ССhapterhapter31. – P. 545–559.31. – P. 545–559.4.4. Symeonova N.K. Pathophysiology / N.K. Symeonova // Kyiv, AUS medicine Publishing. –Symeonova N.K. Pathophysiology / N.K. Symeonova // Kyiv, AUS medicine Publishing. –2010. – P. 493–506.2010. – P. 493–506.5.5. Gozhenko A.I. General and clinical pathophysiology / A.I. Gozhenko, I.P. Gurcalova //Gozhenko A.I. General and clinical pathophysiology / A.I. Gozhenko, I.P. Gurcalova //Study guide for medical students and practitioners. Edited by prof. Zaporozan, OSMU. –Study guide for medical students and practitioners. Edited by prof. Zaporozan, OSMU. –Odessa. – 2005. – P. 283–291.Odessa. – 2005. – P. 283–291.6.6. Silbernagl S. Color Atlas of Pathophysiology / S. Silbernagl, F. Lang // Thieme. Stuttgart.Silbernagl S. Color Atlas of Pathophysiology / S. Silbernagl, F. Lang // Thieme. Stuttgart.New York. – 2000. – P. 280–285.New York. – 2000. – P. 280–285.7.7. Corwin Elizabeth J. Handbook of Pathophysiology / Corwin Elizabeth J. – 3th edition.Corwin Elizabeth J. Handbook of Pathophysiology / Corwin Elizabeth J. – 3th edition.Copyright ВCopyright В.. – Lippincott Williams & Wilkins – 2008. –– Lippincott Williams & Wilkins – 2008. – Chapter 9. – P. 250–251, 262–266.Chapter 9. – P. 250–251, 262–266.8.8. Robbins and Cotran Pathologic Basis of Disease 8th edition./ Kumar, Abbas, Fauto. –Robbins and Cotran Pathologic Basis of Disease 8th edition./ Kumar, Abbas, Fauto. –2007. – Chapter2007. – Chapter 2020. – P.. – P. 758–775758–775..9.9. Copstead Lee-Ellen C. Pathophysiology / Lee-Ellen C. Copstead, Jacquelyn L. Banasik //Copstead Lee-Ellen C. Pathophysiology / Lee-Ellen C. Copstead, Jacquelyn L. Banasik //Elsevier Inc, 4th edition. – 2010. – P. 927–930, 936–937.Elsevier Inc, 4th edition. – 2010. – P. 927–930, 936–937.10.10. Pathophysiology, Concepts of Altered Health States, Carol Mattson Porth, Glenn Matfin. –Pathophysiology, Concepts of Altered Health States, Carol Mattson Porth, Glenn Matfin. –New York, Milwaukee. – 2009.New York, Milwaukee. – 2009. –– PP.. 1030–10471030–1047..

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