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

1. Pathophysiology of thyroid,Pathophysiology of thyroid,
parathyroid and sexualparathyroid and sexual
glands.glands.
By MD, PhD, Marta R. GerasymchukBy MD, PhD, Marta R. Gerasymchuk,
Pathophysiology departmentPathophysiology department
Ivano-Frankivsk National MedicalIvano-Frankivsk National Medical
UniversityUniversity

2. CONTENTCONTENT
1.1. Pathology of thyroid gland. Hypothyroidism: etiology,Pathology of thyroid gland. Hypothyroidism: etiology,
pathogenesis, mechanisms of development of mainpathogenesis, mechanisms of development of main
manifestations.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 immune
mechanisms in its development. Pathogenesis of mainmechanisms in its development. Pathogenesis of main
manifestations of hyperthyroidism.manifestations of hyperthyroidism.
4.4. Pathology of parathyroid glands. Hypo- andPathology of parathyroid glands. Hypo- and
hyperparathyroidism.hyperparathyroidism.
5.5. Pathology of sexual glands. Male hypo- andPathology of sexual glands. Male hypo- and
hypergonadism, etiology and pathogenesis.hypergonadism, etiology and pathogenesis.
Eunochoidism.Eunochoidism.
6.6. Female hypo- and hypergonadism. Disorder of sexualFemale hypo- and hypergonadism. Disorder of sexual
differentiation and development.differentiation and development.
Disorders of cyclic functions of female organism; disordersDisorders of cyclic functions of female organism; disorders
of 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. Actuality of the lectureActuality of the lecture
The 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 glands
functions 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 not
less then 200 millions people suffer by diffuse toxic goiter. Except sporadicless then 200 millions people suffer by diffuse toxic goiter. Except sporadic
cases ofcases of thyreotoxicosisthyreotoxicosis andand myxedemamyxedema, which meet everywhere, on territory, which meet everywhere, on territory
of 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 of
endemic goiter, frequently with manifestations hypo- and hyperfunction of thyroidendemic goiter, frequently with manifestations hypo- and hyperfunction of thyroid
gland. In our district such region is the Carpathians. Recently thegland. In our district such region is the Carpathians. Recently the diseases ofdiseases of
thyroid 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 low
temperature. The amount of persons with the disturbanced function of thyroidtemperature. The amount of persons with the disturbanced function of thyroid
gland 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 large
number and deleted accommodation of the glands of disease and the casualnumber and deleted accommodation of the glands of disease and the casual
damages seldom lead them to destruction of such amount of parathyreoiddamages seldom lead them to destruction of such amount of parathyreoid
tissues to cause it insufficiency. More often hypofunction of this organ meets intissues to cause it insufficiency. More often hypofunction of this organ meets in
the 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 the
thyroid gland the destruction of glands. The second form of parathyreoidthyroid gland the destruction of glands. The second form of parathyreoid
insufficiency is ideopatic. This state, it is a result of autoimune response, whichinsufficiency is ideopatic. This state, it is a result of autoimune response, which
are 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 are
accompanied 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 the
adenoma of one or several endocrine bodies.adenoma of one or several endocrine bodies.

4. Thyroid GlandThyroid Gland

5. The thyroid gland and the
follicular structure

6. Chemistry of thyroid hormoneChemistry of thyroid hormone
productionproduction

7. Hormones of the Thyroid GlandHormones of the Thyroid Gland
• Thyroxine (T4)
• Principle hormone
• Increases energy and protein metabolism
rate
• Triiodothyronine (T3)
• Increases energy and protein metabolism
rate
• Calcitonin
• Regulates calcium metabolism
• Works with parathyroid hormone and
vitamin D

8. Thyroid hormones are synthesised in adults as long as the dietary iodine (I2) supersedes 75 µg daily. This is an
adequate supply to prevent goiter formation. The daily ingestion of iodide is 400-500 µg daily in many areas
and the same amount is excreted in the urine in a steady state.

9. The synthesis in the thyroid gland takesThe synthesis in the thyroid gland takes
place 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 is
rapidly 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 thatthat
requires and concentrates iodide from the circulating blood.requires and concentrates iodide from the circulating blood. IodideIodide isis
transported into the cell against an electrochemical gradient (more thantransported into the cell against an electrochemical gradient (more than
50 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 isis
also 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 the
trap.trap. In the follicular cellIn the follicular cell, iodide passes down its electrochemical, iodide passes down its electrochemical
gradient 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 a
thyroid peroxidasethyroid peroxidase to atomic or molecular iodine (Ito atomic or molecular iodine (I00 or Ior I22) at the colloid) at the colloid
surface of the apical membrane. Thiouracil and sulfonamides block thissurface of the apical membrane. Thiouracil and sulfonamides block this
peroxidase.peroxidase.
 CC. The. The rough endoplasmic reticulumrough endoplasmic reticulum synthesises a large storagesynthesises a large storage
molecule calledmolecule called thyroglobulinthyroglobulin. This compound is build up by a long. This compound is build up by a long
peptide chain with tyrosine units and a carbohydrate unit completed bypeptide chain with tyrosine units and a carbohydrate unit completed by
the Golgi apparatus. Iodide-free thyroglobulin is transported inthe Golgi apparatus. Iodide-free thyroglobulin is transported in vesiclesvesicles
to the apical membrane, where they fuse with the membrane and finallyto the apical membrane, where they fuse with the membrane and finally
release thyroglobulin at the apical membrane.release thyroglobulin at the apical membrane.

10. The synthesis in the thyroid gland takesThe synthesis in the thyroid gland takes
place 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 tyrosine
units (L-tyrosine)units (L-tyrosine) in thyroglobulinin thyroglobulin at one or two positions, forming theat one or two positions, forming the
hormone 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 thyroidthyroid
peroxidaseperoxidase in the presence of hydrogen peroxide -both located at the apicalin the presence of hydrogen peroxide -both located at the apical
membrane. 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 the
inactiveinactive 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 to
one T3.one T3. Thyroglobulin is retrieved backThyroglobulin is retrieved back into the follicular cell asinto the follicular cell as colloidcolloid
dropletsdroplets byby pinocytosispinocytosis. Pseudopods engulf a pocket of colloid. These. Pseudopods engulf a pocket of colloid. These
colloid droplets pass towards the basal membrane and fuse withcolloid droplets pass towards the basal membrane and fuse with lysosomeslysosomes
formingforming phagolysosomes.phagolysosomes.
 FF.. Lysosomal exopeptidasesLysosomal exopeptidases break the binding between thyroglobulin andbreak the binding between thyroglobulin and
T4T4 (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. Only
minor 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. These
molecules are deiodinated by the enzyme deiodinase, whereby iodide canmolecules are deiodinated by the enzyme deiodinase, whereby iodide can
be reused into T4 or T3.be reused into T4 or T3. Normally, only few intact thyroglobulin moleculesNormally, only few intact thyroglobulin molecules
leave the follicular cellsleave the follicular cells..
 HH.. TSHTSH stimulatesstimulates almost all processes involved inalmost all processes involved in thyroid hormonethyroid hormone
synthesis and secretionsynthesis and secretion..

11. The hypothalamic-pituitary-thyroid feedback system, which regulates the
body levels of thyroid hormone.

12. Control of thyroid gland activityControl of thyroid gland activity
 TheThe hypothalamic-pituitary-thyroid axishypothalamic-pituitary-thyroid axis controls the thyroidcontrols the thyroid
gland 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 controlled
byby 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, where
the 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 secretion
in humans.in humans. TSHTSH is released to the systemic blood, by which itis released to the systemic blood, by which it
travels to the thyroid gland. Here,travels to the thyroid gland. Here, TSHTSH stimulates the uptakestimulates the uptake
of iodide, and all other processes that promoteof iodide, and all other processes that promote formation andformation and
release of T4 (and T3).release of T4 (and T3).
 TSHTSH activatesactivates adenylcyclaseadenylcyclase bound to the cell membranes ofbound to the cell membranes of
the 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 as
on theon the expression of the gene for the TRH precursor.expression of the gene for the TRH precursor.

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 the
conversion 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 an
equilibrium between the pool of protein-bound thyroid hormone andequilibrium between the pool of protein-bound thyroid hormone and
the free, biologically active forms (T3 and T4) that can enter the bodythe free, biologically active forms (T3 and T4) that can enter the body
cells.cells.
• Thyroid hormonesThyroid hormones areare lipid-solublelipid-soluble and they canand they can easily crosseasily cross the cellularthe cellular
membrane by diffusionmembrane by diffusion..
• cc.. Inside the cell,Inside the cell, T3T3 binds tobinds to nuclear receptorsnuclear receptors and stimulates cellularand stimulates cellular
metabolism andmetabolism and increasesincreases metabolic ratemetabolic rate..
• dd.. The concentrations ofThe concentrations of T3T3 andand T4T4 in the blood arein the blood are recordedrecorded byby
pituitary and hypothalamic receptorspituitary and hypothalamic receptors..
• ThisThis negative feedback systemnegative feedback system keeps the blood concentrations within normalkeeps the blood concentrations within normal
limits, and there is only alimits, and there is only a minimalminimal nocturnalnocturnal increase in TSH secretionincrease in TSH secretion
and T4 releaseand T4 release..

14. The hypothalamic-pituitary-thyroid axis controls the thyroid gland
function and growth.

15. Actions of thyroid hormonesActions of thyroid hormones
 Thyroid hormones are lipid-soluble and pass through cell
membranes easily. T3 binds to specific nuclear receptor
proteins with an affinity that is tenfold greater than the affinity for T4. The
information alters DNA transcription into mRNA, and the information is
eventually translated into many effector proteins. One type of thyroid
receptor protein is bound to thyroid regulatory elements in target cell
genes.
 Important cellular constituents are stimulated by T3: The mitochondria,
the Na+-K+-pump, myosin ATPase, adrenergic b-receptors, many
enzyme systems and proteins for growth and maturation including CNS
development.
 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, respiratory
enzymes, erythropoietin, b-adrenergic receptors, sex hormones, growth
factors etc);
4) the absorption of carbohydrates in the intestine and the gut excretion of
cholesterol;
5) the modulation of reproductive function.

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 increase
inin oxygen consumptionoxygen consumption. This slow - but long lasting -. This slow - but long lasting - calorigeniccalorigenic andand
thermogenicthermogenic effect is confined to theeffect is confined to the mitochondriamitochondria..
 TheThe thyroid hormones and the catecholaminesthyroid hormones and the catecholamines work togetherwork together inin
metabolic acceleration.metabolic acceleration.
 Thyroid hormonesThyroid hormones increase cardiac rate and output as well asincrease cardiac rate and output as well as
ventilationventilation..
 TheThe high basal metabolic rate raiseshigh basal metabolic rate raises thethe core and shell temperaturecore and shell temperature, so, so
that thethat the peripheral vessels dilatateperipheral vessels dilatate. This. This vasodilatation forces thevasodilatation forces the
cardiac output to increasecardiac output to increase. A. A circulatory shock developscirculatory shock develops,, if the rise inif the rise in
cardiac output is insufficient to match the vasodilatationcardiac output is insufficient to match the vasodilatation - socalled- socalled highhigh
output failureoutput failure..
 A human body overloaded with thyroid hormones for a prolongedA human body overloaded with thyroid hormones for a prolonged
period (period (hyperthyroidismhyperthyroidism) will suffer from) will suffer from muscle atrophia, bonemuscle atrophia, bone
destruction and hunger damagedestruction and hunger damage, due to, due to increased catabolism of cellularincreased catabolism of cellular
proteins and fatproteins and fat. Eventually. Eventually hypothyroidismhypothyroidism may develop due tomay develop due to
suppression.suppression.

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 parathyroidparathyroid
hormone (PTH)-receptorshormone (PTH)-receptors on the osteoclasts. The result is anon the osteoclasts. The result is an
extremely 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 in
treatment 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 the
thyroid glandthyroid gland in response to hypercalcaemiain response to hypercalcaemia and itand it acts to loweracts to lower
plasma [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 andand
inhibits Cainhibits Ca22+ -liberation from bone+ -liberation from bone (ie,(ie, inhibits both osteolysisinhibits both osteolysis
by osteocytes and bone resorption by osteoclastsby osteocytes and bone resorption by osteoclasts). But). But
calcitonincalcitonin reduces plasma phosphate just as PTHreduces plasma phosphate just as PTH..
 CalcitoninCalcitonin probablyprobably inhibits reabsorption of phosphateinhibits reabsorption of phosphate in thein the
distal tubules of the kidney, but calcitonin alsodistal tubules of the kidney, but calcitonin also inhibits the renalinhibits the renal
reabsorp­tion of Careabsorp­tion of Ca22+, Na+ and Mg+, Na+ and Mg22+.+. Calcitonin mayCalcitonin may inhibit gutinhibit gut
absorption of Caabsorption of Ca22++ andand promote phosphate entrance into bonepromote phosphate entrance into bone
and cause important bone remodelling.and cause important bone remodelling.

18.  Calcitonin deficiencyCalcitonin deficiency does not leaddoes not lead toto hypercalcaemiahypercalcaemia, and, and
excessexcess calcitonin from tumours does not lead tocalcitonin from tumours does not lead to
hypocalcaemiahypocalcaemia. Therefore, most effects of calcitonin are. Therefore, most effects of calcitonin are
evidently offset by appropriate regulation through the actions ofevidently offset by appropriate regulation through the actions of
PTHPTH andand vitamin Dvitamin D..
 CalcitoninCalcitonin in plasma declines with age andin plasma declines with age and is lower in womenis lower in women
than in menthan in men. Low levels of calcitonin are involved in accelerated. Low levels of calcitonin are involved in accelerated
bone 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 a
neurotransmitterneurotransmitter inin
the hypothalamusthe hypothalamus
and in other CNSand in other CNS
locations.locations.
 CalcitoninCalcitonin isis
administered toadministered to
postmenopausalpostmenopausal
femalesfemales in attempt toin attempt to
preventprevent
osteoporosis.osteoporosis.

20. 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’s
disease, Goiter) and
Hyperthyroidism (Graves’ disease)

21. HyperthyroidismHyperthyroidism
 TheThe classical hyperthyroidismclassical hyperthyroidism or thyrotoxicosis (Graves thyroiditis, Basedowsor thyrotoxicosis (Graves thyroiditis, Basedows
disease) is a condition characterized by an abnormal rise in basaldisease) is a condition characterized by an abnormal rise in basal
metabolic rate, struma and eye signs (thyroid eye disease). The eyes ofmetabolic rate, struma and eye signs (thyroid eye disease). The eyes of
the patient typically bulge (ie,the patient typically bulge (ie, exophtalmusexophtalmus). Patients with). Patients with thyrotoxicosisthyrotoxicosis havehave
overwhelmingly high metabolic rates.overwhelmingly high metabolic rates.
 Neuromuscular systemNeuromuscular system
 Tremors, hyperactivity, emotional lability, anxiety, inability toTremors, hyperactivity, emotional lability, anxiety, inability to
concentrate, insomniaconcentrate, insomnia
 Thyroid myopathy – proximal muscle weakness with decrease muscleThyroid myopathy – proximal muscle weakness with decrease muscle
massmass
 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 and
reduced volume of trabecular bone)reduced volume of trabecular bone)
 Osteoporosis and increased risk of fracturesOsteoporosis and increased risk of fractures

23. Graves DiseaseGraves Disease
 The disease is named for Robert Graves who inThe disease is named for Robert Graves who in
1835 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 endogenous
hyperthyroidismhyperthyroidism
 Triad:Triad:
– HyperthyroidismHyperthyroidism
– Infiltrative ophthalmopathy with resultantInfiltrative ophthalmopathy with resultant
exophthalmosexophthalmos
– Localized, infiltrative dermopathy (pretibialLocalized, infiltrative dermopathy (pretibial
myxedema)myxedema)

25. HyperthyroidismHyperthyroidism ((Graves DiseaseGraves Disease))
 Thyroid eye diseaseThyroid eye disease (with exophtalmus) is not confined(with exophtalmus) is not confined
to Graves’s hyperthyroidism only. Some exophtalmusto Graves’s hyperthyroidism only. Some exophtalmus
patients 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 are
specific antibodiesspecific antibodies that cause inflammation of thethat cause inflammation of the retro-retro-
orbital tissueorbital tissue withwith swellingswelling of theof the extraocular eyeextraocular eye
musclesmuscles, so, so they cannot move the eyes normallythey cannot move the eyes normally..
 ProptosisProptosis andand lid lagslid lags areare typical signstypical signs, and, and
conjunctivitis and scarsconjunctivitis and scars on the cornea follow due to lackon the cornea follow due to lack
of protective cover.of protective cover.
 TheThe oedematous retro-orbital tissueoedematous retro-orbital tissue may force the eyemay force the eye
balls forward and press on the optic nerveballs forward and press on the optic nerve to such anto such an
extent 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 accompanying
thyrotoxicosis. Other therapeutic measures arethyrotoxicosis. Other therapeutic measures are
palliative.palliative.

26. Lid lag in Graves disease

29. HyperthyroidismHyperthyroidism ((Graves DiseaseGraves Disease))
TSH receptor antibodyTSH receptor antibody ((IgG antibodiesIgG antibodies) release causes Graves’s disease) release causes Graves’s disease
from activated B-cellsfrom activated B-cells. A genetic deficiency is involved, which is shown by. A genetic deficiency is involved, which is shown by
the 50% concordance in monozygotic twins.the 50% concordance in monozygotic twins. Trigger mechanismsTrigger mechanisms areare
presumed to be bacterial or viral infections producingpresumed to be bacterial or viral infections producing autoimmuneautoimmune
phenomenaphenomena 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 TSHTSH
receptors (antigens)receptors (antigens) on theon the surface ofsurface of
the thyroid follicular cellsthe thyroid follicular cells, which they, which they
stimulate just like TSH itself,stimulate just like TSH itself, causingcausing
thyroid hypersecretionthyroid hypersecretion. These. These IgGIgG
antibodiesantibodies are also termedare also termed long-long-
acting thyroid stimulatoracting thyroid stimulator..
2.2. Specific autoantibodiesSpecific autoantibodies causingcausing
retro-orbital inflammation and thyroidretro-orbital inflammation and thyroid
eye diseaseeye disease..
3.3. ThyroglobinThyroglobin antibodiesantibodies against theagainst the
storage molecule, thyroglobin.storage molecule, thyroglobin.
4.4. Microsomal antibodiesMicrosomal antibodies againstagainst
thyroid peroxidasethyroid peroxidase..
TheseThese autoantibodiesautoantibodies can be found incan be found in
the plasma of most cases of Grave’sthe plasma of most cases of Grave’s
disease.disease.

30.  The increasedThe increased metabolic ratemetabolic rate andand sympatho-adrenergic activitysympatho-adrenergic activity dominatedominate
the 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 hyperthyroid
females - like female distance runners - havefemales - like female distance runners - have small fat storessmall fat stores andand greatlygreatly
reduced 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 the
myocardial cellsmyocardial cells. The. The cardiac output is highcardiac output is high even at rest andeven at rest and arrhythmiasarrhythmias
are frequentare frequent (eg, atrial fibrillation).(eg, atrial fibrillation).
 Elderly patientsElderly patients may present with anmay present with an apathetic hyperthyroidismapathetic hyperthyroidism,, wherewhere theythey
complain of tiredness and somnolencecomplain of tiredness and somnolence. Measurement of serum TSH with. Measurement of serum TSH with
T3/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 causing
vasodilatation 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, and
the 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 the
clinical manifestations of Graves’s disease.clinical manifestations of Graves’s disease.

31. The pathogenesis of Graves disease, andThe pathogenesis of Graves disease, and
the clinical manifestations of Graves’sthe clinical manifestations of Graves’s
disease.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 hormone
andand 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, or
patients 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.

33. Toxic goiterToxic goiter andand toxic solitary adenomatoxic solitary adenoma
(Plummers disease) are cases of(Plummers disease) are cases of secondarysecondary
hyperthyroidismhyperthyroidism just as inflammation injust as inflammation in
acute thyroiditisacute thyroiditis andand chronic thyroiditis.chronic thyroiditis.
The cells secrete thyroid hormone withoutThe cells secrete thyroid hormone without
inhibition from the hypothalamo-pituitaryinhibition from the hypothalamo-pituitary
axis.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 lobe
with suppression of the gland.with suppression of the gland.

34. Hypothyroidism
 Primary hypothyroidism is an abnormally low activity of the
thyroid gland with low circulating thyroid hormone levels
caused by thyroid disease.
 Secondary hypothyroidism results from hypothalamic-pituitary
disease.
 Primary hypothyroidism is caused by microsomal
autoantibodies precipitated in the glandular tissue. Lymphoid
infiltration of the thyroid may eventually lead to atrophy with
abnormally low production of T4. Another clinical form starts
out as Hashimotos thyroiditis, often with hyperthyroidism and
goiter.
 Following atrophy caused by microsomal autoantibodies, the
condition ends as hypothyroidism, or the patient is euthyroid.

35. • When hypothyroidismhypothyroidism is congenital both physical and mental
development is impaired and cretinism is the result. Also iodide
deficiency in childhood may also result in a cretincretin or a mentally
retarded hypothyroid dwarf.
• Myxoedema in the adult is severe thyroid gland hypothyroidism with
a puffy swollen face due to a hard, non-pitting oedema (called
myxoedema or tortoise skin). The skin is dry and cold; there is
bradycardia, 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 the
diagnosis primary hypothyroidism. Thyroid autoantibodies are
usually demonstrable in the plasma. Hypercholesterolaemia and
increased concentrations of liver and muscle enzymes (aspartate
transferase, creatine kinase) in the plasma is typical.
• As stated thyroid gland high TSH characterises hypothyroidism. A
test dose of TSH to a patient with thyroid hypothyroidism will not
stimulate the thyroid gland.
• A test dose of TRH (Thyroid releasing hormone) will result in an
increased TSH response in thyroid gland hypothyroidism and
decrease in hyperthyroidism. This is due to the negative feedback of
thyroid hormones on the hypophysis.
• Hypothyroid females often have excessive and frequent menstrual
bleedings (menorrhagia and polymenorrhoea). Hypothyroid patients
exhibit slow cardiac activity.

36.  Secondary hypothyroidismSecondary hypothyroidism is causedis caused
by reduced TSH (by reduced TSH (Thyroid stimulatingThyroid stimulating
hormonehormone) drive due to pituitary or) drive due to pituitary or
hypothalamic insufficiency. A testhypothalamic insufficiency. A test
dose of TRH (dose of TRH (Thyroid releasingThyroid releasing
hormonehormone) to a myxoedema patient) to a myxoedema patient
with hypothalamic or pituitarywith hypothalamic or pituitary
insufficiency will result in a normalinsufficiency will result in a normal
TSH response.TSH response.
 Replacement is given to theReplacement is given to the
hypothyroid patient withhypothyroid patient with
approximately 100approximately 100 µµg T4 daily for theg T4 daily for the
rest of the patients life.rest of the patients life.

37. 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 skin
Structural or functionalStructural or functional
derangement that interfere withderangement that interfere with
the production of adequatethe production of adequate
levels of thyroid hormonelevels of thyroid hormone
Primary, secondary, or tertiaryPrimary, secondary, or tertiary

39. CretinismCretinism
Hypothyroidism that occurs in infancyHypothyroidism that occurs in infancy
or early childhoodor early childhood
Impaired development of the skeletalImpaired development of the skeletal
system and CNSsystem and CNS
Manifests asManifests as severe mentalsevere mental
retardationretardation, short stature, coarse facial, short stature, coarse facial
features, protruding tongue andfeatures, protruding tongue and
umbilical herniaumbilical hernia
Cretinism, also known as
Neonatal hypothyroidism
is decreased thyroid hormone production in a newborn.

40. CretinismCretinismThis 1 year old babyThis 1 year old baby
was diagnosed withwas diagnosed with
Cretinism.The thyroidCretinism.The thyroid
profile showed aprofile showed a
hypothyroid picture.hypothyroid picture.
Replacement therapyReplacement therapy
has been started.has been started.
These four brothers work at a salt
factory in Pakistan. Two of them suffer
from cretinism, caused by iodine
deficiency. All the brothers ensure
they use iodized salt in their
households to prevent cretinism in the
next generation and give their children
the iodine they need for intellectual
development.
 HH → Hypotonia → 1→ Hypotonia → 1
YY → Yellow (icterus >3) →1→ Yellow (icterus >3) →1
PP → Pallor, cold, hypothermia →1→ Pallor, cold, hypothermia →1
OO → Open post. fontanel →1→ Open post. fontanel →1
TT → Tongue enlarged →1→ Tongue enlarged →1
HH → Umbilical hernia →2→ Umbilical hernia →2
YY → absent Y (female) →1→ absent Y (female) →1
RR → Rough dry skin →1→ Rough dry skin →1
OO → Edematous typical face →2→ Edematous typical face →2
I.DI.D.→ Inactive defecation → 2.→ Inactive defecation → 2
Birth weightBirth weight > 3.5 kg →1> 3.5 kg →1
Post.maturePost.mature > 40w →1> 40w →1
Total = 15.Total = 15.
If score > 5If score > 5 suggest hypothyroidism,suggest hypothyroidism,
must investigate.must investigate.
APGAR score of early suspicion of hypothyroidism

41. Simple Mnemonics for ClinicalSimple Mnemonics for Clinical
picture of cretinismpicture of cretinism
at birth & early neonatal :
1- Feeding difficulty, choking & anorexia
2- Constipation, abdomenal distention,
umbilical hernia, delayed passage of
meconium
3- Heavy birth weight (Over weight).
4- Hypothermia, cold skin.
5- Open posterior fontanel.
6- Less activity, always sleep, little cry
hoarse voice.
7- Prolonged physiological jaundice.
8- Bradycardia: ↓ HR (Slow Pulse) .
9- Apneic attacks: ↓ Respiratory rate.
10- X- Ray knee: absent ossific centers
at birth of the lower end of the femur.

42. TypicalTypical
SymptomsSymptoms
& Signs:& Signs:
• 3- Skin:
Pale yellow skin
(carotenemia). & Dry,
rough, cold.
• 4- Abdomen:
Pott's belly abdomen. &
Umbilical hernia.
• 5- C.V.S:
Bradycardia.
• Haemic murmur.
• Cardiomegally → CHF.
• 6- C.N.S:
Hypotonia
• Hyporeflexia,
• apathy.
• A- Delayed growth & development and
metal 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 to
decay.
• 2- Neck:
short & webbed. & thyroid may
palpable.

43. MyxedemaMyxedema
 Hypothyroidism developing in the older child orHypothyroidism developing in the older child or
adultadult
 Gull diseaseGull disease
 Characterized by slowing of physical and mentalCharacterized by slowing of physical and mental
activityactivity
 Accumulation of matrix substancesAccumulation of matrix substances
((glycosaminoglycans and hyaluronic acidglycosaminoglycans and hyaluronic acid) in the) in the
skin, subcutaneous tissues, and visceral sitesskin, subcutaneous tissues, and visceral sites 
edemaedema, broadening and coarsening of facial, broadening and coarsening of facial
features, enlargement of the tongue, andfeatures, enlargement of the tongue, and
deepening of the voicedeepening of the voice
 Measurement of serumMeasurement of serum TSH levelTSH level is the mostis the most
sensitivesensitive screening testscreening test

44. PrimaryPrimary
hypotyrioidismhypotyrioidism
MyxedemaMyxedema

45. Myxedematous Coma.Myxedematous Coma.
• Myxedematous comaMyxedematous coma is a lifethreatening,is a lifethreatening, end-stage expression ofend-stage expression of
hypothyroidismhypothyroidism..
• 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 include
hyponatremia, hypoglycemia, and lactic acidosishyponatremia, hypoglycemia, and lactic acidosis. It occurs most often in. It occurs most often in
elderly women who have chronic hypothyroidism from a spectrum ofelderly women who have chronic hypothyroidism from a spectrum of
causes. It occurs morecauses. It occurs more frequently in the winter monthsfrequently in the winter months, which suggests, which suggests
that cold exposure may be a precipitating factor. Thethat cold exposure may be a precipitating factor. The severelyseverely
hypothyroid person ishypothyroid person is unable to metabolizeunable to metabolize sedatives, analgesics, andsedatives, analgesics, and
anesthetic 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 to
high-risk populationshigh-risk populations, such as, such as women with a history of Hashimoto’swomen with a history of Hashimoto’s
thyroiditisthyroiditis. These persons should be informed about the signs and. These persons should be informed about the signs and
symptoms of severe hypothyroidism and the need for early medicalsymptoms of severe hypothyroidism and the need for early medical
treatment.treatment.

47. 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 producing
nodularitynodularity
– 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 more
mistaken for neoplastic involvement than any othermistaken for neoplastic involvement than any other
form of thyroid diseaseform of thyroid disease

48. 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 FROM
TSHTSH
• NONTOXICNONTOXIC
SIMPLE/ 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

49. 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?

50. NON-TOXIC GOITERNON-TOXIC GOITER
IMPAIRED THYROID HORMONE SYNTHESISIMPAIRED THYROID HORMONE SYNTHESIS
SERUM THYROXINESERUM THYROXINE
PITUITARY SECRETE TSHPITUITARY SECRETE TSH
THYROID GLAND ENLARGESTHYROID GLAND ENLARGES
TO COMPENSATE FOR THE REDUCED LEVEL OF THYROXINETO COMPENSATE FOR THE REDUCED LEVEL OF THYROXINE
IODINE DEFICIENCY ORIODINE DEFICIENCY OR
INTAKE OF GOITROGENIC SUBSTANCESINTAKE OF GOITROGENIC SUBSTANCES

51. G
O
I
T
E
R

52. MultinodularMultinodular
goitergoiter

53. Hashimoto ThyroiditisHashimoto Thyroiditis
 Chronic lymphocytic thyroiditisChronic lymphocytic thyroiditis
 Struma lymphomatosaStruma lymphomatosa
 Most common cause ofMost common cause of
hypothyroidism in areas of thehypothyroidism in areas of the
world where iodine levels areworld where iodine levels are
sufficientsufficient
 Pathogenesis:Pathogenesis:
 CD8+ cytotoxic T-cell mediatedCD8+ cytotoxic T-cell mediated
cell 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, antithyroid
peroxidase Ab’speroxidase Ab’s
A woman presenting with an enlarged
thyroid who has Hashimoto's thyroiditis

54. Hashimoto’s thyroiditisHashimoto’s thyroiditis isis the most common form ofthe most common form of
thyroiditis. It is athyroiditis. It is a form ofform of autoimmuneautoimmune thyroditisthyroditis; more; more
common incommon in women and in late middle agewomen and in late middle age. Thyroid. Thyroid
peroxidase (TPO) antibodies are usually present in thisperoxidase (TPO) antibodies are usually present in this
condition, often in very high levels. It may be associatedcondition, often in very high levels. It may be associated
with other endocrine organ deficiencies such aswith other endocrine organ deficiencies such as diabetesdiabetes
mellitus or Addison's disease.mellitus or Addison's disease.
Hashimoto’s thyroiditisHashimoto’s thyroiditis also occurs more commonly inalso occurs more commonly in
patients 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 can
lead to a goitelead to a goiterr forming. Patients withforming. Patients with Hashimoto’s thyroiditisHashimoto’s thyroiditis
are usuallyare usually hypothyroid or euthyroidhypothyroid or euthyroid. However, they may. However, they may
have 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 condition
which results in anwhich results in an immune response directed against theimmune response directed against the
thyroid cellthyroid cell. This activation may be triggered by a viral. This activation may be triggered by a viral
infection.infection.
Although thyroid lymphoma is rare, the risk of thyroidAlthough thyroid lymphoma is rare, the risk of thyroid
lymphoma is increased 60-fold in patients with Hashimoto’slymphoma is increased 60-fold in patients with Hashimoto’s
thyroiditis. Patients presenting with a new thyroid lumpthyroiditis. Patients presenting with a new thyroid lump
should undergo fine-needle aspiration biopsy.should undergo fine-needle aspiration biopsy.

55. Riedel ThyroiditisRiedel Thyroiditis
 Rare disorder of unknown etiologyRare disorder of unknown etiology
 Extensive fibrosis involving theExtensive fibrosis involving the
thyroid and contiguous neck structuresthyroid and contiguous neck structures
 Hard and fixed thyroid massHard and fixed thyroid mass
 Riedel's thyroiditis is classified as rare. Most patients remainRiedel's thyroiditis is classified as rare. Most patients remain
euthyroideuthyroid, but approximately 30% of patients become, but approximately 30% of patients become
hypothyroidhypothyroid and very few patients areand very few patients are hyperthyroidhyperthyroid. It is most. It is most
seen in womenseen in women..
 RRiedel’s thyroiditisiedel’s thyroiditis is a very rare chronic inflammatory disorderis a very rare chronic inflammatory disorder
that leads tothat leads to progressive fibrosisprogressive fibrosis of the thyroid gland ofof the thyroid gland of
unknown cause. It is often associated with otherunknown cause. It is often associated with other
fibroproliferative disorders (e.g. mediastinal andfibroproliferative disorders (e.g. mediastinal and
retroperitoneal fibrosis, sclerosing cholangitis). Patientsretroperitoneal fibrosis, sclerosing cholangitis). Patients
present with a rock-hard, fixed and painless goitepresent with a rock-hard, fixed and painless goiter.r.

56. Manifestations of Hypothyroid andManifestations of Hypothyroid and
Hyperthyroid StatesHyperthyroid States
Level of Organization Hypothyroidism Hyperthyroidism
Basal metabolic rate Decreased Increased
Sensitivity to
catecholamines
Decreased Increased
General features
Myxedematous features
Deep voice
Impaired growth (child)
Exophthalmos
Lid lag
Decreased blinking
Blood cholesterol levels Increased Decreased
General behavior
Mental retardation (infant)
Mental and physical sluggishness
Somnolence
Restlessness, irritability, anxiety
Hyperkinesis
Wakefulness
Cardiovascular function
Decreased cardiac output
Bradycardia
Increased cardiac output
Tachycardia and palpitations
Gastrointestinal function
Constipation
Decreased appetite
Diarrhea
Increased appetite
Respiratory function Hypoventilation Dyspnea
Muscle tone and reflexes
Decreased Increased, with tremor and fibrillatory
twitching
Temperature tolerance Cold intolerance Heat intolerance
Skin and hair
Decreased sweating
Coarse and dry skin and hair
Increased sweating
Thin and silky skin and hair

57. The Parathyroid GlandsThe Parathyroid Glands
Four glandsFour glands in posterior capsule of thyroid
• Secrete parathyroid hormoneparathyroid hormone (PTH)
• Works with calcitonin to regulate calciumregulate calcium
metabolismmetabolism
• If this gland is not
working properly,
your nerves and
muscles will not
function properly
either due to
calcium deficiency.

58. Parathyroid glandsParathyroid glands

59. Parathyroid HormoneParathyroid Hormone
1. Parathyroid hormone (PTH) increases blood
calcium ion concentration and decreases phosphate
ion concentration.
2. PTH stimulates bone resorption by osteoclasts,
which releases calcium into the blood.
3. PTH also influences the kidneys to conserve
calcium and causes increased absorption of calcium
in the intestines.
4. A negative feedback mechanism involving blood
calcium levels regulates release of PTH.
CalcitoninCalcitonin and PTHPTH exert opposite effects in
regulating calcium ion levels in the blood.

63. Calcium MetabolismCalcium Metabolism
Calcium balance requiresCalcium balance requires
• Calcitriol (dihydroxycholecalciferol)Calcitriol (dihydroxycholecalciferol)
• Produced by modifying vitamin D in liver then inProduced by modifying vitamin D in liver then in
kidneykidney
• Parathyroid hormoneParathyroid hormone
• CalcitoninCalcitonin
Disorders 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)

64. HYPOPARATHYROIDISMHYPOPARATHYROIDISM
 Surgically inducedSurgically induced
 Congenital absenceCongenital absence
 Familial hypothyroidismFamilial hypothyroidism
 Associated with chronic mucocutaneousAssociated with chronic mucocutaneous
candidiasis and primary adrenal insufficiencycandidiasis and primary adrenal insufficiency
 Known asKnown as autoimmune polyendocrineautoimmune polyendocrine
syndrome type Isyndrome type I (APS I)(APS I)
 Mutations in theMutations in the autoimmune regulatorautoimmune regulator
(AIRE) gene(AIRE) gene
 Idiopathic hypothyroidismIdiopathic hypothyroidism

65. HYPOPARATHYROIDISMHYPOPARATHYROIDISM
• Clinical presentationsClinical presentations
• Tetany – neuromuscular irritability
• Mental status changes emotional
instability, anxiety, and depression,
confusional states, hallucinations and
psychosis
• Intracranial manifestations – calcification
of the basal ganglia, parkinson-like
movement disorders, increase ICP
(intracranial pressure)
• Ocular disease – cataract formation
• CV manifestations prolongation of QT
interval
• Dental abnormalities – dental hypoplasia,
failure of dental eruption, defective

67. HYPERPARATHYROIDISMHYPERPARATHYROIDISM
 INCREASED PTH PRODUCTIONINCREASED PTH PRODUCTION
 HYPERCALCEMIAHYPERCALCEMIA
 HYPOPHOSPHATEMIAHYPOPHOSPHATEMIA
 PRIMARY –PRIMARY – TUMOR ORTUMOR OR
HYPERPLASIA OF THE PARATHYROIDHYPERPLASIA OF THE PARATHYROID
GLANDGLAND
 SECONDARY –SECONDARY – COMPENSATORYCOMPENSATORY
OVERSECRETION OF PTH IN RESPONSEOVERSECRETION OF PTH IN RESPONSE
TO HYPOCALCEMIA FROM:TO HYPOCALCEMIA FROM:
 CHRONIC RENAL DSECHRONIC RENAL DSE
 RICKETSRICKETS
 MALABSORPTION SYNDROMEMALABSORPTION SYNDROME
 OSTEOMALACIAOSTEOMALACIA

69. HYPERPARATHYROIDISMHYPERPARATHYROIDISM
S/SX:S/SX:
BONE PAIN : ESP. THE BACK,BONE PAIN : ESP. THE BACK,
PATHOLOGIC FRUCTURESPATHOLOGIC FRUCTURES
 TUBULAR CALCIUMTUBULAR CALCIUM
DEPOSITS - KIDNEY STONES,DEPOSITS - KIDNEY STONES,
RENAL COLIC, POLYURIA,RENAL COLIC, POLYURIA,
POLYDIPSIAPOLYDIPSIA
 MUSCLE WEAKNESSMUSCLE WEAKNESS
 PERSONALITY CX,PERSONALITY CX,
DEPRESSIONDEPRESSION
 CARDIAC ARRHYTHMIAS,CARDIAC ARRHYTHMIAS,
HPNHPN
XRAY:XRAY: BONEBONE
DEMINERALIZATIONDEMINERALIZATION

70. 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 metatarsal
bones, and variable mental deficitsbones, and variable mental deficits
 Hypocalcemia, hyperphosphatemia, and elevatedHypocalcemia, hyperphosphatemia, and elevated
circulating PTHcirculating PTH
 TSH resistance is mild; LH/FSH resistance manifests asTSH resistance is mild; LH/FSH resistance manifests as
hypogonadotrophic 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 without
accompanying multihormonal resistanceaccompanying multihormonal resistance
Normal serum calcium, phosphate, and PTHNormal serum calcium, phosphate, and PTH

72. PHYSIOLOGIC BASIS OF MALE REPRODUCTIVEPHYSIOLOGIC BASIS OF MALE REPRODUCTIVE
FUNCTION AND THEIR DISORDERSFUNCTION AND THEIR DISORDERS
The male sex hormones are calledThe male sex hormones are called androgensandrogens.. TheThe
testes secrete several male sex hormones,testes secrete several male sex hormones,
includingincluding testosterone,testosterone, dihydrotestosteronedihydrotestosterone, and, and
androstenedioneandrostenedione..
TestosteroneTestosterone, which is the most abundant of, which is the most abundant of
these hormones, is considered the main testicularthese hormones, is considered the main testicular
hormone. Thehormone. The adrenal cortex also producesadrenal cortex also produces
androgensandrogens, 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 those
produced in the testes. Theproduced in the testes. The testes also secretetestes also secrete
small quantities of estradiol and estronesmall quantities of estradiol and estrone. The. The
male 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 androgens
result fromresult from increased protein synthesis in target tissuesincreased protein synthesis in target tissues.. Androgens functionAndrogens function
asas anabolic agentsanabolic agents in males and femalesin males and females to promote metabolism andto promote metabolism and
musculoskeletal growthmusculoskeletal growth.. TestosteroneTestosterone and theand the androgensandrogens have a great effecthave a great effect
on the developmenton the development of increasing musculature during puberty, withof increasing musculature during puberty, with boysboys
averaging approximately 50% more of an increase inaveraging approximately 50% more of an increase in muscle mass than domuscle mass than do
girlsgirls..

74. 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 despite
unprotected intercourse for a period ofunprotected intercourse for a period of more than 12 monthsmore than 12 months. About. About 15%15% of allof all
couplescouples 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 about
half 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 often
neglected, mainly because of the high pregnancy rates that can be achieved byneglected, mainly because of the high pregnancy rates that can be achieved by
assisted reproductive techniques (ART). This practice is unfortunate since maleassisted reproductive techniques (ART). This practice is unfortunate since male
infertility can often be cured, sparing the female partner the extensive treatmentinfertility can often be cured, sparing the female partner the extensive treatment
and cost of ART. Furthermore, evidence suggests that ART procedures can beand cost of ART. Furthermore, evidence suggests that ART procedures can be
associated with increased risks for both mother and child. Finally, neglecting toassociated with increased risks for both mother and child. Finally, neglecting to
examine the infertile man properly risks overlooking serious conditions such asexamine the infertile man properly risks overlooking serious conditions such as
testicular 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 of
seminal 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 semen
near the female's cervix;near the female's cervix;
 (6) the spermatozoa must be able to penetrate the cervical mucus and(6) the spermatozoa must be able to penetrate the cervical mucus and
reach the uterine tubes;reach the uterine tubes;
 (7) the spermatozoa must undergo capacitation and the acrosome(7) the spermatozoa must undergo capacitation and the acrosome
reaction, 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.

75. Causes of Testicular AtrophyCauses of Testicular Atrophy
 TraumaTrauma
 Testicular torsionTesticular torsion
 HypopituitarismHypopituitarism
 CryptorchidismCryptorchidism
 Klinefelter's syndrome (47,XXY)Klinefelter's syndrome (47,XXY)
 Alcoholism and cirrhosisInfection (eg, mumpsAlcoholism and cirrhosisInfection (eg, mumps
orchitis, 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 prostatic
cancer)cancer)

76. Cigarette smokingCigarette smoking
 Cigarette smokingCigarette smoking has been associated with an overall reduction inhas been associated with an overall reduction in
semen quality, andsemen quality, and specifically aspecifically a reduction in sperm countreduction in sperm count andand motilitymotility
and 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 semen
quality 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 remains
controversial 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 partner
can affect female fertility. There is, however, some evidence thatcan affect female fertility. There is, however, some evidence that
maternal smoking may be related to decreased sperm counts in thematernal smoking may be related to decreased sperm counts in the
offspring. Finally, the risk of developing erectile dysfunction is almostoffspring. Finally, the risk of developing erectile dysfunction is almost
doubled for smokers compared to nonsmokers, and this can limit maledoubled for smokers compared to nonsmokers, and this can limit male
fertility.fertility.
 Testicular temperaturesTesticular temperatures are approximatelyare approximately 2 °C below core body2 °C below core body
temperature and spermatogenesis is dependent on this coolertemperature and spermatogenesis is dependent on this cooler
temperaturetemperature.. Factors such as clothing, lifestyle, season, and fever canFactors such as clothing, lifestyle, season, and fever can
cause 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..

77. Semen Analysis: Normal Values andSemen Analysis: Normal Values and
Definitions.Definitions.
Characteristic Reference Standard
Ejaculate volume > 2 mL
pH 7.2–7.8
Sperm concentration 20 million/mL
Sperm count 40 million/mL
Sperm motility 50% with normal motility
Sperm morphology 15%1
–30% with normal forms
Term Definition
Normospermia Normal ejaculate (as defined by reference standards
above)
Oligozoospermia Sperm concentration < 20 million/mL
Asthenozoospermia < 50% of spermatozoa with forward progression of
< 25% with rapid progression
Azoospermia No spermatozoa in ejaculate

78. STRUCTURE AND FUNCTION OF THE FEMALESTRUCTURE AND FUNCTION OF THE FEMALE
REPRODUCTIVE SYSTEMREPRODUCTIVE SYSTEM
► Ovarian hormonesOvarian hormones are secretedare secreted
in a cyclic pattern as a result ofin a cyclic pattern as a result of
the interaction between thethe interaction between the
hypothalamic gonadotrophichypothalamic gonadotrophic
releasing hormone (GnRH)releasing hormone (GnRH) andand
thethe pituitary gonadotropicpituitary gonadotropic
hormoneshormones,, follicle stimulatingfollicle stimulating
hormonehormone (FSH), and(FSH), and luteinizingluteinizing
hormonehormone (LH). The secretion of(LH). The secretion of
LH and FSH is stimulated byLH and FSH is stimulated by
GnRH 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 internal
genital organs. The external sex organs of the female are referred to asgenital organs. The external sex organs of the female are referred to as
the 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 located
within the pelvic cavitywithin the pelvic cavity

79. Hypothalamic-pituitary feedback control ofHypothalamic-pituitary feedback control of
estrogen 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.

80. Actions of EstrogensActions of Estrogens
General Function Specific Actions
Growth andGrowth and
developmentdevelopment
• Reproductive organs
• Skeleton
Stimulate development of vagina, uterus, and fallopian tubes in
utero and of secondary sex characteristics during puberty
Accelerate growth of long bones and closure of epiphyses at
puberty
Reproductive processesReproductive processes
Ovulation
Fertilization
Implantation
• Vagina
• Cervix
• Breasts
Promote growth of ovarian follicles
Alter the cervical secretions to favor survival and transport of
sperm
Promote motility of sperm within the fallopian tubes by
decreasing mucus viscosity
Promote development of endometrial lining in the event of
pregnancy
Proliferate and cornify vaginal mucosa
Increase mucus consistency
Stimulate stromal development and ductal growth
General metabolicGeneral metabolic
effectseffects
Bone resorption
Plasma proteins
Lipoproteins
Decrease rate of bone resorption
Increase production of thyroid and other binding globulins
Increase high-density and slightly decrease low-density
lipoproteins

82. Dysfunctional MenstrualDysfunctional Menstrual
CyclesCycles
 Normal menstrual function results fromNormal menstrual function results from
interactions among the central nervous system,interactions among the central nervous system,
hypothalamus, anterior pituitary, ovaries, andhypothalamus, anterior pituitary, ovaries, and
associated target tissues.associated target tissues.
 Although each part of the system is essential toAlthough each part of the system is essential to
normal function, the ovaries are primarilynormal function, the ovaries are primarily
responsible for controlling the cyclic changesresponsible for controlling the cyclic changes
and 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 reproductive
years, menstrual bleeding occurs every 25 toyears, menstrual bleeding occurs every 25 to
35 days, with a median length of 28 days.35 days, with a median length of 28 days.

83. Symptoms of PremenstrualSymptoms of Premenstrual
Syndrome (PMS) by SystemSyndrome (PMS) by System
Body System Symptoms
CerebralCerebral
Irritability, anxiety, nervousness, fatigue, and
exhaustion; increased physical and mental
activity; lability; crying spells; depressions;
inability to concentrate
GastrointestinalGastrointestinal
Craving for sweets or salts, lower abdominal pain,
bloating, nausea, vomiting, diarrhea,
constipation
VascularVascular Headache, edema, weakness, or fainting
ReproductiveReproductive
Swelling and tenderness of the breasts, pelvic
congestion, ovarian pain, altered libido
NeuromuscularNeuromuscular
Trembling of the extremities, changes in
coordination, clumsiness, backache, leg aches
GeneralGeneral Weight gain, insomnia, dizziness, acne

84. Literature:Literature:
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