Prepared by MD, PhD, Associate Professor of pathophysiology department of IFNMU, Ukraine

1. By MD, PhD, Associate ProfessorBy MD, PhD, Associate Professor

2. CONTENTCONTENT
1.1. Pituitary glandPituitary gland.. Hyperfunction andHyperfunction and
hypofunction, Etiology,hypofunction, Etiology,
pathogenesis, and manifestations.pathogenesis, and manifestations.
2.2. Adrenal gland, etiology,Adrenal gland, etiology,
pathogenesis, manifestations ofpathogenesis, manifestations of
hyperfunction and hypofunctionhyperfunction and hypofunction..
3.3. Thyroid gland. Hyperfunction andThyroid gland. Hyperfunction and
hypofunction, Etiology,hypofunction, Etiology,
pathogenesis, and clinicalpathogenesis, and clinical
manifestations.manifestations.
4.4. Parathyroid glands.Parathyroid glands.

3. Actuality of the lecture.Actuality of the lecture.
 The endocrine system is involved in all of the integrative aspects ofThe endocrine system is involved in all of the integrative aspects of
life, including growth, sex differentiation, metabolism, andlife, including growth, sex differentiation, metabolism, and
adaptation to an ever-changing environment. This chapter focusesadaptation to an ever-changing environment. This chapter focuses
on general aspects of endocrine function, organization of theon general aspects of endocrine function, organization of the
endocrine system, hormone receptors and hormone actions, andendocrine system, hormone receptors and hormone actions, and
regulation of hormone levels.regulation of hormone levels.
 The endocrine system uses chemical substances calledThe endocrine system uses chemical substances called hormoneshormones
as a means of regulating and integrating body functions. Theas a means of regulating and integrating body functions. The
endocrine system participates in the regulation of digestion, use,endocrine system participates in the regulation of digestion, use,
and storage of nutrients; growth and development; electrolyte andand storage of nutrients; growth and development; electrolyte and
water metabolism; and reproductive functions. Although thewater metabolism; and reproductive functions. Although the
endocrine system once was thought to consist solely of discreteendocrine system once was thought to consist solely of discrete
endocrine glands, it is now known that a number of other tissuesendocrine glands, it is now known that a number of other tissues
release chemical messengers that modulate body processes.release chemical messengers that modulate body processes.
 The functions of the endocrine system are closely linked with thoseThe functions of the endocrine system are closely linked with those
of the nervous system and the immune system.of the nervous system and the immune system.

5. Hormones chemical nature:Hormones chemical nature:
 аа)) steroid hormonessteroid hormones ((mineralmineral – and– and
glucocorticoidsglucocorticoids, female and male, female and male
sexual hormones);sexual hormones);
 bb)) derivativesderivatives of aminoacidsof aminoacids
((thyreoidthyreoid hormones,hormones, catecholaminescatecholamines,,
melatoninemelatonine););
 cc)) protein peptideprotein peptide hormoneshormones
((releasingreleasing-hormones,-hormones, vasopressinvasopressin,,
oxytocinoxytocin, hormones, hormones ofof
adenohypophysis,adenohypophysis,
insuline, glucagone, parathyrin,insuline, glucagone, parathyrin,
calcitonine).calcitonine).
Somatostatin

6. Lipid-solubleLipid-soluble hormones (steroidhormones (steroid
hormones)hormones) pass easilypass easily throughthrough
cell membranes, whilecell membranes, while water-water-
solublesoluble hormones (polypeptideshormones (polypeptides
and amines)and amines) do notdo not
The solubility of a hormoneThe solubility of a hormone
correlates with the location ofcorrelates with the location of
receptors inside or on thereceptors inside or on the
surface of target cellssurface of target cells
• Water-solubleWater-soluble hormones are secretedhormones are secreted
byby exocytosisexocytosis, travel freely in the, travel freely in the
bloodstreambloodstream, and bind to cell-surface, and bind to cell-surface
receptorsreceptors
• Lipid-solubleLipid-soluble hormones diffusehormones diffuse
acrossacross cell membranescell membranes, travel in the, travel in the
bloodstream bound to transportbloodstream bound to transport
proteins, and diffuse through theproteins, and diffuse through the
membrane of target cellsmembrane of target cells
Signal
receptor
TARGET
CELL
Signal receptor
Transport
protein
Water-
soluble
hormone
Fat-soluble
hormone
Gene
regulation
Cytoplasmic
response
Gene
regulation
Cytoplasmic
response
OR
Signal receptor
Water-
soluble
hormone
Fat-soluble
hormone
TARGET
CELL
NUCLEUS(a) (b)
Transport
protein
Signal
receptor
(a)
NUCLEUS
(b)

7. Glycogen
deposits
β receptor
Vessel
dilates.
Epinephrine
(a) Liver cell
Epinephrine
β receptor
Glycogen
breaks down
and glucose
is released.
(b) Skeletal muscle
blood vessel
Same receptors but different
intracellular proteins (not shown)
Epinephrine
β receptor
Different receptors
Epinephrine
α receptor
Vessel
constricts.
(c) Intestinal blood
vessel

8. Etiology of endocrine disordersEtiology of endocrine disorders
 Reasons and kinds of endocrine disorders.Reasons and kinds of endocrine disorders. Among numerousAmong numerous
ethiological factors of endocrine disorderss it is possible to selectethiological factors of endocrine disorderss it is possible to select
the following main ones:the following main ones:
 a mental trauma,a mental trauma,
 necrosis,necrosis,
 tumour,tumour,
 inflamatory process,inflamatory process,
 bacterial and viral infections,bacterial and viral infections,
 intoxications,intoxications,
 local disorders of blood circulation (hemorrhage, thrombosis),local disorders of blood circulation (hemorrhage, thrombosis),
 alimentary disorders (deficiency of iodine and cobalt in food andalimentary disorders (deficiency of iodine and cobalt in food and
drinking water, redundant consumption of carbohydrates),drinking water, redundant consumption of carbohydrates),
 ionising radiation,ionising radiation,
 inherent chromosome and gene defects.inherent chromosome and gene defects.

9. There are three variants ofThere are three variants of
endocrine functions disorders:endocrine functions disorders:
1. HyperfunctionHyperfunction of endocrine glands
2. HypofunctionHypofunction of endocrine glands
3. DisfunctionDisfunction of endocrine glands
DisfunctionDisfunction is characterized by
different changes of hormonal
production and production physiologic
active precursors of their biosynthesis
in the same endocrine gland or
synthesis and entering in blood of
atypical hormonal products.

10. Pathogenesis of endocrinePathogenesis of endocrine
disordersdisorders
• The mechanisms of function
disorders of an endocrine gland
can be various depending on
localization and character of
process. In pathogenesis of
endocrine disorders it is possible to
select three main mechanismsmechanisms:
1) Disorders of regulation of endocrine
glands – disregulatory disorders;
2) Disorders of biosynthesis of
hormones and their secretion –
glandular disorders;
3) Disorders of the transport, reception
and metabolism of hormones –
peripheral disorders.

12. Control of hormone releaseControl of hormone release
1. Negative feedback ["stimulatory-inhibitory"]
2. Positive feedback ["stimulatory-stimulatory"]
3. Endocrine gland stimuli: humoral stimuli, neural stimuli, hormonal stimuli

14. This gland makes me wake up in theThis gland makes me wake up in the
morning and ready to go!morning and ready to go!
Pineal
Gland
melatonin
"The 3rd Eye""The 3rd Eye"
Midline location above the quadrigeminal plate

15. Production: sperior cervical
sympathetic ganglia stimulates
receptors on pinealocytes
causes release of melatonin into
spinal fluid and blood
Functions: 1) Released at night &
important in sleep/moods and
circadian rhythms;
•2) Used in the treatment of sleep
and mood disorders
1. Visual disturbances
• Paralysis of upward conjugate gaze (Parinaud's syndrome)
2. Obstructive hydrocephalus
• Due to compression of the aqueduct of Sylvius in the third ventricle
Pineal gland disorders
Dystrophic calcification of the
pineal gland begins in childhood.
a. Useful in showing shifts due to
mass lesions in the brain.
b. Approximately 80% are calcified
between 70 and 80 years old.
Pineal tumors
a. Majority are germ cell tumors
resembling seminomas.
b. Minority of tumors are
teratomas.
CLINICAL FINDINGS

16. This glandThis gland
is called theis called the
“master gland”“master gland”
because itbecause it
secretes ninesecretes nine
hormoneshormones
many of whichmany of which
control othercontrol other
endocrineendocrine
glands byglands by
feedbackfeedback
control.control.
Pituitary GlandPituitary Gland

17. Tropic effects only:
FSH
LH
TSH
ACTH
Nontropic effects only:
Prolactin
MSH
Nontropic and tropic effects:
GH

18. Anterior
Pituitary
Posterior
pituitary Stimulates milk
ejection and uterine
contractions
Ovary and testisOxytocin
Conservation of
body water
KidneyAntidiuretic hormone
Control of reproductive
function
Ovary and testisFollicle stimulating
hormone
Control of reproductive
function
Ovary and testisLuteinizing hormone
Milk productionMammary glandProlactin
Stimulates secretion of
glucocorticoids
Adrenal gland cortexAdrenocorticotrophic
hormone
Stimulates secretion of
thyroid hormones
Thyroid glandThyroid stimulating
hormone
Promotes growth (indirectly),
control of protein, lipid and
carbohydrate metabolism
Liver, adipose tissueGrowth hormone
Major physiologic
effects
Major target organsHormone

19. Type ofType of
AdenomaAdenoma
SecretionSecretion StainingStaining PathologyPathology
CorticotrophicCorticotrophic
adenomasadenomas
SecreteSecrete adrenocotrophicadrenocotrophic
hormone (ACTH) andhormone (ACTH) and
ProopiomelanocortinProopiomelanocortin
(POCM)(POCM)
BasophilicBasophilic Cushing’s diseaseCushing’s disease
SomatotrophicSomatotrophic
adenomasadenomas
SecreteSecrete growth hormonegrowth hormone
(GH)(GH)
AcidophilicAcidophilic AcromegalyAcromegaly
(Gigantism)(Gigantism)
ThyrotrophicThyrotrophic
adenomas (rare)adenomas (rare)
SecretSecret thyroid stimulatingthyroid stimulating
hormone (TSH)hormone (TSH)
BasophilicBasophilic OccasionallyOccasionally
hyperthyroidismhyperthyroidism
usually does not causeusually does not cause
symptomssymptoms
GonadotrophicGonadotrophic
adenomasadenomas
SecreteSecrete luteinizing hormoneluteinizing hormone
(LH), follicle stimulating(LH), follicle stimulating
hormone (FSH)hormone (FSH)
BasophilicBasophilic Usually does notUsually does not
cause symptomscause symptoms
ProlactinomasProlactinomas SecretSecret prolactinprolactin AcidophilicAcidophilic Galactorrhea,Galactorrhea,
hypogonadism,hypogonadism,
amenorrhea,amenorrhea,
infertility andinfertility and
impotenceimpotence
Null cellsNull cells
adenomasadenomas
Do not secrete hormonesDo not secrete hormones May stain positiveMay stain positive
for synaptophysinfor synaptophysin

20. Disturbances of functions of hypophysis.
Hypofunction of adenohypophysis
(hypopituitaritism)
There are panhypopituitarity and partial hypopituitarityThere are panhypopituitarity and partial hypopituitarity

22. Panhypopituitarity – is the decrease ofPanhypopituitarity – is the decrease of
formation of all adenohypophysis hormonesformation of all adenohypophysis hormones
• The following clinical forms of panhypopituitarity are known:The following clinical forms of panhypopituitarity are known:
1) Hypophysar cachecsia of SimondsSimonds;
2) Afterbearing necrosis of hypophysis – syndrome of Schegansyndrome of Schegan;
3) Chromophobe hypophysis adenomas, i.e. tumors, which grow from chromophobe cells. For
want of it the tumour squeezes and damages glandular cells of adenohypophysis.
• The clinical manifestationsclinical manifestations of panhypopituitarity are connected with
deficiency of adenohypophysis hormones and disorders of activity of
peripheral endocrine glands (thyroid gland, cortex of adrenal, sexual
glands).
• The first symptomsfirst symptoms of lesion of adenohypophysis occur in damage of 70-
75% of gland tissue, and for development of complete picture of
panhypopituitarity destruction of 90-95 % of adenohypophysis is necessary.
• Vessels disordersVessels disorders in hypophysis and hypothalamus (most frequently
afterbearing longtime spasm of vessels of brain and hypophysis owing of
haemorrhage), trauma of the skull basis, tumour of hypophysis and
hypothalamus, inflammatory damage (tuberculosis,sepsis) of hypophysis,
inherent aplasia and hypoplasia can lead to development of
panhypopituitarity.
• The most frequently gonadotropic functiongonadotropic function of hypophysis and secretion of
STH is damaged with the consequent connection of nonsufficient secretion
of ТТH, ACTH and prolactine.

23. Hypophyseal
Simond’s
cachexia

24. Causes of HypopituitarismCauses of Hypopituitarism
Tumors and mass lesions — pituitary adenomas, cysts,
metastatic cancer, and other lesions: association with multipleassociation with multiple
endocrine neoplasia (MEN) I syndrome (include pituitaryendocrine neoplasia (MEN) I syndrome (include pituitary
adenoma, hyperparathyroidism, pancreatic tumor (Zollinger-adenoma, hyperparathyroidism, pancreatic tumor (Zollinger-
Ellison syndrome or insulinoma);Ellison syndrome or insulinoma);
Pituitary surgery or radiation
Infiltrative lesions and infections — hemochromatosis,
lymphocytic hypophysitis
Pituitary infarction — infarction of the pituitary gland after
substantial blood loss during childbirth (Sheehan’s syndrome)
Pituitary apoplexy — sudden hemorrhage into the pituitary
gland
Genetic diseases — rare congenital defects of one or more
pituitary hormones
Empty sella syndrome — an enlarged sella turcica that is
not entirely filled with pituitary tissue
Hypothalamic disorders — tumors and mass lesions
(e.g., craniopharyngiomas and metastatic malignancies),
hypothalamic radiation, infiltrative lesions (e.g., sarcoidosis),
trauma, infections

25. Partial hypopituitarityPartial hypopituitarity
is the disorder of
formation of separate
hormones
of adenohypophysis
(not all). The following
variants of partial
hypopituitarity are
described:
HypophysarHypophysar
nanismnanism
1) Hypophysar nanism
(dwarfishnessdwarfishness) - deficiency of STHSTH;
2) Secondary hypohonadism -
deficiency of FSH and LHFSH and LH;
3) Secondary hypothyrosisSecondary hypothyrosis -
deficiency of TTHTTH;
4) Secondary hypocorticismSecondary hypocorticism -
deficiency of ACTHACTH.

26. • The insufficiency of STHThe insufficiency of STH results to
development of hypophysar dwarfishness,
or nanism and appears by such disorders:
• 1) decrease of intensity of protein synthesisdecrease of intensity of protein synthesis
that leads to delay and stop of growth (more than
30% from average) and development of bones,
internal organs, muscles. The disorders of protein
synthesis in connective tissue results in loss of its
elasticity;
• 2) decrease of inhibiting action of STHdecrease of inhibiting action of STH on an
absorption of glucose with predominance of
insulinic effect and development of hypoglycemia;
• 3) fallout of fat mobilizingfallout of fat mobilizing action and tendency to
obesity.

27.  Children have delayed puberty;
 Adult females have secondary amenorrhea;
produces osteoporosis, hot flashes (lack of
estrogen), decreased libido;
 Males have impotence, due to decreased
libido from decreased testosterone;
Gonadotropin stimulation test:
 No significant increase of FSH/LH in
hypopituitarism
 Eventual increase of FSH/LH in hypothalamic
disease
Metyrapone test: stimulation test of pituitary
ACTH reserve; metyrapone inhibits
adrenal11-hydroxylase, which causes a
decrease in cortisol and a corresponding
increase in plasma ACTH (pituitary) and 11-
deoxycortisol (adrenal), which is proximal to
the enzyme block; in hypopituitarism, neither
ACTH or 11-deoxycortisol are increased

28.  Insufficiency of gonadotropic hormonesInsufficiency of gonadotropic hormones
results inresults in decrease of ability of Sertoli cellsdecrease of ability of Sertoli cells
toto accumulate androgensaccumulate androgens andand oppression ofoppression of
spermatogenesisspermatogenesis andand ability to impregnationability to impregnation
in menin men..
 In case ofIn case of defect of LGdefect of LG ((LuteinizingLuteinizing))
hormone the function ofhormone the function of Leidig’s cells isLeidig’s cells is
infringedinfringed, the formation of androgens ceases, the formation of androgens ceases
and develops eunuchoidism withand develops eunuchoidism with
preservation of partial ability topreservation of partial ability to
impregnation, as the process ofimpregnation, as the process of
spermatozoids maturing does not stop.spermatozoids maturing does not stop.

29. Decreased GH decreases synthesis and release of IGF-1
Children have growth delay; delayed fusion of epiphyses; bone growth
does not match the age of the child
Adults have hypoglycemia; decreased gluconeogenesis; loss of muscle
mass; increased adipose around waist
Arginine and sleep stimulation tests: no increase in GH or IGF-1;
normally, GH and IGF-1 are released at 5 a.m.
Secondary hypothyroidism: decreased serum
T4 and TSH
Cold intolerance, constipation, weakness
No increase in TSH after thyrotropin-releasing
factor (TRF) stimulation

31. Secondary hypocortisolism: decreased ACTH and cortisol
Hypoglycemia: decreased gluconeogenesis
Hyponatremia: mild syndrome of inappropriate antidiuretic hormone
(SIADH) →→ loss of inhibitory effect of cortisol on ADH;
Weakness, fatigue
Short ACTH stimulation test: no increase in serum cortisol over
decreased baseline levels
Prolonged ACTH stimulation test: eventual increase in cortisol over the
decreased baseline value once the adrenal gland is restimulated
Metyrapone test: no increase in ACTH or 11-deoxycorticosterone

32. By producing too much of one or more hormonesBy producing too much of one or more hormones
• Adrenocorticotropic hormoneAdrenocorticotropic hormone::
– causes weight gain (particularly in the body’s trunk, notcauses weight gain (particularly in the body’s trunk, not
the legs or arms)the legs or arms)
– high blood pressurehigh blood pressure
– high blood sugarhigh blood sugar
– brittle bonesbrittle bones
– emotional changesemotional changes
– stretch marks on the skinstretch marks on the skin
– easy bruising.easy bruising.
The insufficiency of ACTH leads to secondary partialThe insufficiency of ACTH leads to secondary partial
insufficiency of adrenal cortex.insufficiency of adrenal cortex.
The glucocorticoid function suffers mainly.The glucocorticoid function suffers mainly.
Mineralocorticoid function practically does not varyMineralocorticoid function practically does not vary

33. Hyperfunction ofHyperfunction of
adenohypophysisadenohypophysis
(hyperpituitarism)(hyperpituitarism)
 The main reasons ofThe main reasons of
hyperpituitarism development arehyperpituitarism development are
the benign tumours – adenomas of endocrine cells.the benign tumours – adenomas of endocrine cells.
 There areThere are twotwo groups of adenomasgroups of adenomas..
 1.1. Eosinophilic adenomaEosinophilic adenoma, develops from acidophilic cells, develops from acidophilic cells
of adenohypophysis forming STH. Clinicallyof adenohypophysis forming STH. Clinically
hyperproduction of STH appears byhyperproduction of STH appears by giantismgiantism ((if adenomaif adenoma
develops in childrendevelops in children and young people before closing ofand young people before closing of
epiphysar cartilages) andepiphysar cartilages) and acromegaliaacromegalia ((in adultin adult). Giantism). Giantism
is characterized by the proportional increase of all bodyis characterized by the proportional increase of all body
components.components.

34. GigantismGigantism

35. Jane Bunford 2.41mJane Bunford 2.41m
Zeng Jinlian 249 smZeng Jinlian 249 smYao Defen 2.34Yao Defen 2.34

36. • By producing too much of one or more
hormones
• Growth hormone: causes
ACROMEGALY
– a syndrome that includes:
• excessive growth of soft tissues
and bones
• high blood sugar
• high blood pressure
• heart disease
• sleep apnea
• excess snoring
• carpal tunnel syndrome
• pain symptoms (including
headache).
• Acromegaly appears by increased
growth of hands, legs, chin, nose, tongue,
liver, kyphoscoliosis. Besides
that increased metabolic activity of STH
-hyperglycemia, insulin resistanse, even
to development of metahypophysar
diabetes, fatty infiltration of liver develop.

40. BITEMPORAL
HEMIANOPSIA

41. Usually the bitemporal hemianopsia isUsually the bitemporal hemianopsia is
NOT perfectly symmeetrical. Why?NOT perfectly symmeetrical. Why?
Because pituitary tumors are under noBecause pituitary tumors are under no
law to grow perfectly midline.law to grow perfectly midline.

43. • 2. Basophilic adenomaBasophilic adenoma, grows
from basophilic cells of
adenohypophysis which more often
produce ACTH. During this the
Itsenko-CushingItsenko-Cushing disease
develops. It is characterized by:
• а) secondary hypercorticism;
• b) strengthened pigmentation of
skin.
• There are tumors which produce
other hormones of
adenohypophysis less often: TTH,
gonadotropic hormones, prolactin,
MSH.
• The increased level of ACTH during
this disease is combined with
increase of level of other products
of proopiomelanocortin. BASOPHILIC ADENOMA OF HYPOPHYSISBASOPHILIC ADENOMA OF HYPOPHYSIS

45. Hyperfunction of neurohypophysisHyperfunction of neurohypophysis
• Leads to redundant production vasopressin andLeads to redundant production vasopressin and
oxytocin. Their main effects:oxytocin. Their main effects:
• VasopressineVasopressine (antidiuretic hormone) renders the
following influence through V1 and V2 receptors:
1) Acting on tubulus contortus distalis and collective
tubules of kidneys, strengthens reabsorption of
water;
2) Causes contraction of smooth muscles of blood
vessels;
3) Strengthens glycogenolysis and gluconeogenesis in
liver;
4) Stimulates consolidation of memory traces and
mobilization of saved information (hormone of
memory);
5) Endogenic analgetic (depresses pain).

47. • OxytocinOxytocin renders the following functional
influences:
1) Stimulates secretion of milk (lactation) causing
contraction of myoepithelial cells of small-sized
ducts of mammary glands;
2) Initiates and strengthens contractions of uterus of
pregnant woman;
3) Worsens storing and mobilization of information
(amnestic hormone).
• Redundant secretion of vasopressin arises in
tumors of different tissues forming vasopressin,
and also in disorders of hypothalamic endocrine
function regulation. Its main manifestation is
hypervolemia leading to development of constant
arterial hypertension.

48. GG
AA
LL
AA
CC
TT
OO
RR
RR
HH
EE
AA
Prolactinomas are the most common type of pituitary adenoma.
Lactotroph cells secrete prolactin, which results in hyperprolactinemia.
Clinical features include galactorrhea, amenorrhea, and infertility, or
decreased libido and impotence.

49. Hypofunction ofHypofunction of
neurohypophysisneurohypophysis
 Insufficient production of vasopressin results toInsufficient production of vasopressin results to
development ofdevelopment of diabetes insipidusdiabetes insipidus..
There are two pathogenetic variants:There are two pathogenetic variants:
 central (neurogenic)central (neurogenic) during which will a little quantity ofduring which will a little quantity of
vasopressine, is formed andvasopressine, is formed and
 nephrogenicnephrogenic duringduring which the sensitivity of epithelialwhich the sensitivity of epithelial
cells receptors of distal nephron parts and collectivecells receptors of distal nephron parts and collective
tubules to vasopressin action (absence or a little quantitytubules to vasopressin action (absence or a little quantity
receptors) is reduced.receptors) is reduced.
 TheThe decreasing of water reabsorptiondecreasing of water reabsorption in kidneys resultsin kidneys results
toto poliuriapoliuria and decreasing of circulatting blood volumeand decreasing of circulatting blood volume
((hypovolemiahypovolemia),), falling of arterial pressurefalling of arterial pressure andand hypoxiahypoxia..
 TheThe decreasing of oxytocindecreasing of oxytocin production appears byproduction appears by
disorders of lactation, weakness of labor activitydisorders of lactation, weakness of labor activity..

51. Adrenal cortex
- secretes several classes of steroid hormones (glucocorticoids and
mineralocorticoids)
- with three concentric zones of cells that differ in the major steroid
hormones they secrete.
Adrenal medulla
- source of the catecholamines epinephrine and norepinephrine.
- chromaffin cell is the principle cell type.
- The medulla is richly innervated by preganglionic sympathetic fibers
and is, in essence, an extension of the sympathetic nervous system.

53. Effects of
mineralocorticoids:
Effects of
glucocorticoids:
1. Retention of sodium
ions and water by
kidneys
2. Increased blood
volume and blood
pressure
2. Possible suppression of
immune system
1. Proteins and fats broken down
and converted to glucose, leading
to increased blood glucose
Adrenal
gland
Kidney
Adrenal cortex
Adrenal cortex
Glucocorticoids –
glucose from noncarb
sources, such as
muscles
Mineralocorticoids
(aldosterone) –
induces kidneys to
reabsorb water and
salts
Both of these deal with
long-term stress

54. Actions of CortisolActions of Cortisol
Major InfluenceMajor Influence Effect on BodyEffect on Body
Glucose metabolismGlucose metabolism
Stimulates gluconeogenesisStimulates gluconeogenesis
Decreases glucose use by the tissuesDecreases glucose use by the tissues
Protein metabolismProtein metabolism
Increases breakdown of proteinsIncreases breakdown of proteins
Increases plasma protein levelsIncreases plasma protein levels
Fat metabolismFat metabolism
Increases mobilization of fatty acidsIncreases mobilization of fatty acids
Increases use of fatty acidsIncreases use of fatty acids
Anti-inflammatory actionAnti-inflammatory action
(pharmacologic levels)(pharmacologic levels)
Stabilizes lysosomal membranes of the inflammatory cells, preventingStabilizes lysosomal membranes of the inflammatory cells, preventing
the release of inflammatory mediatorsthe release of inflammatory mediators
Decreases capillary permeability to prevent inflammatory edemaDecreases capillary permeability to prevent inflammatory edema
Depresses phagocytosis by white blood cells to reduce the release ofDepresses phagocytosis by white blood cells to reduce the release of
inflammatory mediatorsinflammatory mediators
Suppresses the immune responseSuppresses the immune response
• Causes atrophy of lymphoid tissueCauses atrophy of lymphoid tissue
• Decreases eosinophilsDecreases eosinophils
• Decreases antibody formationDecreases antibody formation
• Decreases the development of cell-mediated immunityDecreases the development of cell-mediated immunity
Reduces feverReduces fever
Inhibits fibroblast activityInhibits fibroblast activity
Psychic effectPsychic effect May contribute to emotional instabilityMay contribute to emotional instability
Permissive effectPermissive effect
Facilitates the response of the tissues to humoral and neural influences,Facilitates the response of the tissues to humoral and neural influences,
such as that of the catecholamines, during trauma and extreme stresssuch as that of the catecholamines, during trauma and extreme stress

55. Disorders of adrenal gland functionDisorders of adrenal gland function
 The most frequently there are followingThe most frequently there are following
manifestations:manifestations:
1)1) HypofunctionHypofunction of adrenal cortex - hypocorticismof adrenal cortex - hypocorticism
Addison diseaseAddison disease ;;
2)2) HyperfunctionHyperfunction of fascicular zone - syndrome ofof fascicular zone - syndrome of
Itsenko-CushingItsenko-Cushing –– Hypersecretion of cortisolHypersecretion of cortisol;;
3)3) HyperfunctionHyperfunction of glomerulose zone –of glomerulose zone –
hyperaldosteronism –hyperaldosteronism – Hyperfunction of adrenalHyperfunction of adrenal
cortex resulting in excess secretion of aldosteronecortex resulting in excess secretion of aldosterone;;
4)4) DysfunctionDysfunction of adrenal cortex - adrenogenitalof adrenal cortex - adrenogenital
syndromesyndrome

56. Insufficiency of adrenal cortex
• According to etiology there are primary and secondary
kinds of adrenal cortex insufficiency.
• Primary insufficiencyPrimary insufficiency arises as a result of adrenals injury,
• secondarysecondary is connected with the defeat of hypotalamus
(deficiency of corticoliberin), or with hypofunction of
adenohypophysis (deficiency of ACTH).
• Insufficiency of corticosteroids can be totaltotal when the
operation of all hormones drops out, and partialpartial fallout of
activity of one adrenal hormone.
• Insufficiency of adrenal cortex can be acuteacute and chronicchronic.
• Examples ofExamples of acute insufficiencyacute insufficiency areare:
а) state after removal of adrenals;
b) hemorrhage in adrenals which arises during sepsis,
meningococci infection (syndrome Waterhouse-Friderixan);
c) syndrome of cancellation of glucocorticoides preparations.
• Fast falling of the adrenals function causes development of
collaps and the patients can die during the first day.

57. • TheThe chronic insufficiencychronic insufficiency of adrenalsof adrenals
cortex is characterized forcortex is characterized for Addison’sAddison’s
diseasedisease (bronzed disease).(bronzed disease).
• The most often reasons of it are:The most often reasons of it are:
а) tuberculose destruction of adrenals;
b) autoimmune process.
Tuberculose of
adrenal gland.
Adison’s
disease

59. Skin hyperpigmentation at case of Adison’s disease

61. ІІ. Manifestation, connected with the falling of. Manifestation, connected with the falling of
mineralocorticoids functions of adrenal cortex:mineralocorticoids functions of adrenal cortex:
• 1) dehydration develops owing to loss of sodium ionsloss of sodium ions (decreases
rearbsortion) with the loss of water (poliuria);
• 2) arterial hypotension is stipulated by decrease of circulating
blood volume;
• 3) hemoconcentration (condensation of blood) is connected with
liquid loss, results to disorders of microcirculation and hypoxiadisorders of microcirculation and hypoxia;
• 4) decreasing of kidney blood circulation is stipulated by
increase of arterial pressure with disturbances of glomerulardisturbances of glomerular
filtrationfiltration and development of intoxicationintoxication (nitrogenemia);
• 5) hyperpotassiumemia is stipulated by decrease of canalesdecrease of canales
secretion of potassium ionssecretion of potassium ions and their output from the damaged
cells. It causes disorders of function of arousing tissues;
• 6) distal canales acidosis. It is connected with disorders ofdisorders of
acidogenesisacidogenesis in distal nephron canales;
• 7) gastro-intestinal disorders (nausea, vomiting, diarrhea). Loss
of sodium (osmotic diarrhea) and intoxication have significant
meaning. This disorders without appropriate correction result to
death.

62. ІІІІ. Manifestations stipulated by disorders of. Manifestations stipulated by disorders of
glucocorticoid function of adrenals. To suchglucocorticoid function of adrenals. To such
manifestations concern:manifestations concern:
• 1) hypoglycemia which results to starvation;
• 2) arterial hypotension (permissive reaction on catecholamines);
• 3) decrease reaction of fat tissue on lipotrophic stimules;
• 4) decrease resistance of an organism on action of different
pathogenic factors;
• 5) decrease of ability to remove water during water load (water
poisoning);
• 6) muscular weakness and fast tiredness;
• 7) emotional disorders (depression);
• 8) delay of growth and development of children;
• 9) sensor disorders - loss of ability to distinguish separate shades
gustatory osmotic acoustical sensations;
• 10) distress-syndrome of a newborn (hyalinic membranosis). It is
stipulated by disorders of surfactant formation in lungs owing to
what lungs are not straightened after birth of a child.

63. Increase of adrenals cortex functionIncrease of adrenals cortex function
• HyperaldosteronismHyperaldosteronism.. Arises during hyperfunction of glomerular zone of
adrenals cortex, which produce mineralcorticoides.
There are primaryprimary and secondary hyperaldosteronismsecondary hyperaldosteronism.
• Primary hyperaldosteronismPrimary hyperaldosteronism (Conn syndromeConn syndrome) arises in adenoma of zone
glomerular, which secretes high quantity of aldosteron. Main manifestations of
this disease:
1) arterial hypertension. It is connected with increase of sodium contents in
blood and in wall of blood vessels, after what the sensitivity of their smooth
muscles to action of pressore factors, particularly catecholamines increases.
2) hypopotassiumaemia (result of hypersecretion of potassium ions in
canaliculas of kidneys). It causes disorders of arousing organs and tissues
(disorders of heart activity, miostenia, pareses);
3) ungas alcalosis. It is connected with amplification of acidogenesis in distall
nephron canaliculas;
4) polyuria arises as a consequence sensitivity of kineys canales epithelium loss
to action of vasopressin. It explains absence of volume increase of circulatting
blood and edema.
• Secondary hyperaldosteronismSecondary hyperaldosteronism is a result of renin-angiotensin system
activation. This state appears by:
a) arterial hypertension;
b) edemas;
c) hypopotassiumaemia;
d) ungas alcalosis.

64. • There are two clinical forms of
hypercorticism with
hyperproduction of
glucocorticoides:
1. Cushing’s diseaseCushing’s disease – basophil
adenoma of anterior
hypophysis part.
2. Cushing’s syndromeCushing’s syndrome:
• а) tumoral – adenoma of zona
fasticulata of adrenal cortex;
• b) ectopic production of
АCТH by some malignant
tumors (pulmonar cancer);
• c) iatrogenic – introduction of
glucocorticoides in an organism
with the medical purpose.

67. MOON
FACIES
BUFFALO
HUMP
STRIAE

68. GlucocorticoidGlucocorticoid
hypercorticism appears by:hypercorticism appears by:
1) arterial hypertension;
2) hyperglycaemia –
metasteroid diabetes
mellitus;
3) obesity;
4) development of infectious
diseases without signs of
an inflammation;
5) gastric hypersecretion and
formation of ulcers in
stomach and duodenum;
6) osteoporosis;
7) muscular weakness;
8) slow of wounds healing.

72. • Adrenogenital syndromeAdrenogenital syndrome results from the
hereditary stipulated blockade of cortisole
synthesis and amplified formation of androgens
from general intermediate products.
• Depending on the level of blockade of cortisole
synthesis there are three variants of adrogenital
syndrome.
• І. Disorders of early stages of synthesis –
deficiency of glucocorticoides, mineralcorticoides
and androgens hyperproduction. Manifestations:
signs of insufficiency of gluco- and
mineralocorticoidal functions of adrenal cortex
features of early sexual maturing in males,
virilization in women (appearance of man's sexual
features).
• ІІ. Disorders of intermediate stages – deficiency
of glucocorticoides, surplus of androgens, formation
of mineralocorticoides is not infringed (classical
androgenic syndrome). Manifestations are the
same, as in the first case, only without signs of
insufficiency of mineralocorticoidal function.
• ІІІ. Disorders at final stages of cortisol synthesis
– deficiency of glucocorticoides, hyperproduction of
androgens and mineralocorticoide. Features of
hyperaldosteronism are connected with
manifestations of classical androgenital syndrome.
AdrenogenitalAdrenogenital
syndromesyndrome

73. Disorders of adrenal medulla functionDisorders of adrenal medulla function
 Hyperfunction ofHyperfunction of
adrenal medullaadrenal medulla arises arises
during tumors ofduring tumors of
chromaphine cells –chromaphine cells –
pheochromocytome.pheochromocytome.
Appears by arterialAppears by arterial
hypertension, tachycardia,hypertension, tachycardia,
extrasystole, flatering ofextrasystole, flatering of
atriums, hyperglycaemia,atriums, hyperglycaemia,
hyperlipidaemia,hyperlipidaemia,
hyperthermia. Developmenthyperthermia. Development
of moderately expressedof moderately expressed
diabetus, thyreotoxicosis isdiabetus, thyreotoxicosis is
possible. In time ofpossible. In time of
paroxizm vertigo,paroxizm vertigo,
headache, hallucinations,headache, hallucinations,
increased excitability of theincreased excitability of the
nervous system, crampsnervous system, cramps
 Hypofunction of adrenalHypofunction of adrenal
medullamedulla happens seldom happens seldom
because of the fact that thesebecause of the fact that these
functions can be accepted byfunctions can be accepted by
other chromaphine cell.other chromaphine cell.

74. HYPOADRENALISMHYPOADRENALISM
Caused by any anatomic or metabolic lesion of the adrenalCaused by any anatomic or metabolic lesion of the adrenal
cortex that impairs output of the cortical steroids.cortex that impairs output of the cortical steroids.
Primary Acute Adrenal InsufficiencyPrimary Acute Adrenal Insufficiency
-- Waterhouse Friderichsen SyndromeWaterhouse Friderichsen Syndrome
due to overwhelming septicemic infection caused bydue to overwhelming septicemic infection caused by
meningococci, but occasionally other virulentmeningococci, but occasionally other virulent
organism such as gonococci, pneumococi andorganism such as gonococci, pneumococi and
staphylococci.staphylococci.
morphology: massive bilateral adrenal hemorrhagemorphology: massive bilateral adrenal hemorrhage

75. Acute adrenal insufficiency is a potentially fatal bilateral hemorrhagic infarction
of the adrenal glands associated with a Neisseria meningitidis infection in
children. It is clinically characterized by disseminated intravascular
coagulation (DIC), acute respiratory distress syndrome, hypotension and shock,
and acute adrenal insufficiency. Treatment is with antibiotics and steroid
replacement.

76. ADRENAL MEDULLAADRENAL MEDULLA
PHEOCHROMOCYTOMA:PHEOCHROMOCYTOMA: "dark/dusky-colored
tumor“, is an uncommon benign tumor of the adrenal medulla, which
produces catecholamines (norepinephrine and epinephrine) . It can
present with severe headache, tachycardia and palpitations,
diaphoresis and anxiety, or hypertensive episodes.
Note the Rule of 10s:
10% occur in children 10% are bilateral
10% are malignant 10% are familial (MEN II and III)
10% occur outside the adrenal gland
• Diagnosis is by demonstrating elevated urinary vanillylmandelic acid (VMA) and
catecholamines.
• Treatment involves controlling the patient's blood pressure and surgical removal of
the tumor.
- occassionally, this tumor produces other biogenic steroids or peptides associated
with Cushing’s Syndrome.
-morphology: - ave . weight of 100 gms
- Zellballen appearance

77.  This large adrenal neoplasmThis large adrenal neoplasm
has been sectioned in half.has been sectioned in half.
Note the grey-tan color of theNote the grey-tan color of the
tumor compared to the yellowtumor compared to the yellow
cortex stretched around it andcortex stretched around it and
a small remnant of remaininga small remnant of remaining
adrenal at the lower right.adrenal at the lower right.
This patient had episodicThis patient had episodic
hypertension. This is a tumorhypertension. This is a tumor
arising in the adrenal medullaarising in the adrenal medulla
- a- a pheochromocytomapheochromocytoma..
T
N

78. MULTIPLE ENDOCRINE NEOPLASIA (MEN)MULTIPLE ENDOCRINE NEOPLASIA (MEN)
SYNDROMESSYNDROMES
 1 . Multiple endocrine neoplasia (MEN) syndromes are autosomal dominant1 . Multiple endocrine neoplasia (MEN) syndromes are autosomal dominant conditions withconditions with
incomplete penetrance that are characterized by hyperplasia and tumors of endocrine glands.incomplete penetrance that are characterized by hyperplasia and tumors of endocrine glands.
 2.2. MEN IMEN I ((Werner syndromeWerner syndrome) features tumors of the) features tumors of the ppituitary gland,ituitary gland, pparathyroids, andarathyroids, and
ppancreas. It is associated with peptic ulcers and the ZollingerEllison syndrome. The affectedancreas. It is associated with peptic ulcers and the ZollingerEllison syndrome. The affected
gene is MEN I, a tumor suppressor gene that encodes a nuclear protein called menin.gene is MEN I, a tumor suppressor gene that encodes a nuclear protein called menin.
 3.3. MEN IIMEN II ((Ila or Sipple syndromeIla or Sipple syndrome) features medullary carcinoma of the thyroid,) features medullary carcinoma of the thyroid,
pheochromocytoma, and parathyroid hyperplasia or adenoma. The genetic mutation involvespheochromocytoma, and parathyroid hyperplasia or adenoma. The genetic mutation involves
RET proto-oncogene, which is a receptor tyrosine kinase for members of the glial cell line-RET proto-oncogene, which is a receptor tyrosine kinase for members of the glial cell line-
derived neurotrophic factor family of extracellular signaling molecules.derived neurotrophic factor family of extracellular signaling molecules.
 4.4. MEN IIIMEN III ((IIbIIb) features medullary carcinoma of the thyroid, pheochromocytoma, and) features medullary carcinoma of the thyroid, pheochromocytoma, and
mucocutaneous neuromas. There is a genetic mutation of RET ("rearranged duringmucocutaneous neuromas. There is a genetic mutation of RET ("rearranged during
transfection") proto-oncogene.transfection") proto-oncogene.

81.  Cardiovascular:Cardiovascular: Coronary arteryCoronary artery
disease, hypertension, stroke, arrhythmia.disease, hypertension, stroke, arrhythmia.
 Muscles:Muscles: Tension headaches, backacheTension headaches, backache
 Connective tissues:Connective tissues: Rheumatoid arthritisRheumatoid arthritis
 Pulmonary:Pulmonary: Asthma.Asthma.
 Immune:Immune: Immunosuppression, deficiency,Immunosuppression, deficiency,
autoimmunityautoimmunity
 Gastrointestinal:Gastrointestinal: Ulcer, irritable bowelUlcer, irritable bowel
syndrome, diarrhea, nausea and vomiting,syndrome, diarrhea, nausea and vomiting,
ulcerative colitisulcerative colitis
 Integumetary:Integumetary: Eczema, neurodermatitis,Eczema, neurodermatitis,
acneacne
 Endocrine:Endocrine: Diabetes mellitus, amenorrheaDiabetes mellitus, amenorrhea
 Central nervous:Central nervous: Fatigue and lethargy, type AFatigue and lethargy, type A
behavior, overeating, depression, insomnia.behavior, overeating, depression, insomnia.

83. The thyroid gland and the follicularThe thyroid gland and the follicular
structurestructure

84. 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

86. 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)

87. Multinodular goiter (nontoxic
goiter) refers to an enlarged
thyroid gland with multiple
colloid nodules.
Females are affected more
frequently than males.
Multinodular goiter is
frequently asymptomatic, and
the patient is typically
euthyroid, with normal T4, T3,
and TSH.
Plummer syndrome is the
development of
hyperthyroidism (toxic
multinodular goiter) late in the
course.
Microscopically, the tissue
shows nodules of varying
sizes composed of colloid
follicles. Calcification,
hemorrhage, cystic
degeneration, and fibrosis can
also be present.

88. HYPERTHYROIDISMHYPERTHYROIDISM
1. The term hyperthyroidism is used when the mean metabolic rate of all
cells is increased due to increased T4 or T3.
Clinical features include: tachycardia and palpitations; nervousness and
diaphoresis; heat intolerance; weakness and tremors; diarrhea; and weight loss
despite a good appetite.
Laboratory studies show elevated free T4. In primary hyperthyroidism,
TSH is decreased, while in secondary and teritiary hyperthyroidism, TSH
is elevated.
2. Graves disease is an autoimmune disease characterized by production of IgG
autoantibodies to the TSH receptor. Females are affected more frequently than
males, with peak age 20 to 40 years.
Clinical features include hyperthyroidism, diffuse goiter, ophthalmopathy
(exophthalmus) , and dermopathy (pretibial myxedema).
Microscopically, the thyroid has hyperplastic follicles with scalloped colloid.
3. Other causes of hyperthyroidism include toxic multinodular goiter;
toxic adenoma (functioning adenoma producing thyroid hormone); and
Hashimoto and subacute thyroiditis (transient hyperthyroidism) .

89. HyperthyroidismHyperthyroidism (Graves Disease)(Graves Disease)
 Thyroid eye diseaseThyroid eye disease (with exophtalmus) is not confined to(with exophtalmus) is not confined to
Graves’s hyperthyroidism only. Some exophtalmus patients areGraves’s hyperthyroidism only. Some exophtalmus patients are
euthyroid or hypothyroid.euthyroid or hypothyroid.
 Common to all types of thyroid eye diseases areCommon to all types of thyroid eye diseases are specificspecific
antibodiesantibodies that cause inflammation of thethat cause inflammation of the retro-orbital tissueretro-orbital tissue
withwith swellingswelling of theof the extraocular eye musclesextraocular eye muscles, so, so they cannotthey cannot
move the eyes normallymove the eyes normally..
 ProptosisProptosis andand lid lagslid lags areare typical signstypical signs, and, and conjunctivitis andconjunctivitis and
scarsscars on the cornea follow due to lack of protective cover.on the cornea follow due to lack of protective cover.
 TheThe oedematous retro-orbital tissueoedematous retro-orbital tissue may force the eye ballsmay force the eye balls
forward and press on the optic nerveforward and press on the optic nerve to such anto such an extent thatextent that
vision is impaired or blindnessvision 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 are palliative.thyrotoxicosis. Other therapeutic measures are palliative.

90. Lid lag in Graves disease
The lids appear congested and edematous –
congestive ophtalmopathy.

91. Lid lag occurs when the sclera B/W upper eye
lid and cornea becomes visible as the patient
gaze follows the examiner fingers down ward
from position of maximum elevation.
The eye moves not in close contact with eye
lid as a delay in lid movement.

92. Exophthalmos – protrusion of
the eye ball
• Appearance of sclera B/W the lower lid and limbus of cornea.
• Symmetrical in Graves disease with hyperthyroidism.
• Caused by increased bulk of orbital contents.
• The fat is increased and the muscles enlarged, infiltrated with
lymphocytes and contain increased amounts of water and
mucopolysccharides.
• Usually alters little with treatment and may be remarkably
persistent.
• In some, it is progressive and may cause loss of vision if
effective treatment not given (malignant exophthalmos).
Unilateral exophthalmos causes:

95.  1. The term hypothyroidism is used when the mean metabolic rate of all cells is
decreased due to decreased T4 or T3.
 a. Clinical features include fatigue and lethargy; sensitivity to cold temperatures;
decreased cardiac output; myxedema (accumulation of proteoglycans and water);
facial and periorbital edema; peripheral edema of the hands and feet; deep voice;
macroglossia; constipation; and anovulatory cycles.
 b. Laboratory studies show decreased free T4. In primary hypothyroidism, TSH
is elevated, while in secondary and tertiary hypothyroidism, TSH is decreased.
 2. Iatrogenic hypothyroidism is the most common cause of hypothyroidism in the
United States, and is secondary to thyroidectomy or radioactive iodine treatment.
Treatment is with thyroid hormone replacement.
 3. Congenital hypothyroidism (cretinism) in endemic regions is due to iodine
deficiency during intrauterine and neonatal life, and in nonendemic regions is due to
thyroid dysgenesis. Aff ected individuals present with failure to thrive, stunted bone
growth and dwarfism, spasticity and motor incoordination, and mental retardation. Goiter
is present in endemic cretinism.
 4. Endemic goiter is due to dietary deficiency of iodine and is uncommon in the
United States and Ukraine.

96. 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

97. CretinismCretinism
Hypothyroidism that occurs in infancy orHypothyroidism that occurs in infancy or
early childhoodearly childhood
Impaired development of the skeletalImpaired development of the skeletal
system and CNSsystem and CNS
Manifests asManifests as severe mental retardationsevere mental retardation,,
short stature, coarse facial features,short stature, coarse facial features,
protruding tongue and umbilical herniaprotruding tongue and umbilical hernia
Cretinism, also known as
Neonatal hypothyroidism
is decreased thyroid hormone production in a newborn.

98. 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

99. PrimaryPrimary
hypotyrioidismhypotyrioidism
MyxedemaMyxedema

100. Myxedematous Coma.Myxedematous Coma.
• Myxedematous comaMyxedematous coma is a lifethreatening,is a lifethreatening, end-stageend-stage
expression of hypothyroidismexpression of hypothyroidism..
• It is characterized by coma,It is characterized by coma, hypothermia, cardiovascularhypothermia, cardiovascular
collapse, hypoventilation, and severe metabolic disorders thatcollapse, hypoventilation, and severe metabolic disorders that
include hyponatremia, hypoglycemia, and lactic acidosisinclude hyponatremia, hypoglycemia, and lactic acidosis. It. It
occurs most often in elderly women who have chronicoccurs most often in elderly women who have chronic
hypothyroidism from a spectrum of causes. It occurs morehypothyroidism from a spectrum of causes. It occurs more
frequently in the winter monthsfrequently in the winter months, which suggests that cold, which suggests that cold
exposure may be a precipitating factor. Theexposure may be a precipitating factor. The severelyseverely
hypothyroid person ishypothyroid person is unable to metabolizeunable to metabolize sedatives,sedatives,
analgesics, and anesthetic drugs, and buildup of these agentsanalgesics, and anesthetic drugs, and buildup of these agents
may precipitate comamay precipitate coma..
• TreatmentTreatment includes aggressive management of precipitatingincludes aggressive management of precipitating
factors; supportive therapy such as management offactors; supportive therapy such as management of
cardiorespiratory status, hyponatremia, and hypoglycemia; andcardiorespiratory status, hyponatremia, and hypoglycemia; and
thyroid replacement therapy.thyroid replacement therapy. PreventionPrevention is preferable tois preferable to
treatment and entailstreatment and entails special attention to high-risk populationsspecial attention to high-risk populations,,
such assuch as women with a history of Hashimoto’s thyroiditiswomen with a history of Hashimoto’s thyroiditis. These. These
persons should be informed about the signs and symptoms ofpersons should be informed about the signs and symptoms of
severe hypothyroidism and the need for early medicalsevere hypothyroidism and the need for early medical

102. 1. Hashimoto thyroiditis is a chronic autoimmune disease characterized by immune
destruction of the thyroid gland and hypothyroidism. It is the most common
noniatrogenic/nonidiopathic cause of hypothyroidism in the United States; it most
commonly causes painless goiter in females more than males, and has peak age 40
to 65 years.
Clinically, Hashimoto thyroiditis most commonly causes hypothyroidism (due to
destruction of thyroid tissue), but the initial inflammation may cause transient
hyperthyroidism (hashitoxicosis).
Hashimoto thyroiditis may b e associated with other autoimmune diseases (SLE,
rheumatoid arthritis, Sjogren syndrome, etc.), and it has an increased risk of non-
Hodgkin B-cell lymphoma.
Pathology. Hashimoto thyroiditis grossly produces a pale, enlarged thyroid gland,
which microscopically shows lymphocytic inflammation with germinal centers and
epithelial “Hürthle cell" changes.
2. Subacute thyroiditis (also called de Quervain thyroiditis and granulomatous
thyroiditis) is the second most common form of thyroiditis; it affects females more
than males and has peak age 30 to 50 years. The condition is typically preceded by a
viral illness, produces a tender, firm, enlarged thyroid gland, and may be
accompanied by transient hyperthyroidism.
Microscopy shows granulomatous thyroiditis. The disease typically follows
a self-limited course.

103. Hashimoto ThyroiditisHashimoto Thyroiditis
 Chronic lymphocyticChronic lymphocytic
thyroiditisthyroiditis
 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

104. Females are affected more frequently than males, with most patients being
middle-aged. Riedel thyroiditis causes an irregular, hard thyroid that is
adherent to adjacent structures.
The condition may clinically mimic carcinoma and present with stridor,
dyspnea, or dysphagia.
Microscopic examination shows dense fibrous replacement of the thyroid
gland with chronic inflammation.
Reidel thyroiditis is associated with retroperitoneal and mediastinal fibrosis.
3. Riedel thyroiditis is a rare
disease of unknown etiology,
characterized by destruction of the
thyroid gland by dense fibrosis and
fibrosis of surrounding structures
(trachea and esophagus).

105. THYROI D NEOPLASIATHYROI D NEOPLASIA
1.1. Adenomas.Adenomas. Follicular adenomas are the most common. Clinically, adenomas areFollicular adenomas are the most common. Clinically, adenomas are
usually painless, solitary nodules that appear "cold" on thyroid scans. They may beusually painless, solitary nodules that appear "cold" on thyroid scans. They may be
functional and cause hyperthyroidism (toxic adenoma).functional and cause hyperthyroidism (toxic adenoma).
2.2. Papillary carcinomaPapillary carcinoma accounts for 80% of malignant thyroid tumors. Females areaccounts for 80% of malignant thyroid tumors. Females are
affected more than males, with peak age 20 to 50 years. Radiation exposure is a riskaffected more than males, with peak age 20 to 50 years. Radiation exposure is a risk
factor. Resection is curative in most cases. Radiotherapy with iodine 1 3 1 isfactor. Resection is curative in most cases. Radiotherapy with iodine 1 3 1 is
effective for metastases. Theeffective for metastases. The prognosisprognosis is excellent, with 20-year survival of 90%is excellent, with 20-year survival of 90%
due to slow growth and metastasis to regional cervical lymph nodes.due to slow growth and metastasis to regional cervical lymph nodes.
Microscopically,Microscopically, the tumor typically exhibits a papillary pattern. Occasional psammoma bodiesthe tumor typically exhibits a papillary pattern. Occasional psammoma bodies
may be seen. Characteristic nuclear features include clearmay be seen. Characteristic nuclear features include clear "Orphan Annie eye" nuclei"Orphan Annie eye" nuclei;;
nuclear grooves; and intranuclear cytoplasmic inclusions. Lymphatic spread to cervical nodes isnuclear grooves; and intranuclear cytoplasmic inclusions. Lymphatic spread to cervical nodes is
common.common.
3.3. Follicular carcinomaFollicular carcinoma accounts for 1 5% of malignant thyroid tumors. Females areaccounts for 1 5% of malignant thyroid tumors. Females are
affected more often than males, with peak age 40 to 60 years. Hematogenousaffected more often than males, with peak age 40 to 60 years. Hematogenous
metastasis to the bones or lungs is common.metastasis to the bones or lungs is common.
4.4. Medullary carcinomaMedullary carcinoma accounts for 5% of malignant thyroid tumors. This tumoraccounts for 5% of malignant thyroid tumors. This tumor
arises from C cells (parafollicular cells) and secretes calcitonin.arises from C cells (parafollicular cells) and secretes calcitonin. MicroscopicMicroscopic
examinationexamination shows nests of polygonal cells in an amyloid stroma. A minority (25%) of casesshows nests of polygonal cells in an amyloid stroma. A minority (25%) of cases
are associated with MEN II and MEN III syndromes.are associated with MEN II and MEN III syndromes.
5.5. Anaplastic carcinomaAnaplastic carcinoma affects females more than males, with peak age greateraffects females more than males, with peak age greater
than 60 years. Anaplastic carcinoma can present with a firm, enlarging, and bulkythan 60 years. Anaplastic carcinoma can present with a firm, enlarging, and bulky
mass; or with dyspnea and dysphagia. The tumor has a tendency for earlymass; or with dyspnea and dysphagia. The tumor has a tendency for early
widespread metastasis and invasion of the trachea and esophagus.widespread metastasis and invasion of the trachea and esophagus. Microscopically,Microscopically,
the tumor is composed of undifferentiated, anaplastic, and pleomorphic cells. This verythe tumor is composed of undifferentiated, anaplastic, and pleomorphic cells. This very

106. 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.

107. 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)

108. Etiology. Adenomas are the most common
cause of primary hyperparathyroidism
(80%), and they may be associated with MEN
I.
Parathyroid hyperplasia accounts for 15%
of cases and is characterized by diffuse
enlargement of all four glands. The enlarged
glands are usually composed of chief cells.
Parathyroid carcinoma is very rare.
Hyperparathyroidism can also occur as a
paraneoplastic syndrome of lung and renal
cell carcinomas.
Clinical features. The excess production of
parathyroid hormone (PTH) leads to
hypercalcemia, with laboratory studies
showing elevated serum calcium and PTH.
Primary hyperparathyroidism is often
asymptomatic, but may cause kidney stones;
osteoporosis and osteitis fibrosa cystica,
metastatic calcifications, or neurologic
changes.

109. Caused by any disease that results inCaused by any disease that results in hypocalcemiahypocalcemia, leading, leading
to increased secretion of PTH by the parathyroid glands. Theto increased secretion of PTH by the parathyroid glands. The
condition can result from chronic renal failure, vitamin Dcondition can result from chronic renal failure, vitamin D
deficiency, or malabsorption.deficiency, or malabsorption.

110. HypoparathyroidismHypoparathyroidism can result from surgical removal of glands during
thyroidectomy, DiGeorge syndrome, or idiopathic cause.
Clinical featuresClinical features.. Laboratory studies show hypocalcemia.
Treatment isTreatment is with vitamin D and calcium.
Chvostek sign demonstrates twitching of the ipsilateral facial muscles after
tapping the muscles, suggestive of neuromuscular excitability caused by
hypocalcemia.
Trousseau signTrousseau sign is performed by inflating a sphygmornanometer cuff above
systolic blood pressure for several minutes so that if hypocalcemia is present,
then muscular contractions, including flexion of the wrist and
metacarpophalangeal joints, hyperextension of the fingers, and flexion of the
thumb on the palm occur, suggesting neuromuscular excitability.
Clinical problemsClinical problems related to hypocalcemia.
The hypocalcemia may also cause psychiatric disturbances and cardiac
conduction defects (ECG: prolonged QT interval) .
Treatment is with vitamin D and calcium.