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Endocrine System
dr. Rhiza Mohammad Ishaq Sobari
Physiology dept.
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• Endocrine it derives from the Greek words endo
(Greek ένδο) meaning inside, within, and crinis
(Greek κρινής) for secrete.
• The endocrine system is an information signalsystem like the nervous system.
• Hormones are substances (chemical mediators)
released from endocrine tissue into the
bloodstream that attach to target tissue and allow
communication among cells.
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• Hormones regulate many functions of an organism,
including – stimulation or inhibition of growth
– mood swings
– induction or suppression of apoptosis
– activation or inhibition of the immune system – regulation of metabolism
– preparation of the body for mating, fighting, fleeing, and
other activity
– preparation of the body for a new phase of life, such as
puberty, parenting, and menopause
– control of the reproductive cycle
– hunger cravings
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Endocrine Glands:
Secretion and Action of Hormones
• Most, if not all, tissues secrete hormones.
• Hormone = chemical secreted into theblood that triggers a preprogrammed
response in the target cell.• Neurotransmitter = chemical secreted into
synaptic cleft that affects ion channels inthe target cell.
• Neurohormone = chemical secreted byneurons into the blood.
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Classification of hormones
1. By composition:a. Amino-acids derivatives,ex: epinephrine (E), norepinephrine (NE),
dopamine (E, NE & dopamine are structurally similar → calledcatecholamines) the thyroid hormones, and melatonin.
b. Peptide
a. Polypeptide,ex: ADH, oxytocin, prolactin
b. Glycoprotein,ex: TSH, LH, FSH
c. Lipid derivatives:
a. Steroid hormone, ex: androgens, estrogens, progesterons,corticosteroids,calcitriol
b. Eicosanoids, ex : leucotrienes, prostaglandins (paracrinefactors)
2. By polarity:
a. Nonpolar (hydrophobic) – soluble in lipids – steroids and thyroidhormones.
b. Polar (hydrophilic) – soluble in water – all others.
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Types of cell-to-cell signaling
• Classic endocrinehormones travel via
bloodstream to target
cells;
• neurohormones arereleased via synapses
and travel via the
bloostream;
• paracrine hormones acton adjacent cells and
• autocrine hormones are
released and act on the
cell that secreted them..
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Regulation of hormone secretion
Sensing and signaling: a biological need is sensed,
the endocrine system sends out a signal to a target
cell whose action addresses the biological need. Key
features of this stimulus response system are: receipt of stimulus
synthesis and secretion of hormone
delivery of hormone to target cell
evoking target cell response
degradation of hormone
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Control of Endocrine Activity
•The physiologic effects of hormones
depend largely on their concentration in
blood and extracellular fluid.
• Almost inevitably, disease results when
hormone concentrations are either too high or
too low, and precise control over circulatingconcentrations of hormones is therefore
crucial.
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Control of Endocrine Activity
The concentration of hormone as seen by
target cells is determined by three factors:
•Rate of production
•Rate of delivery
•Rate of degradation and elimination
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Control of Endocrine Activity
Rate of production: Synthesis and secretion of
hormones are the most highly regulated aspect
of endocrine control. Such control is mediated
by positive and negative feedback circuits, as
described below in more detail.
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Control of Endocrine Activity
Rate of delivery: An example of this effect is
blood flow to a target organ or group of target
cells - high blood flow delivers more hormone
than low blood flow.
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Control of Endocrine Activity
Rate of degradation and elimination:
Hormones, like all biomolecules, have
characteristic rates of decay, and are
metabolized and excreted from the bodythrough several routes.
Shutting off secretion of a hormone that has a
very short half-life causes circulating hormoneconcentration to plummet, but if a hormone's
biological half-life is long, effective
concentrations persist for some time after
secretion ceases.
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Feedback Control of Hormone
Production
Feedback loops are used
extensively to regulate
secretion of hormones inthe hypothalamic-pituitary
axis. An important example
of a negative feedback loop
is seen in control of thyroidhormone secretion
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Inputs to endocrine cells
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Hormone receptor
• A hormone receptor is a receptor protein on thesurface of a cell or in its interior that binds to a
specific hormone. The hormone causes many
changes to take place in the cell.
• Binding of hormones to hormone receptors often
trigger the start of a biophysical signal that can
lead to further signal transduction pathways, or
trigger the activation or inhibition of genes.• Types of Hormone Receptors
– Steroid hormone receptors
– Peptide hormone receptors
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• Hormon mengaktifasi reseptor protein,kompleks
protein-g dan α,β,ɣ yg inaktif akanteraktifasi,mnyebabkan disosiasi subunit α dari
subunit β,ɣ dan protein-g,dan interaksi ini
menginisiasi pnghantaran sinyal intrasel yg akan
mengubah fungsi sel : aktif/inaktif
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Steroid Hormones
• Steroid hormones and thyroid hormone diffuse easilyinto their target cells
• Once inside, they bind and activate a specificintracellular receptor
• The hormone-receptor complex travels to thenucleus and binds a DNA-associated receptor protein
• This interaction prompts DNA transcription to
produce mRNA• The mRNA is translated into proteins, which bring
about a cellular effect
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Figure 16..3
Steroid Hormones
• Hormon binding dgn reseptor sitoplasma/nukleus, kompleks
hormon-reseptor akan berikatan dengan hormon respon
element(promotor) pada DNA,menyebabkan
aktifasi/inaktifasi transkripsi gen+pembentukan
mRNA+sintesis protein
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• ELISA : A sensitiveimmunoassay that uses anenzyme linked to an antibodyor antigen as a marker for the
detection of a specific protein,especially an antigen orantibody. It is often used as adiagnostic test to determineexposure to a particularinfectious agent, such as the
AIDS virus, by identifyingantibodies present in a bloodsample.
• RIA : A procedure that measuresminute amounts of a substance,such as a hormone or drug, byquantitating the binding, or the
inhibition of binding, of aradiolabeled substance to anantibody.
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E
N
DO
C
R
IN
E
G
L
A
N
D
S
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Major Hormones
Where Hormone Is Produced Hormone Function
Pituitary gland Antidiuretic hormone (vasopressin) Causes kidneys to retain water and, along with aldosterone, helps control
blood pressure
Corticotropin (ACTH) Controls the production and secretion of hormones by the adrenal glands
Growth hormone Controls growth and development; promotes protein production
Luteinizing hormone and follicle-stimulating
hormone
Control reproductive functions, including the production of sperm and semen,
egg maturation, and menstrual cycles; control male and female sexual
characteristics (including hair distribution, muscle formation, skin texture and
thickness, voice, and perhaps even personality traits)
Oxytocin Causes muscles of the uterus and milk ducts in the breast to contract
Prolactin Starts and maintains milk production in the ductal glands of the breast
(mammary glands)
Thyroid-stimulating hormone Stimulates the production and secretion of hormones by the thyroid gland
Parathyroid glands Parathyroid hormone Controls bone formation and the excretion of calcium and phosphorus
Thyroid gland Thyroid hormone Regulates the rate at which the body functions (metabolic rate)
Calcitonin In people, function is unclear; in other species, regulates calcium balance
Adrenal glands Aldosterone Helps regulate salt and water balance by retaining salt and water and
excreting potassium
Cortisol Has widespread effects throughout the body; especially has anti-inflammatory
action; maintains blood sugar level, blood pressure, and muscle strength;
helps control salt and water balance
Dehydroepiandrosterone (DHEA) Has effects on bone, mood, and the immune system
Epinephrine and norepinephrine Stimulate the heart, lungs, blood vessels, and nervous system
Pancreas Glucagon Raises the blood sugar level
Insulin Lowers the blood sugar level; affects the processing (metabolism) of sugar,
protein, and fat throughout the body
Kidneys Erythropoietin Stimulates red blood cell production
Renin Controls blood pressure
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Ovaries Estrogen Controls the development of female sex characteristics
and the reproductive system
Progesterone Prepares the lining of the uterus for implantation of a
fertilized egg and readies the mammary glands to secrete
milk
Testes Testosterone Controls the development of male sex characteristics and
the reproductive system
Digestive tract Cholecystokinin Controls gallbladder contractions that cause bile to enter
the intestine; stimulates release of digestive enzymes
from the pancreas
Glucagon-like peptide Increases insulin release from pancreas
Ghrelin Controls growth hormone release from the pituitary
gland; causes sensation of hunger
Adipose (fat) tissue Resistin Blocks the effects of insulin on muscle
Leptin Controls appetite
Placenta Chorionic gonadotropin Stimulates ovaries to continue to release progesterone
during early pregnancy
Estrogen and progesterone Keep uterus receptive to fetus and placenta during
pregnancy
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The Endocrine System
• Consists of several
glands located in
various parts of the
body.
• Pituitary gland: a smallgland located on a stalk
hanging from the base of the
brain.
• “The Master Gland”
– Primary function is to
control other glands.
– Produces many
hormones.
– Secretion is controlled by
the hypothalamus in the
base of the brain.
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The Endocrine System
• The Pituitary Gland isdivided into 2 areas,which differ
– structurally and
functionally – each area has
separate types ofhormone production.
• The two segments are: – Posterior Pituitary:
• produces oxytocinand antidiuretichormone (ADH)
– Anterior Pituitary:• produces thyroid-
stimulating hormone(TSH)
• growth hormone (GH)
• adrenocorticotropin(ACTH)
• follicle-stimulatinghormone (FSH)
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The Endocrine System
– luteinizing hormone
(LH)
– prolactin
• Posterior Pituitary
– Oxytocin (the natural
form of pitocin)
• stimulates gravid
uterus
• causes “let down”
of milk from the
breast.
– ADH (vasopressin)
causes the kidney to
retain water.
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The Endocrine System
• Anterior Pituitary – Primarily regulates
other endocrine glands
– rarely a factor in
endocrinological
emergencies
– TSH stimulates the
thyroid gland to
release its hormones,
thus metabolic rate
• Anterior Pituitary… – Growth hormone (GH)
• glucose usage
• consumption of
fats as an energysource
– ACTH stimulates the
adrenal cortex to
release its hormones
– FSH & LH stimulatesmaturation & release
of eggs from ovary.
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The Endocrine System
• The Thyroid Gland – lies in the anterior
neck just below thelarynyx.
– Two lobes, locatedon either side of thetrachea, connectedby a narrow band oftissue called thei s thmus
. – Sacs inside the
gland contain col lo id
• Within the colloid arethe thyroid hormones:
– thyroxine (T4)
– triiodothyronine (T3)
• When stimulated(by TSH or bycold), these arereleased into thecirculatory systemand themetabolic rate.
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The Endocrine System
• “C” cells within the thyroid produce thehormone calc i tonin
• Calcitonin, when released, lowers the
amount of calcium in the blood.
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The Endocrine System
• Parathyroid Glands
– small, pea-shaped
glands, located in the
neck near the thyroid
– usually 4 - number can
vary
– regulate the level of
calcium in the body
– produce parathyroid
hormone - level of
calcium in blood
– Hypocalcemia can result
if parathyroids are
removed or destroyed.
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The Endocrine System
• Pancreas
– a key gland located inthe folds of theduodenum
– has both endocrine andexocrine functions
– secretes several keydigestive enzymes
• Islets of Langerhans
– specialized tissues inwhich the endocrinefunctions of thepancreas occurs
– include 3 types of cells:
• alpha ( )
• beta ( )
• delta () – each secretes an
important hormone.
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The Endocrine System
• Alpha ( ) cells releaseglucagon, essential forcontrolling bloodglucose levels.
• When blood glucoselevels fall, cells theamount of glucagon inthe blood .
• The surge of glucagonstimulates the liver torelease glucose stores(from glycogen and
additional storagesites).
• Also, glucagonstimulates the liver to
manufacture glucose -
• gluconeogenesis.
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The Endocrine System
• Beta Cells ( ) release
insulin (antagonistic to
glucagon).
• Insulin the rate atwhich various body cells
take up glucose. Thus,
insulin lowers the blood
glucose level.
• Insulin is rapidly broken
down by the liver and
must be secreted
constantly.• Delta Cells () produce
somatostatin, which
inhibits both glucagon
and insulin.
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The Endocrine System
• Adrenal Glands – 2 small glands that sit
atop both kidneys.
– Each has 2 divisions,
each with differentfunctions.
– the Adrenal Medulla
secretes the
catecholaminehormones
• norepinephrine and
epinephrine (closely
related to the sympatheticcomponent of the
autonomic nervous
system).
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The adrenal cortex is composed of 3 zones:1. Zona Glomerulosa – superficial layer
– secretes mineralocorticoids(aldosterone)
2. Zona Fasciculata – middle layer – secretes glucocorticoids (cortisol)
3. Zona Reticularis – deep layer – secretes gluco-corticoids and sex
steroids.Fetal Zone – only in fetus – makes
DHEA for conversion to sex steroids(mostly estrogens) by the placenta.
T
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Gonads • Testes – secreteandrogens; principallytestosterone from Leydigcells of seminiferous
tubules. Androgenscontrol development andmaintenance of sex organsand secondary sexcharacteristics.
• Ovaries – secreteprogesterone andestrogens; principallyestradiol-17. – Estradiol is secreted from
granulosa cells of theovarian follicle.
– Progesterone and estradiolis secreted from the corpusluteum.
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Hipothalamus & Hipofisis
dr. Rhiza Mohammad Ishaq Sobari
Physiology dept.
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Hipothalamus
• Tidak memiliki batas tegas• Bagian atas dibatasi dari daerah thalamus dgn sulcus
hipothalamicus
• Hasilkan hormon
Growth hormon releasing hormon (GHRH)Somatostatin (inhibisi GH & TSH)
Dopamin
Prolactin Releasing Factor
Thyrotropin releasing hormon (TRH)Corticotropin releasing hormon (CRH)
Gonadotropin releasing hormon (GnRH)
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Hipofisis
• Kel hipofisis terletak didasar tengkorak (sella
tursica/fossa pituitaria)
• Terdiri dari :
- hipofisis anterior (adenohipofisis)
- pars intermedius (jadi satu dgn dorsal
hipofisis posterior)- hipofisis posterior (neurohipofisis)
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Fisiologi Adenohipofisis
• Mengeluarkan hormon :1. Hormon pertumbuhan
2. Prolaktin
3. Tiroid Stimulating Hormon (TSH)
4. Adrenocorticotropic hormon (ACTH)
5. Hormon gonadotropin :
- Follicle Stimulating Hormon (FSH)
- Luteinizing Hormon (LH)6. Melanocyte stimulating hormon (MSH)
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Fisiologi pars intermedius
• Mengeluarkan hormon MSH
• Terdiri 2 sub unit alfa & beta
• Beta MSH ~ ACTH
• Pd manusia dewasa rudimenter
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Fisiologi Neurohipofisis
• Menghasilkan hormon :
- Oksitosin
- Anti Diuretik Hormon (ADH/ Arginin
vasopresin)
• Dikendalikan nuklei hipothalamus
• Sekresi oksitosin dikendalikan nukleus
paraventrikularis• Sekresi ADH dikendalikan niklei supraoptici
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Stimuli nukleus paraventrikularis (oksitosin)
- uterus, cervix,vagina
- papilla & areola mammae
Penting proses melahirkan, kontraksimiometrium, menyusui
Nuleus supraoptici (ADH)
Osmoreseptor peka thd perubahan kepekatanplasma
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Fisiologi adenoh
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Endocrine regulation in growth
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The Endocrine System
A system of glands that secrete hormones
Regulate a variety of physiological processes
Endocrine hormone:
Travels through bloodstream to target organ,where it exerts its effects by binding to itsreceptor.
Receptor: Membrane (Protein Hormone)
Nuclear (Steroid Hormone)
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Thyroid Hormones
Hypothalamus TRH (Thyrotropin releasing hormone)
Pituitary
TSH (Thyroid stimulating hormone)
Thyroid
T4 thyroxine T3 thyronine
iodine
Permissive role:
Allow for normal cell function & growthInduce N retention for protein synthesis
Stimulate growth H release
Increases metabolic rate
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Roles
• Metabolic Rate• BMR
• ↑ heat production• Newborns
• Stress
• Weight regulation
• SNS Activity• ↑ -receptors
• ↑ Heart rate
• Brain activity, muscle activity
• Brain development and body growth
• Stimulates GH release
Th id h ( )
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•Thyroid hormones (cont.)
• Secreted by fetus from week 20 on• Necessary for fetal protein synthesis and brain
development
• Thyroid hormone deficiency• In Utero:
• Cretinism (Congenital hypothyroidism mentalretardation, stunting)
• In infancy:
• growth delay, may CNS damage
•
In childhood / adolescence:• growth delay, skeletal maturity delay, does not
CNS damage
• In adulthood:
• T3T4 deficiency obesity
•
T3T4 excess weight loss
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Hypothyroidism
http://www.bupa.co.uk/wellness/images/factsheets/Thyroid_disease1.gif
Goitre: iodine
deficiency
No goitre: TSH
deficiency
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Hyperthyroidism
http://www.bupa.co.uk/wellness/images/factsheets/Thyroid_disease2.gif
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Growth Hormone
Hypothalamus
Anterior pituitary gland
+ GHRH Somatostatin -
GH
Liver
Cartilage and bonegrowthMuscle and otherorgans:-Protein synthesisand growth
Adipose Tissue-lipolysis- release of FFAs
Most Tissuesglucose utilization- blood glucose
IGF-1
Somatomedin
GH levels and effects are
most pronounced during
puberty
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•Growth hormone disorders
• Excess GH
• Pre-puberty: gigantism bone growth, > 7 ft. tall
• Post-puberty: acromegaly Some tissues still grow: cartilage in
nose, hands, feet, ridges of eyebrow,chin, tongue
Metabolic effects: constant increase in
blood sugar, increased insulin type 2diabetes. Can also increase musclenarrowing of arteries, heart attack
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• GH Deficiency
• ↓ GH, ↓ IGF-1
• Short stature
• Metabolic effects
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Insulin
• Hormone of Feasting• From Pancreas - cells from Islets of Langerhans• Allows glucose to enter the cell
• glucose uptake into tissues• Affects glucose transporter
• Energy• Metabolic Processes
• ↑ Glycogen synthesis• ↑ Fat synthesis• ↑ Protein synthesis
•
Growth
• Children with poorly controlled Type I diabetes often haveshort stature
• Glucagon – Hormone of Fasting
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•Insulin Deficiency
• ↑ Lipolysis
• FFA ketone bodies acidifies blood
• ↑ Protein breakdown
• ↑ Plasma Glucose
• Osmotic diuresis
• ↑ water excretion
•
plasma volume• arterial blood pressure
• brain blood flow
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Androgens and Estrogens
• Produced in gonads (ovaries, testes) and adrenalglands, in puberty
• Will fuse epiphysis and stop linear growth• - earlier puberty in women contributes to their
shorter stature
• Androgens• Primarily DHEA (dihydroepiandrosterone)• Converted to estrogens, testosterone in
tissues• Peaks in young adults• Secondary sex characteristics• In women: DHEA stimulates growth in
adolescence, e.g. muscle, bone• Important during fetal period and during
menopause
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Estrogen
During puberty: 2º sex characteristics
Promotes growth of uterus
Stabilizes blood cells in skin Bone strength
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Gangguan fungsi hipofisis
Panhipopituitarisme
• kekurangan hormon :
– GH, TSH, ACTH, Gonadotropin,Prolaktin
• Gejala sesuai kekurangan hormon
• Etiologi :infeksi,iskemia,neoplasma,
granuloma,aneurisma dll
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• Akromegali / gigantisme
Hipersekresi GH / HP
Sesudah epifises menutup : akromegali
Sebelum epifises menutup : gigantismeAkibat tumor hipofisis
Gejala :
Bentuk muka berubah, pertumbuhan gigi tak teratur,
kiposis, atropati, pertumbuhan tulang ekstremitasberlebihan
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• Pembesaran dan penebalan hidung, lidah, bibir,telinga, tangan dan kaki
• Kulit menebal, basah dan beminyak, lipatan kulitkasar dan melebar, penebalan telapak kaki
• Suara parau
• Pada metabolisme : intoleransi glukosa,hiperfosfatemia, hiperlipidemia dan hiperkalsemia,osteoporosis.
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• Gambaran klinis akibat tumor- Pembesaran keatas :
sakit kepala, ggn penglihatan
- Pembesaran ke lateral :
kelumpuhan syaraf III,IV,V dan VI- Penyumbatan pemb darah lokal
- Pertumbuhan ke inferior :
CSF rinorea
- Pertumbuhan ke anterior :
perubahan kepribadian- Infark
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b h
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Gangguan Pertumbuhan
• Defisiensi hormon pertumbuhan
• Manifestasi perawakan pendek (shurt stature)
• Etiologi perawakan pendek
• Defek intrinsik : displasia tulang,kelainan kromosom,kecebolan primordial
• Lingkungan : ggn gizi,gagal ginjal kronik, penyakit
darah dll
• Hormonal : defisiensi HP, defisiensi tiroid, kelebihan
glukokortikoid
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G b h
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Gangguan pertumbuhan
• Gambaran klinis HP <<
perawakan pendek berat (cebol), agak gemuk,
lemak subcutan di abdomen bertambah,
hipoglikemia, proporsi tulangnormal,pematangan tulang terlambat.
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