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INTRODUCTION TO ENDOCRINOLOGY
ANATOMY OF ENDOCRINE ORGAN
BIOCHEMISTRY OF HORMONE
HORMONE ACTION
DIAGNOSTIC TESTING
APPROACH TO THE PATIENT WITH ENDOCRINE DISEASE
FACULTY OF MEDICINE
BRAWIJAYA UNIVERSITY
MALANG
2014
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INTRODUCTION TO ENDOCRINOLOGY
Endocrinology is concerned with the study of the biosynthesis, storage, chemistry, and
physiological function of hormones and with the cells of the endocrine glands and tissues that
secrete them. The endocrine system consists of several glands, in different parts of the body,
that secrete hormones directly into the blood rather than into a duct system. Hormones have
many different functions and modes of action; one hormone may have several effects on
different target organs, and, conversely, one target organ may be affected by more than one
hormone.
In the original 1902 definition by Bayliss and Starling, they specified that, to be classified
as a hormone (derived from Greek phrase meaning to set in motion), a chemical must be
produced by an organ, be released (in small amounts) into the blood, and be transported by the
blood to a distant organ to exert its specific function. This definition holds for most "classical"
hormones, but there are also paracrine mechanisms (chemical communication between cells
within a tissue or organ), autocrine signals (a chemical that acts on the same cell), and
intracrine signals (a chemical that acts within the same cell). A neuroendocrine signal is a
"classical" hormone that is released into the blood by a neurosecretory neuron.
The classic endocrine glands-pituitary, thyroid, parathyroid, pancreatic islets, adrenal,
and gonads-communicate broadly with other organs through the nervous system, hormones,
cytokines, and growth factors. Hormones act by binding to specific receptors in the target organ.
As Baulieu notes, a receptor has at least two basic constituents: 1) a recognition site, to which
the hormone binds, and 2) an effector site, which precipitates the modification of cellular
function. Between these is a "transduction mechanism" in which hormone binding induces
allosteric modification that, in turn, produces the appropriate response.
The interdigitation of endocrinology with physiology processes in other specialties
sometimes blurs the roles of hormones. For example, hormones play an important role of
hormones. For example, hormones play an important role in maintanance of blood pressure,
intravascular volume, and peripheral resistance in the cardiovascular system. Vasoactive
substances such as catecholamines, angiotensin II, endothelin, and nitric oxide are involved in
dynamic changes of vascular tone, in addition to their multiple roles in other tissues. The heart
is the principal source of atrial natriuretic peptide, which acts in classic endocrine fashion to
induce natriuresis at a distant target organ (the kidney).
References
1. Fauci AS, Braunwauld E, Jameson JL et al, Harrisons Endocrinology. 2 nd Edition, China:
McGraw-Hill, 2010.
2. Gardner DG and Shoback D. Basic and Clinical Endocrinology 9th edition, China :
McGraw-Hill, 2011
3. H.M. Kronenberg, Melmed S, Larsen PR, Polonsky KS. Williams Textbook of
Endocrinology 12th edition, Philadelphia : Elsevier, 2011.
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ANATOMY OF ENDOCRINE ORGANS
Histogenesis kelenjar berasal dari invaginasi sel2 epithel. Bila sel2 dibagian bawah
lapisan permukaan tetap ada, akan menjadi ductus excretorius (saluran pengeluaran) dan
menjadi kelenjar eksokrin yang bekerja lokal. Bila sel2 ini menghilang (disappearance) akan
menjadi kelenjar endokrin, yang tidak memiliki saluran pengeluaran, dan sebagai gantinya disitu
banyak pembuluh darah untuk menyalurkan hasil sekresi kelenjar yaitu hormone menuju ke
target organ yang letaknya bisa jauh dri kelenjarnya.
Sistem endokrin adalah sistem kontrol kelenjar tanpa saluran yang hasilnya yaitu
hormone, sebagai pembawa pesan dibawa oleh darah menuju ke target organ yang
melaksanakan pesan tadi sebagai tindakan.
Macam2 kelenjar endokrin :
1. Hypophyse
2. Thyroid
3. Parathyroid
4. Suprarenalis
5. Pulau Langerhans pancreas
6. Testis
7. Ovarium
Kelenjar hipofise lokasinya didalam canium, dibasis cranii, ukuranya sebesar buah
anggur lokal, terdiri dari 3 bagian yaitu lobus anterior, pars intermedia dan lobus posterior.
Masing2 bagian menghasilkan hormone yang berbeda ; misalnya lobus anterior menghasilkan
macam2 hormon, antara lain growth hormon yang bekerja pada tulang, otot dan lemak yang
mengontrol pertumbuhan badan. Bila hormon pertumbuhan ini sangat berlebihan akan terjadi
pertumbuhan raksasa dan bila sangat kurang akan terjadi kerdil. Lobus posterior menghasilkan
oxitocin untuk kontraksi uterus, sehingga bayi bisa lahir, serta ADH untuk mengontrol
pengeluaran urine, bila ada gangguan bisa terjadi diabetes incipidus dimana pengeluaran urine
sangat banyak.
Kelenjar thyroid lokasinya didaerah leher setinggi os thyroid, terdiri dari dua lobus kanan
dan kiri yang dihubungkan oleh bagian yang sempit yaitu isthmus, sehingga bentuknya seperti
huruf H , fungsinya menghasilkan hormon thyroxin untuk mengatur metabolisme tubuh. Bila
membesar disebut struma tanpa melihat fungsinya dan tampak sebagai benjolan didaerah leher
yang ikut bergerak saat orang menelan. Bila fungsi berlebihan disebut hyperthyroid dengan
gejala orang merasa selalu lapar, berkeringat, jantung berdebar, bahkan bisa terjadi tremor. Bila
fungsi berkurang disebut hypothyroid : orang lemah, gemuk dan kulit kasar. Dipermukaan
posterior masing2 lobus kelenjar thyroid, dibagian atas dan agak bawah terdapat kelenjar
parathyroid, jadi ada empat kelenjar parathyroid, ukuran sebesar biji kacang hijau.
Menghasilkan parathyroid hormon untuk mengatur keseimbangan kadar kalcium dalam darah
dan tulang. Bila parathyroid hormon berlebihan (hiperparathyroid), kadar kalcium dalam darah
menjadi tinggi dan kacium dalam tulang turun sehingga tulang menjadi keropos (osteoporosis),
dengan akibat mudah terjadi fraktur (fraktura spontanea). Bila kadar kalcium dalam darah turun
bisa terjadi tetani (kejang otot).
Kelenjar suprarenalis, lokasinya pada kutub atas masing2 ren, bentuk agak segitiga.
Terdiri dari dua bagian yaitu cortex yang lebih luas, dan medula yang lebih sempit.Bagian cortex
ini essential untuk kehidupan, karena menghasilkan hormon yang mengatur keseimbangan
cairan dan elektrolit (ACTH). Bentuk dan susunan sel2 dicortex ini berbeda2 sehingga
menyebabkan cortex terbagi menjadi 3 zona : zona glomerulosa, zona fasciculata dan zona
reticularis. Cortex suprarenalis
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BIOCHEMISTRY OF HORMONE
Module Tasks :
1. Terangkan mengenai klasifikasi hormon
2. Hormon apa saja yang merupakan turunan steroid,
sintesisnya dan fungsi dari hormon tersebut.
3. Hormon apa saja yang memerlukan asam amino tyrosin untuk sintesisnya, jelaskan
proses sintesis dan fungsinya.
4. Jelaskan tentang sintesis insulin, struktur insulin dan efek ssertacara kerja insulin di
dalam sel
5. Jelaskan tentang hormone angiotensin, struktur , sintesisnya dan efeknya terhadap sel
6. Jelaskan tentang POMC family, sistem sintesisnya, dan efek tiap hormon pada tubuh
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MECHANISM OF HORMONE ACTION
By:
dr. Dian Hasanah, M.Biomed
1. Several types of chemical messenger systems:
a. Neurotransmitters are released by axon terminals of neurons into the synaptic
junctions and act locally to control nerve cell functions.
b. Endocrine hormones are released by glands or specialized cells into the circulating
blood and inuence the function of cells at another location in the body.
c. Neuroendocrine hormones are secreted by neurons into the circulating blood and
inuence the function of cells at another location in the body.
d. Paracrines are secreted by cells into the extracellular uid and affect neighboring
cells of a different type.
e. Autocrines are secreted by cells into the extracellular uid and affect the function of
the same cells that produced them by binding to cell surface receptors.
f.
Cytokines are peptides secreted by cells into the extracellular uid and can function
as autocrines, paracrines, or endocrine hormones. Examples of cytokines include
the interleukins and other lymphokines that are secreted by helper cells and act on
other cells of the immune system. Cytokine hormones (e.g., leptin) produced by
adipocytes are sometimes called adipokines.
d. Controlling reproduction.
e. Regulating red blood cell production.
f.
Along with the autonomic nervous system, controlling and integrating activities of
both the circulatory and digestive systems.
4. Definition of hormone:
Hormone is a blood-borne chemical messenger synthesized and released by endocrine
gland that act on target cells located a long distance from the location it released.
5. Definition of tropic hormone:
Tropic hormone is a hormone that its primary function is to regulate hormone secretion
by another endocrine gland.
6. Three general classes of hormones based on their chemical structure:
a. Proteins and polypeptides, including hormones secreted by the anterior and posterior
pituitary gland, the pancreas (insulin and glucagon), the parathyroid gland (parathyroid
hormone), and many others.
b. Steroids secreted by the adrenal cortex (cortisol and aldosterone), the ovaries (estrogen
and progesterone), the testes (testosterone), and the placenta (estrogen and
progesterone).
c. Derivatives of the amino acid tyrosine, secreted by the thyroid (thyroxine and
triiodothyronine) and the adrenal medullae (epinephrine and norepinephrine).
There are no known polysaccharides or nucleic acid hormones.
7. Two classes of hormones based on their solubility in water or lipid:
a. Water-soluble hormones (hydrophilic): peptides and catecholamines.
b. Lipid-soluble hormones (lipophilic): steroid and thyroid hormones.
8. The principle differences of synthesis, storage, secretion, and transport of hormones:
a. Protein and Peptide Hormones
Synthesis: Protein and peptide hormones are synthesized on the rough end of
the endoplasmic reticulum of the different endocrine cells. They are usually
synthesized
rst
as
larger
proteins
that
are
not
biologically
active
endoplasmic reticulum. These are then transferred to the Golgi apparatus for
packaging into secretory vesicles. In this process, enzymes in the vesicles
cleave the prohormones to produce smaller, biologically active hormones and
inactive fragments.
Storage: The vesicles are stored within the cytoplasm, and many are bound to
the cell membrane until their secretion is needed.
Secretion: Secretion of the hormones (as well as the inactive fragments) occurs
when the secretory vesicles fuse with the cell membrane and the granular
contents are extruded into the interstitial uid or directly into the blood stream
by exocytosis. In many cases, the stimulus for exocytosis is an increase in
cytosolic calcium concentration caused by depolarization of the plasma
membrane. In other instances, stimulation of an endocrine cell surface receptor
causes increased cyclic adenosine monophosphate (cAMP) and subsequently
activation of protein kinases that initiate secretion of the hormone.
Transport: The peptide hormones are water soluble. Water-soluble hormones
are dissolved in the plasma and transported from their sites of synthesis to
target tissues, where they diffuse out of the capillaries, into the interstitial uid,
and ultimately to target cells.
b. Steroid Hormones
Synthesis: The chemical structure of steroid hormones is similar to that of
cholesterol, and in most instances they are synthesized from cholesterol itself.
Large stores of cholesterol esters in cytoplasm vacuoles can be rapidly
mobilized for steroid synthesis after a stimulus. Much of the cholesterol in
steroid-producing cells comes from the plasma, but there is also de novo
synthesis of cholesterol in steroid-producing cells.
Storage: Steroid hormones are usually not stored.
Secretion: Because the steroids are highly lipid soluble, once they are
synthesized, they simply diffuse across the cell membrane and enter the
interstitial uid and then the blood.
Transport: Steroid hormones are not water soluble, circulate in the blood mainly
bound to plasma proteins. Usually less than 10 per cent of steroid hormones in
the plasma exist free in solution. Protein-bound hormones cannot easily diffuse
across the capillaries and gain access to their target cells and are therefore
biologically inactive until they dissociate from plasma proteins.
c. Amine Hormones
The two groups of hormones derived from tyrosine, the thyroid and the adrenal
medullary hormones, are formed by the actions of enzymes in the cytoplasmic
compartments of the glandular cells.
i. Thyroid
Synthesis: The thyroid hormones are synthesized in the thyroid gland by the
actions of enzymes in the cytoplasmic compartments and incorporated into
macromolecules of the protein thyroglobulin.
Storage: The thyroid hormone is stored in large follicles within the thyroid gland.
Secretion: Hormone secretion occurs when the amines are split from
thyroglobulin, and the free hormones are then released into the blood stream.
Transport: Thyroid hormones are not water soluble. After entering the blood,
most of the thyroid hormones combine with plasma proteins, especially
thyroxine-binding globulin, which slowly releases the hormones to the target
tissues. Protein-bound hormones cannot easily diffuse across the capillaries
and gain access to their target cells and are therefore biologically inactive until
they dissociate from plasma proteins.
ii. Epinephrine and Norepinephrine
Synthesis: Epinephrine and norepinephrine are formed in the adrenal medulla
by the actions of enzymes in the cytoplasmic compartments, which normally
secretes about four times more epinephrine than norepinephrine.
Storage: Catecholamines are taken up into preformed vesicles and stored until
secreted.
Secretion: Similar to the protein hormones stored in secretory granules,
catecholamines are also released from adrenal medullary cells by exocytosis.
Transport: Once the catecholamines enter the circulation, they can exist in the
plasma in free form or in conjugation with other substances. Catecholamines
are dissolved in the plasma and transported from their sites of synthesis to
target tissues, where they diffuse out of the capillaries, into the interstitial uid,
and ultimately to target cells.
9. Plasma concentration of a hormone is influenced by:
a. Hormone secretion.
b. Peripheral hormone conversion.
c. Hormone transport.
d. Hormone inactivation.
e. Hormone excretion.
10. Hormones are cleared from the plasma in several ways, including:
a. Metabolic destruction by the tissues.
b. Binding with the tissues.
c. Excretion by the liver into the bile.
d. Excretion by the kidneys into the urine.
11. Negative feedback:
After a stimulus causes release of the hormone, conditions or products resulting from the
action of the hormone tend to suppress its further release. In other words, the hormone
(or one of its products) has a negative feedback effect to prevent oversecretion of the
hormone or overactivity at the target tissue.
Positive feedback:
In a few instances, positive feedback occurs when the biological action of the hormone
causes additional secretion of the hormone. One example of this is the surge of
luteinizing hormone (LH) that occurs as a result of the stimulatory effect of estrogen on
the anterior pituitary before ovulation. The secreted LH then acts on the ovaries to
stimulate additional secretion of estrogen, which in turn causes more secretion of LH.
12. Hormones in human and their functions:
Thymus
Thymosin
Skin
Vitamin D
Liver
Promotes growth
Stimulates platelet production
Thrombopoietin
Inhibit absorption of iron into blood
Hepcidin
Pineal
Melatonin
References
1. Guyton AC, Hall JE. Textbook of Medical Physiology. 11th Edition. Philadelphia: Elsevier
Inc., 2006.
2. Sherwood L. Human Physiology From Cells to Systems. 7 th Edition. Canada:
Brooks/Cole Cengage Learning, 2010.
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DIAGNOSTIC TESTING
Topik 1: Pemeriksaan laboratorium untuk diabetes mellitus
Gambaran klinis
Diagnostik
Monitoring
Komplikasi
Lain-lain
DM pada anak
GDM
POCT-SMBG
Pemeriksaan TSH
Tiroglobulin
Buku acuan:
Burtis CA, Ashwood ER, Bruns DE, Tietz Fundamentals of Clinical Chemistry, Sunders
Elsevier, 2008
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APPROACH TO THE PATIENT WITH ENDOCRINE DISEASE
Endocrine diseases are easily recognizable in their more extreme forms. It is hoped that most
patients will be diagnosed well before they progress to that stage; endocrinologists hope to
prevent diseases and their sequelae or detect and treat disease at an early stage.
Several principles should be considered in evaluating endocrine diseases. Symptoms are often
vague and attributable to anxiety or depression or to non-endocrine causes. Early presentation
of these disorders can be masked further by compensatory responses. The clinical presentation
of a given condition can differ depending on its chronicity, and a severe deficiency state can
present as an acute and severe problem in a patient. The clinician must decide whether
treatment should be instituted immediately, before time-consuming tests leading to definitive
diagnosis have been completed. It is sometimes difficult to arrive at a clear diagnosis, and the
procedures needed for definitive diagnosis may impose more risk than the disease over a short
period of time, especially if disease manifestations can be managed symptomatically.
Efficiency and accuracy of diagnosis are priorities. Modern endocrine testing (including
genotyping) often involves considerable cost, but its goal is enhanced efficiency and accuracy of
diagnosis. By combining targeted endocrine testing and imaging with a careful history and
physical examination and sound clinical judgment, the clinician should be able to diagnose and
manage most endocrine diseases.
History & Physical Examination
A carefully performed history and physical examination is critically important. Some diagnoses,
such as hypertension, are based on physical examination findings alone. Clinical data gathering
should focus on issues that will lead to the diagnosis, help determine how much tissue damage
or physical deformity has occurred, and aid in developing a therapeutic plan. Clinical
evaluations should help define how long the disease has been present and provide relevant
data from the social, family, and past medical histories that will facilitate evaluation and
management.
Signs and symptoms of endocrine disorders span the entire clinical spectrum. Manifestations of
endocrine disease that are frequently due to non-endocrine or unknown causes (Table 11)
include fatigue, malaise, weakness, headache, anorexia, depression, weight gain or loss,
bruising, and constipation, and many others.
Table 11. Examples of Manifestations of Endocrine Disease. (The Manifestations Do Not
Occur in All Cases, and the Severity Can Vary Markedly.)
Abdominal pain
Amenorrhea or
oligomenorrhea
Anemia
Anorexia
Constipation
Depression
Diarrhea
Hyperthyroidism,
carcinoma
Fever
Hair changes
Headache
Hypothermia
Hypoglycemia, hypothyroidism
Libido changes
Nervousness
Polyuria
Skin changes
Weakness and
fatigue
Weight gain
Weight loss
Adrenal
metastatic
insufficiency,
carcinoid
anorexia
tumors,
nervosa,
metastatic
cancer
of
medullary
endocrine
thyroid
glands,
Laboratory Studies
Laboratory tests in endocrine diagnosis are performed to measure hormone levels in body
fluids, the effects of the hormone on target cells, or the systemic sequelae of the underlying
process. Tests can be done under random or basal conditions, precisely defined conditions, or
in response to provocative or suppressive maneuvers. In measuring hormone levels, the
sensitivity of the assay refers to the lowest concentration of the hormone that can be accurately
detected, and the specificity refers to the extent to which cross-reacting species are scored
inappropriately in the assay.
Imaging Studies. these procedures are especially useful for evaluation of tumors of the
pituitary and adrenals.
Biopsy Procedures
of other family memberscan distinguish subsets of patients with MODY from those with type 1
diabetes and guide treatment.
Use
Progesterone
Contraceptive, abortifacient
Glucocorticoid
Mineralocorticoid
Androgen
Prostate cancer
Estrogen
Breast cancer
GnRH
Prostate cancer
Adrenergic receptor
Hypertension, hyperthyroidism
Prostaglandin
Angiotensin II
Dikutip dari : Greenspans Basic and Clinical Endocrinology. Editors : Gardner DG and
Shoback D, 9th edition, China : McGraw-Hill, 2011
MODUL TASKS
1. Define the term hormone and briefly outline how the endocrine system contributes to
homeostasis.
2. Describe how both the anterior pituitary and posterior pituitary glands are regulated by
the hypothalamus.
3. Table: The major hormones synthesized and secreted by the pituitary gland.
Hormones
Anterior
pituitary
Posterior
pituitary
4. Feedback mechanisms are of major importance in controlling the various body systems
and maintaining homeostasis. Describe both positive and negative feedback and discuss
one example of each from the endocrine system.
5. The adrenal cortex consists of three distinct zones :
Zona glomerulosa
Zona fasciculata
Zona reticularis
Each zone has a characteristic histology and secretes different types of hormones :
Layer
Most
superficial
cortical layer
Middle cortical
layer
Deepest
cortical layer
Name
Primary Product
Mineralocorticoid
Glucocorticoid and
Androgen