LO 1

Anatomi

Anatomi Kelenjar Adrenal

Letaknya di superomedial ginjal
Dibungkus oleh fascia renalis, tetapi
dipisahkan dari ginjal oleh jaringan lemak
perirenal.
Sisi kanan bentuk piramid
Sisi kiri bentuk bulan sabit

Korteks Adrenal
Bagian luar kelenjar adrenal
Dari mesoderm
Menghasilkan steroid hormon
(glucocorticoid, mineralocorticoid,
sex steroids)

Medula Adrenal
Bagian dalam kelenjar adrenal
Dari sel krista neural
Menghasilkan hormon epinephrine
dan norepinephrine

Vaskularisasi dan Inervasi

Perdarahan:
arteri suprarenalis superior dari arteri phrenica
inferior
arteri suprarenalis media dari aorta abdominalis
arteri suprarenalis inferior dari arteri renalis

Vena:
V.suprarenalis dextra V.cava inferior
V.suprarenalis sinistra + V.phrenica inferior
V.renalis sinistra

Persarafan:
Plexus coeliacus & abdominopelvic

LO 2
Histologi

Histologi Kelenjar Adrenal

Korteks Adrenal
Zona

Medula Adrenal
Terdiri atas deretan sel kromafin, dengan sinusoid
venosa lebar diantaranya.
Terdapat sekelompok kecil sel saraf
Menghasilkan adrenalin & nor adrenalin
Sitoplasma mengandung banyak vesikel berisikan
sekret ini.
Sel tersusun dalam deretan setebal satu sel pada
tepi sinusoid venosa.

LO 3
Faal

Hormon Korteks Adrenal

Hormon hormon adrenokorteks steroid
lipofilik; diangkut oleh protein plasma
dalam darah
60% aldosteron dalam darah terikat ke
protein (terutama albumin nonspesifik)
90% kortisol terikat ke protein plasma
spesifik corticosteroid-binding globulin /
transcortin
98% DHEA terikat albumin

 Pada keadaan normal, androgen &

estrogen adrenal tdk cukup banyak / kuat
utk menimbulkan efek maskulinisasi /
feminiasi
DHEA (dehidroepiandrosteron) efek
bermakna pada wanita pertumbuhan
rambut pubis & ketiak, peningkatan
lonjakan pertumbuhan pubertas,
perkembangan & pemeliharaan dorongan
seks wanita

Sintesis Hormon Adrenokorteks

Pengaruh Mineralokortikoid
~aldosteron
Aktivitas utama tubulus distal ginjal retensi Na+ &
eliminasi K+
Retensi Na+ memicu retensi osmotik H2O volume
CES>> tekanan darah >>
Sangat esensial tanpa aldosteron meninggal
akibat syok sirkulasi
Stimulasi aldosteron
SRAA (o/ krn penurunan Na+ & tekanan darah)
Peningkatan konsentrasi K+ plasma

Pengaruh Glukokortikoid
~kortisol
Efek metabolik
Merangsang glukoneogenesis hati
Menghambat penyerapan glukosa o/ banyak jaringan
kecuali otak
Merangsang penguraian protein di banyak jaringan
terutama otot
asam amino bebas > glukoneogenesis

Meningkatkan lipolisis
asam lemak bebas > sumber bahan bakar pengganti
glukosa

 Efek permisif
Kortisol hrs adekuat agar katekolamin dapat
memicu vasokonstriksi

Peran dalam adaptasi thdp stres

Stresor >
Fisik (trauma, pembedahan, panas, dingin hebat)
Kimia (penurunan pasokan O2, ketidakseimbangan asam
basa)
Fisiologis (olahraga berat, syok perdarahan, nyeri)
Psikologis / emosi (cemas, ketakutan, kesedihan)
Sosial (konflik pribadi, perubahan gaya hidup)

 Pengaruh fisiologis lain

Mengubah suasana hati & prilaku

Efek anti-inflamasi & imunosupresif

Menghambat hamir semua respon
peradangan
Menekan sistem imunitas normal tubuh,
efek inhibitorik pada sistem imun tubuh
keseluruhan anti alergi, rentan infeksi

 Agar sekresi kortisol relatif konstan

letupan letupan sekresi tingkat
sedang & dipisahkan oleh periode
hening (sekresi minimal/tidak ada)
Jumlah total kortisol dapat diubah dgn
mengubah frekuensi letupan sekretorik
Faktor tambahan yg mempengaruhi
sekresi irama diurnal & stres

Kelainan sekresi hormon

adrenokorteks
Hipersekresi aldosteron
Hiperaldosteronisme primer ~ sindrom
Conn
Hiperaldosteronisme sekunder
Gejala hipernatremia & hipokalemia

 Hipersekresi kortisol (sindrom

cushing)
Stimulasi berlebihan korteks adrenal oleh CRH
dan atau ACTH
Tumor adrenal yg secara tdk terkontrol
menghasilkan kortisol yg tdk tergantung ACTH
Tumor penghasil ACTH terutama di paru
Gejala moon face, buffalo hump, striae, lebam &
ekimosis, mudah fraktur

 Hipersekresi
androgen adrenal
Pseudohermafroditis
me wanita
Pseudopubertas
prekoks

 Insufisiensi adrenokorteks
Primer (Addison disease)
Destruksi autoimun atrofi idiopatik kelenjar adrenal
sekresi hormon adrenal <<

Sekunder
Kelainan hipofisis / hipotalamus ACTH <<
kortisol<< ; aldosteron normal
Gejala gejala defisiensi kortisol penurunan respon
thdp stres, hipoglikemia, hiperpigmentasi akibat sekresi
berlebihan ACTH
Gejala gejala addison hiperkalemia & hiponatremia
ggg irama jantung; vol CES < hipotensi

Hormon medula adrenal

Kel adrenal bag dr sistem saraf
simpatis yg termodifikasi; neuron
praganglion yg berasal dr SSP, akson
berakhir di neuron kedua di perifer,
berakhir di organ efektor
Hormon norepinefrin & epinefrin;
disimpan dalam granula kromafin
Epinefrin reseptor alpha, beta-1 &
-2
Norepinefrin reseptor alpha &

Pengaruh hormon medula adrenal

Efek pada sistem organ
Respon fight or flight
Inotropik & kronotropik jantung > CO >
Vasodilatasi pemb darah koroner & otot rangka
Aktivitas pencernaan & rangsang berkemih <
Dilatasi saluran respirasi

Efek metabolik
Glukoneogenesis & glikogenolisis di hati
Lipolisis > asam lemak bebas >
Laju metabolisme >

Efek lain
Keadaan terjaga & kewaspadaan SSP
Keringat > pengeluaran panas
Membesarkan pupil, mendatarkan lensa mata

 Stimulasi katekolamin
Dikontrol o/ masukan simpatis;
peningkatan impuls simpatis ke kelenjar
Faktor2 utama yg mengontrol
Kondisi stres
Trauma fisik atau psikologis, perdarahan,
penyakit, olahraga, hipoksia (O2 arteri rendah),
pajanan dingin, hipoglikemia

Respons terhadap stress

LO 4
Biokimia

CATECHOLAMINES
Family of bioamines and are secretory
products of the sympathoadrenal system
Epinephrine (8085% of stored
catecholamines) is synthesized primarily in
the cells of the adrenal medulla
Norepinephrine (1520% of stored
catecholamines) is synthesized and stored
not only in the adrenal medulla but also in
various areas of the central nervous
system

Biosynthesis of cathecolamines

Secretion of cathecolamines
Stimulators
pain, hemorrhage, exercise, hypoglycemia, and
hypoxia

Hormon release
Stress nerve impulses emanating from
adrenergic nuclei in the hypothalamus release of
the neurotransmitter acetylcholine from
preganglionic neurons that innervate the
adrenomedullary cells rapid entry of extracellular
calcium (Ca ) into the cytosol synthesis and
release of epinephrine and norepinephrine from the
chromaffin granules
2

Physiological effects

Inactivation of
cathecolamines

Renin-angiotensin-aldosteron
system

GLUCOCORTICOIDS
Cortisol (hydrocortisone) is the major
physiologic glucocorticoid (GC) in
humans, although corticosterone also
has some glucocorticoid activity

Biosynthesis of glucocorticoids , adrenal

androgen & mineralocorticoids

Regulation of glucocorticoids secretion

Physiological effects of glucocorticoids

Fuel metabolism effect of

GC

LO 5
Kelainan kelenjar adrenal

Hyperfunction of adrenal cortex

Cushings syndrome
Aldosteronism
Syndrome of adrenal androgen
excess

Cushings syndrome
Etiology
Adrenal hyperplasia
Secondary to pituitary ACTH overproduction
Pituitary-hypothalamic dysfunction
Pituitary ACTH-producing micro- or macroadenomas

Secondary to ACTH or CRH-producing nonendocrine tumors (bronchogenic carcinoma,

carcinoid of the thymus, pancreatic carcinoma, bronchial adenoma)

Adrenal macronodular hyperplasia (including ectopic expression of GIP

receptors in the adrenal cortex)
Adrenal micronodular dysplasia
Sporadic
Familial (Carney's syndrome)

Adrenal neoplasia
Adenoma
Carcinoma

Exogenous, iatrogenic causes

Prolonged use of glucocorticoids
Prolonged use of ACTH

 Clinical signs

Screening overnight dexamethasone suppression test;

measurement of a 24-h urine free cortisol can also be used as
a screening test (>140 nmol/d (50 g/d) is suggestive of
Cushing's syndrome)

Diagnostic tests

Pituitary cushing syndrome ACTH >; cant be

suppressed with low dose dexamethasone
Ectopic ACTH secretion ACTH >; completely
insensitive to low or high doses of exogenous
dexamethasone
Adrenal tumor cushing syndrome ACTH < (feedback
mechanism

 Radiologic test
CT scan of the abdomen adrenal tumors and for
diagnosing bilateral hyperplasia

Pituitary MRI hypersecretion of pituitary ACTH

 Diagnosis

 DD
Pseudo-cushings syndrome
obesity, chronic alcoholism, depression, and
acute illness of any type abnormalities in
steroid output:
elevated urine cortisol
blunted circadian rhythm of cortisol levels
resistance to suppression using the overnight
dexamethasone test

 Treatment
Adrenal neoplasm
resected using laparoscopic techniques
mitotane (o,p'-DDD), an isomer of the
insecticide DDT Mitotane suppresses
cortisol production and decreases plasma
and urine steroid levels
receive long-term glucocorticoid maintenance
therapy, and, in some, mineralocorticoid
replacement is appropriate

Bilateral hyperplasia
surgical removal ACTH- or CRH-producing
tumors

Aldosteronism
Primary Aldosteronism with an
Adrenal Tumor
Primary Aldosteronism without an
Adrenal Tumor
Secondary Aldosteronism

Primary Aldosteronism with an Adrenal

Tumor
aldosterone-producing adrenal adenoma
excessive and inappropriate aldosterone
production (Conns syndrome)
Unilateral adenoma; usually small and may
occur on either side
twice as common in women as in men
usually occurs between the ages of 30 and
50, and is present in ~1% of unselected
hypertensive patients

Primary Aldosteronism Without an Adrenal

Tumor
~idiopathic hyperaldosteronism, and/or nodular
hyperplasia
e/ bilateral cortical nodular hyperplasia; a solitary
adenoma is not found at surgery
Signs & symptoms
diastolic hypertension severe, headache
Potassium depletion muscle weakness and fatigue
Polyuria, polydipsia
structural damage to the cerebral circulation, retinal
vasculature, and kidney
Proteinuria (50%), renal failure (5%)

 Pathophysiology

 Laboratory findings
Hypokalemia may be severe (<3
mmol/L)
Hypernatremia is infrequent
alkalosis is perpetuated by potassium
deficiency
overnight concentration test impaired
ability to concentrate the urine,
probably secondary to the hypokalemia

 Evaluation

Diagnosis
1. diastolic
hypertension
without edema
2. hyposecretion of
renin
3. hypersecretion
of aldosterone
that does not
suppress
appropriately in
response to
volume
expansion

 DD

 Treatment
surgical excision of the adenoma
administration of an aldosterone
antagoniste.g., spironolactone (25
100 mg every 8 h)
Eplerenone (50150 mg every 8 h)
idiopathic bilateral hyperplasia
surgery is indicated only when
significant, symptomatic hypokalemia
cannot be controlled with medical
therapy

Secondary aldosteronism
increased production of aldosterone in response to
activation of the renin-angiotensin system
aldosterone is often higher in patients with secondary
aldosteronism
accelerated phase of hypertension or on the basis of
an underlying edema disorder
e/
primary overproduction of renin (primary reninism)
overproduction of renin secondary to a decrease in renal
blood flow and/or perfusion pressure
renin-producing tumors (primary reninism)

 Signs & symptoms

severe arteriolar nephrosclerosis +
profound renal vasoconstriction
hypertension
increases in plasma renin activity
hypokalemic alkalosis
Edema (e/ cirrhosis or the nephrotic
syndrome)
Thiazides and furosemide often
exaggerate secondary aldosteronism

Syndromes of adrenal androgen

excess
results from excess production of DHEA
and androstenedione, which are converted
to testosterone in extraglandular tissues
Testosteron > virilization
Type
"pure" syndromes of virilization
"mixed" syndromes associated with excessive
glucocorticoids and Cushing's syndrome

 Pathophysiolog
y
Most etiology
Congenital
adrenal
hyperplasia
(21-Hydroxylase
Deficiency) ->
Neonate with
ambiguous
genitalia

Hypofunction of the Adrenal Cortex

Primary Adrenal Insuffiency
Secondary Adrenal Insufficiency
Hypoaldosteronism

Primary Adrenocortical Deficiency

(Addison's Disease)
Incidence
relatively rare, may
occur at any age,
and affect both
sexes equally

Etiology

 Signs &
symptoms

 Laboratory findings
serum sodium, chloride, and
bicarbonate levels are reduced, and the
serum potassium level is elevated
extravascular sodium loss depletes ECFV
and accentuates hypotension
Elevated plasma vasopressin and
angiotensin II levels may contribute to
the hyponatremia by impairing free
water clearance

 Diagnosis

 Treatment
Hydrocortisone (cortisol) is the mainstay of
treatment (2030 mg/d)
maintain an ample intake of sodium (34 g/d)
mineralocorticoid supplementation
administration of 0.050.1 mg fludrocortisone
per day PO
female patients with adrenal insufficiency,
androgen levels are also low 2550 mg of
DHEA PO

Secondary Adrenocortical
Insufficiency
e/ ACTH deficiency
Signs & symptoms
primary disease but are not hyperpigmented
near-normal level of aldosterone secretion

Tests
low-dose (1 g) ACTH test for suspected secondary ACTH deficiency

laboratory findings
low blood cortisol and ACTH levels

Treatment
Glucocorticoid

Adrenal crisis
rapid and overwhelming intensification of chronic
adrenal insufficiency, usually precipitated by sepsis
(Pseudomonas or meningococcemia (WaterhouseFriderichsen syndrome)) or surgical stress
Signs & symptoms
Nausea, vomiting, and abdominal pain may become
intractable
Fever may be severe or absent
Lethargy deepens into somnolence, and hypovolemic
vascular collapse ensues
mineralocorticoid secretion is usually preserved

 Treatment
IV infusion of 5% glucose in normal
saline solution should be started with a
bolus IV infusion of 100 mg
hydrocortisone followed by a continuous
infusion of hydrocortisone at a rate of 10
mg/h
Vasoconstrictive agents (such as
dopamine) may be indicated in extreme
conditions as adjuncts to volume
replacement

Hypoaldosteronism
Isolated aldosterone deficiency
accompanied by normal cortisol
production occurs in association with
hyporeninism
Features
unexplained hyperkalemia, which is often
exacerbated by restriction of dietary sodium
intake
deficiency in renin production

 Tests
Low renin and aldosterone levels hyporeninemic
hypoaldosteronism
high renin levels and low aldosterone levels biosynthetic
defect or a selective unresponsiveness to angiotensin II

Treatment
administration of 0.050.15 mg fludrocortisone PO daily
should restore electrolyte balance if salt intake is adequate
(e.g., 150200 mmol/d)
Hyperenimic hypoaldosteronims higher doses of
mineralocorticoid to correct hyperkalemia

LO3.
Definisi, epidemiologi,
etiologi, patofisiologi, tanda dan
KELAINAN
PADA
gejala, diagnosis, pemeriksaan fisik, pemeriksaan
tatalaksana, komplikasi, prognosis.
MEDULApenunjang,
ADRENAL

Pheochromocytoma
catecholamine-producing tumors derived from
the sympathetic (pheochromocytomas) or
parasympathetic nervous system
(paragangliomas)
Epidemiology
28 out of 1 million persons per year, and about 0.1%
of hypertensive patients harbor a pheochromocytoma
"rule of tens
10% are bilateral, 10% are extraadrenal, and 10% are
malignant

Etiology of most sporadic pheocromocytoma unknown;

mutations in the RET, VHL, NF1, SDHB, SDHC, or SDHD genes

 Clinical
features

 Macro & microscopic

appearance

zellbalen appearance in
microscopic

 Diagnosis

 Treatment
Complete tumor removal is the ultimate therapeutic goal
-Adrenergic blockers (phenoxybenzamine) should be initiated
at relatively low doses (e.g., 510 mg orally three times per day)
Oral prazosin or intravenous phentolamine can be used to
manage paroxysms while awaiting adequate alpha blockade
Before surgery blood pressure should be consistently below
160/90 mmHg
Beta blockers (e.g., 10 mg propranolol three to four times per
day)
Other antihypertensives, such as calcium-channel blockers or
angiotensin-converting enzyme inhibitors
laparoscopy, using either a transperitoneal or retroperitoneal
(for bilateral adrenalectomy)