29/04/2015

HORMON CORTEX ADRENAL

KELAINAN KELENJAR ADRENAL

Maria F. Delong (1015155)

Eggi Erlangga (1015061)

dr. Hoo Yumilia, Sp.PD.,KEMD

BIOSINTESIS HORMON STEROID

3 jenis hormon utama:

1. Glukokortikoid
kortisol
2. Mineralokortikoid
aldosteron
3. Adrogen / estrogen
adrenal androgen precursors
(dehydroepiandrosterone, DHEA)

KORTISOL

EFEK KORTISOL
Pada Metabolisme
Glukoneogenesis >>>, Gula darah >>>
Sintesis glikogen hepar >>>>
Degradasi protein otot >>>
Efek anti insulin uptake glukosa dihambat

Pada Hemodinamik
Cathecolamine pressor effects

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Pada fungsi Imun

Produksi cytokine anti-inflamasi >>>, cytokin pro
inflamasi <<<<
Menurunkan immunitas sellular
Meningkatkan jumlah neutrofil, trombosit dan
eritrosit.

Pada SSP
Mengurangi pelepasan CRH dan ACTH (umpan
balik negatif)

Pada sistem Pencernaan

MINERALOKORTIKOID
Sintesis dan pelepasan
aldosteron diatur oleh
Angiotensin II
Retensi air dan Na+
Ekskresi K+

Meningkatkan sekresi asam lambung

Pengaturan sekresi
CRH ACTH Sekresi dari zona fasciculata
aldosteron

Produksi aldosteron pada keadaan

1. Kehilangan Na+, pemberian K+
2. Penurunan volume cairan ekstraseluler
3. Beta adrenergik / cAMP
4. Penyakit: sirosis hepatis, sindroma nefrotik,
decom. Cordis, hipertensi maligna

SEX HORMON
Androgen adrenal utama
- dehidroeplandrosteron
- androstenedion
bila >> maskulinisasi

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Epidemiologi

Prevalensi Addison disease di dunia USA 40-60 kasus per 1 juta

populasi, Britania Raya ada 39 kasus per 1 juta populasi dan 60 kasus per
1 juta populasi di Denmark.

Adrenal Insufficiency

Mortality/Morbidity
Morbidity and mortality kegagalan/terlambat diagnosis terapi
pengganti glukokortikoid dan mineralokortikoid terlambat diberikan.

Addison Disease

Adrenal crisis death.

Ras tidak spesifik

Usia
Rata-rata usia 30-50 tahun.

Etiologi
Primary adrenal insufficiency
Autoimmune adrenalitis (3040%) 6070%
berkembang Autoimmune Polyglandular
Syndromes (APS)
APS kelainan autosomal resesif mutasi pada
autoimmune regulator gene (AIRE)
Kasus jarang destruksi adrenal disebabkan oleh
infeksi, perdarahan
Tuberculous adrenalitis negara berkembang!!
Metastasis Adrenal jarang jadi insufisiensi adrenal
kecuali bilateral, bulky metastases.

Gejala Klinik
Secondary adrenal insufficiency
Disfungsi dari hipothalamus pituitary ganggu
HPA axis
Kasus terbanyak tumor pituitari/hipothalamus
Supresi iatrogenik
Jarang pituitary apoplexy infark pituitary
atau penurunan suplai darah saat operasi atau
saat melahirkan (Sheehan's syndrome)

Glucocorticoid
Deficiency

Fatigue, lack of energy

Weight loss, anorexia
Myalgia, joint pain
Anemia, nausea,
vomiting.
Slightly increased TSH
Hypoglycemia (more
frequent in children)
Low blood pressure,
postural hypotension

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Other Signs and Symptoms

Hyperpigmentation

Mineralocorticoid
Deficiency
(Primary AI Only)

Dizziness, postural
hypotension
Salt craving
Low blood pressure,
postural hypotension
Increased serum
creatinine (due to
volume depletion)
Hyponatremia
Hyperkalemia

Loss of libido (in

women)
Loss of axillary and
pubic hair (in women)

Adrenal
Androgen
Deficiency

Komplikasi
Krisis Adrenal
Muntah,
Abdominal pain,
Syok hipovolemik.

TERAPI

Pasien dengan acute adrenal crisis, resusitasi cairan segera !!!

Larutan NaCl 0.9% (isotonis) koreksi hipotensi
Beberapa pasien butuh suplementasi glukosa
Stres pasien normal kortisol adrenal keluar 250300mg/24jam.
Maka berikan hydrocortisone yg mudah diserap (hydrocortisone
sodium succinate/phosphate) dgn dosis sesuai paling baik infus
Sebelumnya berikan bolus IV hydrocortisone 100 mg
Berikan 100 mg hydrocortisone dalam 100 cc NaCl 0.9% melalui IV
infus kontinyu 10-12 cc/jam.

Alternatif lain 100 mg hydrocortisone bolus setiap 6-8 jam.

Infus menjaga kortisol plasma stabil meskipun dalam keadaan
stres pasien dgn metabolisme yg cepat dan punya kortisol level
rendah.

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Perkembangan klinis TD meningkat setelah 4-6

jam diberi infus hidrokortison.
Setelah 2-3 hari dosis hydrocortisone diturunkan
100-150 mg infus diganti dengan kristaloid
gastrointestinal bleeding HATI-HATI
Kondisi pasien membaik infus hydrocortisone di
tappering sampai 4-5 hari dosis harian 3 mg/jam
(72-75 mg over 24 h) dosis harian oral
Selama pasien menerima >100 mg hydrocortisone dlm
24 jam butuh mineralocorticoid replacement.
Mineralocorticoid replacement daily adrenal gland
aldosterone output 0.05-0.20 mg every 24 hours.
9-alpha-fludrocortisone dosis 0.05-0.10 mg per hari

ADRENOCORTICAL HYPERFUNCTION
(HYPERADRENALISM)
There are three basic types of hyperadrenal
syndromes:
(1) Cushing syndrome, characterized by an excess of
cortisol;
(2) hyperaldosteronism;
(3) adrenogenital or virilizing syndromes caused by
an excess of androgens.

Hypercortisolism (Cushing Syndrome)

The endogenous causes can, in turn, be
divided into those that are ACTH dependent
and those that are ACTH independent

Hypercortisolism (Cushing Syndrome)

Cushing syndrome can be broadly divided into
exogenous and endogenous causes.
The vast majority of cases of Cushing
syndrome are the result of the administration
of exogenous glucocorticoids ("iatrogenic"
Cushing syndrome).

Cushing's Syndrome

Hypercortisolism (Cushing Syndrome)

ACTH-DEPENDENT
Cushing disease (pituitary adenoma; rarely CRH-dependent pituitary hyperplasia)
Ectopic corticotropin syndrome (ACTH-secreting pulmonary small-cell carcinoma,
bronchial carcinoid)
ACTH-INDEPENDENT
Adrenal adenoma
Adrenal carcinoma
Macronodular hyperplasia (ectopic expression of hormone receptors, including
GIPR, LHR, vasopressin and serotonin receptors)
Primary pigmented nodular adrenal disease (PRKARIA and PDE11 mutations)
McCune-Albright syndrome (GNAS mutations)

1.
2.
3.
4.

Middle-aged 3F/1M
4 main causes:
Pituitary adenoma - secretes ACTH
Adrenal tumors - secrete cortisol
Ectopic production of ACTH
Iatrogenic Cushing's Syndrome

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1. Pituitary adenoma
- secretes ACTH
- 60-70% of cases of pathologic causes
- adrenal glands are hyperplastic
- Biochemistry: Increased ACTH and
cortisol

4. Iatrogenic Cushing's Syndrome

- commonest cause overall
- due to long-term corticosteroid therapy for
treatment of:
- connective tissue diseases
- asthma
- rheumatoid arthritis
- cancer
- transplant rejection
- Biochemistry: High cortisol and ACTH
suppressed

3. Ectopic production of ACTH

- by tumors

2. Adrenal tumors
- secrete cortisol
- 20-25% of cases of Cushing's
- adrenal adenoma (50%), carcinoma (50%)
atrophy of contralateral gland
- Biochemistry: low ACTH and high cortisol

Fat

Moon face,
Bulk neck,
Central obesity,

Muscle weakness

Depressed
immune reaction

Gluconeogenesis
Infection
tendency

Striae

Hyperglycemia
and glucosuria

lung cancer,
bronchial and thymic carcinoids,
medullary thyroid carcinoma,
islet cell cancer

10-15% of cases
adrenals are hyperplastic
Biochemistry: Increased ACTH and cortisol

Clinical findings in Cushing's Syndrome

Cortisol Hypersecretion

Protein Catabolism Decreased

protein synthesis

Occurs as a
consequence of excess
plasma glucocorticoid
levels
o truncal obesity, buffalo hump
and moon face due to fat
deposition
o hypertension
o hirsutism - due to increased
testosterone
o muscle weakness and
breakdown
o menstrual irregularity

o osteoporosis - decreased
calcium absorption, increased
bone resorption and
suppression of bone formation
o impaired glucose tolerance or
diabetes mellitus - due to
insulin resistance
o abdominal striae - due to
inhibition of protein synthesis
and abnormal collagen
maturation
o mental symptoms are
common; depression and
psychosis

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Clinical findings

Tipikal Habitus

97

Increased body weight

94

Weakness

87

Hypertension

82

Hirsutism

80

Amenorrhea

77

Striae

67

Personality changes

66

Echimoses

65

Oedem

62

Polyuria, polydipsi

23

Clitoris hypertrophy

19

Primary Hyperaldosteronism
Hyperaldosteronism is the generic term for a
group of closely related conditions
characterized by chronic excess aldosterone
secretion.

Primary Hyperaldosteronism
Hyperaldosteronism may be primary, or it may be secondary
to an extra-adrenal cause.
Primary hyperaldosteronism stems from an autonomous
overproduction of aldosterone, with resultant suppression of
the renin-angiotensin system and decreased plasma renin
activity.
Blood pressure elevation is the most common manifestation
of primary hyperaldosteronism, which is caused by one of
three mechanisms:

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Bilateral idiopathic
hyperaldosteronism (IHA)

Primary Hyperaldosteronism
Bilateral idiopathic hyperaldosteronism (IHA),
Adrenocortical neoplasm,
Glucocorticoid-remediable hyperaldosteronism

Glucocorticoid-remediable
hyperaldosteronism
Glucocorticoid-remediable hyperaldosteronism is an
uncommon cause of primary familial hyperaldosteronism.
In some families, it is caused by a chimeric gene resulting
from fusion between CYP11B1 (the 11-hydroxylase gene)
and CYP11B2 (the aldosterone synthase gene).
This leads to a sustained production of hybrid steroids in
addition to both cortisol and aldosterone.
The activation of aldosterone secretion is under the influence
of ACTH and hence is suppressible by exogenous
administration of dexamethasone.

Bilateral idiopathic hyperaldosteronism (IHA), characterized

by bilateral nodular hyperplasia of the adrenal glands, is the
most common underlying cause of primary
hyperaldosteronism, accounting for about 60% of cases.
Individuals with IHA tend to be older and to have less severe
hypertension than those presenting with adrenal neoplasms.

Adrenocortical neoplasm
Either an aldosterone-producing adenoma (the most common
cause) or, rarely, an adrenocortical carcinoma.
In approximately 35% of cases, primary hyperaldosteronism is
caused by a solitary aldosterone-secreting adenoma, a
condition referred to as Conn syndrome.
This syndrome occurs most frequently in adult middle life
and is more common in women than in men (2 : 1).
Multiple adenomas may be present in an occasional patient.

Primary hyperaldosteronism

low-renin hyperaldosteronism
too much mineralocorticoid
not due to excess ACTH
0.5% of hypertensives have primary
hyperaldosteronism
Patients exhibit hypokalemia, alkalosis, and low
renin,
Low potassium is likely to cause muscle weakness,
and even paralysis.

Secondary aldosteronism

In secondary hyperaldosteronism, in contrast, aldosterone release occurs

in response to activation of the renin-angiotensin system.
It is characterized by increased levels of plasma renin and is encountered
in conditions such as the following:
Decreased renal perfusion (arteriolar nephrosclerosis, renal artery
stenosis)
Arterial hypovolemia and edema (congestive heart failure, cirrhosis,
nephrotic syndrome)
Pregnancy (due to estrogen-induced increases in plasma renin substrate)

these patients can die from hypokalemia if you give

them thiazide diuretics to treat their high blood
pressure.

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Therapy
Spronolactone : Aldosterone antagonist

Adrenal Androgen Excess

Sindroma ini disebabkan oleh adanya produksi
yang berlebih dari hormone DHEA dan
androstenedion yang dikonversi menjadi
testoteron dalam jaringan ekstraglandular.
(a) Pada anak-anak menyebabkan precocious
puberty
(b) Pada wanita dewasa dapat menyebabkan
vitilisme

Pengobatan non-farmakologis a.l. (l) bleaching, (2) depilatory (3)

epilatory
Terapi Farmakologis ditujukan untuk menghalangi satu atau lebih
tahapan pada jalur sintesis atau pada jalur kerja androgen:
(1) menekan produksi androgen dan/ ovarial androgen;
(2) mempercepat pengikatan androgen oleh plasma binding
protein, teruta-ma SHBG;
(3) mengacau dan merusak konversi peripheral precursor androgen
menjadi androgen yang aktif,
(4) menghambat kerja androgen pada tingkat jaringan target. Hasil
pengobatan baru mulai nampak setelah 3-6 bulan kemudian.

Terapi kombinasi estrogen-progestin dalam

bentuk oral kontraseptif biasanya merupakan
terapi endokrin pilihan (first-line) untuk
pengobatan hirsutisme dan acne, dan diberikan
setelah dilakukan pengobatan secara kosmetik
dan dermatologik.
Komponen estrogen dari kontraseptif yang
dipakai saat ini ialah etinilestradiol atau
mestranol.