KELAINAN

KELENJAR
ADRENAL
Daniel Setiawan Nathan
1115178

dr. Hoo Yumilia, Sp.PD-KEMD

HORMON CORTEX ADRENAL

3 jenis hormon utama:

1. Glukokortikoid
 kortisol
2. Mineralokortikoid

 aldosteron
3. Adrogen / estrogen
 adrenal androgen precursors
(dehydroepiandrosterone,
DHEA)
 BIOSINTESIS HORMON STEROID
EFEK KORTISOL
 Pada Metabolisme
 Glukoneogenesis >>>, Gula darah >>>
 Sintesis glikogen hepar >>>>
 Degradasi protein otot >>>
 Efek anti insulin  uptake glukosa dihambat

 Pada Hemodinamik
 Cathecolamine pressor effects
 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
 Meningkatkan sekresi asam lambung
MINERALOKORTIKOID
Sintesis dan pelepasan
aldosteron  diatur oleh
Angiotensin II
Retensi air dan Na+
Ekskresi K+
PENGATURAN SEKRESI

Produksi aldosteron ↑ pada

keadaan
1. Kehilangan Na+, pemberian K+
2. Penurunan volume cairan
ekstraseluler
3. Penyakit: sirosis hepatis, sindroma
nefrotik, decom. Cordis, hipertensi
maligna
SEX HORMON

Androgen adrenal utama 

- dehidroeplandrosteron
- androstenedion

♀ bila >>  maskulinisasi

ADRENAL INSUFFICIENCY
Addison Disease
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.

 Mortality/Morbidity

Morbidity and mortality  kegagalan/terlambat diagnosis  terapi

pengganti glukokortikoid dan mineralokortikoid terlambat diberikan.

Adrenal crisis  death.

 Ras  tidak spesifik

 Usia

Rata-rata usia 30-50 tahun.

ETIOLOGI
 Primary adrenal insufficiency
 Autoimmune adrenalitis (30–40%)  60–70%
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.
 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)
GEJALA KLINIK
 Fatigue, lack of
energy
 Weight loss, anorexia

Glucocortic  Myalgia, joint pain

 Anemia, nausea,
vomiting.
oid
 Slightly increased
TSH
Deficiency  Hypoglycemia (more
frequent in children)
 Low blood pressure,
postural hypotension
  Dizziness, postural
hypotension
 Salt craving

Mineralocorticoi  Low blood pressure,

postural hypotension
d Deficiency
 Increased serum

(Primary AI Only) creatinine (due to

volume depletion)
 Hyponatremia

 Hyperkalemia
  Loss of libido (in women)
Adrenal  Loss of axillary and
Androgen pubic hair (in women)
Deficiency
 Other Signs and Symptoms
 Hyperpigmentation
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 250-
300mg/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.
 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
KESETARAAN OBAT KORTIKOSTEROID
*(TERHADAP HIDROKORTISON)

Obat Aktivitas Bentuk

(generik) sediaan
Anti Topikal Retensi Na
inflamasi
Glukokortikoid kerja singkat (8-12 jam)

Hidrokortison 1 1 1 Oral,
suntikan,
topikal
kortison 0.8 0 0.8 Oral,
suntikan,
topikal
 Obat Aktivitas Bentuk
(generik) sediaan
Anti Topikal Retensi Na
inflamasi
Glukokortikoid kerja sedang (18-36 jam)

prednison 4 0 0.3 Oral

prednisolon 5 4 0.3 Oral,
suntikan,
topikal
metilprednisolo 5 5 0 Oral,
n suntikan,
topikal
triamsinolon 5 5 0 Oral,
suntikan,
topikal
fluprednisolon 15 7 0 Oral, topikal
Glukokortikoid kerja lama (1-3 hari)
betametason 25-40 10 0 Oral,
suntikan,
 Obat (generik) Aktivitas Bentuk
sediaan
Anti Topikal Retensi Na
inflamasi
Mineralokortikoid

Fludrokortison 10 10 250 Oral,

suntikan,
topikal
Desoksikortikoster 0 0 20 Suntikan
on
ADRENOCORTICAL
HYPERFUNCTION
(HYPERADRENALISM)
 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)
 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).
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)

 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)
CUSHING'S SYNDROME
Middle-aged 3F/1M
4 main causes:
1. Pituitary adenoma - secretes ACTH
2. Adrenal tumors - secrete cortisol
3. Ectopic production of ACTH
4. Iatrogenic Cushing's Syndrome
1. Pituitary adenoma
- secretes ACTH
- 60-70% of cases of pathologic causes
- adrenal glands are hyperplastic
- Biochemistry: Increased ACTH and cortisol
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
3. Ectopic production of ACTH
- by tumors
- lung cancer,
- bronchial and thymic carcinoids,
- medullary thyroid carcinoma,
- islet cell cancer
- 10-15% of cases
- adrenals 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
 Cortisol Hypersecretion

Fat

Protein Catabolism
Decreased Depressed
Moon face, protein synthesis immune reaction
Bulk neck,
Central obesity,
Muscle weakness Gluconeogenesis
Infection
tendency
Hyperglycemia
Striae
and glucosuria
 CLİNİCAL FİNDİNGS İN CUSHING'S
SYNDROME
 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
osteoporosis - decreased
o
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
Clinical findings %
Typical 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:
PRIMARY HYPERALDOSTERONISM
 Bilateral idiopathic hyperaldosteronism (IHA),
 Adrenocortical neoplasm,

 Glucocorticoid-remediable hyperaldosteronism
BILATERAL IDIOPATHIC HYPERALDOSTERONISM
(IHA)
 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.
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 11β-
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.
PRİMARY
HYPERALDOSTERONİSM
 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.
 these patients can die from hypokalemia if you
give them thiazide diuretics to treat their high
blood pressure.
SECONDARY ALDOSTERONİSM
 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)
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.