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KELAINAN KELENJAR ADRENAL
Maria F. Delong (1015155)Eggi Erlangga (1015061)
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 STEROIDKORTISOL 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
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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 (3040%) 6070%
berkembang Autoimmune PolyglandularSyndromes (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 gangguHPA axis
Kasus terbanyak tumor pituitari/hipothalamus
Supresi iatrogenik
Jarang pituitary apoplexy infark pituitaryatau penurunan suplai darah saat operasi atau saat melahirkan (Sheehan's syndrome)
Gejala Klinik
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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Mineralocorticoid
Deficiency
(Primary AI Only)
Dizziness, postural hypotension
Salt craving
Low blood pressure, postural hypotension
Increased serum creatinine (due to volume depletion)
Hyponatremia
Hyperkalemia
Adrenal Androgen Deficiency
Loss of libido (in women)
Loss of axillary and pubic hair (in women)
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.
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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 hyperadrenalsyndromes:
(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 dependentand 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
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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
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
Protein Catabolism Decreased protein synthesis
Depressed immune reaction
Gluconeogenesis
Hyperglycemia and glucosuria
Infection tendency
Muscle weakness
Fat
Striae
Moon face,Bulk neck,Central obesity,
Clinical findings in 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
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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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 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.
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. these patients can die from hypokalemia if you give
them thiazide diuretics to treat their high blood pressure.
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)
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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.