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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.