PEMERIKSAAN LABORATORIUM DAN INTERPRETASI PADA GROWTH RETARDATION
Prof. dr. Burhanuddin Nst. SpPK (K)
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Pendahuluan z
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Masa anak-anak adalah waktu untuk tumbuh, merupakan k proses kkomplek l kd dan melibatkan lib tk interaksi banyak faktor. P t b h adalah Pertumbuhan d l h bi biasa untuk t k organisme i multicellular dan terjadi dengan cara pembelahan sel dan pembesaran sel dan organ differensiasi
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Perkembangan morfologi secara menyeluruh d kkecepatan dan t pembelahan b l h sell pada d berbagai organ pada waktu yang berbeda dan outcome yang diperoleh ditentukan oleh komposisi genetik dari seseorang dan berinteraksi dengan g faktor-faktor eksternal,, termasuk nutrisi, psikososial dan faktor ekonomi
Fase-fase pertumbuhan normal z
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Pertumbuhan terjadi pada kecepatan b b d b d selama berbeda-beda l masa : - Intra uterine - Masa awal dan pertengahan Childhood dan - Masa adolescene Pertumbuhan pre-natal rata-rata 1,2-1,5 cm/minggu
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Midgestational length growth velocity dari 2,5 cm/minggu / i tturun menjadi j di 0 0,5 5 cm/minggu, / i segera akan lahir K Kecepatan t pertumbuhan t b h rata-rata t t ± 15 cm/tahun, selama 2 tahun pertama kehidupan dan perlahan menjadi 6 cm/tahun kehidupan, selama middlle childhood
Growth Retardation (GR) GR diklasifikasikan sbb: I. Primary Growth Abnormalities A. Osteochondrodysplasia B. Chromosomal abnormalities C. Intra Uterine Growth Retardation
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II. Secondary Growth Disorders A. Malnutrition B. Chronic Disease C. Endocrine Disorders
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Sambungan. . . . .
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C. Endocrine Disorders 1. Hypothyroidism 2. Cushing’s Syndrome 3. Pseudohypo Parathyroidism 4. Rickets a vitamin D resistant rickets 5. IGF deficiensy yp dysfunction y a. GHD due to Hypothalamic b. GHD due to pituitary GH deficiency
Sambungan. . . . .
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c. GH resistance 1. Primary GH insensitivity 2. Secondary GH insensitivity d. Primary defects of IGF transport& clearance e. IGF Insensitivityy 1. Defect of the type I/GF receptor p defect 2. Post receptor III. Idiopathic Short Stature
Excess Growth and Tall Stature z z z z z z
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Fetal IGF II Post natal Excess GH secretion Hyperthyroidism Adult androgen or estrogen deficiency Testicular feminization Excess GH
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Hypothyroidism z
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Hypothyroidism is the disease caused by i insufficient ffi i t production d ti off th thyroid id h hormone b by the thyroid gland. C ti i Cretinism iis a fform off h hypothyroidism th idi ffound d in infants.
How To Diagnostic Hypothyroidism ? z
To diagnose hypothyroidism, – – – –
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If the TSH is normal and hypothyroidism is still suspected blood testing ; suspected. – – –
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TSH↑, FT4↓ Æ Primary Hipothyroidism TSH↑ TSH↓, FT4↓, FT3 N ↓Æ Secondary Hipothyroidism TSH↓, FT4 N, FT3↓Æ Secondary Hipothyroidism Suppression of thyrotropin-releasing hormon ( TRH )Æ ( Tertiary Hipothyroidism )
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Free triiodothyronine (fT3) Free levothyroxine (fT4) Total T3 Total T4
The following measurements may be needed: z z z z z z
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24 hour urine free T3 Antithyroid antibodies — for evidence of autoimmune diseases that may be damaging the thyroid gland Serum cholesterol — which may be elevated in h hypothyroidism h idi Prolactin — as a widely available test of pituitary function Testing for anemia, including ferritin Basal body temperature
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Hipotiroid (FF), Laboratorium - T3 menurun - T4 menurun - TSH normal Hipertiroid : - T3 meningkat → T3 Tirotoksikosis g → T4 Tirotoksikosis - T4 meningkat
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Pendekatan untuk penderita Hypothyroidism (FF) Sign/symtoms Hypothyoridism Yes
TSH Level FT4 or FT4I TSH Ï FT4 Ð or FT4I
TSH Ï FT4(N) or FT4I(N)
TSH (N) or Ð TSH (N) FT4 Ð or FT4I Ð FT4(N) or FT4I(N)
Primary Hypothyroidism
Subclinical Hypothyroidism
Consider Central Causes of patients Hypothyroidism Sign & symtoms
Consider other
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Sign & Symtoms Hypothyroidism z z z z z z
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Weakness Dry skin Edema Eye Lids Cold skin Memory ⇓ Constipation
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Weight gain Loss of hair Anorexia Nervousness Sweating ⇓ Parasthesia
Hyperthyroidism z
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Hyperthyroidism is the term for overactive ti tissue within ithi th the th thyroid id gland, l d resulting lti iin overproduction and thus an excess of circulating free thyroid hormones: thyroxine (T4), triiodothyronine (T3), or both
How To Diagnostic Hyperthyroidism ?
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TSH↓, FT4↑ Æ Hiperthyroidism. – Excessive E i iiodide did iintake t k – Overmedication Æ chronic oral thyroxine – Graves Graves’ desease / toxic goiter TSH↓, FT4 normal, FT3↑ Æ Thyrotoxicosis TSH↑, FT4 ↑ Æ TSH secreting tumor anti-TSH-receptor antibodies
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anti-thyroid-peroxidase y p
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Pendekatan untuk penderita Hyperthyroidism Sign/symtoms Hyperthyoridism Yes
TSH Level FT4 or FT4I TSH Ð TSH Ð FT4 Ï or FT4I Ï FT4(N) or FT4I(N) T3
Hyperthyroidism yp y Diffuse goiter + bruit Opthalmopathy Pretibial oedema
Yes Gvave Disease
No
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Subclinical S b li i l Hiperthyroid
Perform P f Radioactive Iodine Uptake test
TSH Ï TSH (N) FT4 Ï or FT4I Ï FT4(N) or FT4I(N) Consider TSH Producing Adenoma
Consider other Causes of patients Sign & symtoms
T3 Thyrotoxicosis
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Sign & Symptoms Hyperthyroidism z z z z z z z z z
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Nervousness Emotional lability Tremor Palpitations Fatigue Weight loss Tachycardia Atrial Fibrilasi Ï diff systole & diastole BP
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Diarrhea Prox Muscle weakness Prox. Heart intolerance Moist skin Fine hair Hair loss Weakness Increase appetite
Cushing's syndrome z
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Cushing's syndrome (hyperadrenocorticism or hypercorticism) is a hormone (endocrine) disorder caused by high levels of cortisol (hypercortisolism) in the blood. There are several possible causes of Cushing's syndrome. – –
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Hormones that come from outside the body are called exogenous (glucocorticoid l ti id d drugs ) hormones that come from within the body are called endogenous. (tumors that produce cortisol or adrenocorticotropic hormone (ACTH). )
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The paraventricular nucleus (PVN) of the h hypothalamus th l releases l corticotropin-releasing ti t i l i hormone (CRH)Æ Pituitary gland to release adrenocorticotropin (ACTH) Æ Adrenal gland (zona fasciculata ) Æ (cortisol). Elevated levels of cortisol exert negative feedback on the pituitary.
Laboratory Diagnostic z z z
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Dexamethasone suppression test 24-hour urinary measurement for cortisol Cortisol in saliva over 24 hours
Cushing Syndrome (CS) z
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CS results p prolong g Exposure p to excessive amounts of endogenous or exogenous corticosteroids Kadar Cortisol plasma lebih besar dari 7 ug/dl (200nmol/L) pada midnight Organ normal : - Paling tinggi pagi hari, malam meningkat sedikit (2ug/dl)
Sambungan. . . . .
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- False positif : Stress (vena puncture), Penyakit berulang-ulang, takut Free Cortisol urin : - Metabolisme cortisol di urin : 17 hydrocorticosteroid atau 17 exogenicsteroid g jjam - Normal 80-120 ug/24 - Bisa normal 8-15% penderita
Dexamethazon Suppression Test z z
1 mg dexamethazon diberi tengah malam Pada jam antara 08-09, bila response normal kadar plasma cortisol < 5 ug/dl
Cushing g Syndrome y z z
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ACTH dependent ACTH independent
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Kadar ACTH antara 11.00-01.00 PM > 23 pg/dl → ACTH dependent Pemeriksaan ACTH dgn Imunoradiometric Klinis : - Centripetal Obesity + Buffalo Hump - Moonface - Hirsutism
Cushing’s Syndrome
Sign & Symtoms Present Perform Screening test for CS 24 hours urin collection for Cortisol or Over night 1 mg DST
24 hours urin Cortisol Cortisol (N) Consider Alternative diagnosis
Perform over night 1 mg DST
Cortisol ↑ Cortisol ↑ > 3 3.5X 5X But not > 3.5X Upper limit normal Upper limit normal Futher evaluation To differentiate Cushing’s from pseudocushing
Cushing s Cushing’s Syndrome
Cortisol > 5 ug/dl Cushing’s Syndromel Plasma ACTH
Perform one of the following: -Dexamethazon-CHR test -Midnight serum cortisol -Late Late night salivary cortisol Stop
Results consistent with pseudocushing’s
Results consistent with Cushing’s
>10-15 pg/dl ⇓ A
< 5 pg/dl, consider Adrenal causes of CS Perform CT / MRI Adrenal Gland 31
A.
Plasma ACTH Plasma ACTH > 10-15 pg/dl
Perform High Dose DST (8 mg Dexamethazon) Suppression (+)
Cushing’s C hi ’ Disease
Suppression (-)
Ectopic ACTH Screening tumor 32
Sign & Symtoms CS z z z z z
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Central Obesityy Proximal Muscle Weakness(hips,shoulders) Hypertension buffalo hump moon face
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Acne Hyperpigmentasion Hirsutism(male-pattern hair growth in a female) Hyperglicemia Hypokalmic metabolik Acidosis
Pseudo hypoparathyroid z z z
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Hipercalcemic Laboratorium Hiperphosphatemic Klinis : - Short stature - Rounded face Albright’s g Hereditary - Obesitas Osteodystrophy - Subcutan Calcification (AHO) - Shortened fourth metacarpal
Rickets z z
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Gangguan mineralisasi dari organik matrik tulang Anak-anak a a a ga gangguan ggua te terjadi jad pada : - Growth plate - Mineralisasi kartilago → terjadi deformitas
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Vitamin D is required for proper calcium absorption b ti ffrom th the gut. t In I the th absence b off vitamin D, dietary calcium is not properly absorbed resulting in hypocalcemia, absorbed, hypocalcemia leading to skeletal and dental deformities and neuromuscular
Laboratorium (Rickets) Infants dengan g Vit. D Deficiency y z Serum Calcium selalu rendah z Serum Phosphat batas normal z serum alkaline phosphatase meningkat
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Disorder Di d off th the Pituitary Pit it & Hypothalamus
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Anterior Pituitary mensintesa : - Growth Hormon - Prolactin - TSH - FSH - LH Hypothalamus mensekresi tropik hormon untuk masing-masing
Pituitary hormon excess z z z z
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Prolactinoma Cushing;s Syndrome Acromegaly and Gigantism TSH Secreting Adenoma
Pituitary hormon deficiency
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Hypoadrenalism Hypothyrodism Hypogonadism Somatomedin deficiency (IGF Deficiency)
Laboratory L b t tests t t for f diagnosis di i off disorders of pituitary and hypothalamus z
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Growth Hormon (GH) Dih ilk & di Dihasilkan disekresi k i oleh l h pituitary it it somatotrope t t cells sebagai respons terhadap GHRH hypothalamus Effek kerja dimediasi melalui Insulin Like Growth Faktor (IGF) Kegunaan : - Differential diagnosis : Short Stature, Stature Slow Growth - Evaluasi Pituitary Function
Insulin-like growth factor z z
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Regulation of growth and development in mammals. l Stimulation of cellular proliferation and growth, th IGF IGF-II has h important i t t effects ff t on carbohydrate, protein and bone metabolism
Meningkat z z z z z z z
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Acromegaly, karena adenoma pituitary tertentu Laron dwarfism (kekurangan GH receptor) GH resistance Renal Failure Uncontrol DM Obat-obatan : Estrogen, Kontrasepsi oral Stravation 2 jam sesudah tidur
Menurun z z z z z
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Gangguan pada hypothalamus (tumor, i f k i h infeksi, hemokromatosis) k t i ) Hypopituitarism (tumor, infeksi, granuloma, radiasi) di i) Dwarfism C ti Corticosteroid t id th therapy Obesity
