PEMERIKSAAN LABORATORIUMDAN INTERPRETASIDAN INTERPRETASI

PADA GROWTH RETARDATION

Prof. dr. Burhanuddin Nst. SpPK (K)

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Pendahuluan

Masa anak-anak adalah waktu untuk tumbuh, k k l k d lib tkmerupakan proses komplek dan melibatkan

interaksi banyak faktor.P t b h d l h bi t k iPertumbuhan adalah biasa untuk organisme multicellular dan terjadi dengan cara pembelahan sel dan pembesaran sel danpembelahan sel dan pembesaran sel dan organ differensiasi

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Perkembangan morfologi secara menyeluruh d k t b l h l ddan kecepatan pembelahan sel pada berbagai organ pada waktu yang berbeda dan outcome yang diperoleh ditentukan olehdan outcome yang diperoleh ditentukan oleh komposisi genetik dari seseorang dan berinteraksi dengan faktor-faktor eksternal, g ,termasuk nutrisi, psikososial dan faktor ekonomi

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Fase-fase pertumbuhan normal

Pertumbuhan terjadi pada kecepatan b b d b d lberbeda-beda selama masa :- Intra uterine- Masa awal dan pertengahan Childhood dan- Masa adolescenePertumbuhan pre-natal rata-rata 1,2-1,5 cm/minggu

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Midgestational length growth velocity dari 2,5 / i t j di 0 5 / icm/minggu turun menjadi 0,5 cm/minggu,

segera akan lahirK t t b h t t ± 15Kecepatan pertumbuhan rata-rata ± 15 cm/tahun, selama 2 tahun pertama kehidupan dan perlahan menjadi 6 cm/tahunkehidupan, dan perlahan menjadi 6 cm/tahun selama middlle childhood

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Growth Retardation (GR)

GR diklasifikasikan sbb:I. Primary Growth Abnormalities

A. OsteochondrodysplasiaB. Chromosomal abnormalitiesC. Intra Uterine Growth Retardation

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II. Secondary Growth DisordersA. MalnutritionB. Chronic DiseaseC. Endocrine Disorders

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Sambungan. . . . .

C. Endocrine Disorders1. Hypothyroidism2. Cushing’s Syndrome3. Pseudohypo Parathyroidism4. Rickets a vitamin D resistant rickets5. IGF deficiensy

a. GHD due to Hypothalamic dysfunction

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yp yb. GHD due to pituitary GH deficiency

Sambungan. . . . .

c. GH resistance1. Primary GH insensitivity2. Secondary GH insensitivity

d. Primary defects of IGF transport& clearancee. IGF Insensitivityy

1. Defect of the type I/GF receptor2. Post receptor defect

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pIII. Idiopathic Short Stature

Excess Growth and Tall Stature

Fetal IGF IIPost natal Excess GH secretionHyperthyroidismHyperthyroidismAdult androgen or estrogen deficiencyTesticular feminizationTesticular feminizationExcess GH

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Hypothyroidism

Hypothyroidism is the disease caused by i ffi i t d ti f th id h binsufficient production of thyroid hormone by the thyroid gland. C ti i i f f h th idi f dCretinism is a form of hypothyroidism found in infants.

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How To Diagnostic Hypothyroidism ?

To diagnose hypothyroidism, – TSH↑ FT4↓ Primary Hipothyroidism– TSH↑, FT4↓ Primary Hipothyroidism– TSH↓, FT4↓, FT3 N ↓ Secondary Hipothyroidism– TSH↓, FT4 N, FT3↓ Secondary Hipothyroidism

Suppression of thyrotropin-releasing hormon ( TRH )– Suppression of thyrotropin-releasing hormon ( TRH )( Tertiary Hipothyroidism )

If the TSH is normal and hypothyroidism is still suspected blood testing ;suspected. blood testing ;

– Free triiodothyronine (fT3)– Free levothyroxine (fT4)

Total T3

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– Total T3 – Total T4

The following measurements may be needed:

24 hour urine free T3 Antithyroid antibodies for evidence of autoimmuneAntithyroid antibodies — for evidence of autoimmune diseases that may be damaging the thyroid gland Serum cholesterol — which may be elevated in h h idihypothyroidism 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 normalHipertiroid :- T3 meningkat → T3 Tirotoksikosis- T4 meningkat → T4 Tirotoksikosis

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g

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Pendekatan untuk penderita Hypothyroidism (FF)Hypothyroidism (FF)

Sign/symtoms HypothyoridismYes

TSH LevelFT4 or FT4I

TSH FT4 or FT4I

TSH (N) or FT4 or FT4I

TSH (N)FT4(N) or FT4I(N)

TSH FT4(N) or FT4I(N)

PrimaryHypothyroidism

Consider CentralHypothyroidism

Consider otherCauses of patientsSubclinical

Hypothyroidism

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Hypothyroidism Hypothyroidism Sign & symtomsHypothyroidism

Sign & Symtoms Hypothyroidism

Weakness Weight gainWeaknessDry skinEdema Eye Lids

Weight gainLoss of hairAnorexiaEdema Eye Lids

Cold skinMemory ⇓

AnorexiaNervousnessSweating ⇓Memory ⇓

ConstipationSweating ⇓Parasthesia

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Hyperthyroidism

Hyperthyroidism is the term for overactive ti ithi th th id l d lti itissue within the thyroid gland, resulting in overproduction and thus an excess of circulating free thyroid hormones: thyroxinecirculating free thyroid hormones: thyroxine (T4), triiodothyronine (T3), or both

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How To Diagnostic Hyperthyroidism ?

TSH↓, FT4↑ Hiperthyroidism.E i i did i t k– Excessive iodide intake

– Overmedication chronic oral thyroxineGraves’ desease / toxic goiter– Graves desease / toxic goiter

TSH↓, FT4 normal, FT3↑ ThyrotoxicosisTSH↑, FT4 ↑ TSH secreting tumorTSH↑, FT4 ↑ TSH secreting tumoranti-TSH-receptor antibodies anti-thyroid-peroxidase

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y p

Pendekatan untuk penderita Hyperthyroidism

Sign/symtoms Hyperthyoridism

TSH LevelYes

TSH LevelFT4 or FT4I

TSH TSH TSH (N)TSHTSH FT4 or FT4I

TSH FT4 or FT4I

TSH (N)FT4(N) or FT4I(N)

TSH FT4(N) or FT4I(N)

Hyperthyroidism Consider TSH Consider otherT3yp y Consider TSHProducingAdenoma

Consider otherCauses of patientsSign & symtoms

T3

N

S b li i l

Diffuse goiter + bruitOpthalmopathy

Pretibial oedemaSubclinical

Hiperthyroid T3 Thyrotoxicosis

Yes No

Gvave P f

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GvaveDisease

PerformRadioactive

IodineUptake test

Sign & Symptoms Hyperthyroidism

NervousnessEmotional lability

DiarrheaProx Muscle weaknessEmotional lability

TremorPalpitations

Prox. Muscle weaknessHeart intoleranceMoist skinPalpitations

FatigueWeight loss

Moist skinFine hairHair loss

TachycardiaAtrial Fibrilasi

WeaknessIncrease appetite

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diastole BP

Cushing's syndrome

Cushing's syndrome (hyperadrenocorticism or hypercorticism) is a hormone (endocrine) disorderhypercorticism) is a hormone (endocrine) disorder caused by high levels of cortisol (hypercortisolism) in the blood. There are several possible causes of Cushing'sThere are several possible causes of Cushing's syndrome.

– Hormones that come from outside the body are called exogenous ( l ti id d )exogenous (glucocorticoid drugs )

– hormones that come from within the body are called endogenous. (tumors that produce cortisol or adrenocorticotropic hormone (ACTH). )

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hormone (ACTH). )

The paraventricular nucleus (PVN) of the h th l l ti t i l ihypothalamus releases corticotropin-releasing hormone (CRH) Pituitary gland to release adrenocorticotropin (ACTH) Adrenal glandadrenocorticotropin (ACTH) Adrenal gland (zona fasciculata ) (cortisol).Elevated levels of cortisol exert negativeElevated levels of cortisol exert negative feedback on the pituitary.

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Laboratory Diagnostic

Dexamethasone suppression test 24-hour urinary measurement for cortisol Cortisol in saliva over 24 hours

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Cushing Syndrome (CS)

CS results prolong Exposure to excessive p g pamounts of endogenous or exogenous corticosteroidsKadar Cortisol plasma lebih besar dari 7 ug/dl (200nmol/L) pada midnightOrgan normal :- Paling tinggi pagi hari, malam meningkat

27sedikit (2ug/dl)

Sambungan. . . . .

- False positif : Stress (vena puncture),Penyakit berulang-ulang, takut

Free Cortisol urin :- Metabolisme cortisol di urin :

17 hydrocorticosteroid atau17 exogenicsteroid

- Normal 80-120 ug/24 jam

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g j- Bisa normal 8-15% penderita

Dexamethazon Suppression Test

1 mg dexamethazon diberi tengah malamPada jam antara 08-09, bila response normal kadar plasma cortisol < 5 ug/dl

Cushing Syndromeg yACTH dependentACTH independent

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ACTH independent

Kadar ACTH antara 11.00-01.00 PM> 23 pg/dl → ACTH dependentPemeriksaan ACTH dgn ImunoradiometricKlinis : - Centripetal Obesity + Buffalo Hump

- Moonface- Hirsutism

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Cushing’s Syndrome

Sign & Symtoms Present

Perform Screening test for CSSyndrome Perform Screening test for CS24 hours urin collection for

Cortisol or Over night 1 mg DST

24 hours urin Cortisol Perform over night 1 mg DST

Cortisol > 5 ug/dlCortisol (N) Cortisol ↑ Cortisol ↑ > 3 5X Cortisol > 5 ug/dl

Cushing’s Syndromel

Cortisol (N) Cortisol ↑But not > 3.5X

Upper limit normalConsider

Alternative

Cortisol ↑ > 3.5XUpper limit normal

Futher evaluation Cushing’s

Plasma ACTH

Alternativediagnosis

Futher evaluationTo differentiateCushing’s frompseudocushing

Cushing sSyndrome

>10-15 pg/dl⇓A

Perform one of the following:-Dexamethazon-CHR test-Midnight serum cortisolLate night salivary cortisol

A

< 5 pg/dl, considerAdrenal causes of CS

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-Late night salivary cortisol

Results consistentwith Cushing’s

Results consistent withpseudocushing’sStop

Perform CT / MRIAdrenal Gland

A. Plasma ACTH

Plasma ACTHPlasma ACTH

> 10-15 pg/dl

Perform High Dose DST(8 mg Dexamethazon)

Ectopic ACTHC hi ’

Suppression (+) Suppression (-)

Ectopic ACTHScreening

tumor

Cushing’sDisease

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Sign & Symtoms CS

Central Obesity AcneyProximal Muscle Weakness(hips,shoulders)

HyperpigmentasionHirsutism(male-pattern hair

Hypertensionbuffalo hump moon face

growth in a female) HyperglicemiaHypokalmic metabolikmoon face Hypokalmic metabolik Acidosis

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Pseudo hypoparathyroid

Hipercalcemic LaboratoriumHiperphosphatemicKlinis :

Laboratorium

- Short stature- Rounded face Albright’s- Obesitas- Subcutan Calcification

gHereditary

Osteodystrophy(AHO)

34- Shortened fourth metacarpal (AHO)

Rickets

Gangguan mineralisasi dari organik matrikGangguan mineralisasi dari organik matrik tulangAnak-anak gangguan terjadi pada :a a a ga ggua te jad pada- Growth plate- Mineralisasi kartilago → terjadi deformitasMineralisasi kartilago → terjadi deformitas

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Vitamin D is required for proper calcium b ti f th t I th b fabsorption from the gut. In the absence of

vitamin D, dietary calcium is not properly absorbed resulting in hypocalcemia leadingabsorbed, resulting in hypocalcemia, leading to skeletal and dental deformities and neuromuscular

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Laboratorium (Rickets)

Infants dengan Vit. D Deficiencyg ySerum Calcium selalu rendahSerum Phosphat batas normalSerum Phosphat batas normalserum alkaline phosphatase meningkat

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Di d f th Pit it &Disorder of the Pituitary & Hypothalamus

Anterior Pituitary mensintesa :- Growth Hormon- Prolactin- TSH- FSH- LH

Hypothalamus mensekresi tropik hormon

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Hypothalamus mensekresi tropik hormon untuk masing-masing

Pituitary hormon excess

ProlactinomaProlactinomaCushing;s SyndromeAcromegaly and GigantismAcromegaly and GigantismTSH Secreting Adenoma

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Pituitary hormon deficiency

HypoadrenalismHypothyrodismHypothyrodismHypogonadismSomatomedin deficiency (IGF Deficiency)Somatomedin deficiency (IGF Deficiency)

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L b t t t f di i fLaboratory tests for diagnosis of disorders of pituitary and hypothalamus

Growth Hormon (GH)Dih ilk & di k i l h it it t tDihasilkan & disekresi oleh pituitary somatotropecells sebagai respons terhadap GHRH hypotha-llamus Effek kerja dimediasi melalui Insulin Like GrowthFaktor (IGF)Faktor (IGF)Kegunaan : - Differential diagnosis :

Short Stature Slow Growth

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Short Stature, Slow Growth- Evaluasi Pituitary Function

Insulin-like growth factor

Regulation of growth and development in lmammals.

Stimulation of cellular proliferation and th IGF I h i t t ff tgrowth, IGF-I has important effects on

carbohydrate, protein and bone metabolism

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Meningkat

Acromegaly, karena adenoma pituitary tertentuLaron dwarfism (kekurangan GH receptor)GH resistanceRenal FailureUncontrol DMObat-obatan : Estrogen, Kontrasepsi oralStravation

442 jam sesudah tidur

Menurun

Gangguan pada hypothalamus (tumor, i f k i h k t i )infeksi, hemokromatosis)Hypopituitarism (tumor, infeksi, granuloma,

di i)radiasi)DwarfismC ti t id thCorticosteroid therapyObesity

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