PEMERIKSAAN LABORATORIUM

DAN INTERPRETASI DAN 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 tk merupakan proses komplek dan melibatkan
interaksi banyak faktor.
P t b h d l h bi t k i Pertumbuhan adalah biasa untuk organisme
multicellular dan terjadi dengan cara
pembelahan sel dan pembesaran sel dan pembelahan sel dan pembesaran sel dan
organ differensiasi
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Perkembangan morfologi secara menyeluruh
d k t b l h l d dan kecepatan pembelahan sel pada
berbagai organ pada waktu yang berbeda
dan outcome yang diperoleh ditentukan oleh dan 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 l berbeda-beda selama 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
/ i t j di 0 5 / i cm/minggu turun menjadi 0,5 cm/minggu,
segera akan lahir
K t t b h t t 15 Kecepatan pertumbuhan rata-rata 15
cm/tahun, selama 2 tahun pertama
kehidupan dan perlahan menjadi 6 cm/tahun kehidupan, dan perlahan menjadi 6 cm/tahun
selama middlle childhood
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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. . . . .
C. Endocrine Disorders
1. Hypothyroidism
2. Cushings Syndrome
3. Pseudohypo Parathyroidism
4. Rickets a vitamin D resistant rickets
5. IGF deficiensy
a. GHD due to Hypothalamic dysfunction
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yp y
b. GHD due to pituitary GH deficiency
Sambungan. . . . .
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
2. Post receptor defect
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p
III. Idiopathic Short Stature
Excess Growth and Tall Stature
Fetal IGF II
Post natal Excess GH secretion
Hyperthyroidism Hyperthyroidism
Adult androgen or estrogen deficiency
Testicular feminization Testicular feminization
Excess GH
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Hypothyroidism
Hypothyroidism is the disease caused by
i ffi i t d ti f th id h b insufficient production of thyroid hormone by
the thyroid gland.
C ti i i f f h th idi f d Cretinism 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, FT3Secondary 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 autoimmune Antithyroid antibodies for evidence of autoimmune
diseases that may be damaging the thyroid gland
Serum cholesterol which may be elevated in
h h idi hypothyroidism
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
- T4 meningkat T4 Tirotoksikosis
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g
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Pendekatan untuk penderita
Hypothyroidism (FF) Hypothyroidism (FF)
Sign/symtoms Hypothyoridism
Yes
TSH Level
FT4 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)
Primary
Hypothyroidism
Consider Central
Hypothyroidism
Consider other
Causes of patients
Subclinical
Hypothyroidism
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Hypothyroidism Hypothyroidism
Sign & symtoms
Hypothyroidism
Sign & Symtoms Hypothyroidism
Weakness Weight gain Weakness
Dry skin
Edema Eye Lids
Weight gain
Loss of hair
Anorexia Edema Eye Lids
Cold skin
Memory
Anorexia
Nervousness
Sweating Memory
Constipation
Sweating
Parasthesia
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Hyperthyroidism
Hyperthyroidism is the term for overactive
ti ithi th th id l d lti i tissue within the thyroid gland, resulting in
overproduction and thus an excess of
circulating free thyroid hormones: thyroxine circulating 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 thyroxine
Graves desease / toxic goiter Graves desease / toxic goiter
TSH, FT4 normal, FT3 Thyrotoxicosis
TSH, FT4 TSH secreting tumor TSH, FT4 TSH secreting tumor
anti-TSH-receptor antibodies
anti-thyroid-peroxidase
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y p
Pendekatan untuk penderita Hyperthyroidism
Sign/symtoms Hyperthyoridism
TSH Level
Yes
TSH Level
FT4 or FT4I
TSH TSH TSH (N) TSH TSH
FT4 or FT4I
TSH
FT4 or FT4I
TSH (N)
FT4(N) or FT4I(N)
TSH
FT4(N) or FT4I(N)
Hyperthyroidism
Consider TSH
Consider other
T3 yp y
Consider TSH
Producing
Adenoma
Consider other
Causes of patients
Sign & symtoms
T3
N
S b li i l
Diffuse goiter + bruit
Opthalmopathy
Pretibial oedema
Subclinical
Hiperthyroid
T3
Thyrotoxicosis
Yes No
Gvave P f
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Gvave
Disease
Perform
Radioactive
Iodine
Uptake test
Sign & Symptoms Hyperthyroidism
Nervousness
Emotional lability
Diarrhea
Prox Muscle weakness Emotional lability
Tremor
Palpitations
Prox. Muscle weakness
Heart intolerance
Moist skin Palpitations
Fatigue
Weight loss
Moist skin
Fine hair
Hair loss
Tachycardia
Atrial Fibrilasi
Weakness
Increase appetite
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diff systole &
diastole BP
Cushing's syndrome
Cushing's syndrome (hyperadrenocorticism or
hypercorticism) is a hormone (endocrine) disorder hypercorticism) is a hormone (endocrine) disorder
caused by high levels of cortisol (hypercortisolism) in
the blood.
There are several possible causes of Cushing's There 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 i hypothalamus releases corticotropin-releasing
hormone (CRH)Pituitary gland to release
adrenocorticotropin (ACTH) Adrenal gland adrenocorticotropin (ACTH) Adrenal gland
(zona fasciculata ) (cortisol).
Elevated levels of cortisol exert negative Elevated 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 p
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
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sedikit (2ug/dl)
Sambungan. . . . .
- False positif : Stress (vena puncture),
Penyakit berulang-ulang, takut
Free Cortisol urin :
- Metabolisme cortisol di urin :
17 hydrocorticosteroid atau
17 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 malam
Pada jam antara 08-09, bila response normal
kadar plasma cortisol < 5 ug/dl
Cushing Syndrome g y
ACTH dependent
ACTH independent
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ACTH independent
Kadar ACTH antara 11.00-01.00 PM
> 23 pg/dl ACTH dependent
Pemeriksaan ACTH dgn Imunoradiometric
Klinis : - Centripetal Obesity + Buffalo Hump
- Moonface
- Hirsutism
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Cushings
Syndrome
Sign & Symtoms Present
Perform Screening test for CS
Syndrome
Perform Screening test for CS
24 hours urin collection for
Cortisol or Over night 1 mg DST
24 hours urin Cortisol Perform over night 1 mg DST
Cortisol > 5 ug/dl Cortisol (N)
Cortisol
Cortisol > 3 5X
Cortisol > 5 ug/dl
Cushings Syndromel
Cortisol (N)
Cortisol
But not > 3.5X
Upper limit normal
Consider
Alternative
Cortisol > 3.5X
Upper limit normal
Futher evaluation
Cushings
Plasma ACTH
Alternative
diagnosis
Futher evaluation
To differentiate
Cushings from
pseudocushing
Cushing s
Syndrome
>10-15 pg/dl

A
Perform one of the following:
-Dexamethazon-CHR test
-Midnight serum cortisol
Late night salivary cortisol
A
< 5 pg/dl, consider
Adrenal causes of CS
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-Late night salivary cortisol
Results consistent
with Cushings
Results consistent with
pseudocushings
Stop
Perform CT / MRI
Adrenal Gland
A. Plasma ACTH
Plasma ACTH Plasma ACTH
> 10-15 pg/dl
Perform High Dose DST
(8 mg Dexamethazon)
Ectopic ACTH
C hi
Suppression (+)
Suppression (-)
Ectopic ACTH
Screening
tumor
Cushings
Disease
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Sign & Symtoms CS
Central Obesity Acne y
Proximal Muscle
Weakness(hips,shoulders)
Hyperpigmentasion
Hirsutism(male-pattern hair
Hypertension
buffalo hump
moon face
growth in a female)
Hyperglicemia
Hypokalmic metabolik moon face Hypokalmic metabolik
Acidosis
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Pseudo hypoparathyroid
Hipercalcemic
Laboratorium
Hiperphosphatemic
Klinis :
Laboratorium
- Short stature
- Rounded face
Albrights
- Obesitas
- Subcutan Calcification
g
Hereditary
Osteodystrophy
(AHO)
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- Shortened fourth metacarpal
(AHO)
Rickets
Gangguan mineralisasi dari organik matrik Gangguan mineralisasi dari organik matrik
tulang
Anak-anak gangguan terjadi pada : a a a ga ggua te jad pada
- Growth plate
- Mineralisasi kartilago terjadi deformitas Mineralisasi kartilago terjadi deformitas
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Vitamin D is required for proper calcium
b ti f th t I th b f absorption from the gut. In the absence of
vitamin D, dietary calcium is not properly
absorbed resulting in hypocalcemia leading absorbed, resulting in hypocalcemia, leading
to skeletal and dental deformities and
neuromuscular
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Laboratorium (Rickets)
Infants dengan Vit. D Deficiency g y
Serum Calcium selalu rendah
Serum Phosphat batas normal Serum Phosphat batas normal
serum 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
Prolactinoma Prolactinoma
Cushing;s Syndrome
Acromegaly and Gigantism Acromegaly and Gigantism
TSH Secreting Adenoma
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Pituitary hormon deficiency
Hypoadrenalism
Hypothyrodism Hypothyrodism
Hypogonadism
Somatomedin deficiency (IGF Deficiency) Somatomedin deficiency (IGF Deficiency)
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L b t t t f di i f Laboratory tests for diagnosis of
disorders of pituitary and hypothalamus
Growth Hormon (GH)
Dih ilk & di k i l h it it t t Dihasilkan & disekresi oleh pituitary somatotrope
cells sebagai respons terhadap GHRH hypotha-
llamus
Effek kerja dimediasi melalui Insulin Like Growth
Faktor (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
l mammals.
Stimulation of cellular proliferation and
th IGF I h i t t ff t growth, IGF-I has important effects on
carbohydrate, protein and bone metabolism
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Meningkat
Acromegaly, karena adenoma pituitary tertentu
Laron dwarfism (kekurangan GH receptor)
GH resistance
Renal Failure
Uncontrol DM
Obat-obatan : Estrogen, Kontrasepsi oral
Stravation
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2 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)
Dwarfism
C ti t id th Corticosteroid therapy
Obesity
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