PEMERIKSAAN LABORATORIUM

DAN INTERPRETASI
PADA GROWTH RETARDATION

Prof. dr. Burhanuddin Nst. SpPK (K)

Pendahuluan
z

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

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

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

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

II. Secondary Growth Disorders

A. Malnutrition
B. Chronic Disease
C. Endocrine Disorders

Sambungan. . . . .

C. Endocrine Disorders
1. Hypothyroidism
2. Cushings 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. . . . .

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

10

Fetal IGF II
Post natal Excess GH secretion
Hyperthyroidism
Adult androgen or estrogen deficiency
Testicular feminization
Excess GH

11

Hypothyroidism
z

12

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,

If the TSH is normal and hypothyroidism is still

suspected blood testing ;
suspected.

13

TSH, FT4 Primary Hipothyroidism

TSH
TSH, FT4, FT3 N Secondary Hipothyroidism
TSH, FT4 N, FT3 Secondary Hipothyroidism
Suppression of thyrotropin-releasing hormon ( TRH )
( Tertiary Hipothyroidism )

Free triiodothyronine (fT3)

Free levothyroxine (fT4)
Total T3
Total T4

The following measurements may be needed:

z
z
z
z
z
z

14

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

15

16

Hipotiroid (FF), Laboratorium

- T3 menurun
- T4 menurun
- TSH normal
Hipertiroid :
- T3 meningkat T3 Tirotoksikosis
g
T4 Tirotoksikosis
- T4 meningkat

17

Pendekatan untuk penderita

Hypothyroidism (FF)
Sign/symtoms Hypothyoridism
Yes

TSH Level
FT4 or FT4I
TSH
FT4 or FT4I

TSH
FT4(N) or FT4I(N)

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

Primary
Hypothyroidism

Subclinical
Hypothyroidism

Consider Central
Causes of patients
Hypothyroidism Sign & symtoms

Consider other

18

Sign & Symtoms Hypothyroidism

z
z
z
z
z
z

19

Weakness
Dry skin
Edema Eye Lids
Cold skin
Memory
Constipation

z
z
z
z
z
z

Weight gain
Loss of hair
Anorexia
Nervousness
Sweating
Parasthesia

Hyperthyroidism
z

20

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 ?

TSH, FT4 Hiperthyroidism.

Excessive
E
i iiodide
did iintake
t k
Overmedication chronic oral thyroxine
Graves
Graves desease / toxic goiter
TSH, FT4 normal, FT3 Thyrotoxicosis
TSH, FT4 TSH secreting tumor
anti-TSH-receptor antibodies

anti-thyroid-peroxidase
y
p

z
z

21

Pendekatan untuk penderita Hyperthyroidism

Sign/symtoms Hyperthyoridism
Yes

TSH Level
FT4 or FT4I
TSH
TSH
FT4 or FT4I FT4(N) or FT4I(N)
T3

Hyperthyroidism
yp
y
Diffuse goiter + bruit
Opthalmopathy
Pretibial oedema

Yes
Gvave
Disease

No

Subclinical
S
b li i l
Hiperthyroid

Perform
P
f
Radioactive
Iodine
Uptake test

TSH
TSH (N)
FT4 or FT4I FT4(N) or FT4I(N)
Consider TSH
Producing
Adenoma

Consider other
Causes of patients
Sign & symtoms

T3
Thyrotoxicosis

22

Sign & Symptoms Hyperthyroidism

z
z
z
z
z
z
z
z
z

23

Nervousness
Emotional lability
Tremor
Palpitations
Fatigue
Weight loss
Tachycardia
Atrial Fibrilasi
diff systole &
diastole BP

z
z
z
z
z
z
z
z

Diarrhea
Prox Muscle weakness
Prox.
Heart intolerance
Moist skin
Fine hair
Hair loss
Weakness
Increase appetite

Cushing's syndrome
z

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.

24

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). )

25

The paraventricular nucleus (PVN) of the

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

Laboratory Diagnostic
z
z
z

26

Dexamethasone suppression test

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

Cushing Syndrome (CS)

z

z
z

27

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. . . . .

28

- 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

29

ACTH dependent
ACTH independent

z
z

30

Kadar ACTH antara 11.00-01.00 PM

> 23 pg/dl ACTH dependent
Pemeriksaan ACTH dgn Imunoradiometric
Klinis : - Centripetal Obesity + Buffalo Hump
- Moonface
- Hirsutism

Cushings
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
Cushings from
pseudocushing

Cushing s
Cushings
Syndrome

Cortisol > 5 ug/dl

Cushings Syndromel
Plasma ACTH

Perform one of the following:

-Dexamethazon-CHR test
-Midnight serum cortisol
-Late
Late night salivary cortisol
Stop

Results consistent with

pseudocushings

Results consistent
with Cushings

>10-15 pg/dl

< 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 (+)

Cushings
C
hi
Disease

Suppression (-)

Ectopic ACTH
Screening
tumor
32

Sign & Symtoms CS

z
z
z
z
z

33

Central Obesityy
Proximal Muscle
Weakness(hips,shoulders)
Hypertension
buffalo hump
moon face

z
z
z
z
z

Acne
Hyperpigmentasion
Hirsutism(male-pattern hair
growth in a female)
Hyperglicemia
Hypokalmic metabolik
Acidosis

Pseudo hypoparathyroid
z
z
z

34

Hipercalcemic
Laboratorium
Hiperphosphatemic
Klinis :
- Short stature
- Rounded face
Albrights
g
Hereditary
- Obesitas
Osteodystrophy
- Subcutan Calcification
(AHO)
- Shortened fourth metacarpal

Rickets
z
z

35

Gangguan mineralisasi dari organik matrik

tulang
Anak-anak
a a a ga
gangguan
ggua te
terjadi
jad pada :
- Growth plate
- Mineralisasi kartilago terjadi deformitas

36

37

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

38

Disorder
Di
d off th
the Pituitary
Pit it
&
Hypothalamus

39

Anterior Pituitary mensintesa :

- Growth Hormon
- Prolactin
- TSH
- FSH
- LH
Hypothalamus mensekresi tropik hormon
untuk masing-masing

Pituitary hormon excess

z
z
z
z

40

Prolactinoma
Cushing;s Syndrome
Acromegaly and Gigantism
TSH Secreting Adenoma

Pituitary hormon deficiency

z
z
z
z

41

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

42

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

43

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

44

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

45

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