GROWTH & PUBERTY

GROWTH

1. Factors
2. Basic concept
3. Growth charts
Standard Normal Curve

50th Percentile

5th 95th
Normal Growth
Growth is a sensitive indicator of a child's
state of health and nutrition

….and genetic background

….and psychosocial
.... environment
 Objectives
1. The use and application of the ICP
model of growth.
2. Describe and evaluate the influences on
growth
3. The use and application of centile charts
 Introduction

• Genetic
• Nutrition
Factors • Hormonal
• Well being (incl psychological)

• Intrauterin
Periode • Extrauterin
 INTRODUCTION
Growth assessment
– Pediatric care
intrinsic part of “well baby” clinics,
to detect & intervene in children with growth
problems
– Community level
to measure the prevalence of under-nutrition and
over-nutrition
to identify groups with increased nutritional and
health needs.
Growth assessment best defines the
health and nutritional status of children
 GROWTH MECHANISM
Environmen
t

Nutrition Well being

GROWTH
Hyperplasia
Hypertrophy
Matrix deposisiton

Genetic Hormone

GH-IGF axis
Growth promoting hormones

FETUS CHILD PUBERTY

GH / IGF-I
IGF-II
GH / IGF-I E2/T
Insulin
T4/T3 Insulin
PDGF,EGF,FGF.
T4/T3

Insulin
HPL PDGF
PDGF
T4/T3 EGF
EGF
IGF-I FGF FGF
 Neuroendocrine control
Emotional well being

Nutrition metabolisme genetic &

environmental
factors

Tissue/skeletal responsiveness
Hormon yang berperan:
(GH,Thyroxin, Insulin, cortisol, sex steroid,
growth factors)
 Growth Hormone
 Growth hormone-
releasing hormone
(GHRH) produced in the
hypothalamus
stimulates GH secretion
 GHRH stimulates GH
gene transcription
 GH released into the
blood in pulses (due to
pulsatile release of
GHRH into portal
system)
  50 % of daily GH
secretion occurs during
the early hours of the
night following the onset 12
of deep sleep
I-C-P Model

INFANT CHILDHOOD PUBERTAL

INFANT PHASE (0-2 yrs)
• Decreasing growth velocity
• Rapid increase in weight and length
• Channelling

CHILDHOOD PHASE (2-11 yrs)

• Growth velocity constant / linear
• Growth according to genetic channel
• GH dependent & thyroid hormone (partially)

PUBERTAL PHASE
• Growth spurt / growth acceleration
• Dependent upon action of sex hormone and GH
• Deceleration and termination of growth
 Growth Parameters
Size - Stature
Velocity - Growth
Proportion
Bone Age

Potential Genetic Height

Mid Parental Height
 Size - Stature
Statistical Concept
– Normal
– Tall > p97
– Short < p3
Sex & race
Velocity
 Stature and growth
(A) (B)

14-15 Maret 2007

©UK Endokrinologi Anak & Remaja
Who is having growth problems? Who is short
IDAI Jaya
Proportion
Growth Chart
Growth Chart
Bone age
 Growth of
ossification centre
 Equivalent to
biological age
 Predict Final Height
(BA>6 yrs old)
 Methods: GP, TW II, 2 yrs 6 m. 10 yrs 12 yrs
RWT
 Left wrist
 Potential Genetic Height
PGH boy = Height F + (Height M + 13) ± 8½ cm
2

PGH girl= (Height F – 13)+ Height M ± 8½ cm

2

Final height (range)

Biological parents
 Growth Chart
Boys
195

Exercise 190

185 PGH
Height (father)167.5 180

cm, Height (mother) 175

170

149 cm. 165

160

Calculate potential 155

150

height son & daughter. 145

Height 140
(cm) 135

130

PGH son= 156,25 – 173,25 cm 125

120
PGH daughter= 143,25 – 160,25 cm 115

110

105

100

95

90

85

80
2 4 6 8 10 12 14 16 18

Age (years)
GROWTH MONITORING
What is your
impression of this
child’s growth?
GROWTH MONITORING
 NORMAL LINEAR GROWTH
 Weight
 twice birth weight at 4-5 months
 3 times birth weight at age year
 4 times at age 2 years
 > 2 yrs old weight increases 2.5-3 kg
year until onset of puberty
 Birth length is 50 cm,
 at 1 yr old 75 cm,
 at 4 yrs old 100 cm
 at 8 yrs old 125 cm.
 Growth velocity 5-7 cm/year until
onset of puberty
 Pre pubertal dip
 BONE GROWTH
 Proliferation of chondrocytes,
followed by hypertrophy
 Matrix around hypertrophied
chondrocytes calcify. Old
chondrocytes disintegrates,
leaving a cavity. Periosteal
cells migrate into cavity
along with osteoprogenitor
cells and other cells giving
rise to marrow
 Osteoblasts lay down bone
on calcified cartliage,
 enlarging marrow cavity. At
maximum growth, epiphyseal
and diaphyseal cavities.
 become continuous
“epiphyseal closure
 Short stature

1.Normal variant short stature

Familial/genetic short stature

CONSTITUTIONAL DELAY OF
GROWTH & PUBERTY
2.Perawakan pendek primer / instrinsik
1.Sindrom-2 yang dihubungkan dengan kelainan
kromosom
– Sindrome Turner, Sindrome Down

2.Sindrom –sindrom lain, misalnya:

– Sindrome Noonan, Sindome Prader-Labhart-Willi
– Sindrome Russell Silver, Sindrme Seckel
– Sindrome Hutchinson Gilfort, Sindrome Cockayne

3.IUGR, yang disebabkan

– genetik atau kelainan metabolik
– Adanya kelainan saat dalam kandungan oleh infeksi, obat-
obatan, alkohol,dll
– Disfungsi plasenta berat

4.Skeletal dysplasia/osteochondrodysplasia

5. Storage disorders (jarang)

 3. Perawakan pendek sekunder /
extrinsik
Penyakit / kelainan sistemik
Malnutrisi
kelainan endokrin
– Hipotiroid
– Growth hormon defisiensi
– IGF-1 defect
– Pseudohypoparathyroidism
– The cushing sindrome
– Mauriac syndrome
– Hypogonadism
– Rickets
Metabolik disorder
Iatrogenic short stature (Terapi steroid, radiasi)
Psychososial short stature atau emotional
4. Perawakan pendek idiopatik

Tidak dijumpai kelainan

Mid-parental height- 200 200
Genetic potensial 190
Father 178 cm 190
Mother 158 cm
180 180

Males = 170 170

M ht + 13 cm + F ht 160 160

2 150 150

Height (cm)
140 140
Range +/- 8.5 cm 130 130
= target range 120 120

Females = 110
MPH = 174.5 cm
110

M ht + F ht - 13 cm 100 +/- 7.5 cm 100

2 90 90
80 Males 0- 18 yrs 80
Range +/- 8.5 cm 70 70
= target range 0 2 4 6 8 10 12 14 16 18
Age (years)
 Tall stature - aetiologies
1. Variants of normal growth
– Constitutional / familial tall stature
– Exogenous obesity
2. Endocrine disorders
– Growth hormone excess (pituitary gigantism)
– Estrogen resistance / inactivity
– MEN IIB
– Precocious (pseudo) puberty
– Hyperthyroidism
– Hyperinsulinism
– Lipodystrophies
 180 GIRLS HEIGHT 180
170 170
160 160
150 150
140 140
Height (cm)

130 130
120 120
110 110
100 100
90 90
80 80
70 70
60 60
0 2 4 6 8 10 12 14 16 18
Age (years)
 Tall stature - aetiologies
3. Chromosomal disorders
– Klinefelter’s syndrome and variants
– XXY, XXX
– Fragile X syndrome

4. Other clinical syndromes

– Marfan syndrome
– Overgrowth syndromes: Sotos syndrome
Weaver syndrome
Marshall-Smith syndrome
5. Metabolic - homocysteinuria
 Basic screen for tall stature

bone age
karyotype
IGF-1, random GH
thyroid function

Others as indicated by clinical findings, eg:

– urine metabolic screen
– GH secretion
– echocardiogram
– gonadotropins, sex steroids
– specific mutations eg. Fibrillin gene
Homocysteinuria

Tall stature
Arachnodactyly
Long thin limbs
Ectopia lentis (down)
Mental retardation
Thromboembolism

Autosomal recessive
Marfan syndrome
Tall stature
Long thin limbs
Arachnodactyly
Loose joints
Dislocated lens (up)
Dilatation of aortic root
Dissecting aortoc aneurysm
Autosomal dominant
Fibrillin gene mutations
Pituitary gigantism

Rapid growth age 8-13,

height
193cm
Note well muscled despite
puberty only just
commenced
Pituitary adenoma removed

Treated with high dose

Testosterone
Final height 198cm
 180 GIRLS HEIGHT 180
170 170
160 160
150 150
140 140
Height (cm)

130 130
120 120
110 110
100 100
90 90
80 80
70 70
60 60
0 2 4 6 8 10 12 14 16 18
Age (years)
97th
Investigate
immediately

50th

Clinical and lab screen

Monitor growth rate
3rd
1st
-3 SD
 Conclusion

Hormone is central to growth

ICP model is useful clinically
Charts should be used in assessing
growth
 2.
puberty
 Learning Objectives

Physiology of puberty
– H-P-G axis
– Hormonal changes
– Physical changes
Somatic changes
Secondary sexual characteristics (Tanner staging)
Schedule of puberty
 INTRODUCTION
Puberty HORMONAL
 Transition period GROWTH LH, FSH, SEX STEROID
HORMONE DHEAS

between childhood to
adult
Maturation of PHYSICAL
GROWTH REPRODUCTIVE ORGAN
reproductive organs SPURT SECONDARY SEX

and attainment of
fertility“
MATURE
Termination of linear FINAL
FERTILITY
growth HEIGHT
 Introduction

 Onset
 Female : 8-13 years old
 Male : 9-14 years old
 Basic changes
 neuroendocrine : gonadotropin, sex steroid, and GH
 biologic/physical : linear growth, body composition,
reproductive organs
 Introduction
Reactivation of GnRH secretion -
Hypothesis
– Height & weight ratio (nutritional
factors).
– Maturation of hypothalamus .
–  CNS neurotransmitter output .
– Onset of adrenal androgen activity
 Gene & HPG Axis

Gene Loss-of-Function Phenotype

GPR54 (G-protein coupled Hypogonadotropic hypogonadism
receptor 54)

KAL-1 (Kallmann’s X-linked Kallmann’s syndrome:

syndrome 1) hypogonadotropic hypogonadism

SFI (steroidogenic factor 1) Sex reversal and adrenal insufficiency

DAX1 (DSS-AHC critical Hypogonadotropic hypogonadism and
region on the X chromosome adrenal insufficiency
1)
 Gene & HPG axis
Gene Loss-of-Function Phenotype
GNRHR (gonadotropin- Hypogonadotropic hypogonadism;
releasing hormone
receptor)

FGFR1 (fibroblast growth Autosomal dominant Kallmann’s

factor receptor 1) syndrome: hypogonadotropic
hypogonadism;

LEP (leptin) Hypogonadotropic hypogonadism and

obesity
LEPR (leptin receptor) Hypogonadotropic hypogonadism and
obesity
 Nutritional theory

Weight gain & %age body fat prerequisite to

puberty → critical weight for activation of
HPG axis
– 47-48 kg / 17% fat
– Slightly obese ( 30% ideal BW) begin puberty
earlier
– >30% fat → delayed puberty
 Gonadostat Hypothesis
Prepubertal:
negative feedback
regulation of FSH /
LH secretion →
low threshold &
sensitive to low
levels of steroids
Puberty: sensitivity

gonadotrophins &
sex steroids 
Hormonal changes at puberty
Adrenarche (“mini puberty”)
– 2-3 yrs before gonadarche → age 6 - 8 yrs
–  cortex adrenal activity →  adrenal
androgens production (DHEA, DHEAS &
androstenedione) → pubic and axillary hair
Gonadarche
– Pulsatile GnRH secretion leads to stimulation
of FSH/LH → activation of gonad →  sex
steroids & completion of gametogenesis →
maturation reproductive organs
Development of H-P-G axis

HPG axis functions during fetal life & during first

few weeks following birth, then becomes quiescent
Puberty: reactivation of HPG axis
 Hormonal changes at puberty
 Prepubertal
 LH/FSH levels low →
insufficient to initiate
gonadal function
 Onset of puberty → 
activity GnRH pulse
generator
  frequency & amplitude
GnRH pulses, especially
during sleep →
progressive  LH/FSH→
initiate gonadal function
 nocturnal gonadotropin
pulses (onset) → daytime
gonadotropin pulses
 Normal pubertal development
Boys Girls

Onset (yrs)
12.5 11.5
(9.-14) (8-13)

1st sign of puberty Testes volume Breast budding

(≥ 4ml)

Max growth velocity (cm/yr) 10.3 9.0

(Tanner III-IV) (Tanner II-III)

Duration of puberty (yrs) 3.2 ± 1.8 2.4 ±1.1

 Percentage body fat
Tanner Stage % body fat
Girls
Tanner I 15.7
Tanner II 18.9
Tanner III 21.6
Tanner IV 26.7
Tanner V unchange

Boys
Tanner I 14.3
Tanner II 11.2
Tanner III Unchanged
Tanner IV Unchanged
Tanner V Unchanged
 SOMATIC CHANGES

Pubarche: development of pubic hair

Thelarche: development of breast in females
Gynecomastia: development of breast tissue in
males
Menarche: first menstruation
Female puberty
 Female hormonal changes
LH surge initiates 1st
ovarian cycle  not
sufficient for ovulation
during 1st cycle
estrogen levels in
blood increase, due to
growing follicles
Estrogen induces
somatic changes
 Female hormonal changes
 Estrogen induces
secondary sex
characteristics:
 growth of pelvis
 deposit of subcutaneous
fat
 growth of internal
reproductive organs,
external genitalia
 androgen release by
adrenal glands
increases > growth of
pubic hair, lowering of
voice, growth of bone,
increased secretion
from sebaceous glands
 Tanner staging (girls)
Stage 1
• Prepubertal; no breast tissue (M1)
• None (P1)

Stage 2
• Areolar enlargement with breast bud (M2)
• A few darker hairs along labia (P2)

Stage 3
• Enlargement of breast & areola as single mound (M3)
• Curly pigmented hairs across pubes (P3

Stage 4
Projection of areola above breast as double mound (M4)
Small adult configuration (P4)

Stage 5
• Mature adult breast with single contour (M5)
• Adult pubic hair distribution (P5)
 Sequence of Sexual Maturation

Age
Event
(years)
Thelarche 10-11
Pubarche 10.5-11.5
Growth Spurt 11-12
Menarche 11.5-13
Adult Breast
12.5-15
Development
Adult Sexual Hair 13.5-16
LH, FSH and E2 - PUBERTAL STAGE

Secondary sexual characteristic

Hormonal changes changes (tanner stage)

1 2 3 4 5
 Female Puberty landmark
Breast budding –
– 1st sign of puberty
Menarche –
– 2 yrs > onset of
puberty
Ovulation-
– 2 yrs > menarche
Growth spurt –
– early Tanner stage
Final Height -
Puberty in males
 Male hormonal changes
 LH and FSH release
increases ~10 yrs. of
age
 spermatogenesis;
androgen secretion
 adrenals also secrete
androgens
 androgens initiate
growth of reproductive
organs (e.g. prostate,
penis), other male
characteristics (facial
hair, growth of larynx
–voice changes)
LH, FSH and Testosterone and
PUBERTAL STAGE
Stadium Pubertas
Tanner
Tanner staging (Boys)
Stage 1
• Prepubertal; testicular length <2.5 cm (G1)
• None (P1)

Stage 2
• The testes >2.5 cm in the longest diameter, and the scrotum thinning and
reddening (G2)
• Sparse growth of slightly pigmented, curved pubic hair, mainly at the base of
the penis( P2)
Stage 3
• Growth of the penis in width and length, and further growth of the testes noted
(G3)
• Thicker, curlier hair spread to the mons pubis (P3)

Stage 4
Penis further enlarged, and testes larger, with darker scrotal skin color (G4)
Adult-type hair, which does not yet spread to the medial thighs (P4)

Stage 5
• Genitalia adult in size and shape (G5)
• Adult-type hair spread to the medial thighs (P5)
 Male Puberty Landmark
Testes enlargement –
– 1st sign of puberty
Spermache –
– Wet dream
– Age 12-14 yrs
Growth spurt –
– late Tanner stage
Final Height –
– Age 18 – 20 yrs
Perkembangan pubertas dianggap abnormal
bila awal pubertas terlampau dini atau
terlambat.
Pubertas prekoks :
tanda seksual sekunder terjadi <usia 8
tahun pada anak perempuan dan < 9 tahun
pada anak laki-laki.
Pada pubertas prekoks  peningkatan
kecepatan pertumbuhan, perkembangan
somatik, dan maturasi tulang.

pubertas terlambat :
tanda seksual sekunder belum ada pada
usia 13 tahun pada anak perempuan dan
pada umur 14 tahun pada anak laki-laki
 Pubertas prekoks
Pubertas prekoks sentral
1.Pubertas prekoks sejati/true /idiopatik
2.Tumor-tumor intrakranial
3.Lesi susunan saraf pusat

Pseudopubertas prekoks/
pubertas prekoks perifer

Variasi perkembangan pubertas

1.Prematur telarche
2.Premature adrenarche
3.Gynecomastia
 Pubertas terlambat
A. Hipogonadisme sementara
Pubertas lambat konstitusi (constitutional delayed of puberty)
Penyakit kronis
Penyakit nutrisi
– Malnutrisi
– Malabsorbsi (penyakit celiac, kistik fibrosis)
– Malignansi
– Latihan yang membutuhkan banyak energi (pesenam)
Gangguan hormonal
– Hipotiroid
– Defisiensi GH terisolir (isolated GH deficiency)
– Kelebihan glukokortikoid (Cushing’s, terapi kortikosteroid)
B. Hipogonadotropik-hipogonadisme
1.Kongenital
– Isolated gonadotropin deficiency (sporadic atau familial)
– Defisiensi LH (fertile eunuch syndrome)
– Polymarfomative syndromes with anosmia (Kallmann’s)
– Polyformative syndromes yang lain (Prader-Willi)
– Panhipopituitarisme ata defisiensi hormon pituitary
multiple (idiopatik, empty sella syndrome)

2.Didapat
– Tumor suprasellar (kraniofaringioma)
– Destruksi pituitary (adenoma, operasi, trauma)
– Hiperprolaktinemia ( adenoma )
C. Hipergonadotropik hipogonadisme

1.Kongenital
– Anomali kromosom seks (Turner’s, disgenesis gonad)
– Anomali biosistesis dan reseptif hormon
– Polimalformative syndromes
– Agenesis ovarium dengan kariotip XX

2.Didapat
- Operasi atau trauma
- Ovaritis autoimun
- Kemoterapi sitotoksik, radioterapi
- Infeksi kronis (tuberculosis)
- Mekanisme tidak jelas (kegagalan ovarium premature)
TERAPI
1.Mengkoreksi etiologi
( jika mungkin )

2.Konsultasi psikologis

3.Hormonal Terapi 
rujuk endokrinologi
anak
 Prognosis : tgt etiologi

Pubertas prekoks :
- rata2 tinggi akhir lebih pendek
- sebagian agak sulit bersosialisasi
-siklus menstruasi normal dan fertil
Pubertas terlambat :
- terlambat konstitusi : normal
- dapat diinduksi untuk faktor psikis walau
kemungkinan infertil besar
Pubarke(adrenarke)
premature
Pubarke(adrenarke) premature
Ginekomastia
LIPOMASTIA
PUBERTAS PRECOX
PUBERTAS PRECOX
PREMATURE TELARCHE
PUBERTAS PRECOX
PUBERTAS PRECOX
 TURNER SINDROM

Papilla mammae inverted Thoraks skutiform

Jarak papilla mammae berjauhan Cubitus valgus
 CONCLUSION
Puberty progress in a
orderly schedule
Reproductive function
& adult height is
attained at end of
puberty
Thank
you