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GROWTH & PUBERTY

Division of Endocrinology Dept of Child Health FMUI-CMGH

GROWTH
1. 2. 3.

Factors Basic concepts Growth Chart

OBJECTIVES
1.

2.

3.

The use and application of the ICP model of growth. Describe and evaluate the influences on growth The use and application of centile charts

INTRODUCTION
Genetic Nutrition Hormonal Well being (incl psychological)

Intrauterin Extrauterin

INTRODUCTION

Growth assessment
Pediatric
intrinsic

care

part of well baby clinics, to detect & intervene in children with growth problems
Community
to

level

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

GROWTH
Hyperplasia Hypertrophy Matrix deposition

Well being

Genetic

Hormone

GH-IGF axis

Growth promoting hormones


FETUS
IGF-II Insulin PDGF,EGF,FGF.

CHILD
GH / IGF-I T4/T3

PUBERTY
GH / IGF-I E2/T Insulin T4/T3

HPL T4/T3 IGF-I

Insulin PDGF EGF FGF

PDGF EGF FGF

GROWTH HORMONE

Growth hormonereleasing hormone (GHRH) stimulates


GH secretion 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 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 Body Proportion Bone Age Potential Genetic Height Mid Parental Height

SIZE - STATURE

Statistical Concept

Normal Tall > p97 Short < p3

Sex & race

STATURE AND GROWTH


(A)

14-15 Maret 2007 UK Endokrinologi Anak & Remaja IDAI Jaya

(B)

Who is having growth problems? Who is short

PROPORTION

GROWTH CHART

Growth Chart

VELOCITY

BONE AGE

Growth of ossification centre Equivalent to biological age Predict Final Height (BA>6 yrs old) Methods: GP, TW II, RWT Left wrist

2 yrs 6 m.

10 yrs

12 yrs

POTENTIAL GENETIC HEIGHT


PGH boy = Height F + (Height M + 13) 8 cm 2
8 cm PGH girl= (Height F 13)+ Height M 2 Final height (range) Biological parents

Growth Chart
Boys

Exercise Height (father)167.5 cm, Height (mother) 149 cm. Calculate potential height son & daughter.
PGH son= 156,25 173,25 cm PGH daughter= 143,25 160,25 cm

195 190 185 180 175 170 165 160 155 150 145

PGH

Height 140 (cm) 135


130 125 120 115 110 105 100 95 90 85 80 2 4 6 8 10 12 14 16 18

Age (years)

VELOCITY

Velocity Chart

BMI

GROWTH MONITORING

What is your impression of this childs growth?

GROWTH MONITORING

NORMAL LINEAR GROWTH

Weight twice birth weight at age 4-5 months, 3 times birth weight at age 1 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, and 125 cm at 8 yrs old. 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

CONCLUSION
Hormone is central to growth ICP model is useful clinically

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 Maturation of reproductive organs and attainment of fertility Termination of linear growth

HORMONAL
GROWTH HORMONE
ADRENARCHE GONADARCHE

PHYSICAL
GROWTH SPURT
REPRODUCTIVE ORGAN SECONDARY SEX

MATURE
FINAL HEIGHT FERTILITY

INTRODUCTION

Onset Female: 8-13 years old Male: 9.5-13.5 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
GPR54 (G-protein coupled receptor 54) KAL-1 (Kallmanns syndrome 1) SFI (steroidogenic factor 1) DAX1 (DSS-AHC critical region on the X chromosome 1)

Loss-of-Function Phenotype
Hypogonadotropic hypogonadism X-linked Kallmanns syndrome: hypogonadotropic hypogonadism Sex reversal and adrenal insufficiency Hypogonadotropic hypogonadism and adrenal insufficiency

GENE & HPG AXIS


Gene
GNRHR (gonadotropinreleasing hormone receptor) FGFR1 (fibroblast growth factor receptor 1) LEP (leptin) LEPR (leptin receptor)

Loss-of-Function Phenotype
Hypogonadotropic hypogonadism;

Autosomal dominant Kallmanns syndrome: hypogonadotropic hypogonadism; Hypogonadotropic hypogonadism and obesity 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
obese ( 30% ideal BW) begin puberty

Slightly

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)


yrs before gonadarche age 6 - 8 yrs cortex adrenal activity adrenal androgens production (DHEA, DHEAS & androstenedione) pubic and axillary hair
2-3

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

Onset of puberty activity GnRH pulse generator

LH/FSH levels low insufficient to initiate gonadal function

frequency & amplitude GnRH pulses, especially during sleep progressive LH/FSH initiate gonadal function nocturnal gonadotropin pulses (onset) daytime gonadotropin pulses

NORMAL PUBERTAL DEVELOPMENT


Boys
Onset (yrs) 1st sign of puberty Max growth velocity (cm/yr) 12.5 (9.5-13.5) Testes volume ( 4ml) 10.3 (Tanner III-IV)

Girls
11.5 (8-13) Breast budding 9.0 (Tanner II-III)

Duration of puberty (yrs)

3.2 1.8

2.4 1.1

PERCENTAGE BODY FAT


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

14.3 11.2 Unchanged Unchanged Unchanged

40

27

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

Event Thelarche

Age (years) 10-11

Pubarche
Growth Spurt Menarche Adult Breast Development Adult Sexual Hair

10.5-11.5
11-12 11.5-13 12.5-15 13.5-16

HORMONAL CHANGES

SECONDARY SEXUAL CHARACTERISTIC CHANGES (TANNER STAGE)

LH, FSH AND E2 - PUBERTAL STAGE

FEMALE PUBERTY LANDMARK

Breast budding

1st sign of puberty


2 yrs > onset of puberty 2 yrs > menarche

Menarche

Ovulation

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

2 4

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


Wet dream Age 12-14 yrs late Tanner stage Age 18 20 yrs

Spermache

Growth spurt

Final Height

CONCLUSION

Puberty progress in a orderly schedule Reproductive function & adult height is attained at end of puberty

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