Short stature and tall stature

Pediatric Endocrinology DivisionH.Adam Malik Hospital/Medical School

University of Sumatera Utara

Growth • Normal growthg

– Infant– Childhood– Puberty

• Growth : change in size & maturation• Stature : size

Growth Velocity Curve

C /t h

Growth Velocity Curve

Cm/tahun

Sex steroidGH

Infant Childhood Puberty

Growth rate by age

1-6 mo : 18 - 22 cm/yr6-12 mo : 14 – 18 cm/yry1 yr : 11 cm/yr2 yr : 8 cm/yr2 yr : 8 cm/yr3 yr : 7 cm/yr4 – puberty : 5 – 6 cm/yr4 – puberty : 5 – 6 cm/yr

INFANT PERIOD

Growth ChartCanalizationCatch-down

Growth ChartCatch-up

Potensi Tinggi Genetik

cm

tahun0 1 2 3

tahun

Evaluation of growth• Anthropometry

– Standing & sitting : proportional– Arm span

• Bone age :• Bone age : – GP, TW, RUT– Normal, delayed, advanced– prediction of final height

Growth chart• Growth curve

– NCHS, Jumadias, Husaini• Plotting growth

– Normal, short, tall• Interpretation of plot• Potential genetic height• Potential genetic height

Growth Chart195

175

180

185

190

97

50

155

160

165

170

50

3

130

135

140

145

150

Height (cm)

110

115

120

125

130

90

95

100

105

110

80

85

2 4 6 8 10 12 14 16 18

Age (years)

Growth Chart195

175

180

185

19097

50

155

160

165

170

3Potential Genetic Height

130

135

140

145

150

Height (cm)

110

115

120

125

130

90

95

100

105

110

HA CA

80

85

2 4 6 8 10 12 14 16 18

Age (years)

Bone age• Greulich & Pyle

– Comparison of left wrist– Prediction of FH after 6 years

Table Bayley & Pinneau– Table Bayley & Pinneau• Tanner Whitehouse II

– Maturation of ossification centerMaturation of ossification center– More reliable : scoring system– complicated

Bone Age• Left wrist

– Greulich – Pyle – Tanner-Whitehouse II– RWTRWT

• Ossification centre• Prediction final height

Short stature

• Height < 2SD• Sex, age and race

• Pattern of growth more important rather than g pabsolute position on growth curve

Short stature

– Variants of normal– Prenatal onset– Post natal onset

Variants of normal (normal growth velocity)• Familial short stature

– Parents height genetically shortnormal bone age– normal bone age

– short adult• Constitutional delay of growth & pubertyConstitutional delay of growth & puberty

– Delayed puberty in the family– Normal growth velocity – normal adult height

Prenatal onset• Primary growth deficiencyy g y

– Malformation– syndromes

• Secondary growth deficiency– Low maternal socioeconomic– Undernutrition– Maternal disorder or disease

Post natal onset• Nutritional• Deprivation syndrome• Cardiac defect• Respiratory insufficiency• Renal disfunctionRenal disfunction• Hormonal• Chronic infection chronic disease• Chronic infection, chronic disease

Etiology• Primary disturbances of growth

– Skeletal dysplasias– Chromosomal abnormalities– Metabolic causes

IUGR– IUGR– Syndromes– GeneticGenetic

Etiology • Secondary growth disturbancesy g

– Undernutrition– Disorder of the bowel, kidney, heart, lung– Psychosocial deprivation– Chronic infection, drugs

E d i di d– Endocrine disorder– Idiopathic growth delay

Diagnostic Approach to Short StatureShort Stature

Normal

Abnormal

Normal

Constitutional DelayNormal Variant y

Proportional Dysproportional

ExtrauterineIntrauterine

Endocrinological causesg• Normal variant : CDGP• GH Deficiencyy• Hypothyroid• Precocious PubertyPrecocious Puberty• Cushing’s syndrome• Pseudohypoparathyroidism• Pseudohypoparathyroidism

Treatment• Depend on the etiologyp gy

– Nutrition– Organic disease

CHD IDDM• CHD, IDDM– Hormonal

• GH, Thyroid, Sex hormone– Mechanical

• Bone lengthening : achondroplasia

GH deficiency• Short stature• Chubby

Abd i l di it• Abdominal adiposity• Micropenis• Single central incisor• Single central incisor• Frontal bossing• Proportionalopo t o a

GH Deficiency• Low growth velocity : < 25%• Retarded bone age• GH level < 10 ng/dl

S i t t l &– Screening tests : sleep & excercise

– Stimulation test• 2 tests : ITT & Arginine,

• Low IGF-1

Causes of GH Deficiency• Congenital

– Idiopathic– Genetic– Assosiated anatomic defect : SOD,midline defectAssosiated anatomic defect : SOD,midline defect

• Acquired– Trauma– Neoplasma– Cranial irradiation– etc

Treatment• Varies: GH 14 - 21 IU/m2/day

6 ti / k• 6 times/week• Monitoring:

– Height, velocityg , y– Side effect

• Terminate :– No response < 2 cm– No response < 2 cm– Epiphyseal plate closure

CDGP• Family historyy y• Growth velocity normal• Bone age retardedg• Puberty : late• Adult height : normalAdult height : normal

• Treatment : No Need• Treatment : No Need

Congenital hypothyroidism• Large posterior fontanelle• Respiratory difficulty• Hypothermia• Feeding difficulty• Feeding difficulty• Lethargy• Delay in passing meconium• Abdominal distention• Vomitting • Prolonged jaundiced• Prolonged jaundiced• Oedema

C hi ’ S dCushing’s Syndrome• Corticosteroid excess• Growth retardation due to

– Interferring protein anabolism– Impairing somatomedin production

• Hypertension• Obesity predominant : trunk and neck,

moon faceDi t b f l t b li• Disturbances of glucose metabolism

• Purple striae, hirsutism, osteoporosis, hypogonadismM l k• Muscular weakness

Pseudohypoparathyroidism• Short stature• Mental retardation• Albright’s osteodystrophyg y p y• Round facies• Ectopic calcificationEctopic calcification

Pola pertumbuhan linierp

Pola pertumbuhanPola pertumbuhan

Conclusion• Short stature

– Etiology : varies; endocrinology – Treatable, depend on the etiology– Psychosocial problem

• Growth monitoring : important• Anthropometric measurement

– Clue to diagnosis

TALL STATURETALL STATURE

Introduction

• Definition Tall stature : height > 97th percentile for age,

&sex & race.• Cause

I t i i– Intrinsic – Acquired

Growth cessation• Puberty → sex steroid• Puberty → sex steroid

(estrogen) ↑ → epiphyseal fusionB• Bone age– Girls 14 – 16 yrs– Boys 18 – 20 yrs

• Sex steroid & growth– Low dose: stimulate– High dose: inhibitg

HEIGHT: UPPER LEVEL

Country (year of ascertainmet)

Height (boys) Height (girls)

Mean or di

(p97) Mean or di

(p97)median median

The Netherlands (1985) 182.0 194.5 168.3 179.8

Germany (1992) 179.9 192.5 167.0 179.0

Sweden (1976) 179.1 192.4 165.5 178.2

Czechia (1993) 178.3 191.7 165.0 176.8

Denmark (1982) 179.4 190.4 166.0 176.0

United Kingdom (1995) 176.4 190.5 163.6 176.0

USA (NHCS) (1977) 176.8 187.6 163.7 173.6

HEIGHT UPPER LEVEL

C t ( fHeight (boys) Height (girls)

HEIGHT: UPPER LEVEL

Country (year of ascertainment) Mean or

median (p97) Mean or median (p97)

France (1979) 175.0 187.0 163.0 174.5

Mexico (1975) 172.8 186.3 160.6 174.5

Turkey (1978) 173.5 186.0 160.0 171.0

Argentina (1987) 172 8 185 6 160 7 172 2Argentina (1987) 172.8 185.6 160.7 172.2

Korea (1979) 170.2 180.0 157.6 166.5

Indonesia (Husaini) 165.1 175.9 153.9 163.4

NCHS(NCHS(-) vs HUSAINI () vs HUSAINI (-))(( ) () ( ))

BOYS GIRLS

200

BOYS

175

GIRLS

150

ght (

cm)

150

ght (

cm)

10012 13 14 15 16 17 18

hei

100

125hei

12 13 14 15 16 17 18

age (years)12 13 14 15 16 17 18

age (years)

Intrinsic tall statureIntrinsic tall stature

Familial genetic tall stature / i i

Intrinsic tall statureIntrinsic tall stature

constitutional

Cerebral gigantism (Soto’s syndrome)Cerebral gigantism (Soto s syndrome)

Marfan syndrome

Homocystinuria

M l i l d i l i 2bMultiple endocrine neoplasia type 2b

Intrinsic tall statureIntrinsic tall statureChromosome

47, XYY; Klinefelter syndrome (46, XXY); Fragile X syndromeFragile X syndrome

Beckwith-Wiedemann syndrome (IGF2)

Weaver syndrome

Simpson-Golabi-Behmel syndrome (GPC3)

Bannayan-Riley-Ruvalcaba syndrome (PTEN)

Deficiency of aromatase/loss of function mutations of estrogen receptor (a) in male

Acquired tall statureq

Infant of diabetic mother (hyperinsulinism)

Ob i ( ll hild l d l h i h )Obesity (tall child normal adult height)

Sexual precocity (tall child but short adult)

Primary hypogonadism (eunuchoid)

H th idiHyperthyroidism

Growth hormone excess (Gigantism, acromegaly)

Evaluation Evaluation –– History & PEHistory & PE• Family history (constitutional, Marfan, familial y y (

precox etc)• Developmental history• Birth weight and length• Stigmata of syndromeg y• Pubertal status

Evaluation Evaluation –– LabLab• Growth pattern

– Parallel or not– Potential genetic height

• Bone age (prediction of final height)g (p g )• As indicated

– Chromosome – Mutation analysis– Mutation analysis– Others (hormonal, imaging, cardiovascular, eye etc)

TherapyTherapy• Causal• Constitutional Tall stature

– reassurance– Boys: testosterone 500mg/m2/month– Girls: estradiol 0,1 mg/day

Marfan-arachnodactyly

Marfan – subluxatio lentis

Marfan – fibrillin (connective)

Fragile-X Syndrome

Soto's syndrome• rare genetic disorder with excessive physical growth

d i th fi t 2 t 3 f lifduring the first 2 to 3 years of life. • mild mental retardation, delayed motor, cognitive,

and social development, hypotonia (low muscle p yp (tone), and speech impairments.

• large at birth, large heads (macrocrania) • disportionately large and long head with a slightly• disportionately large and long head with a slightly

protrusive forehead, large hands and feet, hypertelorism (an abnormally increased distance between the eyes) and downslanting eyesbetween the eyes), and downslanting eyes.