Download - Seminar short stature
References
1. Nelson Textbook of Pediatrics
2. Pediatric Endocrinology, Fifth edition Vol. 2
3. Practical strategies in Pediatric diagnosis and therapy
4. O. P. Ghai, 8th edition
5. Pubmed
IntroductionGrowth is the fundamental physiologic process that characterizes childhood.
Secular trends in growth patterns are followed as indicators of children’s health on a population level.
Growth can be worrisome along two variables: height (short stature) and velocity (growth failure).
Definition of Short Stature
• Height less than the 3rd percentile or 2SD below the mean for age of the population reference standard.
• Excessively short i.e. more than 2 SD below the Mid-Parental Height (MPH) or Target height (TH) even if the height recorded is within the normal population percentiles for age.
• Growth velocity less than 25th percentile on a velocity curve over a period of 6-12 months.
• Dwarfism refers to more severe short stature, defined as height below 3 SD for age & gender norms.
Growth Velocity
• Growth velocity =
𝐻𝑒𝑖𝑔ℎ𝑡 𝑐𝑚 𝑎𝑡 𝑡𝑖𝑚𝑒2―𝐻𝑒𝑖𝑔ℎ𝑡 𝑐𝑚 𝑎𝑡 𝑡𝑖𝑚𝑒1
𝑇𝑖𝑚𝑒2−𝑇𝑖𝑚𝑒1(𝑚𝑜𝑛𝑡ℎ𝑠)× 12(months/year)
• Thus, abnormally slow growth velocity, or height dropping across two major centile lines on the growth chart are the two other definitions of worrisome growth.
Significance• The Social Problem –
Short stature is a cause of psychosocial stress, and the extent to which this is a problem depends on the severity of the height deficit, the degree of tolerance in the local population, and the child’s coping skills.
• The Medical Problem –
Multiple diseases can present solely with growth failure, such as celiac disease, inflammatory bowel disease, cystic fibrosis, renal tubular acidosis, and human immunodeficiency virus (HIV) infection.
Although girls werereferred to an
academic growth center less often andwith greater height
deficits than the boys, a significantly
higher percentage of the girls had underlying
pathology that requires intervention
The distribution of each major diagnosticcategory for (A) boys and (B) girls referred to an academicGrowth Center in 2001.
Normal patterns of Growth
• Fetal Growth & Birth size –
Reflects mainly maternal factors –
maternal or uterine size,
parity and multiparity,
nutrition, and uteroplacental blood flow
small effect of congenital disorders on prenatal growth
• Postnatal Growth –
The rate of linear growth is greatest in infancy
genetic or familial influences begin to exert their effect on height
Growth velocityYEAR INCREMENT (in cms)
1 25
2 10
3,4 7
5,6 6
7 – Puberty 5
Mid - puberty 9 – 10.3
Growth accelerates
again at puberty.
The timing of the
pubertal
growth spurt differs
between girls and boys.
Etiology of Short statureNormal variants –
1. Constitutional growth delay
2. Genetic/ Familial Short stature
3. Combined
Pathological –
1. Nutritional
i. Macronutrient deficiency
ii. Micronutrient deficiency
Decreased intake – kwashiorkor;anorexia nervosa
Decreased absorption – inflammatorybowel ds.;celiac ds.;
cystic fibrosis; malabsorption
Etiology of Short stature
2. Endocrinal causes – Hypothyroidism; Isolated GH deficiency; Hypopituitarism; Glucocorticoid excess; Precocious puberty
3. Chromosomal defects – Turner; Down syndrome; Praderwilli syndrome
4. LBW short stature – Sporadic; Russell Silver syndrome; Cornelia de lange syndrome; Bloom syndrome
5. Defects in Bone development – Achondroplasia; Chondrodystrophies
Etiology of Short stature
6. Metabolic causes – Mucopolysaccharidosis; other storage disorders
7. Chronic diseases – Chronic Liver ds.; Chronic renal ds.; Chronic infections; CHD; Poorly controlled Diabetes Mellitus
8. Psychosocial deprivation
9. Chronic drug intake – Glucocorticoids; High dose estrogens & androgens; Methylphenidate; Dextroamphetamines
Assessment of Short stature
1. Accurate height measurement
2. Assessment of height velocity
3. Comparison with population norms
4. Comparison with child’s own genetic potential
5. Assessment of body proportion
6. Sexual maturity rating
7. Bone age
Accurate height measurement• <2 years: supine length; infantometer
• >2 years: standing height ; stadiometer
• Bulky diapers removed
• Child is placed supine on the infantometer
• Head held firmly against a fixed upright head board by one person
• Legs straightened, feet at right angles to legs
Accurate height measurement• Without footwear
• Heels, buttocks, scapulae and occiput
touching the wall
• Lower border of the eye socket in the same
horizontal plane as external auditory meatus
( FRANKFURT PLANE)
• Looking straight ahead
• Gentle but firm pressure upwards applied to
the mastoids from underneath
• A Harpenden stadiometer which determines height accurately (within 0.1 cm) is the most sophisticated instrument.
Assessment of Height velocity
YEAR INCREMENT (in cms)
1 25
2 10
3,4 7
5,6 6
7 – Puberty 5
Mid - puberty 9 – 10.3
• Rate of increase in height over a period of time expressed as cm/ yr.
• All pathological causes of short stature will cause a poor growth velocity.
Comparison with population norms
• The height should be plotted on appropriate growth charts.
• Any child who falls behind in growth across major percentiles in the chart should be evaluated, even when the height is not below the third percentile.
• Use any chart but adjust for mid-parental height.
Examples of Growth charts –
1. IAP (IAP Growth Monitoring guidelines 2007)2. WHO (MGRS Study 2006)3. CDC 4. British 20055. ICMR6. 1989 Affluent Indian
(Agarwal et al)7. 2009 Affluent Indian
(Khadilkar et al)
Comparison with child’s own genetic potential
• Mid parental height (MPH) gives an estimate of the child’s genetically determined potential.
MPH for boys =𝑀𝑜𝑡ℎ𝑒𝑟′𝑠 +𝐹𝑎𝑡ℎ𝑒𝑟′𝑠 ℎ𝑒𝑖𝑔ℎ𝑡 (𝑐𝑚)
2+ 6.5 cm
MPH for girls =𝑀𝑜𝑡ℎ𝑒𝑟′𝑠+𝐹𝑎𝑡ℎ𝑒𝑟′𝑠 ℎ𝑒𝑖𝑔ℎ𝑡 (𝑐𝑚)
2- 6.5 cm
• The target height obtained by this method is then applied to the 20-year line of the gender-appropriate growth chart.
The projected height is determined by
extrapolating the child’s growth along his or her own channel. If
the projected final height is within 5cm of the midparental target
height, the child’s height is appropriate
for the family
Assessment of Body proportion
Proportionality is assessed by –• Upper segment : Lower segment Ratio
• Comparison of arm span with height
Based on this, short stature can be
• Normally US : LS Ratio –
Birth: 1.7
3 years: 1.3
6 years: 1.1
10 years: 1
Adults: 0.9
Proportionate
Disproportionate
• Increase in US : LS ratio –
- Rickets
- Achondroplasia
- Untreated Congenital Hypothyroidism
• Decrease in US : LS ratio –
- Spondylo-epiphyseal dysplasia
- Vertebral anomalies
• Conditions that adversely affect the vertebrae, such as scoliosis or irradiation, may result in growth retardation and disproportionately long arms.
• In case of disproportionate short stature,
further measurements of the various limb
segments should also be made.
Normally, SE/EMC = 1
Rhizomelia = 0.98
Sexual Maturity Rating (SMR)
• SMR stage should be assessed in older children.
Short stature:
precocious puberty due to early epiphyseal fusion.
Delayed puberty as growth spurt is delayed.
Skeletal Maturation
• The pattern of skeletal maturity is also helpful in differentiating the type of short stature.
• BONE AGE - method of assessing skeletal maturity observed directly by visualization of epiphyseal growth plates on X-ray.
• X-rays useful to determine skeletal age –
1. <1 year: shoulder x-ray
2. 1-13 years: hands and wrists
3. >13 years: elbow and hip
• Bone age is necessary:
- in the diagnosis of FSS and CGD;
- for interpreting hormone levels in pubertal age;
- for diagnosis of precocious puberty or hyperandrogenism;
- for deciding whether to treat or not the above mentioned conditions;
- for predicting adult height in normal children;
- in evaluating any child with growth and/or puberty disorders;
- in deciding the time to start replacement therapy in hypogonadism;
- in monitoring children on growth hormone therapy.
Methods for bone age evaluation
1. Greulich & Pyle method - In their method for each of these bones an elaborate description of its developmental stages is included.
2. Tanner and Whitehouse method - It is based on a set of bone’s standard maturity for each age population.
3. Roche–Wainer–Thissen – The five predictor variables in the RWT method are recumbent length, weight, bone age, chronological age, and parental heights.
Computer programs have been developed for the calculation of both mid-parental target heights and predicted adult heights (by all three methods).
Evaluating a child with short statureHistory –
Maternal History
Birth History
Growth pattern
Developmental milestones
Family History
Dietary History
Medical History
Physical Examination –
• Measurements: weight, standing height, sitting height, head circumference.
• Height in relation to previous heights (height velocity), parents’ heights, stage of puberty, weight.
• Genitalia and pubertal development
• Body composition: subcutaneous fat and muscle bulk
• Unusual or dysmorphic features
• Signs of specific diseases
History and Presentation
• Hypoglycemia, prolonged - Congenital GH deficiencyjaundice, small penis
• Antenatal - IUGR• Puffy extremities - Turner syndrome• Fever, weight loss, - Chronic infections
anorexia• Chronic diarrhoea/ - Malabsorption
bulky frothy stools• Dyspnea, cough, cyanosis - Systemic diseases• Headache, vomiting, - Pituitary or hypothalamic SOL
diplopia• Polyuria - CRF, RTA• Weight gain, obesity - Cushing syndrome• Constipation, lethargy, - Hypothyroidism
delayed milestones
Clues on Examination• Pallor - Anemia• Hypertension - CRF, Cushing syndrome• Dysmorphism - Genetic disorders• Midline defect - Hypopituitarism• Vitamin deficiency, - Malabsorption, PEM
Wt for Ht• Frontal bossing, - Congenital GH deficiency
depressed nasal bridge• Disproportionate body - Skeletal dysplasia, Rickets
proportion• Central obesity, - Cushing syndrome
proximal weakness• Papilloedema, visual defect, - Pituitary Tumor
optic atrophy• Goiter, delayed dentition, - Hypothyroidism
Short lower limbs
APPROACHMeasurement
Normal Abnormal
Clues H/O & EXAM
Present Absent
Assess growth rate & bone age
<4 cm/yr >4 cm/yr
Bone age Bone age
delayed normal normal delayed
do screenning inv. Genetic ds GSS CGD
Stepwise investigative work - up• Level-1 investigations –
1. CBC
2. CRP & ESR
3. Urinalysis
4. Stool examination
5. S. Electrolytes
6. Liver and Renal
function tests
7. Bone age
• Level-2 investigations –
1. Thyroid function tests
2. Karyotyping
3. Prolactin
4. Neuroimaging
• Level-3 investigations –
1. Coeliac serology & duodenal biopsy
2. GH stimulation test & serum IGF-1 levels
Differential Diagnosis
• Variants of Normal
– Familial short stature
– Constitutional delay
• Pathologic/Growth Failure
– Endocrinal
– Genetic
– Systemic
– Psychosocial
Familial/Genetic short stature• Birth weight and length below 3rd percentile for GA
• Although the growth channel is low,
it parallels the normal growth curve.
• Family history of short stature
• Normal onset of puberty
• Bone age appropriate for
chronological age
• The adult height is likely to be shorter
than average.
Constitutional growth delay• The most common cause of
short stature and sexual
infantilism in the adolescent.
• Delayed onset of puberty
• A late adolescent growth
spurt (Late Bloomers)
• Final height is normal
• Bone age delayed
A positive family history of delayed but normal puberty and growth, a normal sense of smell (to exclude Kallmann syndrome), and normal
neurologic findings favor constitutional delay.
Intrauterine Growth Retardation
• Small for gestational age at birth
• Slow growth from early infancy
• Normal bone age,sexualdevelopment
• Normal GH levels
• Normal growth pattern in family
• Serum IGF-1 levels were lower,
and GH levels higher
• Higher basal and stimulated
suggested GH resistance
IUGR infant who maintains normal growth rates but does notexhibit catch-up growth.
Growth hormone deficiency
• Congenital -
-idiopathic
-associated with midline defects (absent septum pellucidum, optic nerve hypoplasia [septooptic dysplasia], cleft palate, holoprosencephaly, single central incisor)
-defects in the genes for GH
• Acquired –
-birth injury
-head injury
-cranial irradiation
-craniopharyngioma
• Growth hormone insensitivity (Laron syndrome)
• Clinical features –- Normal birth size
- Mid-facial crowding
- Round cherubic facies
- Depressed nasal bridge
- Micropenis
- Frontal bossing
- Heightage < weight age
- Neonates – hypoglycemia/
prolonged jaundice
- Bone age is delayed
- Body proportions are normal
• Lab. Diagnosis –- subnormal GH levels (<7 or 10 ng/mL)
in response to two pharmacologic
stimuli (clonidine, arginine,
insulin-induced hypoglycemia).
- Low IGF-1 and IGFBP3.
- Neuroimaging for acquired causes.
• Treatment –- Replacement therapy with hGH.
- Recommended dose of hGH is
0.18-0.3 mg/kg/wk. It is administered
subcutaneously in seven divided doses
until near final height is achieved.
Hypothyroidism
• May be congenital or acquired
• Clinical features –- Prolongation of physiologic icterus
- Birth size normal
- Feeding difficulty, sluggishness
- Large tongue, large abdomen
- Poor appetite
- Umbilical hernia
- Cold & mottled extremities
- Wide open ant. & post. Fontenelle
- Short stature, Bone age delayed
- Myxoedema
- Dry skin, delayed puberty
A.Congenital hypothyroidism in an infant6 mo of age
B.Four mo after treatment, decreased puffinessalert appearance
Lab. Diagnosis –-Newborn screening for congenital Hypothyroidism is routine - If abnormal repeat- Elevated serum TSH and low T4.- Positive TSH receptor-blocking antibodies- diagnosis for transient congenital Hypothyroidism- If normal TSH & low T4, look for Pituitary or hypothalamic cause- Thyroid antibodies (antithyroglobulin, antimicrosomal antibodies) is consistent with autoimmune thyroiditis.
Treatment –-In neonates, the initial starting dose is 10-15 μg/kg.- Children with hypothyroidism require about 4 μg/kg/24 hr.- Monitoring of free T4 (or FTI) and TSH is essential for optimizing the dose of medication.- Educate parents and child about disease.
Achondroplasia• Most common osteochondrodystrophy.• caudal narrowing of spinal canal• Autosomal dominant disease.• But there are studies present which
shows the germline and somatic mosiacismin achondroplasia
[J Med Genet 2000;37:956-958 doi:10.1136/jmg.37.12.956].
• Treatment –
- Counselling of parents- Dietary advice- Psychological counselling- Annual monitoring of height and weight- Drugs: GH
Turner syndrome- classic form being 45,XO
- progressive deviation of height
away from the normal growth curve
- Streak gonads
- small birth size and dysmorphic
features
- Abnormally high levels of the
gonadotropins, LH, FSH
Treatment –• GH therapy
• sex steroid replacement therapy
Psychosocial Dwarfism/ HyperphagicDwarfism
• Profound short stature without
apparent malnutrition.
• Characterized by functional
hypopituitarism.
• Low IGF-1 levels & inadequate
response to GH stimulation.
• Less stressful environment
is beneficial.Between ages 6 and
8 years, he had chemicalevidence of growth hormone (GH)deficiency. B, After placement in a
chronic care facility (arrow), hisgrowth rate improved markedly, and
his GH levels reverted to normal.
Take Home Message
• Take height by proper method and plot it on appropriate growth chart.
• Use Growth Charts appropriately.• Every child must have proper growth monitoring so as to know
whether the child is on his proper road to growth.• Any child with short stature is not always familial and should
evaluated completely.