robert p. schwartz, md wake forest university school of ... · pdf file• growth velocity...
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Robert P. Schwartz, MD
Wake Forest University School of Medicine
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Faculty Disclosure Informationcu y sc osu e o o
“I have no relevant financial relationships with the pmanufacturers(s) of any commercial products(s) and/or provider of commercial services discussed in this CMEprovider of commercial services discussed in this CME activity.
“I do not intend to discuss an unapproved/investigative use of a commercial product/device in my presentation ”use of a commercial product/device in my presentation.
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Evaluation of Child with Small Stature
• Pathophysiology of GH/IGF Axisp y gy• Definitions – FTT and small stature• Measurement Technique• Measurement Technique• Growth velocity and midparental (Target) Height• Workup – History, physical, lab studies/x-rays• Differential diagnosis of small stature g
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FAILURE TO THRIVEFAILURE TO THRIVE
Definition: Weight reduced out ofproportion to height
Causes: ° Inadequate caloric intake° Malabsorption° Chronic diseaseChronic disease
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SMALL STATURESMALL STATURE
Height that is more than two standardHeight that is more than two standard deviations below the mean for age (<3rd
il )percentile)
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Calculating Midparental andT H i hTarget Heights
Midparental (Father’s height – 5 inches) + (Mother’s height)height 2for girls
Midparental (Mother’s height + 5 inches) + (Father’s height)Height 2For boys
Target HeightMidparental Height ± 2 SDp g
(1 SD = 2 inches)
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EVALUATION OF GROWTH RATE
• Abnormally slow growth rate- Ages 3 to 12 years: Less than 2 inches/year(5 cm/year)(5 cm/year)
• Downwardly crossing centile channels on growth chart after the age of 18 monthsafter the age of 18 months
• Height below third percentile (-2 SD)• Height significantly below genetic potential (-2 SD
below midparental height)
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HISTORY
• Prenatal and postnatalPrenatal and postnatal• Length, weight and gestational age at birth
A f h d i• Age at onset of growth retardation• Developmental and social history• Pubertal development• Dietary history (caloric intake)Dietary history (caloric intake)• Review of systems to rule out chronic disease
F il hi t (h i ht f t )• Family history (height of parents)
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PHYSICAL EXAMINATIONPHYSICAL EXAMINATION
• Accurate measurements of height and weight• Accurate measurements of height and weight• Pubertal staging• Signs of chronic disease• Signs of skeletal dysplasia or syndromes• Signs of skeletal dysplasia or syndromes• Signs of endocrine disorders
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Laboratory Studies For Small Staturebo o y S ud es o S S u e
Initial Studies Specialized Tests
CBC IGF-1, IGFBP3 Urinalysis Karyotype for girls Chemistry Panel GH stimulation testsC e s y e G s u o es sFree T4, TSHBone Age
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CHRONIC SYSTEMIC DISEASES
• Malnutrition• Malnutrition• GI disorders (IBD, celiac disease)• Neurologic disease• Pulmonary disease• Pulmonary disease• Heart disease• Renal disease• Metabolic disorders• Metabolic disorders
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FAMILIAL SHORT STATUREFAMILIAL SHORT STATURE
• Family history of short staturey s o y o s o s u e• Growth rate – Parallel to normal curve but < 5th percentile• Pubertal development – NormalPubertal development Normal• Laboratory studies – Normal• Bone age = Chronologic ageBone age Chronologic age• Final height – Short but consistent with family height
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CONSTITUTIONAL GROWTH DELAY
• Birth weight and length – Normal• Birth weight and length – Normal• Growth rate – Normal prepubertal growth rate• Puberty – Delayed (“late bloomer”)• Family history of delayed puberty• Family history of delayed puberty• Bone age = Height age < Chronologic age• Endocrine studies – Normal• Adult height normal range• Adult height – normal range
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Psychosocial Development of Children with y pSmall Stature
• Risk factors affecting adaptation include being teased, a boy and having younger but taller siblingboy, and having younger but taller sibling.
• Protective factors were temperament characteristics, coping strategies and social supportcoping strategies, and social support.
• Hormone treatment is a means to improve height, but not a means to solve psychosocial problems.means to solve psychosocial problems.
Visser-van Balen H et al Arch Dis Child 2006; 91:433-439Visser van Balen H et al. Arch Dis Child 2006; 91:433 439.
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Small for Gestational Age (SGA) ChildrenSmall for Gestational Age (SGA) Children
D fi i i bi h i h d/ l h h 2SD b l• Definition: birth weight and/or length more than 2SD below mean for gestational age (<3rd percentile).
• Most SGA children catch up in growth by 2-3 years of ageMost SGA children catch up in growth by 2-3 years of age.• 10% of SGA children remain small and have increased risk (RR
5.2-7.1) for adult small stature.)• BA=CA• SGA children have increased risk of insulin resistance,
dyslipidemia, hypertension, and type 2 diabetes.
L PA t l P di t i 2003 111 1253 1261Lee PA et al. Pediatrics 2003; 111: 1253-1261.
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Growth Hormone Treatment of SGAGrowth Hormone Treatment of SGA
• Response to GH treatment in SGA children is variable.E li i h• Earlier treatment improves growth response.
• Insulin resistance may increase during GH treatment.hild h ld b i d f h i l• SGA children should be monitored for changes in glucose,
lipids, and BP.
Lee PA et al. Pediatrics 2003; 111: 1253-1261.
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Growth Hormone Deficiency
D d h i ht l it• Decreased height velocity• Other systemic causes of short stature ruled out• Delayed bone age• Decreased IGF-1, IGFBP3Decreased IGF 1, IGFBP3• Etiology – CNS tumors, malformations, trauma,
anatomic defects gene mutations cranial irradiationanatomic defects, gene mutations, cranial irradiation, idiopathic.
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FDA Indications for GH TreatmentFDA Indications for GH Treatment
• Growth hormone deficiencyCh i l f il• Chronic renal failure
• Turner Syndromed illi d• Prader-Willi Syndrome
• Small for gestational age (SGA)• Idiopathic small stature (ISS)
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Potential Risks of GH TreatmentPotential Risks of GH Treatment
• Edema, carpal tunnel syndromeP d b i• Pseudotumor cerebri
• Insulin resistance (glucose intolerance)i f li i• Worsening of scoliosis
• Slipped capital femoral epiphysis • Hypothyroidism• Pancreatitis• Second neoplasms after leukemia
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Turner SyndromeyShort Stature 100%Gonadal dysgenesis >95%Short neck with low hairline >70%Short neck with low hairline >70%Cubitus valgus >70%Sh l l 50%Short metacarpals or metatarsals >50%Pigmented nevi >50%“Webbed” neck 40%Renal anomalies >40%Renal anomalies >40%Edema of hands and feet 20%C di l li 20%Cardiovascular anomalies >20%
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Eligibility for GH Treatment of ISSEligibility for GH Treatment of ISS• Height standard deviation score (SDS) more than 2.25 SDS
below mean (1.2 percentile).• Unlikely to reach normal adult height.• Workup excludes other causes of short stature.• Epiphyses are not closed.
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Effect of GH Treatment on Final Height in gChildren with ISS – a Meta-analysis
• 10 controlled trials (434 patients) and 28 uncontrolled trials (655 patients) met inclusion critieriatrials (655 patients) met inclusion critieria.
• Increased growth velocity in first year of treatment.• GH produced average gain in adult height of 4 6 cm (range• GH produced average gain in adult height of 4-6 cm (range
2.3 – 8.7cm).
Finkelstein BS et al. Arch Pediatr Adolesc Med 2002; 156:230-240156:230 240.
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Cost Effectivness of GH Treatment of ISSCost Effectivness of GH Treatment of ISS
• Cost of GH treatment $5,000-$40,000/year.• Cost effectiveness ratio of GH treatment compared with no• Cost effectiveness ratio of GH treatment compared with no
treatment was $52,634 per inch.• Height gain of 1.9 inches (4.8cm) in 5 yrs of treatmentg g ( ) y• Cost per child was approximately $100,000.• Potential cost to treat all eligible children is $40 billion.g
Lee JM et al. Arch Pediatr Adolesc Med 2006; 160:263-269.
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Growth Hormone Treatment of“Normal” Small ChildrenNormal Small Children
• Who is “short” or not “tall enough?”• Who is short or not tall enough?• Should we treat the 1st, 5th, 10th percentile?• Will treatment increase final height?• Will treatment be of psychologic benefit?p y g• Will parents and children have unrealistic
expectations?expectations?• What is the cost effectiveness ratio?
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