1. Sunrise Teaching 14th April 2016 Susan knox st1 Anne-Marie McClean st3
Short Stature
Sunrise Teaching
14th April 2016
Susan knox st1
Anne-Marie McClean st3

2. Aims Case: 8 year old boy with short stature Definition History
Examination
Investigations
Aetiology
Making the diagnosis

3. Investigations U+E FBP CRP BP Karotype TFTs
Coeliac Disease Antibody Screen
Urine
Growth Hormone Provocation Testing
Serum IGF1
X-ray left hand and wrist
Investigations[3] 
U+E
FBP, CRP (chronic inflammation/disease)
BP (bone disorder)
Karotype (chromosomal abnormalities, especially Turner’s syndrome)
TFTs
Serum IGF1 (growth factor deficiency)
Coeliac Disease Antibody Screen
Urinanalyis
X-ray left hand and wrist (Bone age)
Growth Hormone Provocation Testing
Investigations indicated to confirm or exclude possible underlying causes are based on the clinical assessment. They may include:
Blood tests:
FBC: anaemia blood dyscrasia and infections.
Renal function tests and electrolytes: renal disease and electrolyte abnormalities - eg, Bartter's syndrome, diabetes insipidus and other renal and metabolic disorders.
LFTs.
TFTs.
ESR and CRP: chronic inflammatory conditions.
Urinalysis and urine pH level: renal tubular acidosis.
Karyotyping may be helpful where examination suggests features of genetic syndromes. It should be performed in all girls with short stature as this may be the only feature of Turner syndrome.
Specific tests for suspected underlying or associated diseases - eg, coeliac disease, Cushing's disease, cystic fibrosis, growth hormone deficiency, vitamin D deficiency.

4. Bone Age
Estimation of skeletal maturation from assessment of the ossification of the epiphyseal centres.
Comparison of a frontal XR L hand and wrist with Greulich-Pyle atlas standards.
Delayed Bone age: 2 SDs below chronological age.
Familial short stature- bone age normal
CDGP- bone age corresponds with height age and is delayed (up to 2 SDs)
Pathological short stature-bone age is severely delayed (>2SDs)
Over-emphasis of bone age evaluation can be misleading if not used in the proper settings. The predictions do not apply to children with endocrine or bone pathologies affecting growth. Bone age estimates skeletal maturation from an assessment of the ossification of the epiphyseal centres.
The most widely used method is based on comparing a frontal radiograph of the left hand and wrist with standards from the Greulich-Pyle atlas.
Bone age is considered delayed if it is two standard deviations below the chronological age.
Bone age is usually normal for age in children with familial short stature.
In children with CDGP the bone age corresponds with height age and is delayed (up to two standard deviations).
In children with pathological short stature, the bone age is severely delayed (more than two standard deviations)
Skeletal maturation is assessed by radiography. The appearance of representative epiphyseal centres on the x-ray is compared with age- and gender-appropriate published standards.
The most commonly used method is that of Greulich and Pyle, which examines the left wrist and hand, but other methods such as the knee examination maybe more helpful in infants.
Bone age may also be used to predict final height, using the tables of Bayley and Pinneau.
Many conditions that cause poor linear growth may also cause a delay in skeletal maturation, so the finding of maturation delay is not diagnostic of any particular condition.
Delayed bone age does, however, indicate that the short stature is partially reversible, because linear growth will continue until the epiphyses fuse.

5. Aetiology of Short Stature
European Society for Paediatric Endocrinology (ESPE) classification:
Primary growth disorders:
- condition is intrinsic to the growth plate.
2. Secondary growth disorders:
-growth plates change as a consequence of the condition.
3. Idiopathic:
-no identifiable cause of short stature.
-Familial Short stature
-Constitutional Delay of Growth & Maturation
The European Society for Paediatric Endocrinology classification system was published in 2007 in the Hormone Research Journal which is the official journal of the ESPE.

6. Primary growth disorders
1. Clinically defined genetic syndromes
2. IUGR with failure to catch up
3. Congenital bone disorders
Clinically defined genetic syndromes, such as:
Down's syndrome
Prader-Willi syndrome
Silver- Russell syndrome
Noonan's syndrome
Turner syndrome
Intrauterine growth restriction with failure to catch up:
Fetomaternal factors
Prematurity
Placental dysfunction
Congenital bone disorders such as:
Achondroplasia
Hypochondroplasia
Osteogenesis imperfecta
Pics: 1. russell silver syndrome, acondroplasia,4.. osteogenesis imperfecta.

7. Secondary growth disorders
Chronic Illnesses
Metabolic
Diabetes mellitus
Malnutrition
Psychosocial deprivation
Medications
Endocrine
Insufficient nutrient intake , Chronic Illnesses
Growth Hormone Deficiency- congenital and acquired Endocrine:
Hypothyroidism.
Panhypopituitarism.
Hypothalamic or pituitary lesions (eg, trauma or tumour).
Laron's syndrome (growth hormone insensitivity).
Cushing's syndrome.
Growth hormone deficiency or insufficiency.
Precocious puberty.
Disorders of the growth hormone insulin-like growth factor I axis.
Metabolic:
Mucopolysaccharidoses.
Glycogen storage diseases.
Diabetes mellitus (poor control).
Chronic disease:
Cardiovascular disease.
Respiratory disease (eg, cystic fibrosis).
Haemoglobinopathies.
Renal disorders disease.
Malignancy.
Neurological (eg, hydrocephalus).
Juvenile arthritis.
Malnutrition:
Poverty or neglect.
Inflammatory bowel disease.
Coeliac disease.
Bowel obstruction.
Enzyme deficiencies.
Chronic bowel infection.
Short bowel syndrome.
Anorexia nervosa.
Rickets.
Psychosocial deprivation, including hyperphagic short stature syndrome.
Medication: steroid therapy
Cardiac disorders Q20–28 1B.2b Pulmonary disorders, e.g. cystic fibrosis J40–99 (E84) 1B.2c Liver disorders K70–77 1B.2d Intestinal disorders, e.g. Crohn’s disease, malabsorption syndromes, short bowel syndrome K50–52 K90–93 1B.2e Renal disorders, e.g. Fanconi syndrome, renal acidosis N10–19 N25–29 1B.2f Chronic anaemia D50–64 1B.2g Multiorgan disordersMuscular and neurological disorders, e.g. Duchenne muscular dystrophy, congenital myotonia
G71–73
1B.2i Connective tissue diseases, e.g. juvenile arthritis M08 1B.2y Other specified organ or systemic disorders

8. Idiopathic Familial Short Stature
Constitutional delay of growth and maturation
Constitutional delay of growth and maturation is a diagnosis of exclusion essentially

9. Making the Diagnosis History Family History Systemic Q Diet
Examination
Blood Tests
Bone Age

10. Genetic Causes History Growth velocity Decreased Diet N Family -
Growth velocity
Decreased
Diet N
Family -
General health
Specific to syndrome
TURNERS CAN BE ASYMPTOMATIC
Examination
General & systemic
Phenotypic features
Mid-p centiles
N ( most are mutations)
Investigations
Bone age
may be delayed
Blood investigations
Chromosomes/DNA
always check karyotype in a short female
Management
Multi-disciplinary
Including genetics
INDICATIONS FOR growth hormone in some cases
Adult height potential
Short
Genetic/chromosomal
SHOX gene mutation
Turners
Trisomies
Russel silver microdeletions

11. Skeletal Dysplasia History Growth velocity Decreased Diet N Family AD
Growth velocity
Decreased
Diet N
Family AD
General health
delayed dentition
General
And systemic Examination
Short limb
Short trunk
UPPER LIMB/LOWER LIMB RATIO*
Mid-p centiles
1 parent
Investigations
Bone age
Typical limb/trunk abnormaility
Blood investigations
genetics
Management
Supportive
Adult height potential
Short

12. Endocrine Causes History Growth velocity Decreased Diet N Family
Growth velocity
Decreased
Diet N
Family
Known thyroid or other
General health
Symptoms of hypothyroidism
Or growth hormone deficiency
Examination
General
And systemic
Hypothyroidism
Examine Mid-facial features
Mid-p centiles
Investigations
Bone age
Delayed in hypothyroidism
Blood investigations
TFT
IGF-1 
Advanced
GH stimulation test
Management
Endocrine referral Thyroxine
Growth hormone
Adult height potential
Variable

13. Chronic Disease History Growth velocity Decreased Diet N Family -
Growth velocity
Decreased
Diet N
Family -
General health
Specific to system
Examination
General
And systemic
Mid-p centiles
N unless strong F/H
Investigations
Bone age
May be delayed
Blood investigations
 Depend on clinical features
Management
Referral to appropriate specialty
Adult height potential
Variable
x-ray chest, ecg, echo, esr, urine
Coeliac screen, sweat test

14. Nutritional Causes History Growth velocity Decreased Diet Deficient
Growth velocity
Decreased
Diet
Deficient
Family
Socioeconomic/neglect
General health
Macro and micronutrient deficiency symptoms
Examination
General
And systemic
Deficiencies-pallor, stomatitis, skin
Mid-p centiles N
Investigations
Bone age
Blood investigations
FBC-low HB
Bone- high ALP or normal
VD-low
Management
Dietetic & Social input
Monitor
Adult height potential
N if well supported

15. Constitutional Delay of Growth & Maturation
History
Growth velocity N
Diet
Family
Delayed puberty
General health
Examination
General
And systemic
Mid-p centiles
Investigations
Bone age
Delayed
Over 2 SD
Blood investigations
FBC,
Bone profile
Management
Monitor growth
Adult height potential
Complications[1] 
Children with short stature may be teased or bullied, with potential emotional and psychological consequences. This is a source of parental anxiety although, in general, studies are reassuring and suggest long-term complications are infrequent.[11] Because short stature causes anxiety and may prompt consultation it may draw attention to underlying conditions which will then get treated, with consequent improvement in general health.

16. Familial Short Stature
History
Growth velocity N
Diet
Family
Short parent
General health
Examination
General
And systemic
Mid-p centiles
LOW
Investigations
Bone age
Blood investigations
FBC, bone profile
Management
Monitor growth
Adult height potential
Short

17. RBHSC Referral Criteria
Height <0.4th centile
Height below target centile range(TCR)
Height >3 centiles below mid parental centile(MPH)
Drop of >2 centile lines after 3 years of age
Height velocity 3years to puberty
IUGR <2nd centile at 4 years(Fail to show catch-up growth)
Turner syndrome
Prader-Willi syndrome
SHOX mutations
Height: fails to progress along the appropriate centile curve.
Growth velocity: decreased growth velocity for age.
Genetic potential: projected height varies from mid-parental height by more than 5 cm (2 in).
Multiple syndromic or dysmorphic features: abnormal facies, midline defects, body disproportions.
Bone age: delayed by more than two standard deviations.

18. NICE Guidelines for GH Use
GH- use somatropin- produced using recombinant DNA technology.
Indications
Have growth hormone deficiency.
Have Turner syndrome.
Have Prader-Willi syndrome.
Have chronic kidney disease.
Are born small for gestational age with subsequent growth failure at 4 years of age or later.
Have short stature homeobox-containing gene (SHOX) deficiency.
Treatment should be discontinued if:
Growth velocity increases by less than 50% from baseline in the first year of treatment.
Final height is approached and growth velocity is less than 2 cm total growth in one year.
Adherence is poor and cannot be improved.
Final height is attained.
Growth hormone of human origin (somatotrophin) has been replaced by a growth hormone of human sequence (somatropin) which is produced using recombinant DNA technology.
The National Institute for Health and Care Excellence (NICE) recommends that somatropin be used for the treatment of growth failure for children with growth failure who:[6]
Have growth hormone deficiency.
Have Turner syndrome.
Have Prader-Willi syndrome.
Have chronic kidney disease.
Are born small for gestational age with subsequent growth failure at 4 years of age or later.
Have short stature homeobox-containing gene (SHOX) deficiency.
Treatment should be discontinued if:
Growth velocity increases by less than 50% from baseline in the first year of treatment.
Final height is approached and growth velocity is less than 2 cm total growth in one year.
Adherence is poor and cannot be improved.
Final height is attained.
Growth hormone therapy in children with idiopathic short stature seems to be effective in partially reducing the deficit in height as adults, although the magnitude of effectiveness is on average less than that achieved in other conditions for which growth hormone is licensed.[7] Treated individuals remain relatively short when compared with peers of normal stature.[8] Mecasermin, a recombinant human insulin-like growth factor-I (rhIGF-I), is licensed to treat growth failure in children and adolescents with severe primary insulin-like growth factor I deficiency.[9][10] 

19. Summary
History and examination together with basic investigations are key for making the diagnosis
Constitutional delay of growth and maturation is the most common diagnois but also a diagnosis of exclusion
Tertiary centre referral criteria are useful
Psychological support

20. Questions?

21. Resources
BMJ Best Practice Assessment of Short Stature- updated August Accessible from:
Clinical Dilemmas in Evaluating the Short Child
Melissa D. Garganta, MD; Andrew A. Bremer, MD, PhD
Pediatric Annals
August Volume 43 · Issue 8:
UK Restricted Growth Foundation (

22. Diagnostic Aid