Dos and Don’ts in Short Stature Assessmentmedgress.com/virtualm/videos/aace2017/Presentations/IBN...
Transcript of Dos and Don’ts in Short Stature Assessmentmedgress.com/virtualm/videos/aace2017/Presentations/IBN...
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Dos and Don’ts in Short Stature Assessment
Walid Kaplan, MD, Tawam Hospital
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Objectives
• Recognize normal vs. abnormal short stature
• Treatable versus non-treatable short stature
• Initial work up
• Treat or make timely referral
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Short Stature: First Encounter
Do:
• Determine if the condition is:
• Abnormal
• Treatable
• Presented on time
Don’t
• Under-estimate
• Over-react.
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Short Stature: First Encounter
• Is it abnormal?
• Is it treatable?
• Is it presented on time?
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Statistical Short Stature
2.5% are short
2.3% 97.7%
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However,
Short stature≠ GH deficiency
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How Common is GHD Worldwide?
USA
UK
Belgium
China
1/3500
1/4000
1/5600
1/8600
Chin Med Jour. 105(5):401-5.Lindsay et al. J Pediatr, 1994, Eur. J. Endocrinol 2004;151(1):67-72.
5% of short stature was secondary to endocrine abnormality, 48% had GHD
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GHD vs. Short Stature
• Short stature:
– 2.5% of the population are “statistically” short.
• GHD
– 2.5% of short children has GHD (Utah Study)
• ~ 1/40 cases of short stature is due to GHD
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Height assessment
1. Accurate measurement
2. Growth velocity (the longer the better)
3. Mid-parental height
4. Predicted final height (PFH)
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Accurate Height Management
Do Don’t
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Unreliable measurements!!
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Height assessment
• Accurate measurement ✓
• Growth velocity (the longer the better)
• Mid-parental height
• Predicted Final Height (PFH)
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Growth velocity assessment
Do• Monitor for 6-12 months
• Reliable measurement
Don’t• Use short period data
• All measurements
Seasonal variation in GV (summer-time growth is up to 60-67% of the whole year growth)
-Int J Pediatr Endocrinol. 2013; 2013(1): 2.-Am. J. Hum. Biol. 1997, 9: 709–715
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Growth velocity assessment
Do
• Monitor for 6-12 months
• Reliable measurement
Don’t
• Use short period data
• All measurements
• Compare to an age-matched reference
• Compare to a different gender or age group
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Normal versus Slow GV
OK135S057 OK135S057
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Estimation of normal height
4yr-pubertal spurt: ~5cm/year
Average birth length = 50cm1st year: 25cm2nd year: 10-12cm (1/2)3rd year: 8-9cm (1/3)4th year: 7cm (1/4)4th Birthday:(Height=100cm OR
Double birth length)
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Height assessment
1. Accurate measurement ✓
2. Growth velocity (the longer the better) ✓
3. Mid-parental height
4. Predicted Final Height (PFH)
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Mid=Parental Height
OK135S057
Mother: 160 cmFather: 172cm
MPH (MALE): (172+157+13)/2= 171cm
MPH (FEMALE):(172+157-13)/2= 158 cm
Mean
-2SDS
+2SDS
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Height assessment
1. Accurate measurement ✓
2. Growth velocity (the longer the better) ✓
3. Mid-parental height ✓
4. Predicted Final Height (PFH)
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BONE AGE
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Methods of Adult Height Prediction (AHP)
• Bayley–Pinneau method (1952)
• Whitehouse method, TW Mark I (1975)
• TW Mark II (1983)
• TW3 (2001)
• Roche–Wainer–Thissen (1975)
• Roche–Wainer–Thissen (1993)
• BoneXpert method (2009)
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Methods of Adult Height Prediction (AHP)
• Limitations:
1. AHP is based on bone age “estimation”
2. Comparing short children to a normal control
3. Does not consider timing of puberty
4. Over-estimation of AHP in short children and with delayed bone age
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Height assessment
1. Accurate measurement ✓
2. Growth velocity (the longer the better) ✓
3. Mid-parental height ✓
4. Predicted Final Height (PFH) ✓
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Is it abnormal?
• IF:
– Height < -2SDS (matched age and gender)
– Subnormal GV (dropping height Z-score)
– PFH < -2SDS of MPH
THEN, IT IS ABNORMAL
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Short Stature: First Encounter
• Is it abnormal?
• Is it treatable?
• Is it presented on time?
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INDICATION APPROVAL YEAR
Childhood GHD 1985
Chronic renal insufficiency (CRI) 1993
HIV-wasting 1996
Adult GHD 1997
Turner syndrome (TS) 1997
Prader-Willi syndrome (PWS) 2000
Small for gestational age (SGA) 2001
Idiopathic short stature (ISS) 2003
Short bowel syndrome 2004
SHOX haploinsuffciency 2006
Noonan syndrome (NS) 2007
GH, FDA APPROVED
INDICATIONS
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INDICATION APPROVAL YEAR
Childhood GHD 1985
Chronic renal insufficiency (CRI) 1993
HIV-wasting 1996
Adult GHD 1997
Turner syndrome (TS) 1997
Prader-Willi syndrome (PWS) 2000
Small for gestational age (SGA) 2001
Idiopathic short stature (ISS) 2003
Short bowel syndrome 2004
SHOX haploinsuffciency 2006
Noonan syndrome (NS) 2007
GH, FDA APPROVED
INDICATIONS
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Clinical Suspicion of GHD
• Severe short stature:– Height <-3SDS– Height <-1.5SDS of mid-parental height
• Slow GV:– < 1.5SDS for 2 years– <-2SDS for 1 year– Height Z score drops >0.5 SDS in 1 year
• Neonatal hypoglycemia• Midline defects• CNS abnormalities
GH Research Soc.2000
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Laboratory Testing of Short Stature
– General: • CBC, CMP, UA
• Celiac panel
– Endocrinology:• IGF-I and IGF-BP3
• Bone age
• TFTs
• Others (cortisol, Ca/PTH, vitamin D)
• GH Provocative test
– Genetic testing
When weight and height are both low
Endocrine causes of short stature:• GHD• Hypothyroidism• Cushing• PHPT (AHO)
Do✓
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Genetic Testing
• Familial cases
• Multiple hormonal deficiency
• Syndromes
– TS, NS, RSS, PWS
– SHOX testing
– Familial IGHD
– Pituitary transcription factors
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Laboratory Testing of GHD- Don’t
• Random GH level
• IGF-BP3 in children > 3y/o
• GHST, as the sole diagnostic test (or one Rx)
• LH, testosterone in pre-pubertal patients– Female <13yr., Males <14 yr.
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Unapproved Indications of GH
• Skeletal dysplasia (U/L segment ratio)
• Down syndrome
• Silver Russell Syndrome
• Cystic fibrosis
• Metabolic diseases
• Others…
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Short Stature: First Encounter
• Is it abnormal?
• Is it treatable?
• Is it presented on time?
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Recommended Age to Start GH
• SGA:– USA: 2 years
– Europe: 4 years
• TS:– As soon as slow GV is noticed (usually 2-3 years)
• GHD:– As early before puberty as possible
• ISS:– Age 5 to pre-puberty
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How Early Has GH Treatment Been Started?
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The Average Age at GH Initiation
• SAGhE (n=25000) 10-14yr
• KIGS (n=4685): 10 years
• SAGhE-France (n=6874): 11 years
• KIGS (SGA) (n=1909) 9.1 years
• Clayton et al (SGA) (n=360): 8.4 years-Horm Res Paediatr. 2015 Sep; 84(3): 172–183 -Horm Res 2006, 65(Suppl 3):153-159-J Clin Endocrinol Metab 2007, 92(3):804-810 -Int J Pediatr Endocrinol 2010
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Bone age % of mature height
BOYS GIRLS
1 42.2 44.6
2 48.5 52.1
3 53.5 57.1
6 65.3 70.2
9 75.6 81.1
12 84 92.6
14 91 98.3
16 97.1 99.6
18 99.5 99.9
Greulich & Pyle Second Edition
Bone Age and Growth Maturation
150x0.2= 30cm
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Does the starting age have an affect on the FH?
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Factors Affecting Response to GH
• 121 pre-pubertal children with GHD
• Adult height correlated positively with
– Duration of treatment
– Height at the treatment initiation
– GV in the first year of treatment
• Negative correlation with
– Age at treatment initiation
– Bone age delay
J Clin Endocrinol Metab 82: 418–420, 1997
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• 77 patients with SGA• GH treatment (before puberty) till reached final height
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Final Height is Children with SGA
• Correlates negatively with the following factors at treatment initiation:
– Age
– Height
– Weight
Pediatr Res, 2005(57): 216–222
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• 1002 children on GH treatment for
– GHD
– MPHD
– SGA
– TS
– ISS
• Assess ΔHt.SDS after 2 years of treatment
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Effects of Age at Treatment Start
Int J Pediatr Endocrinol. 2011; 2011(1): 6.
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Short Stature: First Encounter
• Is it abnormal?
• Is it treatable?
• Is it presented on time?
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Abnormal Timing
• Too early
– <2 yr. of age in the absence of hypoglycemia
• Too late:
– Near or post menarche
– After full fusion of growth plates
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Short Stature: First Encounter
• Is it abnormal?
• Is it treatable?
• Is it presented on time?
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Short Stature: First Encounter
• Is it abnormal No
• Is it treatable No
• Is it presented on time No
Assurance or support
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Short Stature: First Encounter
• Is it abnormal Yes
• Is it treatable Yes
• Is it on time Yes
Refer or treat
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Summary
• Endocrine disorders are very rare causes of short stature
• Classification of short stature requires accurate measurements and GV monitoring
• Diagnostic tests should be guided by clinical assessment
• Approved indications of GH must be identified and referred as early as possible
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The Tallest Population:
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The Tallest Population:
Sweden Netherland Germany
USA Ghana Denmark
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The Tallest Population:
Sweden Netherland Germany
USA Ghana Denmark
12
3
7
?9
Live and Invest Overseas News, 2013
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THANK YOU