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Dos and Don’ts in Short Stature Assessment

Walid Kaplan, MD, Tawam Hospital

Objectives

• Recognize normal vs. abnormal short stature

• Treatable versus non-treatable short stature

• Initial work up

• Treat or make timely referral

Short Stature: First Encounter

Do:

• Determine if the condition is:

• Abnormal

• Treatable

• Presented on time

Don’t

• Under-estimate

• Over-react.


• Is it abnormal?

• Is it treatable?

• Is it presented on time?

Statistical Short Stature

2.5% are short

2.3% 97.7%

However,

Short stature≠ GH deficiency

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

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

Height assessment

1. Accurate measurement

2. Growth velocity (the longer the better)

3. Mid-parental height

4. Predicted final height (PFH)

Accurate Height Management

Do Don’t

Unreliable measurements!!

Height assessment

• Accurate measurement ✓

• Growth velocity (the longer the better)

• Mid-parental height

• Predicted Final Height (PFH)

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

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

Normal versus Slow GV

OK135S057 OK135S057

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)

Height assessment

1. Accurate measurement ✓

2. Growth velocity (the longer the better) ✓

3. Mid-parental height

4. Predicted Final Height (PFH)

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

Height assessment



3. Mid-parental height ✓

4. Predicted Final Height (PFH)

BONE AGE

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)

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

Height assessment



3. Mid-parental height ✓

4. Predicted Final Height (PFH) ✓

Is it abnormal?

• IF:

– Height < -2SDS (matched age and gender)

– Subnormal GV (dropping height Z-score)

– PFH < -2SDS of MPH

THEN, IT IS ABNORMAL


• Is it abnormal?



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

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

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✓

Genetic Testing

• Familial cases

• Multiple hormonal deficiency

• Syndromes

– TS, NS, RSS, PWS

– SHOX testing

– Familial IGHD

– Pituitary transcription factors

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.

Unapproved Indications of GH

• Skeletal dysplasia (U/L segment ratio)

• Down syndrome

• Silver Russell Syndrome

• Cystic fibrosis

• Metabolic diseases

• Others…


• Is it abnormal?



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

How Early Has GH Treatment Been Started?

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

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

Does the starting age have an affect on the FH?

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

• 77 patients with SGA• GH treatment (before puberty) till reached final height

Final Height is Children with SGA

• Correlates negatively with the following factors at treatment initiation:

– Age

– Height

– Weight

Pediatr Res, 2005(57): 216–222

• 1002 children on GH treatment for

– GHD

– MPHD

– SGA

– TS

– ISS

• Assess ΔHt.SDS after 2 years of treatment

Effects of Age at Treatment Start

Int J Pediatr Endocrinol. 2011; 2011(1): 6.


• Is it abnormal?



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


• Is it abnormal?




• Is it abnormal No

• Is it treatable No

• Is it presented on time No

Assurance or support


• Is it abnormal Yes

• Is it treatable Yes

• Is it on time Yes

Refer or treat

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

The Tallest Population:


Sweden Netherland Germany

USA Ghana Denmark


Sweden Netherland Germany

USA Ghana Denmark

12

3

7

?9

Live and Invest Overseas News, 2013

THANK YOU

dos and don’ts in short stature assessmentmedgress.com/virtualm/videos/aace2017/presentations/ibn...

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