Approach to Short Stature

Lorna R. Abad, MDJuly 08, 2015

Objectives: At the end of the session, residents are expected to:

• 1. Recognize growth failure/growth retardation

• 2. Collect relevant information towards establishing etiology

• 3. Plot measurements and interpret graph• 4. Request and interpret appropriate

laboratory tests • 5. Formulate plan of management

Outline

• 1. definition and causes of short stature• 2. approach to diagnosis• 3. indications of growth hormone therapy

Important questions to ask

• 1. Is the child short?• 2. Does the child have dysmorphic features or

disproportionate short stature? • 3. Does the child have growth failure or failure

to thrive? • 4. Although the child is short, is his or her

growth velocity normal or impaired?

● How short is the child?●Is the child’s height velocity (HV) impaired?●What is the child’s likely adult height?

Definition of Short Stature(Is the child short?)

Definition

• Short Stature

– Height below the 3rd percentile or less than 2 SD below the median height for age and sex according to the population standard

Essential Pediatrics, 7th Edition, OP Ghai; Fima Lifschitz- Pediatric Endocrinology

When is a child considered to be short?

• Height 2 standard deviations below the mean for a particular age

OR

• Height below the 3rd percentile for age

● Height above the 2.3rd percentile (>-2 SD) – These children generally do not require further specific evaluation Height below the 2.3rd percentile (≤-2 SD) – These

children have short stature and should undergo a more detailed evaluation, starting with evaluation of growth rate

Height less than the 1st percentile (≤-2.25 SD) –extreme short stature and usually should be referred to an appropriate subspecialist for a detailed evaluation

Causes of Short Stature

• Antenatal History• complications of pregnancy• pre-eclampsia, hypertension• maternal history of smoking, alcohol• exposure to toxins in-utero• infections

• Birth• gestational age• birth weight and height• mode of delivery (breech, forceps)• APGAR score• Neonatal complications• presence of midline craniofacial abnormalities,

microphallus, septo-optic dysplasia, neonatal hypoglycemia, and prolonged jaundice may be early indicators for presence of GH deficiency

• Nutrition• dietary history is important to r/o malnutrition as a

cause of growth retardation• general well being: appetite, energy, sleep, and

bowel habits• pattern of growth from birth

• Developmental milestones

• Maternal/child and social relationship• effort should be made to detect any psychosocial

stress factors at home or school that may impact the child's growth

• Medical history• evaluate for the presence of chronic illnesses

(pulmonary, cardiac, renal, gastrointestinal diseases, malabsorption, celiac disease or HIV)

• past history of intracranial tumors• treatment modalities in the form of chemotherapy,

cranio-spinal irradiation, bone marrow transplantation, immuno-suppressive therapy, and high dose steroid regimens

• Family History• short stature (3 generations).• age of onset of puberty in family members of the

same sex• diseases in the family

• Growth Velocity

– the most sensitive indicator for growth retardation changes for height over time

Age Growth

Birth-1 yr 25 cm

1-2 yrs 12 cm

2-3 yrs 8 cm

3 yrs-puberty 4.5-7 cm (5cm/yr)

• Age two to four years: 5.5 to 9 cm/year (2.2 to 3.5 inches/year)• Age four to six years: 5 to 8.5 cm/year (2 to 3.3 inches/year) •Age six years to puberty: 4 to 6 cm/year for boys (1.6 to 2.4 inches/year) 4.5 to 6.5 cm/year for girls (1.8 to 2.6 inches/year)

Physical and Neurologic Exam

Physical Examination and Assessment of Growth

Weight head circ sitting height arm span Forearm length Facial and body

dysmorphic features

• ratios of upper to lower segments» obtained by measuring the height above

and below the symphysis pubis» 1.7 at birth» 1.3 at 3 years of age» 1.0 at 7 years of age» <1.0 in adults

• General Appearance and Behavior• dysmorphism• pubertal staging

• Family Measurements• measure height of parents for mid-parental height

(MPH)» allows predictions of the ultimate height of

the child• Boys : Father’s height + (mother’s height +13)/2• Girls : Mother’s height + (father’s height -13)/2

Oostdijk, W, et al. Diagnostic Approach in Children with Short Stature. Horm Res 2009;72:206–217

Oostdijk, W, et al. Diagnostic Approach in Children with Short Stature. Horm Res 2009;72:206–217

Oostdijk, W, et al. Diagnostic Approach in Children with Short Stature. Horm Res 2009;72:206–217

Oostdijk, W, et al. Diagnostic Approach in Children with Short Stature. Horm Res 2009;72:206–217

Nonspecific radiographic and lab exam

What are the screening laboratory test that should be performed to these patients?

Oostdijk, W, et al. Diagnostic Approach in Children with Short Stature. Horm Res 2009;72:206–217

Bone Age

• standardized x-ray of left hand & wrist• comparison of selected bones with atlas of reference

standards (Tanner & Whitehouse 2, RUS)• comparison of bone age with chronological age• delayed bone age implies delayed maturation and improves

height prognosis• advanced bone age implies accelerated maturation and

predicts earlier cessation of growth• adult height can be predicted from bone age and measured

height

Delayed skeletal maturity• bone age is less than chronological age• child will enter puberty later than peers and have a delayed

growth spurt• growth will continue beyond the age at which the average

child of the same sex stops growing• final height centile may be greater than height centile in

childhood

Accurately measure and plot height

Ht centile < weight centile

(failure to grow)

Wt centile < ht centile(failure to thrive)

Evaluate caloric intake and consider evaluation of kidney, bowel, and

thyroid function

Wt centile < ht centile(failure to thrive)

Failure to Thrive Inadequate caloric intake Caloric losses (e.g., from

malabsorption, diabetes) Excess caloric needs (e.g., from pulmonary or cardiac disease, hyper- thyroidism,

the diencephalic syndrome, neuro- ectodermal tumors)

Height percentile < weight percentile (failure to grow)

Normal or near-normal growth

velocityBA=CA

Normal growth velocity

BA < CA

Subnormal growth velocity

BA < CA

Determine growth velocity and bone age(BA)

Intrinsic Shortness

Familial short stature Genetic syndrome of short stature (e.g., Turner syndrome, Silver–

Russell syndrome) stature (e.g., Turner syndrome, Silver–Russell syndrome)

Other congenital disorders (e.g., IUGR, bone dys- plasia)

Acquired growth limitation (e.g., from spinal irradi- ation)

Normal GV; BA=CA

Delayed Growth

Constitutional delay of growth and

puberty

Mild chronic disease Prior, resolved

growth- attenuating disorder

Normal GV; BA< CA

Attenuated Growth

Endocrine disorders (e.g., GHD, hypothyroidism, Cushing syndrome,

hypogonadism)

Marked delay of pubertySevere chronic disease

(chronic renal insufficiency, IBD, celiac disease)Medications (e.g., stimu- lants, glucocorticoids)

Subnormal GV; BA < CA

Key History and Physical Examination Findings that may Indicate Growth Hormone Deficiency (GRS 2000 Criteria)

• Neonate: hypoglycemia, prolonged jaundice, microphallus, traumatic delivery

• Cranial Irradiation• Head trauma or CNS Infection• Consanguinity and/or affected family

member• Craniofacial midline abnormalities

Growth Hormone Deficiency

• Neonatal seizures due to hypoglycemia• Prominent forehead/frontal bossing• Cherubic facies• Hypoplastic nasal bridge• Delayed dentition• High-pitched voice• Pubertal delay

Indications for growth Hormone

Arch Dis Child Educ Pract Ed 2005;90:ep7–ep9. doi: 10.1136/adc.2004.061382

• Stimulation Tests– Insulin Tolerance Test– Glucagon Test– Cloidine– LevoDopa

European Journal of Endocrinology (2007) 157

Idiopathic Short Stature (ISS)

• condition in which the height of an individual is more than 2 SD score (SDS) below the corresponding mean height for a given age, sex, and population group

• without evidence of :systemic, endocrine, nutritional, or chromosomal abnormalities

• normal birth weight • GH sufficient

Ranke MB 1996 Towards a consensus on the definition of idiopathic short stature. Horm Res 45 (Suppl 2):64–66

Idiopathic Short Stature (ISS)

• heterogeneous group of children consisting of many presently unidentified causes of short stature

• approximately 60–80% of all short children at or below 2 SDS fit the definition

• short children labeled with constitutional delay of growth and puberty (CDGP) and familial short stature

Lindsay R, Feldkamp M, Harris D, Robertson J, Rallison M 1994 Utah Growth Study: growth standards and the prevalence of growth hormone deficiency. J Pediatr 125:29–35

Criteria for Treating Children with ISS

• Auxological• GH treatment for children shorter than 2.25 SDS (1.2

percentile)• appropriate height below which GH treatment could be

considered ranged from 2 to 3 SDS• optimal age for initiating treatment is 5 yr to early

puberty

Cohen, P. J Clin Endocrinol Metab, November 2008, 93(11):4210–4217

Criteria for Treating Children with ISS

• Biochemical• no accepted biochemical criteria for initiating GH

treatment in ISS• Psychological

• would generally not be recommended for the short child who is unconcerned about his/ her stature

• psychological benefits of GH therapy in such children have yet to be proven

Cohen, P. J Clin Endocrinol Metab, November 2008, 93(11):4210–4217

Turner Syndrome

• about 50 per 100 000 girls• one of the most frequent chromosomal

aberrations in females

Gravholt, C. European Journal of Endocrinology (2004) 151 657–687

Turner Syndrome: Clinical Features

Short stature2

• Average adult stature 20 cm shorter than target height

• Chromosomal disorder in females in approximately 1:2000 live births1 • Complete or partial absence of the second sex chromosome

(45,X karyotype)2

1. Lippe BM, Saenger PH. In: Sperling MA. Pediatric Endocrinology. 2nd ed. Philadelphia, PA: Saunders; 2002:519-564.2. Bondy CA et al. J Clin Endocrinol Metab. 2007;92(1):10-25.

Characteristic facial features1,2

• Ptosis• Hypertelorism• Retrognathic face• Micrognathia• Ear malformations

Cardiovascular system2

• Aortic coarctation• Bicuspid aortic valve• Conduction abnormalities

Genitourinary system1,2

• Ovarian failure• Renal malformation

Other manifestations1,2

• Melanocytic nevi• Hypertension• Hyperlipidemia• Strabismus• Hyperopia• Hearing loss• Webbed neck• Thyroiditis• Wide-spaced nipples/poor

breast development• Tooth anomalies

54

Lower Extremities

Dry sktn • Asymmetry of set of

ears• Neck is short

Posterior Chest

Wide spaced nipples

Recommendations

• For karyotyping: • all girls with short stature (less than the third percentile

or below -2 sd on female growth curves)• even those below 2 yr of age, performed if there are

any features of TS present• more than 2.5 sd below the female growth curve• performed regardless of the presence or absence of

clinical features of TS• Heights of girls with TS plotted on TS-specific growth curves

SAENGER, P, et al. JCE & M 2001 Vol. 86 No. 7

Recommendations

• Initiation of GH therapy should be considered as soon as a patient with TS has dropped below the fifth percentile of the normal female growth curve

• may be started as early as 2 yr of age• GH therapy - directed by a pediatric

endocrinologist

SAENGER, P, et al. JCE & M 2001 Vol. 86 No. 7

Chronic Renal Failure

• Growth failure in CRF depends on the ff:

– underlying renal disease– age at onset– nutritional status– presence of renal osteodystrophy, metabolic

acidosis and associated alterations in the GH-IGF-I growth axis

Prader Willi Syndrome (PWS)

• chromosomal disorder characterized by deletion of the paternal alleles at chromosome 15q 11-13

• prevalence of about 1:15,000 live births• characterized by

• Hypotonia• Obesity• short stature• hyperphagia• hypogonadism• mental retardation

Lee PDK et al. Consensus statement – The Endocrinologist 10(4): 71-73.

Available Growth Hormone in the Philippines

Brand Name Generic Name

Company Preparation Price

Genheal Somatropin United Lab Powder for injection4 IU x 1 ml

1527

Norditropin Simplexx

Somatropin Novo Nordisk

Inj (penfill) 5 mg/1.5 ml

7,700

Saizen Somatropin Merck Powder for injection4 IU x 1 ml, 10 IU;Click easy pack 8 mg x 1

Scitropin A Somatropin SciGen Powder for injection15 IU x 1 ml

7,700

MIMS Phil 133rd Ed 2012

Summary points

1. Assessment for short stature requires accurate height measurements, taken serially and compared with population-appropriate height and height-velocity standards

2. Short stature is most commonly familial or due to constitutional growth delay or a combination of both

3. Short stature may rarely (in <5% of the shortest 1.3% of children) be associated with a serious underlying medical condition; treatable conditions need to be diagnosed early

•Questions

The most common cause of short stature in a 10 year healthy boy is:

a. familial short statureb. hypopituitarismc. constitutional delayd. idiopathic short stature

A 7 year old boy was brought to the clinic for slow growth. His birth & maternal, nutritional ,past history are unremarkable. Present height is 106 cm while his weight is 20 kgs. Which of the following is the best indicator of a non-pathologic cause of short stature?

a) Height one year ago of 100 cmb) Upper segment lower segment ratio of 1:3c) Arm span of 102 cmd) Presence of 16 teeth

A 7 year old boy was brought to the clinic for slow growth. His birth & maternal, nutritional ,past history are unremarkable. Present height is 106 cm while his weight is 20 kgs. Father’s ht is 170 cm while mother’s height 147 is cm Which of the following is the most likely cause of his slow growth?

a. familial short stature• b. hypopituitarism• c. constitutional delay• d. idiopathic short stature

• A 13 year old girl was brought for short stature but otherwise asymptomatic. Height is 130 cm. She is prepubertal. The most important exam to request is:

• A. Bone age x-ray• B. GH stimulation test• C. Chromosomal analysis• D. FSH,LH

Which of the following causes disproportionate short stature?

a. Growth hormone deficiencyb. congenital hypothyroidismc. Hypoparathyroidismd. Chronic malnutrition

The best evidence of growth hormone deficiency in a short child is:

a. Absence of puberty by age 13 in a male b. Presence of 28 teeth in a 6 year old childc. Growth velocity of 2.5 cm/yeard. Absence of menses by age 14

obese

overweight

normal

thinness

Severe thinness

Height percentile < weight percentile (failure to grow)

Normal or near-normal growth

velocityBA=CA

Normal growth velocity

BA < CA

Subnormal growth velocity

BA < CA

Determine growth velocity and bone age(BA)