short stature

CATALINA RUIZ, MDPL1SBH

11/18/10

OBJECTIVESDefinitionGrowth physiologyEvaluation: History, PE, growth chartEtiologyLaboratoryGrowth hormone therapy

DEFINITION

Analysis of the child’s height in the context of expected genetic potential conferred by the parents

Child’s growth curve is crossing percentilesChild’s growth rate is < 5cm/yearHeight is >2 SD (10cm) below from the midparental

height.

SHORT STATURE

MIDPARENTAL HEIGHT:

GIRLS: (father’s height – 13) + mother’s height /2

BOYS:Father’s height + (mother’s height + 13)/2

The parents height are in cm

TARGET HEIGHT:Midparental height +/- 2SD (10cm)

FAILURE TO THRIVE:

Impairment in weight gain greater than linear growth. Can be associated with short stature or slow growth velocity.

PHYSIOLOGY

Growth depends on:GeneticNutritional: calories, protein, calcium, minerals,

vitaminsHormones: GH, ILGF- I, thyroid, insulin, sex

steroids, glucocorticoidsOthers: absence of toxins, adequate sleep, exercise,

psychosocial factors.

PHYSIOLOGY

GH PRIMARY CONTROLLERS:

•Growth Hormone Releasing Hormone (GHRH)

•Somatostatin or somatotropin release inhibiting hormone (SRIH)

•Ghrelin

FETAL GROWTH : maternal factors (placental sufficiency, nutrition), insulin and IGFBP.

GROWTH IN LATE INFANCY AND CHILDHOOD: GH/IGF- I axis, thyroid hormone, nutrition and

insulin. IGF- I and IGFBP- 3 levels are low during the first 5

years of life.

First 3 years:

25cm/year 12cm/year 8cm/year

Then: 4-7cm/year

Small linear growth deceleration often is seen before the onset of puberty

During the first 3 years children are adjusting to their genetic potential, is normal to see shifts in the growth curve.

PUBERTAL GROWTH: sex hormones as well as GH/IGF –I axis and thyroid gland.

The pubertal growth spurt in girls occurs approximately 2 years earlier than in boys.

Peak velocity is slower in girls (8.3cm/y) than in boys (9.5cm/y). This factor combined with a 2 year longer duration of growth in boys, results in an average 13cm difference in adult height between the 2 sexes.

EVALUATION

1. HISTORY2. PHYSICAL EXAM3. GROWTH CURVE4. BONE AGE (BA)5. BODY PROPORTIONS

1.HISTORYBirth historyDevelopmentNutritionMedicationsGeneral healthAge of pubertal

development

Significant medical events (illnesses, head Tx, Sx)

Activity/exerciseFamily history: parents

and siblings heights, age of onset of puberty, history of consanguinity, congenital anomalies

2.PHYSICAL EXAMFacial appearance and apparent maturation,

abnormal faciesDysmorphic featuresSkin: birth marks, acne, hairBody proportionsHands: short metacarpals, palmar creasesChest: widely spaced nipples, pectus excavatum,

shield shape chest

2.PHYSICAL EXAMBreast developmentGeneral examination (lungs, heart, abdomen, neuro)Genitalia: Female: pubic hair stage, clitoris size, labia, vagina,

estrogen effect. Male: pubic hair stage, genital stage, including

phallic and testicle length (>2.5cm max. length signifies entry into puberty)

3. GROWTH CURVEIs the most important step.Consider:Reliability of measurementsAbsolute heightGrowth velocity: accurate determination requires at

least 3 and preferably 6 monthsWeight for height ratio: it has some diagnostic value

in identifying the cause of growth retardation in a short child.

4. BONE AGEGives a level of bone maturation based on centers of

ossification and closure of epiphyses.

The method most commonly used to asses BA is that of Greulich and Pyle, which examines epiphyseal maturation of hand and wrist

5. BODY PROPORTIONSThe U/L ratio indicates whether the short stature is

proportionate or disproportionate. It varies with age and race.

The lower segment: from the upper border of the symphysis pubis to the floor in a standing patient.

The upper segment: subtracting the lower segment from the standing height.

U/L RATIO:1.7 at birth1.4 at 2 years1 at 10 years0.9 at adulthood

Skeletal dysplasia involving primarily the spine (spondylodysplasia) are often associated with decreased U/L ratio for age.

Those dysplasia involving especially the long bones (achondroplasia) frequently are associated with increased U/L ratio.

5. BODY PROPORTIONSArm span is approximately equal to height in

children > 8 years. Can be used as a surrogate for height measurement and for monitor of growth velocity in children who have spina bifida, or leg contractures or after spinal irradiation.

ETIOLOGYNORMAL GROWTH PATTERNS:

Normal growth velocity in a short childFamilial short stature:

Normal growth velocity, normal timing of development of puberty, and bones fuse at the appropriate age. Height is short because of short mother and/or father. BA=CA.Constitutional delay of growth and puberty:

Normal or near normal growth velocity, delayed timing of puberty, delayed BA. Family history of late bloomers.

ETIOLOGYPathologic causes of short stature

Proportionate short stature with increased weight for height ratio: (deceleration of linear growth in a well nourished or obese child)

Endocrinopathy should be suspected, such as hypothyroidism, glucocorticoid excess and GH deficiency.

GHD: congenital or acquired and can be associated with other pituitary defects. Congenital can be related to perinatal asphyxia or associated with embryologic malformations (CNS, midface abnormalities). Acquires occurs most commonly as idiopathic diagnosis, but may result from tumors, head Tx, CNS infections, irradiation, Sx.

The child has short stature, slow growth velocity, delayed BA, low IGF-I and IGFBP-3 values.

GH insensitivity: autosomal recessive. Caused by defects in the GH receptor.

Phenotype similar to GHD, but biochemically increased GH levels, low IGF-I, IGFBP-3 and GHBP.

Hypothyroidism: if untreated the growth velocity is slow and BA is delayed relative to CA.

Glucocorticoid excess: usually iatrogenic, but also tumors.

Growth velocity is slow, BA delayed, weight gain and hypertension.

ETIOLOGY Proportionate short stature with decreased weight for height ratio: (deceleration of linear growth in a thin child)

Systemic diseases, most common undernutrition or malnutrition. With restoration of adequate nutrition, growth usually accelerates (catch up). Also inflammatory bowel disease, celiac disease, kidney disease.

ETIOLOGY Disproportionate shortening and dysmorphic features: genetic or syndromic causes of short stature.

Skeletal dysplasia: abnormal U/L ratio, BA=CA.

Chromosomal disorders: Turner, Down, Prader Willi.

LABORATORYGENERAL SCREENING TESTS:CBC with diff. BMP, UA, BA, TSH, T4, IGF-I (if >5

years)

SPECIALIZED TESTS: Karyotype, growth hormone stimulation test,

dexamethasone suppression test.

GROWTH HORMONE STIMULATION TESTENDOCRINOLOGY

A GH level by itself is meaningless in the evaluation of short stature.

Provocative agents include clonidine, L-dopa, arginine, insulin, glucagon, and GHRH.

Fasting 8-12 hours5 blood samples: the first is between 6 and 8 am, then the

provocative agent is injected, 30 minutes after that another blood sample, continue every 30 minutes.

Normal GH peak value (pass): >8ng/ml

GROWTH HORMONE THERAPYFDA approved indications for the use of GHGHDTurner syndromeRenal insufficiencyPrader Willi syndromeSGAIdiopathic short stature (predicted target height in girls

< 4’11; boys <5’3.)

GROWTH HORMONE THERAPYAdministration and dosage:Subcutaneous injection starting at 0.3mg/kg/wk given

6-7 days/wk.Adverse effects: slipped capital femoral epiphysis,

glucose intolerance/diabetes, pseudotumor cerebri, scoliosis.

SUMMARY