Transcript Short Stature 11/18/10 Continuity Lecture

CATALINA RUIZ, MD
PL1
SBH
11/18/10
OBJECTIVES
 Definition
 Growth physiology
 Evaluation: History, PE, growth chart
 Etiology
 Laboratory
 Growth hormone therapy
SHORT STATURE
DEFINITION
 Analysis of the child’s height in the context of
expected genetic potential conferred by the parents
 Child’s growth curve is crossing percentiles
 Child’s growth rate is < 5cm/year
 Height is >2 SD (10cm) below from the midparental
height.
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:
 Genetic
 Nutritional: calories, protein, calcium, minerals,
vitamins
 Hormones: GH, ILGF- I, thyroid, insulin, sex steroids,
glucocorticoids
 Others: 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
During the first 3 years
children are adjusting to
their genetic potential, is
normal to see shifts in the
growth curve.
Then: 4-7cm/year
Small linear growth deceleration often is seen before
the onset of puberty
 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. HISTORY
2. PHYSICAL EXAM
3. GROWTH CURVE
4. BONE AGE (BA)
5. BODY PROPORTIONS
1.HISTORY
 Birth history
 Significant medical
 Development
events (illnesses, head
Tx, Sx)
 Activity/exercise
 Family history: parents
and siblings heights,
age of onset of puberty,
history of consanguinity,
congenital anomalies
 Nutrition
 Medications
 General health
 Age of pubertal
development
2.PHYSICAL EXAM
 Facial appearance and apparent maturation,
abnormal facies
 Dysmorphic features
 Skin: birth marks, acne, hair
 Body proportions
 Hands: short metacarpals, palmar creases
 Chest: widely spaced nipples, pectus excavatum,
shield shape chest
2.PHYSICAL EXAM
 Breast development
 General 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 CURVE
Is the most important step.
Consider:
 Reliability of measurements
 Absolute height
 Growth velocity: accurate determination requires at
least 3 and preferably 6 months
 Weight for height ratio: it has some diagnostic value
in identifying the cause of growth retardation in a
short child.
4. BONE AGE
Gives 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 PROPORTIONS
The 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 birth
1.4 at 2 years
1 at 10 years
0.9 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 PROPORTIONS
 Arm 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.
ETIOLOGY
NORMAL GROWTH PATTERNS:
Normal growth velocity in a short child
Familial 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.
ETIOLOGY
Pathologic 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.
LABORATORY
 GENERAL 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 TEST
ENDOCRINOLOGY
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 hours
5 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 THERAPY
 FDA approved indications for the use of GH
GHD
Turner syndrome
Renal insufficiency
Prader Willi syndrome
SGA
Idiopathic short stature (predicted target height in girls
< 4’11; boys <5’3.)
GROWTH HORMONE THERAPY
 Administration 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
CDGP
NORMAL
VARIANT
FSS
INCREASED
WT/HT
SHORT
STATURE
(ENDOCRINOPAT
HIES)
PROPORTIONATE
DECREASED
WT/HT
PATHOLOGIC
DISPROPORTIONATE
ASSOCIATED WITH
DYSMORPHIC
FEATURES
(MALNUTRITION,
RENAL DISEASE,
CHRONIC
DISEASE)