Introduction

• Growth hormone secretion is pulsatile, with peak levels at night

stimulated by hypothalamic GH-releasing factor and other factors
( e.g ghrelin, sex steroid hormones, clonidine, hypoglycemia)

• And inhibited by GH release inhibitory factor (somatostatin, somatotropin

release- inhibiting factor [SRIF])

• Growth hormone circulates bound to a GH-binding protein (GHBP)

• Growth hormone stimulates IGF-1 production in the liver along with

production of the the IGF-binding protein (IGF-BP3)
Growth hormone effects
• IGF-1 acts primarily as a paracrine and
autocrine agent

• IGF-1 production is influenced by disease

states such as malnutrition, chronic renal
and liver disease.
 What is growth
Normal growth is the initial common pathway of many factors, •
including endocrine, environmental, nutritional, and genetic
influences
 Measurements of Growth
By plotting the following on the growth chart:
• Height (standing) or length (lying down)
• Weight
• Mid-parental
 Measurements of Growth

Height Measuring:
• Arm span
Arm span is measured as the distance between the tips of the
fingers when the patient holds both arms outstretched
horizontally .
In children whose age < 5 y/o = 1-2 cm smaller than body length
During 10 – 12 years = height
Adults = >2cm
Short/large arm span when you expect to see it ?
Large arm span in ; marfan , klinfeltr ,
Short arm span in achondroplasia + short limb dwarfism
 Measurements of Growth

• The upper-to-lower segment ratio

determined by subtraction of the measurement from the
symphysis pubis to the floor [known as the lower segment] from
the total height
A normal term infant has an upper-to-lower ratio of 1.7 : 1
A 1-year-old has a ratio of 1.4 : 1
 Short Stature
Growth failure is a sign of a slow growth rate and eventually a slow growth rate leads to short stature.
 

Defined as:
1. Height with 2 SD below the mean for children of the same age and sex
2. Crossing 2 percentiles
3. 2 SD below mid-parental height.
4. Height velocity below the 5th percentile for age .
causes
 Non-Endocrine causes

Chronic diseases leading to nutrition deficiency and failure to thrive (short and underweight)
Inadequate nutrition may be due to insufficient food, restricted diets or poor appetite, or from
the increased nutritional requirement from a raised metabolic rate.

Psychological difficulties, in which the child develops functional temporary GH deficiency and
poor growth as a result of psychological abuse; leading to psychosocial or deprivation
dwarfism.

Constitutional delay (variation of normal growth) where the bone age is delayed, but the growth
rate remains mostly within the lower limits of normal and usually leads to a delay in secondary
sexual development and pubertal onset, a family history of delayed puberty is often present.

Familial short stature refers to the stature of a child of short parents, who is expected to reach
a lower than average height and yet normal for these parents. Bone-age X-rays may be within
normal limits for age.
 Non-Endocrine causes

Small for gestational age and extreme prematurity: about 10% of children
born small for gestational age or who were extremely premature remain
short

Chromosomal disorders and syndromes such as :Down syndrome is usually

diagnosed at birth, but Turner syndrome may be particularly difficult to
diagnose clinically and should be considered in all short females.
 Endocrine causes
Hypothyroidism : autoimmune thyroiditis , Congenital •
hypothyroidism

Corticosteroid excess, Cushing syndrome •

Congenital or acquired Growth hormone deficiency •

 Clinical feature
Short stature is a symptom that could be accompanied by others like
delay in secondary sexual development.► Constitutional
Short parents ► short familial height
 syndromes
• hypotonia, acquired obesity with an insatiable appetite ► Prader-Willi

• shield chest, wide-spaced nipples, high-arched palate ► Turner

• Triangular face, whipping of neck ► noonan (AD )

• short 4th & 5th digits (Albright Osteodystrophy)

• ► Pseudohypoparathyroidism + resistance to parathyroid hormone

and resultant hypocalcemia, and elevated levels of serum phosphorus
Short stature is a symptom that could be accompanied by others like

GH deficiency (classical)
chubby , immature appearance high-pitched, voice
microphallus ,hypoglycemia

Resistance: (Laron syn)(AR):

A very rare cause of growth failure is GH resistance
or GH insensitivity, caused by abnormal number
or function of GH receptors or by a post-receptor
defect.
prominent forehead, hypo-plastic nasal bridge, delayed
dentition, blue sclera .
 DIAGNOSIS
• Basic evaluation: History, physical examination, and bone
age determination. 
• In familial short stature, height velocity (HV) and bone
age are within the normal range and one or both parents
are short.
• In CDGP, bone age is delayed. There is often a family
history of delayed growth and/or puberty.
 DIAGNOSIS
Family or other medical history (chronic disease)
Metabolic panel to evaluate kidney and liver function
Complete blood count (CBC) to rule out anemia
Celiac panel to rule out celiac disease
Erythrocyte sedimentation rate (ESR)
Thyroid function testing, and IGF-1, IGFBP-3 for children under age 3 years.
A urine study to assess renal function and evaluate for renal tubular acidosis.
In a girl, a karyotype to rule out Turner syndrome.
An X-ray to establish bone age and skeletal maturation.
 GH Provocative test ( Stimulatory
test)
 Random sample is insufficient to diagnose !
A normal response is a vigorous secretory peak after stimulation; the lack of such a
peak is consistent with GH deficiency.
Bone Age
Bone age estimation with a standard PA view of the hand and wrist could be used for evaluation and serial
measurements are also used to assess the effectiveness of treatments.
Various methods have been developed to compute bone age score from these radiographs by comparing
the maturity of hand & wrist bones to idealized standards.
 TREATMEN
T
• Treat underlying cause
• GH deficiency is treated with biosynthetic recombinant DNA derived GH.
• Treatment with GH carries the low risk of an increased incidence of slipped capital
femoral epiphysis, especially in rapidly growing adolescents, and of pseudotumor
cerebri.
INDICATION OF GH-THERAPY:
Turner syndrome & chronic renal failure > increase the growth rate & final height
Prader-Willi syndrome > increase the final height & treat muscle weakness
Children born small for gestational age who have not exhibited catch-up growth by 2 years
of age
long-term treatment of idiopathic short stature with height 2.25 SDs or less below the
mean.