PG teaching

1. dr.n.shruthi

2. Introduction
• Growth is characterized by an increase in size of the body – in height, weight
and other measurable areas. Growth can be divided into fetal, infancy,
childhood and pubertal phases.
• Development is qualitative. It refers to physiological, social and psychological
maturation. It is the gaining of behavior and skills

4. Parameters of growth
1. Target height
2. Growth velocity
3. Bone age
4. Body proportions
5. Arm span
6. Weight-for-Height Ratio

5. Height measurement
1. Height should be measured with the child
standing back to the wall with head in
Frankfort horizontal position, heels at the
wall, ankles together, and knees and spine
straight against a vertical metal rule.
2. Height is measured at the top of the head by
a sliding perpendicular plate (or square
wooden block).
3. A Harpenden stadiometer is a mechanical
measuring device capable of such accurate
measurement.

6. Target height
Mid parental height
1. Boys: [(mother’s height + 13) + father’s height] / 2 cm +/- 8.5 cm.
2. Girls: [(father’s height -13) + mother’s height] / 2 cm +/- 8.5 cm.
3. Child should achieve within 8 cm of midparental height. A range 8 cm above
or below this predicted height is considered within the 3rd to 97th
percentile.
4. A child whose current height percentile differs greatly from his or her target
percentile is considered short for his or her genetic potential

7. Growth velocity
• Growth velocity is change in height (cm) / year.
• Growth velocity is 25 cm in first year; 12.5 cm in second year; 6 cm/year till puberty
• Height:
• At birth: 50 cm
• 1 year: 75 cm
• 4 years: 100 cm
• 8 years: 125 cm
• 12 years: 150 cm
• Poor linear growth is defined as linear growth velocity more than 2 SDs below the mean

8. Growth velocity

9. Growth Chart

10. Skeletal maturation:Bone age
• Epiphyseal centers obtained on
radiography is compared with
published standards.
• Greulich and Pyle (GP) and the Tanner
e Whitehouse (TW2) method.
• Xrays:
• knee: < 3yers
• wrist: < 6 yers
• Elbow: > 6 yers

11. Body proportions
The upper-to-lower body segment (U/L) ratio
• Normal proportion
• At birth: 1.7
• 3 years: 1.3
• 7 years: 1.1
• 10 yeras: 1

12. Arm span
1. Equal to height in 8 years of age
2. Arm span can be measured as the distance
from left fingertips to right fingertips in a
patient standing, arms spread, against a wall.
3. Used as a surrogate for height who have
scoliosis, spina bifida, or leg contractures or
after spinal irradiation.

13. Weight-for-Height Ratio
• Increased: Obesity in endocrine disorders:
1. GH deficiency
2. Thyroid hormone deficiency
3. Glucocorticoid excess (Cushing’s disease)
• Decreased: Thin for stature in systemic disorders like:
1. Malnutrition
2. Chronic illness etc.

14. SHORT STATURE

15. Definitions
1. Short stature is defined as a height less than two standard
deviation or below the third percentile for that population.
2. More than two standard deviations below the midparental height
3. The child is consistently having a poor growth velocity i.e. height
deceleration across two major percentile lines on the growth chart

16. Practical Classification of short stature
Proportional:
1. Equal height weight ratio: GHD
2. Weight more than height: Cretinism, Cushing
3. Height more than weight: Chronic illness, Malnutrition
Disproportional:
1. Short limb: Achondroplasia
2. Short trunk: Hurler, Hunter, Morquio

17. Classification of short stature-II
1. Physiological:
1. Familial short stature
2. Constitutional growth delay
2. Pathological:
1. Growth hormone deficiency
2. Insulin like growth factor-1
deficiency
3. Hypothyroidism
4. Cushing syndrome
5. Precocious puberty
6. Diabetes mellitus
7. Rickets
8. IUGR
9. Inborn errors of metabolism:
1. Mucopolysachharidoses
2. Other storage disorders
10. Intrinsic disease of bone:
1. Achondroplasia
2. Fibrous dysplasia
11. Chromosomal:
1. Autosomal:
1. Down
2. Prader-Willi
3. Noonan
2. Sex chromosome:
1. Turner

18. 12. Chronic illness:
1. CHD
2. Inflammatory bowel disease
3. Chronic infection and infestation
4. Hematologic: Thalassemia
5. Pulmonary : cystic fibrosis; Bronchial asthma
6. Renal disease
7. Cancers

19. Classification of Growth hormone deficiency
1. Genetic causes:
Receptor mutation; Gene deletion; GH resistance
2. Congenital:
Associated with septo-opic dysplacia and ectopic pituitary
3. Acuired:
1. Parental deprivation syndrome
2. Craniopharyngeoma
3. Histiocytosis
4. Germinoma
5. Cranial irradiation
4. Idiopathic:
1. Isolated GH deficiency
2. Combined pituitary hormone deficiency

20. Familial Short stature
1. Father or mother is short
2. Normal weight and length at birth
3. Growth velocity is decreased in first two years and then resumes normal
growth
4. Bone age and puberty are normal
5. Adult height is appropriate for the family

21. Familial short stature

22. Constitutional growth delay
1. Normal parents
2. Normal weight and length at birth
3. Growth pattern is similar to FSS
4. Delay in bone age
5. Delay in onset of puberty, reflecting the pattern of one parent.
6. Growth is decreased in first 3 years
7. But growth continues beyond the average period of growth.
8. Finally reaches the target height

23. Constitutional delay

24. Growth Hormone Deficiency
• Hypopituitarism :
1. Incidence is 1 in 4000-10,000
2. Multiple hormone deficiency- 20%
3. Isolated growth hormone deficiency- 13%
• Growth hormone:
1. Secreted by ant.pituitary; stimulated by GHRH; inhibited by somatostatin
2. GH released in response to sleep, exercise and hypoglycaemia
3. Promotes growth by stimulating insulin like growth factor: IGF1

25. GH Deficiency
1. Mutation : Septo optic dysplasia:
1. incomplete development of septum pallucidum,
2. optic nerve hypoplasia, Midline abnormalities in brain
3. Nystagmus , Visual impairment, Ant and post hormone deficiency
2. Isolated pituitary hypoplasia
3. Acquired pituitary defects:
1. Craniopharyngeoma; Germinoma; Histiocytosis
2. Tuberculosis; Sarcoidosis ; Toxoplasmosis
3. Meningitis; Trauma- shaken baby syndrome
4. ICBI (birth injuries)

26. Clinical manifestations
Congenital hypopituitorism
1. Normal length at birth; Growth rate below 25%
2. Hypoglycaemia, prolonged jaundice and apnoea and cyanosis and seizures at birth
3. Microphallus in boys, Round head, broad and short face
4. Small saddle shaped nose; nasolacrimal folds
5. Bulging eyes, Small chin, Crowded teeth
6. High pitched voice
7. Proportional extremities
8. Delay or absent sexual maturation
9. Delayed skeletal age; Normal intelligence

27. Hypopituitorism before and after treatment

28. Evaluation Of Short Stature

30. History
1. The duration of gestation,
2. Birth weight and length,
3. Onset and duration of catch-up or catch-down growth.
4. The child’s growth pattern
5. General nutrition

31. Physical Examination
1. Dysmorphic features of genetic syndromes
2. Growth hormone deficiency from hypopituitarism may cause micropenis, midface hypoplasia, and
midline defects.
3. Cushing syndrome can cause obesity, moon facies, violaceous striae, and cessation of linear
growth.
4. Chronic renal failure can cause pallor, ashen skin discoloration, and edema.
5. Severe hypothyroidism can cause increased bmi from profound growth arrest with continued
weight gain, sallow complexion, and delayed relaxation of the deep tendon reflexes.
6. Girls with classic turner syndrome present with short stature, a webbed neck, shield-shaped
chest, and a low posterior hairline;
7. Rickets may cause craniotabes, bulbous wrists, and bowing of the extremities.
8. Children with fetal alcohol syndrome present with short stature, low birth weight, poor weight
gain, microcephaly, epicanthal folds, smooth philtrum, a flat nasal bridge, and a thin upper lip.

32. Dental Examination
1. Comparing a child’s dental age with established norms provides an indirect
assessment of skeletal age.
2. Some conditions may cause delayed tooth eruption, leading to delayed
dental age.
3. The eruption of primary and secondary teeth may be delayed for up to 1.3
years in children with growth hormone deficiency, up to 1.5 years in children
with constitutional delay of growth and puberty,17 and more than two years
in children with severe hypothyroidism.

33. Laboratory screening of a child with proportionate short stature
Test Function
Complete blood count with
differential
Evaluates for anemia, blood dyscrasia, and
infections
Basic metabolic panel Rules out renal disease and electrolyte
abnormalities that could occur with Bartter
syndrome, other renal or metabolic
disorders, and diabetes insipidus
Liver function testing Assesses metabolic or infectious disorders
associated with liver dysfunction
Urinalysis and urine pH level Assesses kidney function and rules out renal
tubular acidosis
Erythrocyte sedimentation rate Evaluates for chronic inflammatory states

34. Focused Diagnostic Tests
Cause Tests Ancillary tests
Celiac disease Celiac antibody panel: antiendomysial, antigliadin, and
tissue transglutaminase antibodies
Endoscopy
Cushing disease Midnight serum cortisol, salivary cortisol, 24-hour urinary
free cortisol estimations
Dexamethasone
suppression test
Cystic fibrosis Sweat chloride test —
GH deficiency IGF-I, IGF-binding protein 3 GH stimulation test
Hypothyroidism Free thyroxine, TSH —
Inflammatory
disorders
Sedimentation rate, C-reactive protein Endoscopy
Iron deficiency Ferritin Iron, TIBC
Turner syndrome Karyotype Echocardiography, renal
ultrasonography
Vitamin D deficiency 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D, parathyroid
hormone, ALK-P
Wrist radiography

35. Body Proportion
• Decreased U/L ratio for age:
1. Skeletal dysplasias involving primarily the spine (eg, spondylodysplasias)
2. Eunichoidism
3. Delayed or incomplete puberty (eg, Klinefelter or Kallmann syndrome)
• Increased U/L ratio
1. Those dysplasias involving especially the long bones (eg, achondroplasia)
2. Because puberty is associated with relatively greater truncal than limb
growth, an increased U/L ratio for age may be seen in precocious puberty.

36. Bone age
• Familial short stature (FSS) is associated with normal skeletal maturation
• Bone age is delayed in:
• constitutional growth delay,
• malnutrition, and
• endocrine causes of short stature (eg, hypothyroidism, cortisol excess, growth
hormone deficiency)

37. Specific investigations in a child with short stature19,20
Suggested investigation Interpretation
MRI Visualization of hypothalamus, pituitary.
Growth hormone (GH) provocation
test
Growth hormone deficiency
Genetic analyses Genetic disorders Genetic defects in one of the
components(pituitary GH secretion, GH receptor
(GHR), post-receptor signaling and IGF-I)

38. X-Ray pituitary
Normal adenoma

39. MRI
Small pituitary fossa containing a reduced volume
of anterior pituitary tissue.
The stalk cannot be seen
The posterior pituitary bright spot (arrow) is lying in
an ectopic location within the hypothalamus.
Normal

40. Treatment of GH deficiency
• Subcutaneous recombinant GH for 7 days- total dose 0.1 to 0.3 mg/kg
• IGF 1 for resistant cases

41. Short stature with syndromic features
1. Trisomy 21: hypotonia, upward slanting of palpebrum
2. Turner's syndrome: webbed neck, low hairline, broad chest, increased carrying angle,
hypertelorism, posteriorly rotated ears
3. Russell-Silver syndrome: triangular face, asymmetry, clinodactyly, maternal uniparental
disomy (UPD) on chromosome 7
4. Prader-Willi syndrome: obesity, small hands and feet; hypotonia, hypogonadism, down-
turned mouth, seven genes on paternal chromosome 15 are deleted
5. DiGeorge syndrome: minor facial dysmorphism, cleft palate
6. Noonan's syndrome: hypertelorism, backward rotated ears

42. Turner Russell Silver

43. Prader Willi Digeorge

44. Noonan

45. Disproportionate short stature
1. Skeletal dysplasias: Achondroplasia:
2. the cartilage cells developed into bone more slowly than normal in the long
bones of the arms and legs, leading to shorter bones and shorter overall
height.
3. The trunk is relatively normal in length but the arms and legs are short with
more proximal shortening.
4. ‘fibroblast growth factor receptor-3’(FGFR3) is defective

48. Tall stature

49. Definition and etiology
• Tall stature is defined as a height that is two standard
deviations above the mean for age and sex (greater
than the 95th percentile)
• Aetiology of tall stature.
1. Familial tall stature
2. Constitutional tall stature
3. Obesity
4. Endocrinopathy
5. Precocious puberty
6. Hyperthyroidism
7. Familial glucocorticoid deficiency
8. GH excess – gigantism/acromegaly
• Genetic syndromes
1. Beckwith–Wiedemann
2. Homocystinuria
3. Klinefelter (XXY)
4. Marfan syndrome
5. Simpson–Golabi–Behmel
6. Sotos
7. Weaver
8. XXX
9. XYY

50. Familial Tall Stature
• Children with familial tall stature are usually tall from an early age (2 years of
age or younger) with one or more parents who are also tall. They have a high
normal growth rate and bone age consistent with chronological age.
• Clinical examination and evaluation of parental heights are all that is required
to confirm the diagnosis.
• If there is one tall parent and one normally statured parent, consideration
should be made of the possibility of an autosomal dominant condition (such as
Marfan syndrome) before making a diagnosis of familial tall stature.

51. Constitutional tall stature
1. Children are born of normal stature and grow rapidly during the first 4 years of
life; after which growth velocity drops and becomes parallel to the 50th centile.
2. Bone age may be slightly advanced.
3. Puberty is usually within the early normal range and final height usually within
the target range.
4. Children with obesity from early childhood are usually tall with a slightly
advanced bone age.

52. Precocious Puberty
1. Although precocious puberty results in a reduction in final height due to
restricting the number of years of prepubertal growth, at the time of onset
of puberty, height is generally increased.
2. Therapy should be directed at the underlying pubertal disorder and most
commonly involves GnRH analogue therapy for gonadotropindependent
precocious puberty that decreases sex steroid production and IGF‐I
concentrations, thereby reducing growth rate.

53. GH Excess
1. GH excess is extremely rare.
2. Causes include:
1. GH‐secreting pituitary micro‐ or macroadenomas,
2. Ectopic GHRH production and
3. Genetic abnormalities affecting GH secretion (mccune–albright syndrome and carney
complex).
3. Benign GH‐secreting adenomas are the most common cause of GH excess.
4. The commonest symptom is rapid growth.

54. Syndromes Associated with Tall Stature
1. Klinefelter Syndrome and 47,XYY: The legs are long and arm span is usually greater than
height. A rapid increase in growth velocity is seen during the childhood period but the
adolescent growth spurt is not of increased magnitude. Thus boys with Klinefelter
syndrome who are normally statured at the beginning of adolescence can be reassured
that their final height will not be increased
2. Marfan syndrome is an autosomal dominant multisystem connective tissue disease
caused by mutations in the fibrillin 1 gene.
3. Homocystinuria is an autosomal recessive trait caused by loss‐of‐function mutations in the
gene encoding cystathionine beta‐synthase. Affected individuals are tall and thin with
increased arm span. Other clinical features shared with Marfan syndrome include pectus
deformities, myopia and scoliosis.

55. 4. Sotos syndrome (also called cerebral gigantism) is a sporadic disorder caused by mutations
or deletions in the NSD1 gene. It is characterized by macrocephaly, dysmorphic facial
features (high broad forehead, long narrow face, down‐slanting palpebral fissures,
prominent jaw), poor coordination and learning difficulty.
5. Weaver syndrome is phenotypically distinct from Sotos syndrome with hypotonia,
looseness of skin, wide philtrum, deep‐set nails and advanced bone age (not found in
Sotos syndrome) and is caused by autosomal dominant mutations in EZH2.
6. Beckwith–Wiedemann syndrome is characterized by overgrowth including visceromegaly
and hemihypertrophy, ear lobe creases, hypoglycaemia, omphalocele and an increased risk
of tumours. The genetic causes of Beckwith–Wiedemann syndrome are complex and
include paternal uniparental disomy of chromosome 11 and hypermethylation at the H19
differentially methylated region, both of which lead to increased expression of IGF‐II.

56. Evaluation

57. Management of Tall Stature
1. There is usually no medical reason for treatment of tall stature and the decision to treat is based
upon the acceptability for the patient and parents of the predicted final height.
2. In boys the treatment has traditionally been the use of intramuscular injections of testosterone
esters given at supraphysiological doses – up to 500 mg/m2/ month (given as 1–2 injections per
month).
3. In girls high‐dose oestrogen treatment was most commonly given as oral ethinylestradiol at 100
μg/day (physiological adult replacement is equivalent to 30 μg/ day) in combination with an oral
progesterone for 7–10 days per month. Mean reductions in height of up to 6 cm were observed
and similarly to boys, treatment was more effective when started at a lower bone age.
4. Early induction of puberty with physiological doses of testosterone in boys and oestrogen in girls
may be beneficial, without the additional risks of high‐dose oestrogen therapy.