Approach to tall stature pediatric endocrinology

2. Approach to tall
stature.
By: Dr Inayat Ullah.
PGY-II Pediatrics Shifa
International Hospital Islamabad

3. Definition.
• Tall stature is defined as height beyond 97th
percentile (i.e., over two standard deviations)
of mean for age and sex.
•
• Excessive growth is defined as an abnormally
rapid growth velocity, which could manifest as
height acceleration across two major percentile
lines on the growth chart.

4. Growth charts.
• Height charts
• Weight charts
• BMI charts
• Proportionate charts
– Sitting height
– Sub-ischial leg length
• Growth velocity charts.

5. Predictors of height.
• Genetics, nutrition, hormones (growth hormone,
thyroid hormone, estrogen and testosterone) and
overall health.
• The growth spurt around puberty occurs around
2 years earlier in girls when compared to boys,
but the boys tend to be taller when it begins.

6. Height Predictors (MPH)
• Mid-parental height (MPH):
• Target height for boy = ([Father’s height + 13] + Mother’s
height)/2 cm.
• Target height for girl = (Father’s height + [Mother’s height
– 13])/2 cm.
• MPH is an indicator of child’s genetic potential for growth.
The value is plotted as adult height at 18 years and the
target range is 6 cm on either side of the target height (TH).
This becomes the target range and if the child’s height is
within these percentiles, it is considered as normal.

7. Regulation of growth
Normal human growth can be divided into three
overlapping stages each under the control of different
factors:
1. Infancy:
o Largely under nutritional regulation
o Wide inter-individual variation in rates of growth
o Many infants show significant ‘catch-up’ or ‘catch-
down’ in weight and length
o By 2 years, length is much more predictive of final
adult height than at birth

8. Regulation of growth
2. Childhood:
o Growth hormone (GH) and thyroxine
o Mini-growth spurts with intervening stasis, each phase lasting
several weeks
o Over years, a child will tend to maintain their centile position
on height charts, with a height velocity between the 25th and
75th centiles
3. Puberty:
o The combination of GH and sex hormones promotes bone
maturation and a rapid growth acceleration or ‘growth spurt’.
o In both sexes, oestrogen eventually causes epiphyseal fusion,
resulting in the attainment of final height.

9. Assessment of growth
• To minimize error in the calculation of height
velocity (cm/year), height measurements should be
taken
• at least 6 months apart
• using the same equipment and
• Ideally by the same person.

10. Height measurements
• From birth to 2 years
old, supine length is
measured ideally using
a measuring board (e.g.
Harpenden
neonatometer).
• Two adults are needed
to ensure that the child
is lying straight and legs
extended.

11. Height measurements
• From 2 years old, standing height is
measured against a wall-mounted or
free-standing stadiometer
• Without footwear
• Heels & back touching the wall
• Looking straight ahead
• Gentle but firm pressure upwards
applied to the mastoids from underneath
• US / LS ratio
• Horizontal Arm span

13. Etiology of Tall Stature.
• Familial:
– (constitutional) tall stature common cause
• Nutritional:
– Exogenous obesity.
• Endocrine:
– Precocious puberty (early stage), pituitary gigantism,
McCune-Albright syndrome, thyrotoxicosis,
androgen/estrogen deficiency, estrogen resistance (in
males), testicular feminization, adrenocorticotropic
hormone (ACTH)/cortisol deficiency, ACTH/cortisol
resistance and aromatase deficiency.

14. Etiology (cont’d)
• Chromosomal:
– Klinefelter syndrome (XXY), fragile X syndrome, XYY
syndrome.
• Collagen vascular:
– Marfan syndrome.
• Metabolic:
– Homocystinuria.
• Fetal overgrowth syndrome:
– Maternal diabetes mellitus, cerebral gigantism (Sotos
syndrome), Beckwith-Wiedemann syndrome, Weaver
syndrome, Simpson-Golabi-Behmel overgrowth syndrome,
other (IGF)-2 excess syndrome.

15. Causes of tall stature
• Familial Tall Stature:
• Most common cause of tall stature seen in
childhood and adolescence.
• Length of the child may be above average at
birth.
• History of a very tall parent or a close relative

16. Marfan’s Syndrome.
Marfan syndrome:
Hypotonia, joint laxity (thumb
sign and wrist sign), lax skin,
ectopia lentis, abnormally flat
cornea, blue sclera,
iridodonesis,

17. Marfan's syndrome
arachnodactyly, dolichocephaly,
malar hypoplasia, retrognathia,
downslanting palpebral fissures,
high arched palate, crowding of
teeth, pectus excavatum or
carinatum, scoliosis,
aortic aneurysm, aortic
regurgitation, mitral valve
prolapsed

18. Homocystinuria:
• Ectopia lentis, cataracts,
• Arachnodactyly,
• Pectus excavatum or carinatum,
• Genu valgum, pes cavus,
• High arched palate,
• Scoliosis,
• Crowding of teeth

19. Klinefelter syndrome
• Gynecomastia, small testes,
• Sparse facial hair,
• Micropenis,
• Delayed pubertal development,
• Cryptorchidism,
• Hypospadias
• Thin and tall for age
• Low upper/lower segment ratio
(long legs)

20. The XYY Syndrome
• Newborns are normal
• Many adult males are normal
• Tall stature, hypospadias and/or
cryptorchidism, severe acne, radio-ulnar
synostosis
• Mild or moderate mental retardation, but
findings of an XYY karyotype in newborn
does NOT predict intelectual function

21. Sotos Syndrome =
Cerebral Gigantism
• Unknown etiopathogenesis
• Transmitted AD & AR
• Large at birth (W&H), rapid growth in first year of life, above
97% for height at 1 year of age
• Rapid growth in first 3-4 years
• Arm span > 5cm above height (normally negative up to age 12
years)
• Irritability, feeding problems, delayed developmental milestones
(esp. impaired fine motor control), IQ around 70.
• Mildly dilated cerebral ventricles, sometimes abnormal EEG,
• Poor intelectual prognosis
• Supposed to be at risk for hepatic neoplasm

22. Beckwith-Wiedemann syndrome
• Hepatosplenomegaly,
• Nephromegaly,
• Macrososmia,
• Macroglossia,
• Omphalocele,
• Renal malformations,
• Ear creases/pits,
• Facial nevus flammeus
• Post natal gigantism and asymmetry:
high risk for wilm’s tumor.
• Transient hyperinsulinemia and
hypoglycemia
Diagnostic triad at
birth

23. Omphalocele
Visceromegaly

24. Mc-Cune Albright Syndrome
• Polyostotic Fibrous Dysplasia
• Café au lait spots, irregular border, unilateral
and asymmetrical
• Endocrinopathies,most common
Hyperthyroidism and Precocious Puberty

26. Weaver syndrome
• Broad forehead and face,
• Ocular hypertelorism,
• Prominent wide philtrum,
• Micrognathia,
• Deep horizontal chin groove,
• Deep-set nails

27. Simpson-Golabi-Behmel syndrome
• Large protruding jaw,
• Widened nasal bridge,
• Macroglossia,
• Upturned nasal tip,
• Coarse face, ‘bulldog-like’ appearance,
supernumerary nipples,
• Generalized muscular hypotonia, congenital
heart defect

28. Physical Examination
• Meticulous measurement of parameters height, weight,
BMI, upper segment/lower segment ratio, arm span and
height/arm span ratio is essential.
• Accurate plotting of anthropometric parameters on
growth chart
• Crossing height percentiles between infancy and onset of
puberty always warrants further evaluation.
• Specifically look for signs of obesity, signs of precocious
or delayed puberty, dysmorphism, stigmata of specific
disorders known to be associated with tall stature.
• Tanner sexual maturity rating (SMR) should be done in
all children presenting with tall stature as a routine
practice..

29. MANOEUVRES TO ASSES FOR
TALL STATURE
• HANDS AND FEET TOGETHER:
• Hemihypertrophy
• Unilateral growth arrest
• Genu valgum
• Genu recurvatum
• Pes planus

30. MANOEUVRES (cont’d)
• Bend over and touch toes:
– Scoliosis (Marfan, homocystinurea,sotos,NF-1)
– Kyphosis (with scoliosis as above, pituitary
gigantism)

31. MANOEUVRES (cont’d)
• Mobility:
– Hyper mobility (Marfan's)
– Limitation of extension (homocystinuria)
• Arachnodactyly
– To detect marfan’s syndrome.
• Tremors:
– To detect hyperthyroidism.

33. Investigation

34. MANAGEMENT

35. TREATMENT
• Reassurance of the family and the patients is
the key to the management of normal variant
tall stature.
• The use of the bone age and a careful
assessment of pubertal status to predict adult
height
• General supportive discussions on the social
acceptability of this condition

36. TREATMENT (Cont’d)
• Even though treatment is available for girls
and boys with excessive growth.
• Its use should be restricted to patients with:
– Predicted adult height > 3 SD above the mean
(78 inches or 198 cm in male patients, 71 inches or
180 cm in female patients) and
– Evidence of significant psychosocial
impairment.

37. Treatment
• For those with extreme tall familial height or those with
Marfan’s syndrome
• Sex steroid will cause early epiphyseal fusion and
growth arrest and will accelerate puberty
• Oral ethinyl estradiol at a dose of 0.15-0.5 mg/24 hr
until cessation of growth occurs has been used
successfully in girls. If necessary, a progestational agent
can be added after 1 year of unopposed estrogen.
• In boys, treatment should begin before the bone age
reaches 14 yr; testosterone enanthate is used at a dose
of 500 mg IM every 2 wk for 6 mo

38. Treatment of growth hormone
oversecretion.
• The goals of therapy:
– to remove or shrink the pituitary mass,
– to restore GH and secretory patterns to normal,
– to restore IGF-I and IGFBP-3 levels to normal,
– to retain the normal pituitary secretion of other hormones, and to
prevent recurrence of disease.
• For well-circumscribed adenomas, transsphenoidal surgery The
likelihood of surgical cure depends greatly on the surgeon's
expertise as well as on the size and extension of the mass
• The goal of treatment:
– Normalize GH levels.
– GH levels (<1 ng/mL within 2 hr after a glucose load) and serum IGF-I
levels (age adjusted normal range) are the best tests to define a
biochemical cure.

39. • If surgery fails to normalize growth hormone
level:
– Medical theraphy
– Radiation
• Tumor growth is arrested in 99 % cases by
radiations but it has delayed efficacy in
lowering GH level
• Hypopituitarism is predictable outcome in 40-
50 % cases after 10 yr irradiation.

40. Medical management
• Somatostatin analogs: highly effective in the treatment
of patients with GH excess.
– Octreotide suppresses GH to less than 2.5 ng/mL in 65%
of patients with acromegaly and normalizes IGF-I levels in
70%
• For cases that have both GH and prolactin
oversecretion, dopamine agonists, such as
bromocriptine, should be considered which bind to
pituitary dopamine type 2 (D2) receptors and suppress
GH secretion
• It is generally used as adjuvant medical treatment for
GH excess. Its effectiveness may be additive to that of
octreotide.