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BRANCH VII
THE TAMILNADU Dr. MGR MEDICAL
UNIVERSITY
CHENNAI
APRIL 2012
INSTITUTE OF CHILD HEALTH AND HOSPITAL
FOR CHILDREN
EGMORE, CHENNAI.
CERTIFICATE
M.D.(Branch VII)Paediatrics.
Declaration
Dr. D.SURESH
PLACE : CHENNAI
DATE :
SPECIAL ACKNOWLEDGEMENT
execution of my study.
ACKNOWLEDGEMENT
this study.
would never have been able to gather and compile these materials.
I wish to pay humble regards and thanks to my respectful
the study and their parents for their consent and continuous
CONTENTS Page No.
1. INTRODUCTION 1
2. REVIEW OF LITERATURE 24
3. AIM 35
4. STUDY JUSTIFICATION 36
6. OBSERVATION 45
7. DISCUSSION 59
8. LIMITATIONS 68
9. SUMMARY 69
10. CONCLUSION 70
11. RECOMMENDATIONS 71
12. BIBLIOGRAPHY 72
13. ANNEXURE
CONSENT FORM
INTRODUCTION
Normal growth:
clear. Many genes have been identified that are required for normal
development and function of the pituitary and that control the growth
1
most common referral to paediatric endocrinologist is a concern of
growth failure.
Definition:
one’s growth potential depends upon general well being, nutrition and
form all the major organ systems in the body. In the second trimester,
2
the fetus undergoes major cellular hyperplasia and in the third, organ
These can act locally in a paracrine manner [eg. IGF-I and IGF-II,
hormone.
the hormones and receptors within the GH–IGF axis also play their
that alterations in dietary intake are likely to have the greatest impact
By 4 years of age, average growth velocity has declined to 7
wide variation in pubertal timing within each sex. The later onset of
with chronic disease, for example atopy, but more often occurs in
is blunted. Although constitutional delay in growth and puberty may
actually present in the pubertal years, some children may have shown
tall stature and early puberty, which is associated with more intense
pubertal growth than normal. The net result is that both early and late
IGFs, but there are many other hormones that contribute, including
5
Hypothalamic control of GH secretion:
discrete pulses every 3–4 hr, with very low concentrations of growth
somatostatin[7].
6
transcripts generates a 20 kDa species that lacks amino acids 32–46
and accounts for the remaining 10–20%. Deletion of the GH-N gene in
secretion secretion
Exercise Hypothyroidism
Stress Obesity
Hypoglycemia Hyperglycemia
Sleep (7)
7
Growth hormone in the circulation:
decline towards birth and fall further after the first 2 weeks of
hormone release.
8
release generates large peaks of GH lasting 1–2 h separated by periods
normal growth.
its direct effects at the growth plate and indirect effects via IGF1.
receptor defects and the presence of neutralizing GH antibodies (10).
high androgens limit the height potential. Most patients with CAH
1. Chronic malnutrition
Cardiac diseases
Respiratory diseases
Celiac disease
10
3. Endocrine causes
a. Idiopathic
b. Genetic
i. HESX1
ii. PROP1
e. Congenital
b. Septo-optic dysplasia
c. Holoprosencephaly
d. Arachnoid cyst
11
ii. Associated with midline facial defects
b. Cleft lip/palate
c. Nasal dimple
f. Acquired
i. Perinatal trauma
iv. Trauma
v. Cranial irradiation
i. Craniopharyngioma
ii. Glioma/astrocytoma
iii. Germinoma
i. Histiocytosis
ii. Lymphoma
i. Transient
12
j. Psychosocial deprivation
B. Larons dwarfism
C. Hypothyroidism
D. Cushing syndrome
6. Chromosomal abnormalities
1:3500 children.
13
Clinical presentations:
birth weight and birth length but impairment of linear growth will
occur in the first two years of life. In the neonatal period, episodes of
bones and poor development of the bridge of the nose. Closure of the
14
anterior fontanel may be delayed and dental eruption and skeletal
maturation are usually quite delayed. The penis is often small and this
Acquired
15
Table 1. Guidelines for initial clinical evaluation of a child with
short stature (10)
16
Growth charts:
Commonly used growth charts are the height, weight and BMI
short stature, velocity charts are used to follow his or her progress
17
AGARWAL GROWTH CHART FIOR BOYS
15
AGARWAL GROWTH CHART FOR GIRLS
16
charts for all children under the age of 5 years around the world and
government of India has given a directive for use of these charts for
under 5 children in India in all areas and across all socio economic
classes.(42)
Radiologic evaluation:
to determine the 'bone age' of the left hand and wrist, using the method
of Greulich and Pyle (17). Children younger than 2 years of age should
have their bone age estimated from x-rays of the knee. Tanner and
18
Whitehouse-Marshall-Carter and Roche-Wainer-Thissen.
onwards.
height, the age of menarche in girls and the Tanner bone age. (18) TW2
differs from the BP method in that the TW2 lowers the minimal age of
height, weight, bone age and midparental height (MPH) and then
19
Biochemical evaluation of GH deficiency:
other causes of low IGF have been excluded. Age and gender
mandatory.
GH secretion.
for several days (3-5days) with serum IGF1 and IGFBP3 levels
in IGF1 and IGFBP3 levels would exclude severe forms of
stimulation tests (27). To prevent false positive results, some centers use
levels are very sensitive to the nutritional status (IGFBP3 less so), and
also that the normative range for IGF1 and IGFBP3 values are
pathological.
(100)
may pass GH stimulation tests . In the case of unexplained short
traumatic delivery.
22
5. Midline CNS defects, pituitary hypo or aplasia, pituitary stalk
MRI.
Treatment:
23
It is critically important to maximize height with GH therapy
24
REVIEW OF LITERATURE
1. A descriptive observational study was carried out by Choudhri,
the 2170 total attendees of the target group. Thus, the proportion of the
CHOUDHURY, et al
Hypothyroidism 29%
GH deficiency 15%
26
tertiary referral centre, S.S. Hospital,Institute of medical
Bhadada, et al
FSS 15.09%
CGD 21.02%
females. Majority of the patients were seen between the age group of
years. In the remaining age groups male to female ratio was almost
equal.
27
Normal variant short stature (36.1%) [Constitutional growth
delay (21.02%) and familial short stature (15.09%)] were the most
they had height below 3rd percentile for age and sex, no any
10ng/dl (in two tests), were considered as growth hormone
Sheidey assar, et al
GHD 11.8%
and weight for age in 79.2% was ≥ 10 percentile. These data showed
especial concern on the prevalence of GH deficiency and to
Heshmat moayeri, et al
In total 426 subjects, boys were 272 and girls were 154 among
4-18 years with short stature. The decision to investigate the growth
hormone axis was taken with the knowledge that other explanations
subjects.
30
They found that normal variants of growth including
as the most common causes of growth failure in this study. The results
most children with short stature will not have an endocrine disorder,
430 children referred for the evaluation of SS, 100 (23%) were
female ratio was 1.94 : 1. Less than 10% belonged to the lower
31
Meena desai et al
GHD 23%
MPHD 12%
deficiency and in three of the organic group. The height age was much
32
more retarded than chronological age in the GH resistant group (p ~
0.05) and the HA/BA ratio was also lowest in this group (p ~ 0.001).
than the mean peak levels of children with GH deficiency (1.52 + 1.36
ng/ml). Very high peak levels (62.8 + 19.8 ng/ml) were obtained in the
GH resistance group.
the basal levels ranged between 1.28 to 4.93 ng/ ml, with a mean level
peak level of 1.1 ± 1.07 ng/ml and the mean peak level with insulin
where it was done as one of the two tests. A second test for GH was
conducted in Bombay showed nutritional disorders and chronic
Suraj gupte55 found out that 10% of cases were due to endocrine
school children.
34
AIM OF THE STUDY
referral centre.
d) Anthropometric measurements
To find out the possible risk factors for short stature growth
hormone deficiency.
35
STUDY JUSTIFICATIONS
are very few studies from Indian subcontinent. Since multiple factors
populations.
designed.
36
MATERIALS AND METHODS
Methodology:
Study population:
Inclusion criteria
Exclusion criteria
inflammation.
3. Hypotensives.
37
Sample size - All children with the above inclusion criteria who
review board.
Maneuvre:
investigations.
38
development, hypoglycemic attacks, dysmorphic facies, constipation ,
examination)
Anthropometric measurements
Proportionate disproportionate
Normal
39
Standing height:
with upper border of tragus. The children were drawn upto their full
Arm Span:
tape.
extends from pubis to heel. First lower segment was measured and
Height Age:
40
Bone Age:
left hand wrist, and left elbow following a standard chart based on a
Growth Formula:
Target height:
inches)/2 + 2.5inches.
41
This value plotted as adult height at 18 years and the spread for
percentile curve to get the anticipated adult height and correlated with
height velocity and body proportions are some of the important tools
was drawn for basal level of GH estimations. Then the child was given
oral clonidine
42
4 microgram/kg body weight. Blood samples were drawn at 30 mins,
the procedure, the subjects were kept in recumbent position and blood
Hormone assay :
and inter assay variability ranging between 5-10%. Only basal and
post clonidine values were taken into account. Peak value >7 ng/ml is
deficiency.
TSH assay was done in all subjects using the TSH Immuno
43
IGF1 : IGF1 estimation was done to rule out pure GH deficiency,
Larons dwarfism.
MRI Brain : MRI Brain was done to rule out CNS pathology.
STATISTICAL ANALYSIS:
44
OBSERVATION
45
Fig.2 Etiological profile of short stature
n =33 n =51 n = 84
46
Of the total study population, clustering (38.1%) of short stature noted
11 (35.5%)
2-5 years 14 (26.4%) 25 (29.8%)
9 (29%)
6-9 years 23 (43.4%) 32 (38.1%) 0.413
11 (35.5%)
10-12 years 16 (30.2) 27 (32.1%)
47
Maximum number of short stature were observed in 6 to 9 years
12 years group with 30.2% and finally 2 to 5 years group with 26.4%.
than 5 year of age, 23(43.2%) belong to the age group 6 to 9 years ,16
age , 9(29%) belong to the age group 6 to 9 years ,11 (35.5 %) belong
48
In this study of short stature, we had seen wide variations in age
7.25 ± 3.41.
delay. Both male and female were equally affected in familial short
stature..
49
Table 4. Perinatal features & clinical symptom among children
presented with short stature
SYMPTOMS N Percentage
APH 5 9.4%
Breech 58 69%
NNH 15 17.9%
Neonatal 12 14.2%
hypoglycaemia
Consanguinity 49 58.3%
Hypothyroidism 12 14.2%
MPHD 10 11.9%
50
The study population was analysed based on their clinical
51
TABLE 6.Distribution of birth asphyxia in GHD vs. non GHD
Non GHD
Birth asphyxia GHD (n = 53) P Value
(n=31)
52
TABLE 8. Distribution of Birth Weight in Short Stature
Below 1 kg 2 2.38%
1-1.5 kg 6 7.14%
1.5-2 kg 8 9.52%
2-2.5 kg 19 22.61%
Total 84 100%
Non GHD
Consanguinity GHD (n=53) P Value
(n=31)
53
TABLE 10. Distribution of dysmorphic facies in GHD
crowding, central incisors, cleft lip & palate ) out of 53 cases of GHD.
CST n Mean ± SD
Larons
GH – Basal 8 26.22 ± 13.98
dwarfism
GH – Larons
8 48.64 ± 11.63
Postclonidine dwarfism
TABLE 12. Clonidine stimulation test in true GHD & Larons
dwarfism
GH
30 min 60 min 90 min
basal
55
(n=45) 3.35 2.09 2.36 2.63 2.02 0.89 0.18
Larons
6.25 ± 1.96 ± 4.29 ± 2.69 ± 3.69 ± 0.63 ± 0.3 ±
Dwarfism 2.87 1.92 2.41 1.49 2.22 0.34 0.22
(n=8)
TOTAL
(n=84) 7.25 ± 3.19 ± 4.06 ± 4.29 ± 2.99 ± 0.83 ± 0.4 ±
3.33 2.27 2.17 2.84 1.97 0.71 0.19
and 0.72 respectively. We can make out that both mean height age and
mean bone age retarded in larons dwarfism than GHD. In both GHD
and larons dwarfism, mean height age is more retarded than mean
bone age.
56
Fig. 5
This is graphical representation of mean level of GH secretion
Fig. 6
57
In this figure, we can make out that both mean HA and mean
absent pituitary stalk whereas remaining 65% had normal MRI Brain
study.
58
DISCUSSION
getting admitted at Institute of child health who met the inclusion and
We had
59
2500 children admitted in hospitals. Khadgawat et al45 have reported
prevalence of short stature, lesser than that of our study. In this study,
60
CHOUDHURY, et al In our study
Bhadada, et al In our study
62
Sheidey assar37, et
In our study
al
SS-Male to female
1.49:1 1:1.54
ratio
was 11.8% which was more commonly seen in males as general short
63
Heshmat moayeri38, et
In our study
al
And our sample size was only 84. So further studies need to be
64
Meena desai40, et
In our study
al
which was the most common endocrine cause in our study because the
study was done at ICH which is a tertiary referral centre and most of
65
the normal variants of growth disorders would have been screened at
delay.
less than that observed in Bombay based study (31%)50 but more than
observed in the present study. This is much higher than any other
48.8% of cases , the truncal obesity was found only in one case. This
our country.
66
Unlike previous Indian studies, the maximum number of short
All the male children in the present study were noticed to have
present study the retardation of height age was more severe than that
of bone age.
found height age was more severely retarded than bone age in Larons
67
LIMITATIONS
¾ The study was done at a tertiary care centre ,So the study
68
SUMMARY
its significance will pave way for proper approach to short stature
children.
pathological short stature met the inclusion and exclusion criteria and
they were recruited for the study after obtaining informed consent.
measures were arrived and statistical analysis done using Chi Square
CONCLUSION
short stature were analysed for etiological and clinical profile. This
MPHD.
deficiency while considering its low HA/BA ratio. MRI Brain plays
vigilant about the problem for detection at its earliest stage for getting
70
RECOMMENDATIONS
crowding.
71
BIBLIOGRAPHY
1. Freeman JV, Cole TJ, Chinn S, Jones PR, White EM, Preece
MA. Cross sectional stature and weight reference curves for the
velocity: British children, 1965. Arch Dis Child 1966; 41: 454–
71.
Genetics1998; 18:147-149.
14. Pfäfle RW, Di Mattia GE, Parks JS et al. Mutation of the POU-
Pediatr1992; 151:266-270.
Press.
19. Bayley N Tables for predicting adult height from present height
23. Bayley N, Pinneau SR. Tables for predicting adult height from
24. Roche AF, Wainer H, Thissen D. The RWT method for the
86:3882-3888.
Pediatr2003; 143:415-421.
541.
29. Blethen SL, Breen TJ, Attie KM. Overview of the National
30. Root AW, Kemp SF, Rundle SC, Dana K, Attie K 1998. Effect
2000;23:721-723.
2:44-52.
2005;90:6396-6402.
(7) : 545-547.
37. Shideh Assar MD, Hajieh Shahbazian MD, Kourosh Riahi MD,
42.
Saunders; pp 136-172.
42. Prinja S, Thakur JS, Bhatia SS. Pilot tesing of WHO child
43. Frindik JP, Kemp SF, Hunold JJ. Near adult heights after
57-8.
1998;35:859-65.
2004;34:84-8.
press,1980,32:45-55.
ANNEXURE
Patient name:
Age / sex:
Endocrine no:
Address:
Date:
SE status:
CLINICAL HISTORY
SYNCOPE YES / NO
CONSTIPATION YES / NO
POLYUREA YES / NO
FEVER / LETHARGY YES / NO
SEIZURES YES / NO
PRECOCIOUS PUBERTY YES / NO
DEFORMITIES YES / NO
TRAUMA YES / NO
TREATMENT HISTORY
FEATURES OF IINCREASED
YES / NO
ICP
VISUAL DISTURBANCES YES / NO
OBTRETIC HISTORY:
ANTENATAL HISTORY:
HEMARRHAGE
MODE OF DELIVERY NATURAL / LSCS /FORCEPS
PRESENTING PART VERTEX / BREECH
BIRTH WEIGT
BIRTH ASPHYXIA YES / NO
NEONATAL
YES / NO
HYPERBILIRUBINEMIA
MATERNAL HISTORY:
PUBERTY AGE
MATERNAL SMOKING /
YES / NO
ALCOHOL
FAMILY HISTORY:
CONSANGUINITY
FAMILY H/O SHORT
STATYRE
\
EXAMINATION:
MIDLINE DEFECTS
GENITALIA
CRYPTORCHIDISM
HYPERPIGMENTED SKIN
FUNDUS
DENTAL EXAM
BP
HORMONAL STUDIES
THYROID TSH T4 T3
PROFILE
Sr.CORTISOL:
Sr.ACTH :
KARYOTYPING if indicated:
MRI SCAN.
I agree not to restrict the use of any data or results that arise from
this study.
ABBREVIATIONS