الفهرس 
Material and methodsOnly 14 pages are availabe for public view
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Abstract
SUMMARY & CONCLUSION
This study consisted of 26 cases qf children presenting With short
stature and nine control cases from the D.E.M.P.O. Clinic in the Cairo
University Children’s Hospital. The followin” is a summary of its most
prominent findings :-
1. Growth delay was the commonest cause of understature forming about
35% of the overall cases, 66.7% of whom were males and 33.3% were
females. Fifty percent of the males in the study were growth delayed
and only 20% of the females were so diagnosed.
2. Growth hormone deficiency (GHD) formed 19% of Egyptian children
presenting with short stature in our clinic of whom 80% were males and
20% were females. whereas 25% of the males in the study were GHD
and only 10% of the females were GHD.
3. Juvenile primary hypothyroids formed about 12% of the cases and
were all females.
4. The remainder of the cases comprising the miscellaneous group
consisted of a Laron dwarf, an end organ unresponsiveness to somatomedin,
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a Mauriac syndrome, a Russell-Silver syndrome a query case of prolactin
insufficiency, a hypogonadal short prepubertal boy and two cases with
familial short stature with superimposed growth delay.
5. Stature was most severely affected in the Laron dwarf, being far
below -4 SO from the mean (of French standards). Patients with GHD were
4 SO below the mean, patients with thyroid failure were 3 SO below the
mean and those with growth delay ranged from -2 SO to -4 SO below the
mean. So that the extent of height deficit correlated with the extent
to which the hormone affected was involved in skeletal growth. This
indicates that skeletal (linear) growth is primarily controlled by SM
followed by GH and last but not least thyroid hormones. Growth delay,
being due to the interaction of a multiplicity of factors including some
transient hormonal disturbance and consisting of a heterogenous group
of delayed children. showed this wide range in height deficit among the
group.
6. Underweight was common in all the cases. mainly below the mean
(mostly -3 SO). Skinfold thickness was normal in the GHD group, but
markedly affected in the growth delayed one, reflecting probably the
degree of malnutrition, and hence the role played by the latter in the
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pathogenesis of growth delayed children.
Z. The combination of estimation of SM activity together with a combined
hypothalamo-pituitary function test (ITT + TRH) proved to be very
successful in the diagnosis of our cases. The ITT test was simple and
rapid to perform, required minimal personnel and minimal handling of
the patients, and has minimal side-effects, was considerably cheap
compared to other tests, and hence very convenient to use in developing
countries such as Egypt.
8. Aetiologically; GHD was due to perinatal insult. idiopathic andl
or hereditary. Hypothyroidism was due to late decompensation in a
congenital disorder and autoimmune thyroiditis. Growth delay was due
to a combination of hereditary. environmental and social factors.
Malnutrition and parasitism played a major role in pathogenesis.
9. The growth delayed group fell into two well defined categories; a
muscular variety in which hereditary factors predominated and a lean
variety in which nutritional and parasitic factors played a major role.
Growth delay was difficult to differentiate from conditions such as
familial short stature, hypogonadism and cases with transient GHD.
10. We have described three peculiar cases of short stature:- The first
was a GHD male Russell-Silver who did not respond to GH therapy, had a
lean body appearance. was dysmorphic and cryptorchoid. The second was
a male with slow growth in the first two years of life, no organic
disorder and hypothalamo-pituitary function tests suggestive of diminished
prolactin reserve. The third case was a female with dysmorphic features.
infantile body proportions. stunted growth and high bioassayable SM activity
and very much resembling a case described by Lanes et al (1980). The
defect being probably due to a cellular insensitivity to somatomedin.
11. We have also detected two cases with an enlarged sella turcica.
The first case was a juvenile hypothyroid ~nd the second was a Loron
dwarf. The enlarged sella was due to hyperplasia of the cells
secreting thyrotropin - in the first case - and to GH _ in the second
case - secondary to thyroxine and somatomedin deficiency respectively.
The second part of the study consisted of analysing hormonal
interrelationships. Positive conclusive data included briefly the
following:
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1. Peak responses of growth hormone (GH) were higher in girls than
boys in the pubertal age period.
2. The peak response and the degree of response of GH to insulin
induced hypoglycaemia was the same in the late childhood and
pubertal age periods and double that seen in early childhood.
3. Very high peak GH responses were observed in some patients of the
lean variety of growth delay indicating some type of peripheral
resistance to GH. Partial GH responses were present in patients of
the muscular variety of growth delay indicating a transient type
of GHD in these children.
4. Somatomedin (SM) activity was observed to increase with age in the
male control group of this study.
5. Bioassayable 8M activity measurement in the growth delayed group
gave a wide range of values varying from marked inhibition «0.1
units/nU) to values of 1.8 unitsknl, giving a fair idea of the
state of the growth conditions in the child at that particular time.
SM activity gave a flat response in the prepubertal GHD patients and
a marginally low 8M activity in one of the hypothyroid patients.
6. There was a significant correlation between the basal SM activity
and the degree of response of GH during an ITT that increased with
age in the cases of the study as a whole.
7. Patients with GHD and hypothyroidism showed a significant correlation
between the degree of GH response in an ITT and the basal SM activity.
Patients with hypothyroidism also showed a significant correlation
between their basal 8M activity and peak GH response during an ITT.
The correlation coefficient was high in patients with hypothyroidism
indicating that 8M deficiency in these patients is related mainly
to the secretory status of GH in this dis~ase While in patients with
GHD, 8M activity is under the net control of other hormones,
especially that thyroid hormones are secreted normally in these
patients.
8. In the growth delay group the disruption of the normally present
correlation between basal SM activity and the degree of response
of GH to ITT indicates a disturbance in growth in these patients
and may be a diagnostic feature for this condition.
9. Basal and peak TSH levels decreased with age in the cases of the
study as a whole. On analysing the sex differences during puberty,
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males showed the progressive decline in the basal and peak levels.
while in females the degree of response of TSH to TRH was
significantly higher in girls in puberty than in boys of the same
age group. Also there was a highly significant correlation
between the basal and peak TSH values that increased with age.
Furthermore it was the female sex that evidenced this correlation.
males showed a weaker correlation only at puberty. Basal and
peak responses of TSH were negatively correlated with the basal
levels of thyroxine only in females prepubertally. from the
study of basal. peak and degree of responses of TSH to TRH and
basal T4 in hypothyroid patients. it was deduced that the most
useful diagnostic tool in detecting hypothyroid patients is the
basal TSH levels.
10. Under physiological states there is no evident correlation between
basal GH. TSH and T4 in relation to age and sex. In hypothyroidism
GH peak levels were reduced. On the other hand thyroid function
in patients with GHD is not entirely normal.
11. The type of prolactin secretory response during the combined ITT
and TRH test was analysed and correlated with other hormones. the
following was observed:-
The PRL responses to the TRH+ ITT test observed fell into six
distinct patterns. namely. the normal. the persistently elevated.
the exaggerated. the delayed and the poor responses. On analysing
the responses in relation to age. sex and in relation to other
hormones the following was observed:-
1. There were no sex differences in the PRL responses which tended to
be increasingly’hormal” with age.
2. Lowered.absent or inhibited 8M activity was associated with raised
or normal PRL responses. indicative of some positive interrelation.
whether direct or indirect. between both hormones.
3. High PRL responses were a common finding in cases with poor GH
response but not vice versa. While a poor PRL response was not
affected or associated with the abnormal GH response and was found
to be an independent finding. It was also common to find delayed
responses of PRL when the GH response was delayed but not vice versa.
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It was concluded that the high PRL response in the cases with poor
GH response may enable us to differentiate between isolated GHDof
pituitary origin and that of hypothalamic origin. as PRL responses
will be raised in the former not in the latter. Also that isolated
PRL deficiency is a primary condition independent of other pituitary
hormones and should be taken into account when diagnosing multiple
pituitary hormone deficiency. Finally that the delayed responses
of PRL in a ,TRH + ITT test are due to the response of PRL to
hypoglycaemia and is usually higher because of the priming effect
the TRH has on the PRL secreting cells.
4. Persistently elevated PRL responses were characteristic to
hypothyroidism whether primary. secondary or tertiary,probably related
to the modality in which TRH is secreted. Hence PRL and TSH are
regulated independently from one another.
Last but not least. by analysing our control group and comparing it
with our delay group we were able to identify a new entity of delay.
namely. the marginal growth delay. which have some endocrine features
in common with the delay group but are clinically normal.