High growth hormone levels in clinically short stature children.
ABSTRACT Growth Hormone (GH) is secreted from the anterior pituitary gland. It binds to receptors on the surface of target cells, stimulates production of Insulin-like growth factor-I (IGF-I) leading to growth of almost all tissues of the body capable of growing. Growth failure (height below 3rd centile) occurs in children who do not secrete sufficient amount of GH. In some children, however, short stature is present in the presence of high levels of GH in their blood and they also secrete normal to increased amounts of GH in response to stimulation tests when tested for possible deficiency of GH. This condition is known as GH resistance syndrome or Larons syndrome (LS).
All patients after a thorough clinical evaluation underwent GH evaluation protocol as follows. On arrival in the lab a blood sample was collected for basal GH level in each patient. Screening was performed by subjecting the patients to exercise stimulation test and/or L-dopa stimulation test. Patients with GH deficiency underwent insulin tolerance test (ITT) after one week for confirmation. All the basal and post-stimulation samples were analyzed for GH levels. A level below 10mIU/L indicated GH deficiency, between 10-20mIU/L as borderline and an adequate response was defined as a GH >20mIU/L. Patients with a basal GH level of >20mIU/L and/or a post-stimulation level of >40mIU/L were arbitrarily considered as having exaggerated GH levels. This article evaluates the high plasma growth hormone levels among clinically short stature children undergoing growth hormone stimulation tests.
Two hundred ninty-three patients reported for GH evaluation. Twenty were excluded for various reasons. Thus 273 patients were included for GH evaluation out of which 66(24.2%) showed GH deficiency, 89(32.6%) were borderline while 118(43.2%) patients exhibited adequate response, with GH levels of >20mIU/L. A number of patients unexpectedly showed very high GH levels on screening tests. Out of 118 patients, 21 showed either very high basal levels of >20mIU/L and/or a much-exaggerated response to stimulation tests with levels more than about 40mIU/L. Close consanguinity was found in 67% of patients showing very high GH levels.
Some children with idiopathic short stature may show high levels of GH during their evaluation for GH deficiency. We identified a considerable number of such patients. These patients require further investigations.
- Annals of Clinical Biochemistry 12/1991; 28 ( Pt 6):542-55. · 1.92 Impact Factor
Article: Growth hormone deficiency.Annals of Clinical Biochemistry 10/1987; 24 ( Pt 5):429-34. · 1.92 Impact Factor
- [show abstract] [hide abstract]
ABSTRACT: Laron-type dwarfism, which is characterized by the clinical appearance of isolated growth hormone deficiency with elevated serum levels of growth hormone and decreased serum levels of insulin-like growth factor I (IGF-I), has been described in approximately 50 patients. This condition is caused by a deficiency of the cellular receptor for growth hormone, and it is transmitted as an autosomal recessive trait, as indicated by an equal sex distribution and a high rate of consanguinity in affected families. We studied 20 patients (19 females and 1 male, 2 to 49 years of age), from an inbred Spanish population in southern Ecuador, who had the clinical features of Laron-type dwarfism. Seventeen patients were members of two large pedigrees. Among the 13 affected sibships, there were 19 affected and 24 unaffected female siblings and 1 affected and 21 unaffected male siblings. The patients' heights ranged from 10.0 to 6.7 SD below the normal mean height for age in the United States. In addition to the previously described features, 15 patients had limited elbow extensibility, all had blue scleras, affected adults had relatively short extremities, and all four affected women over 30 years of age had hip degeneration. Basal serum concentrations of growth hormone were elevated in all affected children (30 to 160 micrograms per liter) and normal to moderately elevated in the adults. The serum level of growth hormone-binding protein ranged from 1 to 30 percent of normal; IGF-I concentrations were low--less than or equal to 7 micrograms per liter in the children and less than or equal to 66 micrograms per liter in the adults (normal for Ecuadorean women, 98 to 238). Serum levels of IGF-II and growth hormone-dependent IGF-binding protein-3 were also low. We describe an inbred population with a high incidence of growth hormone-receptor deficiency resulting in a clinical picture resembling Laron-type dwarfism but differing principally in showing a marked predominance of affected females. This population, of Mediterranean origin, may be genetically related to other reported populations with Laron-type dwarfism, but with the genetic defect linked to a trait resulting in the early fetal death of most affected males.New England Journal of Medicine 12/1990; 323(20):1367-74. · 51.66 Impact Factor
J Ayub Med Coll Abbottabad 2006;18(2)
HIGH GROWTH HORMONE LEVELS IN CLINICALLY SHORT
Tariq Mahmood Awan, Abdus Sattar,* Ihsan Gul Khattak**
Department of Chemical Pathology, Army Medical College, Rawalpindi, *Department of Chemical Pathology, AFIP, Rawalpindi,
**Department of Pathology, CMH Mardan
Background: Growth Hormone (GH) is secreted from the anterior pituitary gland. It binds to
receptors on the surface of target cells, stimulates production of Insulin-like growth factor-I (IGF-
I) leading to growth of almost all tissues of the body capable of growing. Growth failure (height
below 3rd centile) occurs in children who do not secrete sufficient amount of GH. In some
children, however, short stature is present in the presence of high levels of GH in their blood and
they also secrete normal to increased amounts of GH in response to stimulation tests when tested
for possible deficiency of GH. This condition is known as GH resistance syndrome or Larons
syndrome (LS). Methods: All patients after a thorough clinical evaluation underwent GH
evaluation protocol as follows. On arrival in the lab a blood sample was collected for basal GH
level in each patient. Screening was performed by subjecting the patients to exercise stimulation
test and/or L-dopa stimulation test. Patients with GH deficiency underwent insulin tolerance test
(ITT) after one week for confirmation. All the basal and post-stimulation samples were analyzed
for GH levels. A level below 10mIU/L indicated GH deficiency, between 10-20mIU/L as
borderline and an adequate response was defined as a GH >20mIU/L. Patients with a basal GH
level of >20mIU/L and/or a post-stimulation level of >40mIU/L were arbitrarily considered as
having exaggerated GH levels. This article evaluates the high plasma growth hormone levels
among clinically short stature children undergoing growth hormone stimulation tests. Results:
Two hundred ninty-three patients reported for GH evaluation. Twenty were excluded for various
reasons. Thus 273 patients were included for GH evaluation out of which 66(24.2%) showed GH
deficiency, 89(32.6%) were borderline while 118(43.2%) patients exhibited adequate response,
with GH levels of >20mIU/L. A number of patients unexpectedly showed very high GH levels on
screening tests. Out of 118 patients, 21 showed either very high basal levels of >20mIU/L and/or a
much-exaggerated response to stimulation tests with levels more than about 40mIU/L. Close
consanguinity was found in 67% of patients showing very high GH levels. Conclusion: Some
children with idiopathic short stature may show high levels of GH during their evaluation for GH
deficiency. We identified a considerable number of such patients. These patients require further
KEY WORDS: Growth Hormone, Resistance Syndrome, Short Stature, Exercise, L-dopa, Insulin
Tolerance Test (ITT).
GH is secreted from the anterior pituitary gland in
the form of pulses throughout the day and night.
These bursts of secretion increase the total daily GH
secretion during the periods of maximal growth in
adolescence. A substantial part (20-40%) of total 24h
secretion of GH occurs during the first 90 minutes of
During the day GH secretions and hence the
serum levels are influenced by exercise, stress and
nutrient intake. Due to its pulsatile secretion and a
short half life of 10 minutes, the basal level alone has
no role in the diagnosis of GH deficiency. Therefore
dynamic function tests, which include various types
of physiological and pharmacological stimuli, are
necessary for evaluation of GH response in an
Like other peptides and protein hormones
GH binds to the cell membrane associated receptors
on the surface of target cells. The sites of action of
GH are ubiquitous.1 It exerts pleotropic effects on
growth and metabolism and it causes growth of
almost all tissues of the body that are capable of
growing.6 GH action requires dimerization of two
receptors with a single GH moiety and subsequent
activation of a complex cascade of tyrosine kinases.
GH stimulates production of Insulin-like growth
factor-I (IGF-I) after its attachment to the cell
receptors.4 IGF-I further
characteristic of GH.
GH action is modified by the soluble serum
growth hormone binding protein (GHBP) that is
identical to the extra-cellular domain of the GH
receptors. Majority of GH circulates normally in
blood bound to these proteins.7 Growth failure
(height below 3rd percentile) occurs in children who
do not secrete sufficient amount of GH. In some
children, however, short stature is present in the
presence of high levels of GH in their blood and they
exerts the actions
J Ayub Med Coll Abbottabad 2006;18(2)
also secrete normal to increased amounts of GH in
response to pharmacologic stimulation.
Laron and colleagues were the first to
describe short stature with characteristic features of
isolated GH deficiency but with elevated serum
levels of GH in these children.8,9 The condition is
now known as Laron Syndrome (LS). It is a familial
disorder with an autosomal recessive form of
The cause of growth failure in the majority
of these children has remained unknown.10 The
condition was originally thought to result from an
abnormal growth hormone. However subsequent
studies have shown that these children have a defect
in the ability of the target cells to respond to GH due
to defective GH receptor.6 Such a defect, indeed,
could occur in either the GH receptor (type I) or the
intra-cellular mediators of GH signaling (type II).
Thus these children have been found to have low
levels of serum growth hormone binding proteins
(GHBP) and a failure to produce Insulin-like growth
factor I (IGF-I) in the presence of very high
circulating GH levels.9,11
MATERIALS AND METHODS
The study was carried out in the Department of
Chemical Pathology and Endocrinology, AFIP
Rawalpindi, during a period of one year from June
1999 to July 2000.
The study population consisted of 293
patients out of which only 273 short stature
ambulatory children were evaluated for their GH
secretion. All the patients underwent a routine
evaluation including medical history and physical
examination, although children had already been
medically examined by the referring physicians To
keep a record and define the selection criteria a pre-
designed proforma, for each child, was filled in
which included the name, age, sex, place of
residence, perinatal history, height and weight,
heights of siblings, parental heights, history of any
medical treatment and performance at school.
Patients having any chronic disease, dysmorphism,
evidence of endocrine disease like hypothyroidism
and Cushing’s syndrome,
psychosocial deprivation or any evidence of delayed
onset of puberty were excluded. Height and weight of
each child were recorded on standard growth charts.
Only patients with heights below 3rd percentile were
included. For bone age determination, a radiograph of
non-dominant hand and wrist was considered
The initial screening of GH was carried out
by subjecting the patients to Exercise Stimulation
Test and L-dopa Stimulation Test.
After an overnight fast, a basal blood sample
for GH was collected, and each child performed a 20
minutes exercise on a treadmill under direct
supervision of an attending doctor. On completion of
exercise a venous blood sample was collected. Now
L-dopa stimulation test was carried out by
administering tablet L-dopa orally along with routine
breakfast. The dose of L-dopa was 125mg for a child
weighing < 15 Kg, 250mg for15 to 30 Kg and 500 mg
for > 30 Kg. A blood sample was collected after 90
min of L-dopa administration. Patients who showed
GH deficiency on screening tests were subjected,
after a gap of 1 week, to insulin tolerance test (ITT).
All the blood samples for GH estimation
were collected in disposable plastic syringes. Serum
was separated in disposable sterilized, plain plastic
tubes and stored at –20C till analyzed for GH.
Serum samples were analyzed for GH on
"IMMULITE", an Automated
Analyzer of Diagnostic Products Corporation (DPC),
USA. The assay is based on the principle of a solid
phase two-site chemiluminescence
immunometric assay. It calculates test results for
controls and patient samples from the observed
signals, using a stored Master Curve, and generates a
printed report. The assay has a working (reportable)
range of GH from 0.13 to 104mIU/L. The intra-assay
and inter-assay coefficient of variability for this kit at
the decision limits were 2.5% and 3.8%,
Individual investigators have used their own
test protocols and arbitrary cut off values for test
results.13 In our setup all patients with basal and
post-stimulation GH levels of <10mIU/L were
regarded as GH deficients, between 10 to 20mIU/L as
borderline cases, while those with a GH level of
>20mIU/L in any of the blood samples were
considered as having adequate GH reserves.
Patients showing either very high basal
levels of >20mIU/L and/or a post stimulation GH
level more than 40mIU/L were arbitrarily regarded as
those with unusually elevated GH levels.
Data was analyzed using SPSS version 11.0.
Data was found to be non-normally distributed
therefore results were expressed as median and range.
A total of 293 patients were referred for evaluation of
GH deficiency. Twenty were excluded; eight had
heights above 3rd percentile and twelve had an
organic basis for their short stature. Thus only 273
patients were included for GH evaluation and data
analysis. Out of 273 children 189 (69%) were males
and 84 (31%) females with an age range of 2 years to
J Ayub Med Coll Abbottabad 2006;18(2)
Table-1: Patients with exaggerated GH responses (n=21)
stimulation GH levels (n=14)
Patients with high basal+ high
post-stimulation GH levels (n=7)
(GH response: basal >20mIU/L and/or post stimulation >40mIU/L)
Response Post exercise Median
Post L-dopa Median
22.9 (11.5-100.0) Patients with high 2.4 (1.0-12.0)
25.4 (20.0-53.0) 51.3 (37.8-68.0) 25.1 (14.5-37.0)
On screening tests, 118(43.2%) patients
showed a normal response with GH levels of
>20mIU/L, a borderline response in 89(32.6%), while
66 patients (24.2%) exhibited GH deficiency with
Out of 118 patients exhibiting normal
responses on stimulation tests a considerable number
(n=21) comprised of those who had unexpectedly
very high GH levels with either very high basal levels
of >20mIU/L and /or a very exaggerated post-
stimulation response with levels more than 40mIU/L.
The data was found to be non-normally distributed
therefore median and ranges were calculated. Out of
these 21 patients, 14 had median basal GH levels of
2.4mIU/L but they showed a post-stimulation hyper-
response and had median post exercise and post L-
dopa GH levels of 46.1 and 22.9mIU/L respectively.
The other 7 patients had median basal GH level of
25.4mIU/L. These patients also showed a hyper-
response to exercise stimulation test with median GH
of 51.3mIU/L, while the median post L-dopa
stimulation GH was 25.1mIU/L. (Table-1)
Out of these 21 patients with elevated GH
levels 14 were males (age range of 5-16.5years) and
7 were females (age range of 5-17years). All patients
had proportionate short stature. In one case two sibs
while in two cases each had one sib with short stature
too. The parents were first cousins in 33.3%, second
cousins in another 33.3%, while the remaining 33%
Laron and colleagues in Israel were the first to
describe short stature with the characteristic features
of isolated GH deficiency but with elevated serum
levels of GH in children.8,9,11,14 The condition initially
termed Laron-type dwarfism is currently known as
Laron syndrome (LS), Growth hormone resistance
syndrome, primary GH insensitivity (GHI), GH
receptor insensitivity syndrome,
syndrome. Numerous independent populations of
Laron syndrome patients have been identified in
Europe, Africa, North and South America and Asia.
We found a considerable number of short
stature children with either basal and/or post-
stimulation very high GH levels. Some patients had
low basal GH but very high post-stimulation GH
levels, for example in a 12 years old male child post
exercise and L-dopa stimulation GH levels rose to
more than 74mIU/L and 100mIU/L respectively over
basal level of 10mIU/L. While others had high basal
GH levels and also showed a similar hyper-response
on stimulation tests with marked rise of >40mIU/L in
their GH levels especially after exercise stimulation
test and a moderately high GH levels after L-dopa
stimulation tests. This indicates release of maximum
of the GH reserve during exercise stimulation test.
Laron and coworkers, in various studies, have
reported upon the dynamics of GH secretion in these
patients. They found very high overnight fasting GH
levels and noticed that nocturnal pulses in these
patients may reach peak levels of 70-100mIU/L.9
This disorder phenotypically resembles GH
deficiency. These patients may also demonstrate the
metabolic consequences of GH deficiency including
truncal obesity, delayed puberty and hypoglycemia
despite normal or elevated concentrations of
biologically active GH. Laron syndrome (LS),
although, is traditionally associated with dysmorphic
facial features however many GH resistant patients
show normal facial appearance.15 Besides genetic
factors environmental factors are also thought to
contribute to the large amount of variation in
phenotype of these patients.16 Our patients had no
marked dysmorphic facial features but had a
proportional short stature. Moreover none of the
children had any known disease at the time of study.
No child had evidence of malnutrition as judged by
history and physical examination. The family
psychosocial structures in all cases were clinically
The etiology and characteristics of this
disease have been extensively reviewed.17,18 This
condition was originally thought to result from an
abnormal growth hormone molecule.19,20 Later it was
shown that these patients have defective GH
receptors on the cell surface. The defect was first
demonstrated by experiments showing the absence of
binding of GH to hepatocytes of these patients.8
Indeed more than 30 different mutations in the GH
receptor gene have been identified ranging from exon
deletions to nonsense, frameshift and splice and
J Ayub Med Coll Abbottabad 2006;18(2)
missense mutations of exons and introns and majority
are in the extracellular domain of the receptor.9,15
GHBP are the solubilized extracellular
fragment/domain of the GH receptor. It has been
found that in such patients the levels of GHBP are
low. Determination of serum GHBP can be used as a
simple quantitative estimation of the extracellular
domain of GH-R. Its deficiency reflects the relative
lack of cell surface GH receptors.9,10,21
GH leads to production of IGF-I after its
binding with the target cells. IGF-I also acts as a
negative feed back for GH secretion and its absence
thus leads to still more secretion of GH from the
somatotrophs of anterior pituitary gland.4,22,23 These
patients show very low serum IGF-I concentrations.24
A somatomedin generation test and also GH
treatment in these children do not show any rise in
their serum IGF-I concentration or stimulate growth.
This also indicates that this syndrome is due to
abnormal or deficient cellular growth hormone
receptors.23,25,26 leading to end organ resistance to the
For about 20 years since its original
description, Laron syndrome remained a very rare
untreatable condition. However in late 1980s
recombinant IGF-I became available and treatment
with IGF-I was demonstrated to accelerate linear
growth.27 Effects of recombinant human IGF-I
(rhIGF-I) on linear growth of children with receptor
mutations have proven beneficial and it has been
recommended as a long-term replacement therapy for
patients with Laron’s syndrome.28 Identification of
these children is therefore important. Our patients
require further investigations and need IGF-I and
GHBP-3 estimation but due to lack of facilities we
could not perform these estimations.
During clinical evaluation,
our patients were found to have no endocrine
disturbances besides the GH anomaly. The number of
male patients is more as compared to females,
probably because of the fact that parents are more
concerned about the overall health of their sons as
compared to their daughters in our society. Close
consanguinity, in these patients with elevated GH
levels, has been reported in the literature.8,11,29 This
indicates that this type of dwarfism is inherited as an
autosomal recessive disorder. There was close
consanguinity (67%) among the parents of these
children with high levels of GH.
In our study, the number of children with
elevated GH levels appears fairly high. The condition
initially described in Jewish communities and in
patients of Mediterranean origin, is also not
uncommon in our people. These patients require
identification and further investigations. They need
estimation of IGF-I levels before and after human
GH administration for the confirmation of diagnosis
and documentation. Serum assays for IGF-I and
GHBP-3 are now commercially available and require
to be included in the existing repertoire for the
complete evaluation of such patients.
Some children with idiopathic short stature may show
very high levels of GH during their evaluation for
GH deficiency. In our study, a considerable number
of children showed elevated GH levels. It is not an
uncommon condition in our people. These patients
require identification and further investigations like
estimation of IGF-I levels in their blood.
1. Martin JB. Neural Regulation of Growth Hormone Secretion.
N Eng J Med 1973; 188: 1384-1393.
Rappaport R, Souberbielle JC. Growth Disorders In: Soldin
SJ, Rifai N, Hicks JMB ed. Biochemical Basis of Pediatric
Disease. Washington: American Association for Clinical
Chemistry 1992; 141-64.
Hintz RL. Symptoms of Growth Disorders. In: Finberg L ed.
Saunders Manual of Pediatric Practice. Philadelphia: WB.
Saunders Company 1998; 727 – 731.
Rudd BT. Growth, Growth Hormone and the Somatomedins:
A historical perspective and current concepts. Ann Clin
Biochem 1991: 28; 542-555.
Gunn I. Growth Hormone Deficiency. Ann Clin Biochem
1987; 24: 429 –434.
Guyton and Hall. The Pituitary Hormone and their Control
by the Hypothalamus. In: Guyton and Hall. Eds. Textbook of
Medical Physiology. Philadelphia: W.B. Saunders Company
Rosenfeld RG, Reiter OE. Normal and aberrant Growth. In:
Wilson JD, Foster DW, Kronenberg HM, Larsen PR eds.
Williams Text Book of Endocrinology, 9th edition.
Philadelphia: W.B.Saunders Company 1998; 1427-1507.
Rosenbloom AL, Aguirre JG, Rosenfeld RG, Fielder PJ. The
Little Women of Loja- Growth Hormone Receptor
Deficiency in an Inbred Population of Southern Ecuador. N
Eng J Med 1990; 323: 1365-1374.
Laron Z. Laron Syndrome (Primary Growth Hormone
Resistance or Insensitivity): The Personel Experience 1958-
2003. J Clin Endocrinol Metab 2004: 89; 1031-1044
10. Andrey DG et al. Mutations of Growth Hormone Receptor in
Children with Idiopathic Short Stature. N Eng J Med 1995;
11. Najjar SS, Khachadurian AK, Ilbawi MN, Blizzard RM.
Dwarfism with Elevated Levels of Growth Hormone. N Eng
J Med 1971; 284: 809-812.
12. Technical Instructions IMMULITE for HGH Assay,
Diagnostic Products Corporation (DPC), Los Angeles, USA
1995: 1 – 6.
13. Dattani MT, Pringle PJ, Hindmarsh PC, Brook CG. What is a
normal stimulated growth hormone concentration? J
Endocrinol 1992; 133: 447-450.
14. Bjarnson R, Savage MO. Growth Hormone Insensitivity: a
widening diagnosis. Arch Dis Child 1999; 8(5): 378-379.
15. Hull KL, Harvey S. Growth Hormone Resistance: clinical
states and animal models. J Endo1999; 163:165-172
16. Woods KA, Dastot F, Pierce MA, Clark AJ, Postel-Vinay
MC, Chatelain PG, Ranke MB, Rosenfeld RG, Amselem S
and Savage MO. Phenotype: phenotype relationships in
J Ayub Med Coll Abbottabad 2006;18(2)
growth hormone insensitivity syndrome. J Clin Endo Metab
17. Laron Z. Prismatic cases: Laron syndrome (primary growth
hormone resistance) from patients to laboratory to patient. J
Clin Endo Metab 1995; 80: 1526-1531
18. Johnston LB, Woods KA, Rose SJ, Clark AJL and Savage
MO. The broad spectrum of inherited growth hormone
insensitivity syndrome. Trends in Endocrinology and Metab
19. Kowarski AA, Schneider J, Ben-Galim E, Weldon VV,
Daughaday WH. Dwarfism due to inactivity of endogenous
growth hormone. J Clin Endocrinol Metab 1978; 47: 461-3
20. Frazer T, Gavin JR, Daughaday WH, Hillman RE, Weldon
VV. Growth hormone dependent growth failure. J Pediatr
1982; 10: 12-15
21. Daughaday WH, Trivedi B. Absence of serum growth
hormone binding protein in patients with growth hormone
receptor deficiency (Laron dwarfism). Proc Natl Acad Sci
USA 1987; 84: 4636-40.
22. Maclean DB, Jackson IMD. Molecular Biology and
Regulation of the Hypothalamic Hormones.In. Sheppard MC
ed. Bailliere’s Clinical Endocrinology and Metabolism.
London: Baillier Tindall 1988; 835-868.
23. Kastrup KW, Andersen,
immunoreactive plasma and urinary growth hormone in
growth retardation with defective generation of somatomedin
(Laron’s Syndrome). Acta Paediatr Scand 1975; 64(4): 613-
Address For Correspondence:
Dr Tariq Mahmood Awan , Department of Pathology, Army Medical College, Rawalpindi
Telephone Office:051-561-31457-257(Ext), Cellular: 0300-9762167
24. Baumbach L, Schiavi A, Bartlett R, Perera E, Day J, Brown
MR et al. Clinical, biochemical, and molecular investigations
of a genetic isolate of growth hormone insensitivity (Laron’s
Syndrome). J Clin Endocrinol Metab 1997; 82(2): 444-451.
25. Walker JL, Ginalska-Malinowska M, Romer TE, Pucilowska
JB Underwood LE. Effects of the Infusion of Insulin-like
growth factor I in a child with growth hormone insensitivity
syndrome (Laron Dwarfism). N Eng J Med 1991; 324: 1483-
26. Mariani P, Gourmelen M, Carnot JF, Saignes F, Cayroche P.
Severe dwarfism with high plasma hGH levels and no
somatomedin activity: Laron’s Syndrome. Sem Hosp 1980;
27. Laron Z, Klinger B, Erster B, Anin S. Effect of acute
administration of insulin-like growth factor I in patients with
Laron-type dwarfism. Lancet 1988;ii: 1170-2
28. Mauras N, Martinez V, Rini A, Guevara-Aguirre J.
Recombinant human Insulin-like growth factor I has
significant anabolic effects in adults with growth hormone
receptor deficiency: studies on protein, glucose and lipid
metabolism. J Clin Endocrinol Metab 2000; 85(9): 3036-42.
29. Ferrandez A, Nengual J, Bastaros JC, Gonzalvo N, Laron Z,
Silbergeld A. Nanism with high values of GH and no
generation of Somatomedin after hGH (Laron’s Syndrome).
Clinico-biochemic Study of 8 Cases. An Esp Pediatr 1985;
Hanssen AI. Increased