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Article history:
Received 22 January 2016
Received in revised form 11 February 2016
Accepted 21 February 2016
Available online xxxx
Keywords:
Growth hormone
Short stature
Growth failure
Chronic disease
Nutritional decits
Celiac disease
a b s t r a c t
Growth is a good indicator of a child's health. Growth disturbances, including short stature or growth failure,
could be indications of illnesses such as chronic disease, nutritional decits, celiac disease or hormonal abnormalities. Therefore, a careful assessment of the various requirements for normal growth needs to be done by history,
physical examination, and screening laboratory tests. More details will be reviewed about the GH-IGF axis, its abnormalities with special emphasis on GH deciency, its diagnosis and treatment. GH treatment indications in the
US will be reviewed and a few only will be highlighted. They will include GH deciency, as well as the treatment
of children born SGA, including the results of a US study using FDA approved dose of 0.48 mg/kg/week. GH deciency in adults will also be briey reviewed. Treatment of patients with SHOX deciency will also be discussed.
Possible side effects of GH treatment and the importance of monitoring safety will be highlighted.
2016 Elsevier Ltd. All rights reserved.
Corresponding author.
http://dx.doi.org/10.1016/j.ghir.2016.02.004
1096-6374/ 2016 Elsevier Ltd. All rights reserved.
Please cite this article as: E. Teran, et al., Growth and growth hormone: An overview, Growth Horm. IGF Res. (2016), http://dx.doi.org/10.1016/
j.ghir.2016.02.004
E. Teran et al. / Growth Hormone & IGF Research xxx (2016) xxxxxx
serum GHBP. This nding may reect alternate exon usage in lymphoid
cells, and indicates that GH has a distinctive role in the immune system
[7].
The diagnosis of GH deciency can include low growth rate, low IGF1 and IGFBP-3, and low GH secretion, characterized by spontaneous
(12/24) or stimulated. GH stimulation tests have been with us for decades, but as time has gone by, we have had more and more questions
about their validity in management of pediatric growth disorders. The
threshold for diagnosis of GH deciency has moved with time, from 5
to 7 to 10 ng/mL and while the extremes are obviousthe patient
who does not respond at all to stimulation, or the patient who produces
a peak of 50 or 100 ng/mLthe threshold that denes true GH deciency in childhood is unclear. Additional investigations, such as an
MRI scan, may be ordered to assist in the diagnostic process [8].
In Turner syndrome, a condition in which a female is partly or
completely missing an X chromosome causes major growth defects,
one of the symptoms, a web neck, is formed by redundant skin that initially stretched over the cystic hygroma [9]. During late gestation, when
the truncal lymphatics nally communicate with the venous system,
the lymph collection comprising the nuchal hygroma resolves, leaving
loose, redundant skin. Peripheral lymphedema, present dorsally on
the hands and feet, may be the initial presenting sign in Turner syndrome and is found in approximately one third of affected infants.
Lymphedema tends to improve with age. In contrast to the distribution
of edema in congestive heart failure or in venous insufciency, there is
usually a crease across the ankle joint and less edema distal to the
metatarsophalangeal joint line.
Human GH treatment started in 1921 when Evans and Long administered beef pituitary extracted to rats, producing gigantism [10]. GH
rst was isolated from the human pituitary gland in 1956, by both Li
and Papkoff, in California, and Raben, in Massachusetts, but its biochemical structure was not elucidated until 1972. In 1958, Raben reported the
results of the rst trial to show the effects of human GH on growth. By
1960 it was clear that GH decient children would benet from pituitary GH [11].
The rst recombinant human GH (rhGH) was developed in 1981 by
a biosynthetic process (Genentech, South San Francisco, CA). Later, an
improved process to develop rhGH was developed called protein secretion technology [11]. Then and in a few years, Eli Lilly launched a competing natural sequence GH. Many companies, including Pzer, Novo
Nordisk, Merck Serono, Ferring Pharmaceuticals, Sandoz, and Teva
supply.
In more than 12,000 children in the United Sates, who received recombinant GH daily for up to 7 years, as part of the National Cooperative
Growth Study [12], the average age at which GH therapy was initiated
was 9.2 4.1 years, and it was found that the growth velocity increased
from 4.4 2.8 cm per year to 10.0 3.1 cm per year after 1 year of
treatment. The standard deviation (SD) score for height changed from
2.6 1.1 to 0.5 1.1 after 7 years of therapy.
Rapaport et.al [13] researched the predictors of rst-year growth response to GH treatment in children born small for gestational age. Within the scope of the US SGA study to assess pretreatment predictors of the
response to GH in the SGA child, their aim was to evaluate the effects of
GH (Genotropin) therapy at a dose of 0.48 mg/kg/week on carbohydrate
metabolism and, specically, to investigate whether GH might inuence
glucose tolerance in short children born SGA. They enrolled 139 patients
meeting the inclusion criteria. An assessment of fasting oral glucose tolerance, using an OGTT, and HbA1c was made for each patient at baseline
and at the end of the 12-month study. Insulin resistance was determined using HOMA and QUICKI calculations and the American Diabetes
Association criteria were used to estimate glucose tolerance. Results
showed that GH at 0.48 mg/kg/wk. was well tolerated and improved
growth in children born SGA. The IGF-I was not predictive of the
12 month height SDS gain, while the height SDS at 3 and 6 months
were predictive. Finally, underweight children grew as well as normal
weight children, and both groups showed improved body composition
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j.ghir.2016.02.004