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Cole
and colleagues explored the relationships among a variety of
anthropometric, demographic, and clinical variables in an attempt to
identify those that contribute significantly to the variance in
growth response to exogenous growth hormone (GH). The authors
utilized the UK Pharmacia KIGS database; 337 children were identified
with the diagnosis of isolated GH deficiency and met the inclusion
criteria (age <10 years, Tanner pubic hair stage 1, GH provocation
test result <20mU/L, follow-up at least 1 year). Children with
cranial tumors or history of radiation therapy were excluded. The
primary outcome variable was linear growth in the first year of
therapy, while the secondary outcome variable was growth response
during the second year. Covariates included height and weight SDS at
the initiation of treatment, age, sex, birthweight SDS, gestation,
midparental height SDS, GH dose, injection frequency, growth velocity
in the year prior to treatment, and maximal GH provocation test
result. Multiple regression analysis was used to identify factors
predicting growth response. Ten
factors predicted 42% of the variance in the first year’s
growth response: time between visits (years), age at baseline
(years), age2 at baseline (year2), height SDS
at baseline, weight SDS at baseline, midparental height SDS, birth
weight SDS, maximum GH peak, GH dose, and number of GH
injections/week. The maximum GH response to provocative stimulation
was the most predictive factor, accounting for 9.9% of the variance.
Only 3 factors predicted the growth response in the second year:
maximum GH response to stimulation, GH dose, and injection rate;
these 3 factors explained 6.8% of the variance. However, when the
first year’s response to GH and baseline height SDS were added
to the model, 21.6% of the variance was accounted for and the results
of the provocative test no longer contributed significantly. The
authors discussed the importance of the GH provocative test results
as a predictor of the first year’s growth response to exogenous
GH and the correlation between the first year’s response and
the growth rate during the second year (r=0.45).They also discussed
previously published information regarding the high sensitivity but
low specificity of GH provocative testing in detecting GH deficiency.
They encouraged more standardization of GH provocative testing
procedures and of serum GH analyses as one way of reducing the
different findings presented in various forums as to the relevance of
such testing to the diagnosis of GH deficiency. They conclude that
the GH response to 2 provocative tests (<20mU/l) should be used to
decide whether or not a trial of GH should be initiated, but that the
result of the first year’s response should be the criterion for
determining whether or not to continue such therapy.
Cole TJ, Hindmarsh PC, Dunger D. Growth hormone (GH) provocation tests and
the response to GH treatment in GH deficiency. Arch Dis Child.
2004;89;1024–1027.
Editor’s
Comment: GH stimulation tests are used by most pediatric
endocrinologists in the United States to determine, at least
initially, which short children will receive exogenous GH. Indeed,
the results of such testing remain the sole criteria used by most
third-party payors in deciding whether or not GH therapy will be a
covered prescription drug benefit. Only recently have criteria been
loosened for some very specific clinical conditions, ie, chronic
renal failure, Turner syndrome, children with intrauterine growth
retardation, etc. Most short children do not fit into these specific
categories for which stimulation testing is not a requirement, and
the decision as to whether or not to prescribe GH remains
problematic. The results presented in the paper by Cole and
colleagues seem to justify using the “gold standard” as
an important criterion in making that decision. It should be noted,
however, that all of the
children studied had been classified in the registry as GH deficient
and thus, children with other causes of short stature may have been
excluded from the analyses. That such children might benefit from GH
therapy, ie, increase their predicted adult height regardless of
their response to provocative testing, is not explored in this paper.
Perhaps the rigor of standardized testing and serum GH analyses will
increase our ability to make these decisions, but such testing should
never be the sole criteria for medication trials.
William L. Clarke, MD
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Current GGH - Vol. 24 No. 1
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