Growth Hormone Deficiency in Down's Syndrome ... - GGH Journal

Growth Hormone Deficiency in Down's Syndrome Children
In this study, the capacity to secrete growth hormone (GH) was stimulation tests. Additional endocrine testing revealed no thyroid
investigated
20 children with Down syndrome (OS) to determine or prolactin abnormalities in any of these patients; serum luteinizing
if GH deficiency plays a role in growth retardation in OS. The hormone, follicle-stimulating hormone, and testosterone levels
subjects (13 boys, 7 girls) were aged between 15 months and 13.9 were appropriate for age; and insulin-like growth factor 1 (IGF-1)
years, had a height standard deviation score (SOS) ranging from levels were normal in all OS patients.
-1.19 to -5.48, a weight SOS of -0.21 to -4.58, and a head The authors conclude that the growth retardation observed in
circumference SOS from -0.4 to -6.6 below the mean for normal these OS children was associated with a reduced serum GH
children of the same age and sex. All but 1 severely mentally response to levodopa and clonidine stimulation tests, disparity in
retarded child attended infant stimulation programs. All but 2 responses to the stimulatory tests, and low 24-hour IG-GH.
subjects had moderate to severe expressive language impairment
and were institutionalized from early infancy. GH was evaluated in Caste1lsS, TorradoC, Bastian W, et ill. J Intell Disabil Res 1992;36:29-4
all 20 patients by levodopa (125 mg up to 15 kg, and 240 mg
between 15 to 30 kg) and clonidine (0.15 mg m2) stimulation tests. Editor's comment: This study invites us to think that reduced GH
GH secretory patterns were assessed in 4 patients via integrated secretion plays a role in growth retardation in OS. The authors
24-hour GH concentration (IG-GH) using a constant withdrawal speculate that OS children have fewer neurons and neuronal
pump with continuous blood collection every 30 minutes. Normal connections in the CNS, which accounts for the abnormalities in
IG-GH values were considered to be above 3.2 ng/mL. Peak serum GH secretion found. However, as the authors pointed out, the
GH after levodopa and clonidine stimulation was found to be below discriminator of 10 ngimL for peak serum GH responses to pro-
10 ng/mL for both tests in 7 of the 20 children studied. Twelve vocative stimuli is rather arbitrary. Decreased levels after stimulachildren
showed a disparity between levodopa and clonidine tion tests (false-negatives) and disparity among test responses are
testing. Peak serum GH after levodopa administration was found we/l known to occur even in normal short children. In these studies,
to be below 10 ng/mL in 5 children; and peak serum GH following the peak response was between 7and 10ngimL forlevodopa in2
administration of clonidine was found to be below 10 ng/mL in 7 patients, for clonidine in 3 patients, and for both levodopa and
children. Fourchildren had reportedly abnormal 12- or 24-hour clonidine in another patient. The authors did not have their own
IG-GH, with mean values below 1.5 ng/mL. These 4 subjects had control values forGH levels. In many laboratories using the same .
previously shown GH levels above 10 ng/mL in at least 1 of the GHkit(Quintitape;Ka/lestadlnc., Austin, Texas) used in this study, ~
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values between 7 to 10 ngimL could be considered adequate and
would rule out GH deficiency. Moreover, some IC-GH measurements
were made with the Hybritech Tandem kit, which records
lower GH levels than many other assays. Finally, all of these OS
patients had normallGF-1levels for age. Therefore, the patients
did not meet biochemical criteria for classic GH deficiency to
account for growth failure. Unfortunately, only 4 of the patients
who had appropriate responses to at least 1 pharmacologic stimuli
had IC-GH measured, all 4 being abnormal. There were no such
measurements made in the other 16 patients described in this
report. Thus, no conclusion should be derived from these very
few cases that the etiology of growth failure in OS patients results
from inadequate spontaneous GH secretion.
A major pitfall of the study is the fact that obesity was not
considered in the equation. Most of the OS patients were obese,
as evidenced by the weight and height data; the majority of them
were overweight for height. Since obesity is known to cause
hyporesponsiveness of GH secretion to provocative stimuli and to
reduce IC-GH, it is very possible that these obese OS patients
could have responded normally after priming with pyridostigmine,
as has been demonstrated in obese normal children. 1 Elsewhere
these authors reported data that showed benefits of GH therapy in
OS patients.2 (This information was reviewed previously in GGH.3)
Caution must be exercised in obtaining incomplete data and
extrapolating results of GH testing to establish the diagnosis of GH
alterations in OS to justify treatment with GH. Other genetic
mechanisms that relate directly or indirectly to gene abnormalities
of chromosome 21 may be most important in determining height in
OS patients.
Fima Lifshitz, MD
1. CordidF,DieguezC,CasanuevaFF. Effect of central cholinergic
neutrotransmission enhancement by pyridostigmine on the
growth hormone secretion elicited by clonidine, arginine, or
hypoglycemia in normal and obese subjects. JCEM 1990;7(5):
1361-1370.
2. Torrado C, Vastian W, Wisniewski, et al. Treatment of children
with Down syndrome and growth retardation with recombinant
human growth hormone. J Pediatr 1991;119:478-483.
3. Lifshitz F. Growth, Genetics, and Hormones 1991;8(1):15.