Variability of Growth Hormone Response to Pharmacological and Sleep Tests Performed Twice in Short Children

Abstract

Forty-nine children with short stature (age range, 4.1-15.9 yr) were examined. Twenty-four (group 1) were submitted twice to an arginine and a sleep test (12-h overnight GH profile). Twenty-five patients (group 2) were submitted twice to an arginine and L-dopa test. Coefficients of variation were calculated between both the results of pharmacological (peak and area under the curve) and sleep tests [mean GH concentration (MGHC), peak, area under the curve, number of peaks above 5 micrograms/L, and peak area]. In group 1 the coefficient of variation of sleep test parameters was significantly lower than that of pharmacological tests (P less than 0.01 to less than 0.001). In the sleep test the area under the curve and MGHC were the most constant parameters. Group 2 showed no difference between the coefficients of variation of the two pharmacological tests. Considering groups 1 and 2 together, the coefficients of variation of the sleep test, in particular the MGHC and area under the curve, were lower than those of the two pharmacological tests. Eight of 24 subjects in group 1 showed a low GH level in 1 series of tests, and a normal level in the other series. Five of 18 subjects in group 2 showed an abnormally low GH response to the arginine and L-dopa tests and a normal response to the 2 repeated tests. Therefore, to prevent an erroneous interpretation of the GH test results, it is very important to perform a sleep test and repeat it whenever GH secretion seems to be deficient or at the lower limits of normalcy.

Final height of patients treated for isolated GH deficiency: examination of 83 patients

“…Arginine and L-dopa tests were performed as previously described (17). For the sleep test, a constant withdrawal pump, as described by Kowarski et al (22), was used at a rate of approximately 2.5 ml/h.…”

“…However, insufficient numbers of patients, different therapy durations, and changes in the time of the dosage prescribed, due, in particular, to a greater availability of the hormone, have led to different results (10,11). In addition, the modifications recently made in the therapy schedule and administration route, as well as the uncertainties of the diagnostic criteria indicating the subjects to be treated (13)(14)(15)(16)(17)(18)(19)(20)(21), will probably further change the final results of the treatment. It is certain, however, that the experience acquired to date has not enabled us to adopt an optimal therapeutic approach, either for the single patient or for the whole group, casting doubt on the auxological outcome of the patients treated.…”

Retesting the childhood-onset GH-deficient patient

“…These studies have generally been performed in different cohorts of GHD patients with classical provocative tests that are known for their poor reproducibility (30)(31)(32)(38)(39)(40). This evidence clearly led to the statement that there is no justification for the view that patients diagnosed in childhood to be GHD should continue on therapy into adult life without their GH status being reinvestigated and shown to be persistently abnormal.…”

“…The inability to confirm GHD in adulthood could reflect transient GHD in childhood (34) or, alternatively, could merely reflect the lack of reproducibility of classical provocative tests (30)(31)(32)(38)(39)(40). It also has to be considered that even patients with normal GH response to provocative tests but showing impairment of spontaneous GH secretion are presently considered as GH insufficient (the so-called GH neurosecretory dysfunction) and treated with rhGH for replacement (41).…”

Central reassessment of GH concentrations measured at local treatment centers in children with impaired growth: consequences for patient management

“…Considerable variability becomes apparent when patients diagnosed as GH deficient are retested (2,3).…”