Reproducibility of Growth Hormone Testing Procedures: A Comparison between 24-hour Integrated Concentration and Pharmacological Stimulation

Zadik, Zvi; Chalew, Stuart A.; Gilula, Zvi; Kowarski, A. Avinoam

doi:10.1210/jcem-71-5-1127

Cited by 117 publications

(72 citation statements)

References 14 publications

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“…It is reported [17][18][19][20] that GH stimulation tests are sometimes not reproducible and they have false positive results.…”

Section: Discussionmentioning

confidence: 99%

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Comparison Between Insulin-Like Growth Factor-I(IGF-I) and IGF Binding Protein-3(IGFBP-3) Measurement in the Diagnosis of Growth Hormone Deficiency.

Hasegawa

Aso

et al. 1993

Endocr J

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Abstract. To analyze the utility of insulin-like growth factor-I (IGF-I) and insulin-like growth factor binding protein-3 (IGFBP-3) radioimmunoassay in the diagnosis of growth hormone deficiency (GHD) we measured IGF-I and IGFBP-3 in sera from normal children (n=309), short children (n=99) and patients with GHD (n=73). In 80% and 93% of classical GHD (cGHD), IGF-I and IGFBP-3 levels, respectively, were below the age-related cutoff levels (lower limit). In 81% and 88% of normal short children (NS), IGF-I and IGFBP-3 levels, respectively, were above the age-related cutoff levels. Thus, both IGF-I and IGFBP-3 were good parameters for screening GHD. In contrast, in more than half of partial GHD (pGHD), either IGF-I or IGFBP-3 was above the age-related cutoff levels. The poor discrimination between patients with pGHD and NS by using these two parameters may be the result of their relatively similar GH levels, as compared to cGHD, or due to the limitations of GH stimulation tests. In about 80-90% of NS, IGF-I and IGFBP-3 were above the age-related cutoff levels at all ages. A hundred percent of cGHD under 10 years old had IGFBP-3 below the age-related cutoff levels, whereas 79% of cGHD under 10 years old had IGF-I below the age-related cutoff levels. Thus in the younger age groups, IGFBP-3 may be more sensitive than IGF-I. It may be because IGFBP-3 levels are relatively higher than those of IGF-I in younger subjects. IGFBP-3 may be less sensitive for diagnosing GHD in older children than in younger children because IGFBP-3 levels may also increase during puberty by mechanisms independent of the GH-IGF-I axis. There was a significant correlation between IGF-I and IGFBP-3 in all the subjects. However, IGF-I and IGFBP-3 classified subjects differently in 25% of patients with GHD and 19% of those with NS. This may reflect differences in daily coefficient of

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“…It is reported [17][18][19][20] that GH stimulation tests are sometimes not reproducible and they have false positive results.…”

Section: Discussionmentioning

confidence: 99%

“…One reason for this difference is easy to understand: by definition the severity of deficiency is greater in cGHD than in pGHD. It is also possible that GH stimulation tests have limitations [17][18][19][20]. Some patients with GHD (especially pGHD) might have been diagnosed from false positive results.…”

Section: Discussionmentioning

confidence: 99%

Comparison Between Insulin-Like Growth Factor-I(IGF-I) and IGF Binding Protein-3(IGFBP-3) Measurement in the Diagnosis of Growth Hormone Deficiency.

Hasegawa

Aso

et al. 1993

Endocr J

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“…However, this should be partly compensated for by the design of this study with age-and sex-matched healthy controls. The evaluation of 12 or 24 h GH profiles has been suggested to be superior to stimulation tests (37,38), but this is still controversial (39).…”

Section: Cf-ngt Cf-dm Cf-ngt and Cf-dmmentioning

confidence: 99%

Normal spontaneous and stimulated GH levels despite decreased IGF-I concentrations in cystic fibrosis patients

Laursen¹,

Lanng

Rasmussen

et al. 1999

European Journal of Endocrinology

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Objective: The aim of the present study was to investigate whether patients with cystic fibrosis (CF) are GH resistant with increased GH release and decreased concentrations of IGF-I as a result of malabsorption, increased catabolism and impaired glucose tolerance. Design: Twenty CF patients were included, ten with normal glucose tolerance (five male, five female, median age 25.5 years (range 20-31)) and ten with diabetes mellitus (five male, five female, median age 25.3 years (range 17-45). Twenty healthy individuals served as controls (ten male, ten female, median age 28.4 years (range 18-36)). Methods: GH status was evaluated by 12 h spontaneous GH release during the night time, argininestimulated GH release and the basal concentrations of IGF-I and insulin-like growth factor-binding protein-3 (IGFBP-3). Twelve hour spontaneous GH profiles were estimated using a constant blood withdrawal technique with sampling every 30 min and the Pulsar method was used for the analysis of profiles. Results: No significant differences were found in spontaneous and stimulated GH release in CF patients compared with healthy controls, whereas IGF-I and IGFBP-3 were significantly decreased in CF patients compared with healthy controls. The combination of reduced IGF-I and IGFBP-3 with normal GH release points to a relative GH resistance or a disturbance in the pituitary axis in patients with CF. The spontaneous GH release, the stimulated GH release and the basal concentrations of IGF-I and IGFBP-3 were not significantly different in diabetic CF patients compared with CF patients with normal glucose tolerance and the presence of diabetes mellitus was not consistent with increased GH resistance in CF patients. Conclusion: CF patients with normal glucose tolerance and diabetic CF patients had normal GH release and decreased concentrations of IGF-I indicating a relative GH resistance.

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“…In particular, of the nine patients with an increment in height for BA in the first 3 years of therapy, as many as six (67%) exceeded target height and attained a final height SDS of ¹0.67 with a mean improvement vs CA height SDS measured at the start of therapy of 1.24 Ϯ 0.62. These findings, as well as the uncertainties in diagnosing GH deficiency (16,17,21), emphasize the importance of follow-up to evaluate yearly the height for BA in order to continue therapy only in those patients showing an improvement. A suspension of treatment and a deeper examination of the GH-insulinlike growth factor-I (IGF-I) axis (20,21) are indicated for those whose stature SDS worsens.…”

Section: All Patientsmentioning

confidence: 99%

“…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.…”

Section: Introductionmentioning

confidence: 99%

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

Cacciari

Cicognani

Pirazzoli

et al. 1997

European Journal of Endocrinology

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The aim of the present study was to evaluate retrospectively the influence of various auxological and laboratory parameters on final height in a group of GH-deficient children after replacement therapy and to compare their final height with that of a group of short children with normal GH secretion and hence not treated.The final height was evaluated of 83 patients (51 males and 32 females) affected by idiopathic isolated GH deficiency and treated with recombinant human GH (hGH) for 2-7 years. Inclusion criteria at the start of treatment were short stature (mean height for chronological age in standard deviation score (SDS) ¹2.21) due to idiopathic isolated GH deficiency (GH peak <8 mg/l after two pharmacological tests and/or mean GH concentration <3.3 mg/l during the night) and treatment with recombinant hGH for at least 2 years at a dose of 15-20 U/m 2 per week by s.c. injection for 6 or 7 days/ week. Mean chronological age at diagnosis was 12.2 Ϯ 1.7 years; 35 were prepubertal and 48 pubertal. The final height of 51 untreated short stature (mean height for chronological age in SDS ¹2.13 at diagnosis) subjects (42 males and 9 females; 29 prepubertal and 22 pubertal at diagnosis with mean chronological age 11.6 Ϯ 2.4 years) with normal GH secretion was also evaluated.In the treated subjects final height SDS was higher than that of the untreated group (¹1.3 vs ¹1.7 SDS; P ¼ 0.01). Both treated and untreated subjects showed a final height lower than target height, but 39% of the treated subjects vs only 20% of the untreated group (P ¼ 0.035) had a final height greater than target height. In the treated subjects this percentage was higher in the patients improving their height for bone age in the first years of therapy. While treated females showed a positive correlation only between target and final height (P ¼ 0.0001), in treated males final height correlated with the Bayley-Pinneau prediction at diagnosis, height for chronological age and bone age at diagnosis and target height. Patients who started therapy before puberty also showed these correlations with data calculated at the onset of puberty, together with a correlation with chronological age at the onset of puberty.When considering the influence of GH response at tests on final height, the percentage of subjects exceeding target height increased progressively according to the severity of the GH deficiency. There was no difference in height gain between the patients starting therapy before or during puberty. The height gain, however modest, obtained by our treated patients, the number of patients with final height greater than target height and the favourable comparison with the untreated short-stature subjects represent a promising result, which could be improved by personalizing treatment. European Journal of Endocrinology 137 53-60

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Reproducibility of Growth Hormone Testing Procedures: A Comparison between 24-hour Integrated Concentration and Pharmacological Stimulation

Cited by 117 publications

References 14 publications

Comparison Between Insulin-Like Growth Factor-I(IGF-I) and IGF Binding Protein-3(IGFBP-3) Measurement in the Diagnosis of Growth Hormone Deficiency.

Comparison Between Insulin-Like Growth Factor-I(IGF-I) and IGF Binding Protein-3(IGFBP-3) Measurement in the Diagnosis of Growth Hormone Deficiency.

Normal spontaneous and stimulated GH levels despite decreased IGF-I concentrations in cystic fibrosis patients

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

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