scholarly journals Impact of IGF-1 Normative Datasets on Indication and Outcome of Growth Hormone Stimulation Testing

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A678-A679
Author(s):  
Prim de Bie ◽  
Annemieke C Heijboer ◽  
Martine M L Deckers

Abstract In the Netherlands, the diagnosis of growth hormone deficiency in children follows the Dutch national guidelines for Triage and Diagnosis of Growth Disorders in Children. Initial biochemical evaluation includes an IGF-1 measurement as screening parameter for growth hormone deficiency. Based on the clinical probability of growth hormone deficiency and the IGF-1 Z-score, a growth hormone stimulation test is performed if serum IGF-1 Z-score is < 0 SD in case of a high probability and if serum IGF-1 Z-score is < -1 SD in case of low probability. An IGF-1 Z-score > 0 SD virtually excludes a growth hormone deficiency disorder. The interpretation of growth hormone stimulation testing is dependent on both the peak growth hormone concentration, but also on the baseline IGF-1 Z-score, particularly in cases of partial deficiency. Although, nation wide, Dutch laboratories have harmonized their measurement for IGF-1 (as was previously done for growth hormone), a Dutch harmonized normative data set has not been widely adopted. Moreover a clinical evaluation of the implementation of this dataset based on dynamic testing has not been published. To assess the impact of choice of a particular normative dataset on the diagnosis of growth hormone deficiency we recalculated Z-scores of IGF-1 measurements between 2016 and 2019, using our home reference values based on de normative dataset by Elmlinger (E)1, and using the normative datasets defined by Bidlingmaier (B)2 and by the Dutch IGF-1 harmonization program (NL). Based on these three Z-scores, the outcomes of growth hormone stimulation tests performed in this period (n=86) were reassessed according to the interpretation described in the Dutch guideline. Using all three normative datasets the same 4 patients were identified as likely to have a growth hormone deficiency, whereas 10(E), 10(B), or 8(NL) patients were identified as possible partial growth hormone deficiency. In 70(E), 66(B) or 72(NL) patients the growth hormone stimulation test was unaffected. Using normative dataset B, 6 patients displayed a pattern associated with a possible growth hormone resistance, or of bio-inactive growth hormone syndromes, which based on its incidence would be unlikely for a secondary care setting. A striking observation was however, that of all patients with a normal stimulation test 9 (E)/16 (B) or 30 (NL) had a IGF-1 Z-score of > 0 SD. This implies that, for the diagnosis of growth hormone deficiency, it is safe to implement the Dutch harmonized dataset, which in addition could result in a reduction in the number of growth hormone stimulation tests that have to be performed. References: 1. Elmlinger MW et al. Clin Chem Lab Med. 2004;42(6):654-64. 2. Bidlingmaier M et al. J Clin Endocrinol Metab. 2014 May;99(5):1712-21.

2014 ◽  
Vol 27 (5) ◽  
pp. 587
Author(s):  
Jean-Pierre Gonçalves ◽  
Filipa Correia ◽  
Helena Cardoso ◽  
Teresa Borges ◽  
Maria João Oliveira

<p><strong>Introduction:</strong> The incidence of short stature associated with growth hormone deficiency has been estimated to be about 1:4000 to 1:10000. It is the main indication for treatment with recombinant growth hormone.<br /><strong>Objectives:</strong> The aims of the study were to evaluate the results of growth hormone stimulation tests and identify the growth hormone deficiency predictors.<br /><strong>Material and Methods:</strong> A cross-sectional, analytical and observational study was conducted. We studied all the children and adolescents submitted to growth hormone pharmacological stimulation tests between January 2008 and May 2012. Growth hormone deficiency diagnosis was confirmed by two negatives growth hormone stimulation tests (growth hormone peak &lt; 7 ng/ml). The statistical analysis was performed using student t-test, chi-square, Pearson correlation and logistic regression. Statistical significance determined at the 5% level (p ≤ 0.05).<br /><strong>Results:</strong> Pharmacological stimulation tests were performed in 89 patients, with a median age of 10 [3-17] years. Clonidine (n = 85) and insulin tolerance test (n = 4) were the first growth hormone stimulation tests performed. Growth hormone deficiency was confirmed in 22 cases. In cases with two growth hormone stimulation tests, the growth hormone peak showed a moderate correlation (r = 0.593, p = 0.01). In logistic regression model height (z-score) and the growth hormone peak in first stimulation test were predictors of growth hormone deficiency diagnosis (each one unit increase in z-score decrease the growth hormone deficiency probability).<br /><strong>Discussion:</strong> Measurement of IGF-1 cannot be used in diagnosing growth hormone deficiency.<br /><strong>Conclusion:</strong> Auxological criteria associated with a positive test seems to be a reliable diagnostic tool for growth hormone deficiency.</p><p><br /><strong>Keywords:</strong> Growth Disorders; Human Growth Hormone/blood.</p>


2013 ◽  
Vol 20 (03) ◽  
pp. 385-389
Author(s):  
MUHAMMAD NADEEM HAMEED ◽  
FAUZIA SADIQ ◽  
ASIM MUMTAZ ◽  
Hina Mohiuddin ◽  
Sana Khan ◽  
...  

Introduction: Despite the use of growth hormone replacement therapy for decades, our ability to make a definitive diagnosisof growth hormone deficiency in children is limited. Growth hormone stimulation tests have been used to discriminate between Growthhormone deficiency and idiopathic short stature. However all these tests lack reproducibility, accuracy, cost affectivity and safety. Insulinlikegrowth factor-1 is an effector hormone and its serum level may be used as simple, easy to perform diagnostic test for growthhormone deficiency. Objective: To determine the efficacy of IGF-1 as a diagnostic tool in children with growth hormone deficiency. StudyDesign: Prospective cross sectional survey. Place of Study: Departments of Pediatrics and Pathology, Shalamar Medical & DentalCollege, Lahore. Duration of study: 1st July to 31st December, 2011. Material & Methods: We included 40 children of 3.5 – 17 year ageand detailed clinical data was collected. All these children were subjected to stimulation by standardized exercise on treadmill, after takingbasal blood samples for GH and IGF-1. Post stimulation growth hormone was recorded to identify growth hormone deficient children.Results: 17 (42.5%) children had post stimulation growth hormone level <10ng/ml while 23 (57.5%) had values >10ng/ml. Postexercise stimulation GH level showed weak correlation with IGF-1 in either of the two study groups. P value was found >0.05 in deficientas well as sufficient groups, depicting non significance of IGF-1 in relation to post stimulation GH level. Conclusions: IGF-1 is not asuitable surrogate diagnostic marker for growth hormone deficiency. Diagnosis should always be based on combination of auxologicalbiochemical, radiological and genetic considerations, Abbreviations: GHD – Growth Hormone Deficiency, GH – Growth Hormone,GHSTs – Growth Hormone Stimulation Tests, IGF-1 – Insulin-like Growth Factor-1, MPH – Mid Parental Height, BA – Bone Age.


2018 ◽  
Vol 64 (4) ◽  
pp. 151-156
Author(s):  
Iulia Armean ◽  
Raluca Pop ◽  
Iuliana Gherlan ◽  
Ionela Pașcanu

AbstractObjective: The objective of this study was to analyze the performance of 2 stimulation tests used in the diagnosis of growth hormone deficiency.Method: A retrospective study was conducted on a non-random sample of 310 patients, between 2 and 20 years old, who were hospitalized in the Mureș County Hospital’s Endocrinology Department and in the National Institute of Endocrinology C.I. Parhon with short stature between 2009-2015. Inclusion criteria: all subjects who underwent growth hormone stimulation tests in accordance with the national protocol. Microsoft Office Excel was used for data collection and MedCalc v 12.5 was used for statistical analysis.Results: From the total of 310 patients, 102 were diagnosed in Târgu Mureș and 208 in Bucharest. Sex ratio favored boys (boys:girls 1.64:1). In 173 subjects growth hormone deficiency was confirmed. For both tests the percentage of maximum response was the highest for the 60 minutes blood sample regardless if the test were positive or not. Both tests have 100% sensitivity and negative predictive value, with the highest specificity for the 60 minutes clonidine and 30 minutes insulin. The false positive rate was 60% for the insulin test and 27.2% for clonidine for Târgu Mureș sample and 86.9% for the insulin test and 62.5% for clonidine for Bucharest sample. The concordance of the 2 tests was 49.36%.Conclusions: Stimulating growth hormone testing has a number of limitations but is still needed in some auxological circumstances. We recommend performing the clonidine test first to exclude idiopathic short stature and then the insulin tolerance test for the diagnosis of growth hormone deficiency.


Author(s):  
George M Bright ◽  
Peter A Morris ◽  
Ron G Rosenfeld

Given the low prevalence rate of growth hormone deficiency (GHD) and the high false positive rates for growth hormone stimulation tests, the probability of GHD in a child with short stature and positive growth hormone stimulation tests is 0.028 (about 1 in 36). Without further information, most positive growth hormone stimulation tests will be false positives. Further study may yield the necessary improvements in the diagnostic accuracy for GHD in children.


2021 ◽  
Vol 12 ◽  
Author(s):  
Regis Coutant ◽  
Jordi Bosch Muñoz ◽  
Cristina Patricia Dumitrescu ◽  
Dirk Schnabel ◽  
Caroline Sert ◽  
...  

ObjectiveThe International Cooperative Growth Study, NutropinAq® European Registry (iNCGS) (NCT00455728) monitored long-term safety and effectiveness of recombinant human growth hormone (rhGH; NutropinAq® [somatropin]) in paediatric growth disorders.MethodsOpen-label, non-interventional, post-marketing surveillance study recruiting children with growth disorders. Endpoints included gain in height standard deviation score (SDS), adult height, and occurrence of adverse events (AEs).Results2792 patients were enrolled. 2082 patients (74.6%) had growth hormone deficiency (GHD), which was isolated idiopathic in 1825 patients (87.7%). Non-GHD diagnoses included Turner syndrome (TS) (n=199), chronic renal insufficiency (CRI) (n=10), other non-GHD (n=498), and missing data for three participants. Improvements from baseline height SDS occurred at all time points to Month 132, and in all subgroups by disease aetiology. At Month 12, mean (95% CI) change in height SDS by aetiology was: idiopathic GHD 0.63 (0.61;0.66), organic GHD 0.71 (0.62;0.80), TS 0.59 (0.53; 0.65), CRI 0.54 (-0.49;1.56), and other non-GHD 0.64 (0.59;0.69). Mean height ( ± SD) at the last visit among the 235 patients with adult or near-adult height recorded was 154.0 cm ( ± 8.0) for girls and 166.7 cm ( ± 8.0) for boys. The most frequent biological and clinical non-serious drug-related AEs were increased insulin-like growth factor concentrations (314 events) and injection site haematoma (99 events). Serious AEs related to rhGH according to investigators were reported (n=30); the most frequent were scoliosis (4 events), epiphysiolysis (3 events), and strabismus (2 events).ConclusionsThere was an improvement in mean height SDS in all aetiology subgroups after rhGH treatment. No new safety concerns were identified.


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