scholarly journals When is a positive test for pediatric growth hormone deficiency a true positive test?

2021 ◽  
Author(s):  
George M Bright ◽  
Peter A Morris ◽  
Ron G Rosenfeld
Keyword(s):  
Growth Hormone ◽  
Diagnostic Accuracy ◽  
Growth Hormone Deficiency ◽  
Positive Test ◽  
Hormone Deficiency ◽  
True Positive ◽  
Hormone Stimulation ◽  
Positive Growth ◽  
Stimulation Tests ◽  
Low Prevalence

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.

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
Keyword(s):  
Growth Hormone ◽  
Growth Hormone Deficiency ◽  
Stimulation Test ◽  
Hormone Deficiency ◽  
Growth Disorders ◽  
Z Score ◽  
Hormone Stimulation ◽  
Stimulation Tests ◽  
Z Scores ◽  
The Impact

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.

scholarly journals GROWTH HORMONE ESTIMATION;

2013 ◽  
Vol 20 (03) ◽  
pp. 385-389
Author(s):  
MUHAMMAD NADEEM HAMEED ◽  
FAUZIA SADIQ ◽  
ASIM MUMTAZ ◽  
Hina Mohiuddin ◽  
Sana Khan ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Growth Hormone Deficiency ◽  
Hormone Replacement ◽  
Growth Hormone Level ◽  
Hormone Deficiency ◽  
P Value ◽  
Cross Sectional Survey ◽  
Cross Sectional ◽  
Hormone Stimulation ◽  
Stimulation Tests

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.

scholarly journals New Insights in Growth Hormone Stimulation Tests Protocols

2018 ◽  
Vol 64 (4) ◽  
pp. 151-156
Author(s):  
Iulia Armean ◽  
Raluca Pop ◽  
Iuliana Gherlan ◽  
Ionela Pașcanu
Keyword(s):  
Growth Hormone ◽  
Growth Hormone Deficiency ◽  
Short Stature ◽  
False Positive Rate ◽  
Tolerance Test ◽  
Hormone Deficiency ◽  
Hormone Stimulation ◽  
Stimulation Tests ◽  
Insulin Test ◽  
Microsoft Office

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.

scholarly journals O Papel dos Testes de Estimulação Farmacológica no Diagnóstico da Deficiência de Hormona do Crescimento em Crianças e Adolescentes

2014 ◽  
Vol 27 (5) ◽  
pp. 587
Author(s):  
Jean-Pierre Gonçalves ◽  
Filipa Correia ◽  
Helena Cardoso ◽  
Teresa Borges ◽  
Maria João Oliveira
Keyword(s):  
Growth Hormone ◽  
Logistic Regression ◽  
Growth Hormone Deficiency ◽  
Hormone Deficiency ◽  
Growth Disorders ◽  
Z Score ◽  
Hormone Stimulation ◽  
Growth Hormone Peak ◽  
Pharmacological Stimulation ◽  
Stimulation Tests

<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>

scholarly journals Insulin-like growth factor-1 level is a poor diagnostic indicator of growth hormone deficiency

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Hideyuki Iwayama ◽  
Sachiko Kitagawa ◽  
Jyun Sada ◽  
Ryosuke Miyamoto ◽  
Tomohito Hayakawa ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Growth Factor ◽  
Diagnostic Accuracy ◽  
Growth Hormone Deficiency ◽  
Screening Test ◽  
Characteristic Curve ◽  
Hormone Deficiency ◽  
Height Velocity ◽  
Insulin Like Growth Factor ◽  
Predictive Values

AbstractWe evaluated the diagnostic accuracy of insulin-like growth factor-1 (IGF-1) for screening growth hormone deficiency (GHD) to determine the usefulness of IGF-1 as a screening test. Among 298 consecutive children who had short stature or decreased height velocity, we measured IGF-1 levels and performed growth hormone (GH) secretion test using clonidine, arginine, and, in cases with different results of the two tests, L-dopa. Patients with congenital abnormalities were excluded. GHD was defined as peak GH ≤ 6.0 ng/mL in the two tests. We identified 60 and 238 patients with and without GHD, respectively. The mean IGF-1 standard deviation (SD) was not significantly different between the GHD and non-GHD groups (p = 0.23). Receiver operating characteristic curve analysis demonstrated the best diagnostic accuracy at an IGF-1 cutoff of − 1.493 SD, with 0.685 sensitivity, 0.417 specificity, 0.25 positive and 0.823 negative predictive values, and 0.517 area under the curve. Correlation analysis revealed that none of the items of patients’ characteristics increased the diagnostic power of IGF-1. IGF-1 level had poor diagnostic accuracy as a screening test for GHD. Therefore, IGF-1 should not be used alone for GHD screening. A predictive biomarker for GHD should be developed in the future.

A Review of Growth Hormone Stimulation Tests in Children

PEDIATRICS ◽  
1974 ◽  
Vol 53 (6) ◽  
pp. 929-937
Author(s):  
S. Douglas Frasier
Keyword(s):  
Growth Hormone ◽  
Growth Hormone Deficiency ◽  
Hormone Deficiency ◽  
Current Evidence ◽  
Oral Glucose ◽  
Normal Children ◽  
Small Magnitude ◽  
Arginine Infusion ◽  
Sequential Administration ◽  
Stimulation Tests

No suggested screening test meets all of the criteria set for such a procedure. The minimum incidence of a positive response in normal children detected in a single blood sample after diethylstilbestrol, sleep or exercise is approximately 70%. This is higher than that observed when a single sample is obtained following oral glucose. While both sleep and exercise are physiologic stimuli, the former may be quite inconvenient unless an outpatient facility staffed with appropriate personnel is available. An exercise test employed in the office may well be the best screening procedure for the practicing physician. The optimal criteria for a definitive test of growth hormone function are also not met by any single stimulus. Insulin-induced hypoglycemia, arginine infusion, intramuscular glucagon and oral 1-DOPA are all useful procedures. None alone discriminate completely between the normal and the growth hormone-deficient child. Despite potential hazards, insulin-induced hypoglycemia remains the standard against which other stimuli are judged. Arginine and 1-DOPA appear to be equally effective. The literature contains insufficient data to allow adequate evaluation of intramuscular glucagon alone, and the results of combined propranolol-glucagon stimulation, while promising, require confirmation. Because of an inconstant and/or small magnitude of response leading to results which are difficult to interpret, the use of glucose, pyrogen, vasopressin and ACTH are not adequate tests of growth hormone function. Bovril® is a satisfactory stimulus for those children who will take it. Those factors which modify the growth hormone response must be considered in evaluating the results of stimulation tests. Blunted responses should be interpreted with extreme caution in the obese child. A fasting growth hormone concentration ≥ 7 ng/ml is presumptive evidence of intact growth hormone function regardless of the subsequent response to stimulation. It is essential that patients be euthyroid in order to interpret the results of growth hormone function tests. Physiologic glucocorticoid replacement therapy should not confuse the interpretation of results. Whether or not pretreatment with sex steroids is worthwhile in the routine evaluation of children for suspected growth hormone deficiency is an open question. Although it is agreed that the definitive diagnosis of growth hormone deficiency depends on the demonstration of failure to respond to two stimuli, which two are most satisfactory is not settled. The sequential administration of arginine and insulin on the same day appears to limit significantly the incidence of false-positive laboratory diagnoses of growth hormone deficiency. The significance of intermediate values in response to stimulation remains unclear. Caution should be exercised in assigning a child to the category of partial growth hormone deficiency. This question must be answered ultimately by the response to HGH therapy in the individual patient. Finally, several points should be kept in mind. All of the tests described depend on the detection and quantitation of immunologically active HGH and biological activity is not necessarily associated with the material(s) being measured. Since many of the stimuli used in the evaluation of growth hormone function are clearly pharmacologic, the physiological significance of the response to such stimuli must be interpreted with caution. The best current evidence suggests that all of the stimuli described act through an intact hypothalamus and pituitary. Differentiation between hypothalamic and pituitary sites of defective growth hormone function awaits the availability of growth hormone-releasing factor(s).

Diagnostic accuracy of IGF-1 for screening growth hormone deficiency: a prospective, single-center, diagnostic accuracy study

2021 ◽  
Author(s):  
Hideyuki Iwayama ◽  
Sachiko Kitagawa ◽  
Jyun Sada ◽  
Ryosuke Miyamoto ◽  
Tomohito Hayakawa ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Diagnostic Accuracy ◽  
Growth Hormone Deficiency ◽  
Predictive Value ◽  
Screening Test ◽  
Characteristic Curve ◽  
Area Under The Curve ◽  
Rank Correlation ◽  
Hormone Deficiency ◽  
Height Velocity

Abstract Purpose We evaluated the diagnostic accuracy of insulin-like growth factor-1 (IGF-1) for screening growth hormone deficiency (GHD) to determine the usefulness of IGF-1 as a screening test. Methods On 298 consecutive children who had short stature or decreased height velocity, we measured IGF-1 levels and performed growth hormone (GH) secretion test using clonidine, arginine, and, in cases with different results of the two tests, L-dopa. Patients with congenital abnormalities were excluded. GHD was defined as peak GH ≤ 6.0 ng/mL in the two tests. Results We identified 60 and 238 patients with and without GHD, respectively. The mean IGF-1 (SD) was not significantly different between the GHD and non-GHD groups (p = 0.23). Receiver operating characteristic curve analysis demonstrated the best diagnostic accuracy at an IGF-1 cutoff of −1.493 SD, with sensitivity of 0.685, specificity of 0.417, positive predictive value of 0.25, negative predictive value of 0.823, and area under the curve of 0.517. Spearman’s rank correlation coefficient showed that IGF-1 (SD) was weakly correlated with age, bone age, height velocity before examination, weight (SD), and BMI (SD) and very weakly correlated with height (SD), target height (SD), and maximum GH peak. Conclusion IGF-1 level had poor diagnostic accuracy as a screening test for GHD. Correlation analysis revealed that none of the items increased the diagnostic power of IGF-1. Therefore, IGF-1 should not be used alone in the screening of GHD. A predictive biomarker for GHD should be developed in the future.

scholarly journals Isolated growth hormone deficiency presenting with recurrent hypoglycaemia in a toddler

2019 ◽  
Vol 12 (7) ◽  
pp. e231056
Author(s):  
Hiya Boro ◽  
Alpesh Goyal ◽  
Rajesh Khadgawat
Keyword(s):  
Growth Hormone ◽  
Growth Hormone Deficiency ◽  
Hormone Deficiency ◽  
Laboratory Evaluation ◽  
Age Group ◽  
Metabolic Defects ◽  
Stimulation Tests ◽  
Work Up ◽  
Detailed Work ◽  
In Infants And Children

Hypoglycaemia in infants and children is caused by a number of endocrine and metabolic defects, some of which are unique to this age group. Growth hormone deficiency (GHD) has been rarely reported as a cause of recurrent fasting hypoglycaemia in children. An 18-month-old male child presented to us for evaluation of neuroglycopenic symptoms caused by recurrent episodes of fasting hypoglycaemia. Laboratory evaluation revealed ketotic hypoinsulinaemic hypoglycaemia. The child was diagnosed to have GHD on the basis of two failed stimulation tests. A detailed work-up for metabolic and other hormonal causes of hypoglycaemia was negative. We present the case for its rarity and to highlight the importance of a detailed metabolic and hormonal assessment in evaluation of childhood hypoglycaemia.

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