The shortened combined clonidine and arginine test for growth hormone deficiency is practical and specific: a diagnostic accuracy study
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Reem Al Khalifah
Abstract
Background: The growth hormone (GH) stimulation protocols for clonidine and arginine tests are non-standardized and can be lengthy. We examined the specificity of both tests using a shorter duration of timed samples: 90 min for clonidine and 60 min for arginine.
Methods: We retrospectively studied all children who had GH stimulation with clonidine and arginine to test for GH deficiency (GHD). We compared the diagnostic accuracy of both reference and new shortened test (index).
Results: We reviewed 243 charts (11.4±4.1 years old; 74.5% males). The combined reference test was performed on 159 children, 29 (18.3%) tested positive for GHD on the combined index test, Kappa 0.98, false positive rate 1 (0.8%), specificity 0.99, 95th CI (0.96–1), and p=1.0. The specificity of both the clonidine and arginine single index tests was 0.98%.
Conclusions: The shortened clonidine and arginine stimulation index tests have good specificity. This is a viable option for testing children for GHD.
Acknowledgments
We would like to thank Dr. Elise Mok for her help in the statistical analysis of the study.
Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.
Research funding: None declared.
Employment or leadership: None declared.
Honorarium: None declared.
Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.
References
1. Wilson TA, Rose SR, Cohen P, Rogol AD, Backeljauw P, et al. Update of guidelines for the use of growth hormone in children: The Lawson Wilkins Pediatric Endocrinology Society Drug and Therapeutics Committee. J Pediatr 2003;143: 415–21.10.1067/S0022-3476(03)00246-4Search in Google Scholar
2. Carrillo AA, Bao O. Hormonal dynamic tests and genetic tests used in pediatric endocrinology. In: Lifshitz F, editor. Pediatric endocrinology. 2. 5th ed. New York: Informa Healthcare, 2006:787.Search in Google Scholar
3. Consensus Guidelines for the Diagnosis and Treatment of Growth Hormone (GH) Deficiency in Childhood and Adolescence: Summary Statement of the GH Research Society. J Clin Endocrinol Metab 2000;85:3990–3.10.1210/jc.85.11.3990Search in Google Scholar
4. Galluzzi F, Quaranta MR, Salti R, Stagi S, Nanni L, et al. Diagnosis of growth hormone deficiency by using the arginine provocative test: is it possible to shorten testing time without altering validity? Horm Res 2009;72:142–5.10.1159/000232487Search in Google Scholar
5. Amed S, Delvin E, Hamilton J. Variation in growth hormone immunoassays in clinical practice in Canada. Horm Res 2008;69:290–4.10.1159/000114860Search in Google Scholar
6. Bossuyt PM, Reitsma JB, Bruns DE, Gatsonis CA, Glasziou PP, et al. The STARD statement for reporting studies of diagnostic accuracy: explanation and elaboration. Clin Chem 2003;49:7–18.10.1373/49.1.7Search in Google Scholar
7. Lindsay R, Feldkamp M, Harris D, Robertson J, Rallison M. Utah growth study: growth standards and the prevalence of growth hormone deficiency. J Pediatr 1994;125:29–35.10.1016/S0022-3476(94)70117-2Search in Google Scholar
8. Carley S, Dosman S, Jones S, Harrison M. Simple nomograms to calculate sample size in diagnostic studies. Emerg Med J 2005;22:180–1.10.1136/emj.2003.011148Search in Google Scholar PubMed PubMed Central
9. Harris PA, Taylor R, Thielke R, Payne J, Gonzalez N, et al. Research electronic data capture (REDCap) – a metadata-driven methodology and workflow process for providing translational research informatics support. J Biomed Inform 2009;42:377–81.10.1016/j.jbi.2008.08.010Search in Google Scholar PubMed PubMed Central
10. Rudolfer SM, Zhou X-H, Obuchowski NA, Mcclish DK. Statistical methods in diagnostic medicine. Biometrics 2003;59:203–4.10.1111/1541-0420.00266Search in Google Scholar
11. Cohen J. A coefficient of agreement for nominal scales. Educ Psychol Meas 1960;20:37–46.10.1177/001316446002000104Search in Google Scholar
12. Morris AH, Harrington MH, Churchill DL, Olshan JS. Growth hormone stimulation testing with oral clonidine: 90 minutes is the preferred duration for the assessment of growth hormone reserve. J Pediatr Endocrinol Metab 2001;14:1657–60.10.1515/JPEM.2001.14.9.1657Search in Google Scholar
13. Gil-Ad I, Topper E, Laron Z. Oral clonidine as a growth hormone stimulation test. Lancet 1979;2:278–9.10.1016/S0140-6736(79)90293-9Search in Google Scholar
14. Muster L, Zangen DH, Nesher R, Hirsch HJ, Muster Z, et al. Arginine and clonidine stimulation tests for growth hormone deficiency revisited – do we really need so many samples? J Pediatr Endocrinol Metab 2009;22:215–23.10.1515/JPEM.2009.22.3.215Search in Google Scholar PubMed
15. Mulherin SA, Miller WC. Spectrum bias or spectrum effect? Subgroup variation in diagnostic test evaluation. Ann Intern Med 2002;137:598–602.10.7326/0003-4819-137-7-200210010-00011Search in Google Scholar PubMed
16. Fraser NC, Seth J, Brown NS. Clonidine is a better test for growth hormone deficiency than insulin hypoglycaemia. Arch Dis Child 1983;58:355–8.10.1136/adc.58.5.355Search in Google Scholar PubMed PubMed Central
©2016 by De Gruyter
Articles in the same Issue
- Frontmatter
- Review
- Role of nutrition in preventing insulin resistance in children
- Original Articles
- Reduced frequency and severity of ketoacidosis at diagnosis of childhood type 1 diabetes in Northwest Saudi Arabia
- Differences in parental involvement in the care of children and adolescents with type 1 diabetes mellitus on multiple daily insulin injections versus continuous subcutaneous insulin infusion
- Value of the intrarenal arterial resistivity indices and different renal biomarkers for early identification of diabetic nephropathy in type 1 diabetic patients
- Remission of congenital hyperinsulinism following conservative treatment: an exploratory study in patients with KATP channel mutations
- Relationship between visceral obesity and plasma fibrinogen in obese children
- Diagnostic approach in children with unusual symptoms of acquired hypothyroidism. When to look for pituitary hyperplasia?
- The shortened combined clonidine and arginine test for growth hormone deficiency is practical and specific: a diagnostic accuracy study
- Bone maturation along the spectrum from normal weight to obesity: a complex interplay of sex, growth factors and weight gain
- Outcomes analysis of radioactive iodine and total thyroidectomy for pediatric Graves’ disease
- Direct sequencing of FAH gene in Pakistani tyrosinemia type 1 families reveals a novel mutation
- Odontoiatric perspectives and osteonecrosis of the jaw as a possible adverse effect of bisphosphonates therapy in fibrous dysplasia and McCune-Albright syndrome
- The relation of urinary bisphenol A with kisspeptin in girls diagnosed with central precocious puberty and premature thelarche
- Pattern of teen menstruation among secondary school girls in south east Nigeria
- Should children with isolated premature adrenarche be routinely evaluated for non-classical congenital adrenal hyperplasia?
- Anxiety, depression and self-esteem levels in obese children: a case-control study
- Case Reports
- Transient congenital hypothyroidism caused by compound heterozygous mutations affecting the NADPH-oxidase domain of DUOX2
- Isolated methylmalonic acidemia with unusual presentation mimicking diabetic ketoacidosis
- A first case report of UDP-galactose-4′-epimerase deficiency in China: genotype and phenotype
- A novel mutation in the glutamate dehydrogenase (GLUD1) of a patient with congenital hyperinsulinism-hyperammonemia (HI/HA)
- Letter to the Editor
- Partial biotinidase deficiency: identification of a single novel mutation (p.H314R) in a Greek newborn
Articles in the same Issue
- Frontmatter
- Review
- Role of nutrition in preventing insulin resistance in children
- Original Articles
- Reduced frequency and severity of ketoacidosis at diagnosis of childhood type 1 diabetes in Northwest Saudi Arabia
- Differences in parental involvement in the care of children and adolescents with type 1 diabetes mellitus on multiple daily insulin injections versus continuous subcutaneous insulin infusion
- Value of the intrarenal arterial resistivity indices and different renal biomarkers for early identification of diabetic nephropathy in type 1 diabetic patients
- Remission of congenital hyperinsulinism following conservative treatment: an exploratory study in patients with KATP channel mutations
- Relationship between visceral obesity and plasma fibrinogen in obese children
- Diagnostic approach in children with unusual symptoms of acquired hypothyroidism. When to look for pituitary hyperplasia?
- The shortened combined clonidine and arginine test for growth hormone deficiency is practical and specific: a diagnostic accuracy study
- Bone maturation along the spectrum from normal weight to obesity: a complex interplay of sex, growth factors and weight gain
- Outcomes analysis of radioactive iodine and total thyroidectomy for pediatric Graves’ disease
- Direct sequencing of FAH gene in Pakistani tyrosinemia type 1 families reveals a novel mutation
- Odontoiatric perspectives and osteonecrosis of the jaw as a possible adverse effect of bisphosphonates therapy in fibrous dysplasia and McCune-Albright syndrome
- The relation of urinary bisphenol A with kisspeptin in girls diagnosed with central precocious puberty and premature thelarche
- Pattern of teen menstruation among secondary school girls in south east Nigeria
- Should children with isolated premature adrenarche be routinely evaluated for non-classical congenital adrenal hyperplasia?
- Anxiety, depression and self-esteem levels in obese children: a case-control study
- Case Reports
- Transient congenital hypothyroidism caused by compound heterozygous mutations affecting the NADPH-oxidase domain of DUOX2
- Isolated methylmalonic acidemia with unusual presentation mimicking diabetic ketoacidosis
- A first case report of UDP-galactose-4′-epimerase deficiency in China: genotype and phenotype
- A novel mutation in the glutamate dehydrogenase (GLUD1) of a patient with congenital hyperinsulinism-hyperammonemia (HI/HA)
- Letter to the Editor
- Partial biotinidase deficiency: identification of a single novel mutation (p.H314R) in a Greek newborn
