Early Retesting by GHRH + arginine Test Shows Normal GH Response in Most Children with Idiopathic GH Deficiency

Overview

Journal J Endocrinol Invest

Publisher Springer

Specialty Endocrinology

Date 2014 Nov 8

PMID 25376365

Citations 4

Authors

C Bizzarri

S Pedicelli

B Boscherini

G Bedogni

M Cappa

S Cianfarani

Affiliations

Soon will be listed here.

Abstract

Purpose: Most children with idiopathic isolated GH deficiency (IGHD) normalize GH response to stimulation tests when retested at the completion of growth. The objective of this study was to test the effectiveness of early retesting in challenging the diagnosis of idiopathic IGHD and critically review the diagnostic workup leading to this diagnosis in children with short stature.

Methods: We cross-sectionally retested 38 children with idiopathic IGHD and still on GH treatment. The initial diagnosis of idiopathic IGHD was based on subnormal GH responses to two stimulation tests and normal brain imaging or minor/nonspecific findings at magnetic resonance. The GH response normalization at retesting was considered as the main outcome measure. Clinical features of children who were falsely classified as idiopathic IGHD based on first GH testing were retrospectively analyzed.

Results: GH secretion was normal in 36/38 children (95%). Two children showed slightly reduced peak GH responses and normal IGF-I levels. Fourteen children underwent GH retesting before puberty, 24 children during puberty.

Conclusion: The diagnostic process should be improved to minimize the rate of false positive at GH testing and, in case of unsatisfactory response to GH treatment, the diagnosis of isolated idiopathic GHD should be challenged with early retesting.

Citing Articles

Transient Isolated, Idiopathic Growth Hormone Deficiency-A Self-Limiting Pediatric Disease with Male Predominance or a Diagnosis Based on Uncertain Criteria? Lesson from 20 Years' Real-World Experience with Retesting at One Center.

Smyczynska J, Hilczer M, Smyczynska U, Lewinski A, Stawerska R Int J Mol Sci. 2024; 25(11).

PMID: 38891927 PMC: 11171613. DOI: 10.3390/ijms25115739.

Effectiveness, economical and safety aspects of growth hormone (GH) therapy in growth promoting doses in patients with isolated GH deficiency after the attainment of near-final height. Is there a need to modify the criteria of therapy withdrawal?.

Smyczynska J, Hilczer M, Lewinski A, Smyczynska U, Stawerska R Pediatr Endocrinol Diabetes Metab. 2022; 27(4):258-265.

PMID: 35114767 PMC: 10226357. DOI: 10.5114/pedm.2021.112694.

A Proposal for the Interpretation of Serum IGF-I Concentration as Part of Laboratory Screening in Children with Growth Failure.

Wit J, Bidlingmaier M, de Bruin C, Oostdijk W J Clin Res Pediatr Endocrinol. 2019; 12(2):130-139.

PMID: 31842524 PMC: 7291410. DOI: 10.4274/jcrpe.galenos.2019.2019.0176.

Pre-treatment growth and IGF-I deficiency as main predictors of response to growth hormone therapy in neural models.

Smyczynska U, Smyczynska J, Hilczer M, Stawerska R, Tadeusiewicz R, Lewinski A Endocr Connect. 2017; 7(1):239-249.

PMID: 29242356 PMC: 5793807. DOI: 10.1530/EC-17-0277.

References

Marin G, Domene H, Barnes K, Blackwell B, Cassorla F, Cutler Jr G . The effects of estrogen priming and puberty on the growth hormone response to standardized treadmill exercise and arginine-insulin in normal girls and boys. J Clin Endocrinol Metab. 1994; 79(2):537-41. DOI: 10.1210/jcem.79.2.8045974. View

Mitchell H, Dattani M, Nanduri V, Hindmarsh P, Preece M, Brook C . Failure of IGF-I and IGFBP-3 to diagnose growth hormone insufficiency. Arch Dis Child. 1999; 80(5):443-7. PMC: 1717917. DOI: 10.1136/adc.80.5.443. View

. Consensus guidelines for the diagnosis and treatment of growth hormone (GH) deficiency in childhood and adolescence: summary statement of the GH Research Society. GH Research Society. J Clin Endocrinol Metab. 2000; 85(11):3990-3. DOI: 10.1210/jcem.85.11.6984. View

Bellone J, Aimaretti G, Bellone S, Baffoni C, Corneli G, Origlia C . Sequential administration of arginine and arginine plus GHRH to test somatotroph function in short children. J Endocrinol Invest. 2000; 23(2):97-101. DOI: 10.1007/BF03343686. View

Tauber M, Moulin P, Pienkowski C, Jouret B, Rochiccioli P . Growth hormone (GH) retesting and auxological data in 131 GH-deficient patients after completion of treatment. J Clin Endocrinol Metab. 1997; 82(2):352-6. DOI: 10.1210/jcem.82.2.3726. View

Geffner M, Dunger D . Future directions: growth prediction models. Horm Res. 2008; 68 Suppl 5:51-6. DOI: 10.1159/000110476. View

Wu R, St Louis Y, DiMartino-Nardi J, Wesoly S, SOBEL E, Sherman B . Preservation of physiological growth hormone (GH) secretion in idiopathic short stature after recombinant GH therapy. J Clin Endocrinol Metab. 1990; 70(6):1612-5. DOI: 10.1210/jcem-70-6-1612. View

Bang P, Ahmed S, Argente J, Backeljauw P, Bettendorf M, Bona G . Identification and management of poor response to growth-promoting therapy in children with short stature. Clin Endocrinol (Oxf). 2012; 77(2):169-81. DOI: 10.1111/j.1365-2265.2012.04420.x. View

Ghigo E, Bellone J, Aimaretti G, Bellone S, Loche S, Cappa M . Reliability of provocative tests to assess growth hormone secretory status. Study in 472 normally growing children. J Clin Endocrinol Metab. 1996; 81(9):3323-7. DOI: 10.1210/jcem.81.9.8784091. View

10.

Tanner J, Goldstein H, Whitehouse R . Standards for children's height at ages 2-9 years allowing for heights of parents. Arch Dis Child. 1970; 45(244):755-62. PMC: 1647404. DOI: 10.1136/adc.45.244.755. View

11.

Maghnie M, Ghirardello S, Genovese E . Magnetic resonance imaging of the hypothalamus-pituitary unit in childrensuspected of hypopituitarism: who, how and when toinvestigate. J Endocrinol Invest. 2004; 27(5):496-509. DOI: 10.1007/BF03345298. View

12.

Loche S, Bizzarri C, Maghnie M, Faedda A, Tzialla C, Autelli M . Results of early reevaluation of growth hormone secretion in short children with apparent growth hormone deficiency. J Pediatr. 2002; 140(4):445-9. DOI: 10.1067/mpd.2002.122729. View

13.

Longobardi S, Merola B, Pivonello R, Di Rella F, Di Somma C, Colao A . Reevaluation of growth hormone (GH) secretion in 69 adults diagnosed as GH-deficient patients during childhood. J Clin Endocrinol Metab. 1996; 81(3):1244-7. DOI: 10.1210/jcem.81.3.8772606. View

14.

Aimaretti G, Baffoni C, Bellone S, Di Vito L, Corneli G, Arvat E . Retesting young adults with childhood-onset growth hormone (GH) deficiency with GH-releasing-hormone-plus-arginine test. J Clin Endocrinol Metab. 2000; 85(10):3693-9. DOI: 10.1210/jcem.85.10.6858. View

15.

Cacciari E, Milani S, Balsamo A, Dammacco F, De Luca F, Chiarelli F . Italian cross-sectional growth charts for height, weight and BMI (6-20 y). Eur J Clin Nutr. 2002; 56(2):171-80. DOI: 10.1038/sj.ejcn.1601314. View

16.

Barth J, Smith J, Clarkson P . Wide diversity in measurements of growth hormone after stimulation tests in short children are due to assay variability. Ann Clin Biochem. 1995; 32 ( Pt 4):369-72. DOI: 10.1177/000456329503200403. View

17.

Marshall W, Tanner J . Variations in pattern of pubertal changes in girls. Arch Dis Child. 1969; 44(235):291-303. PMC: 2020314. DOI: 10.1136/adc.44.235.291. View

18.

Maghnie M, Strigazzi C, Tinelli C, Autelli M, Cisternino M, Loche S . Growth hormone (GH) deficiency (GHD) of childhood onset: reassessment of GH status and evaluation of the predictive criteria for permanent GHD in young adults. J Clin Endocrinol Metab. 1999; 84(4):1324-8. DOI: 10.1210/jcem.84.4.5614. View

19.

Tanner J, Whitehouse R . Clinical longitudinal standards for height, weight, height velocity, weight velocity, and stages of puberty. Arch Dis Child. 1976; 51(3):170-9. PMC: 1545912. DOI: 10.1136/adc.51.3.170. View

20.

Ranke M, Lindberg A, Chatelain P, Wilton P, Cutfield W, Albertsson-Wikland K . Derivation and validation of a mathematical model for predicting the response to exogenous recombinant human growth hormone (GH) in prepubertal children with idiopathic GH deficiency. KIGS International Board. Kabi Pharmacia International Growth.... J Clin Endocrinol Metab. 1999; 84(4):1174-83. DOI: 10.1210/jcem.84.4.5634. View