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LETTER TO THE EDITOR
Year : 2014  |  Volume : 3  |  Issue : 3  |  Page : 214-215

Insulin-like growth factor-1 generation test: A marker of growth hormone sensitivity


1 Prime Hospital, KPHB, Hyderabad, Andhra Pradesh, India
2 ESI Hospital, Hyderabad, Andhra Pradesh, India
3 Care Hospital, Hyderabad, Andhra Pradesh, India

Date of Web Publication17-Sep-2014

Correspondence Address:
Mounika Guntaka
Flat No-A 904, Sri Sai Ram Towers, Beside Alwyn Colony Water Tank, Hafeezpet, Hyderabad - 500 049. Andhra Pradesh
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/2277-8632.140954

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How to cite this article:
Guntaka M, Hanmayyagari B, Srinagesh. Insulin-like growth factor-1 generation test: A marker of growth hormone sensitivity. J NTR Univ Health Sci 2014;3:214-5

How to cite this URL:
Guntaka M, Hanmayyagari B, Srinagesh. Insulin-like growth factor-1 generation test: A marker of growth hormone sensitivity. J NTR Univ Health Sci [serial online] 2014 [cited 2020 Apr 1];3:214-5. Available from: http://www.jdrntruhs.org/text.asp?2014/3/3/214/140954

Sir,

Insulin-like growth factor-1 generation test (IGFGT-1) was developed 30 years ago, [1],[2] primarily to differentiate growth hormone insensitivity (GHI) from other disorders characterized by low serum IGF-1. Like other endocrine stimulation tests, the IGFGT measures hormonal production in response to stimulation by a pituitary trophic factor. It is an easy test to perform on an out-patient basis and can identify growth hormone deficiency children who will benefit from human growth hormone (hGH) treatment. The major limitations have included variability in protocols for administration of GH, timing of samples, differences in IGF assay methodologies and lack of adequate normative data. [3] One of the most widely used is the "standard IGFGT," which is performed over 5 days and requires four recombinant hGH (rhGH) injections (33 μg/kg/day). [4] In several studies in the 1990s, the diagnosis of severe GHI syndrome was based presumptively on a scoring system that included the standard IGFGT, However, from these initial studies, cut-off values were arbitrarily defined as twice the intra-assay coefficient of variation [5] or an absolute IGF-1 increment of 15 ng/ml indicating GH sensitivity. [6] Blum also suggested that measuring IGF binding protein-3 (IGFBP-3) levels may improve the significance of the test, with an arbitrary cut-off of 0.4 mg/l for the absolute IGFBP-3 increment. [6]

A 12-year-old boy presented to the endocrinology department with the complaint of short stature. History revealed that he was born of a non-consanguineous marriage, full term, delivered by cesarean section. His birth weight was 2.5 kg, milestones were normal and he was shorter than his peers all these years and there was no history of chronic systemic disease. On examination, height was 118 cm, upper segment/lower segment ratio -0.9, standard deviation score was -5, weight 20 kg, he had no dysmorphic features and sexual maturity rating was prepubertal. Routine laboratory investigations including complete blood picture, erythrocyte sedimentation rate, serum proteins and thyroid profile were normal; his bone age was 8 years. GH dynamics with clonidine stimulation resulted in a peak GH of 18 ng/ml and IGF-1 was 80 ng/ml (183-850). This is suggestive of GHI.

Then we did an IGFGT-1 in this child to distinguish insensitivity to GH or from other disorders characterized by low serum IGF-1, as basal serum levels of GH or IGF-1 has proven to be problematic, because biochemical profiles frequently overlap in these above conditions. [7]

The 5-day IGF-1 generation was performed in Department of Biochemistry, where blood samples were obtained for IGF-1 prior to the test and human GH was administered daily for 4 days subcutaneously at a dose of 33 μg/kg/day. IGF-1 sampling done 12 h after the last GH injection. All samples were placed on ice, immediately centrifuged in a refrigerated centrifuge and stored at -70°C until tested. The basal IGF-1 was 80 ng/ml, stimulated value was 220 ng/ml suggestive of GH sensitivity in this child. In case of GH insensitivity, the IGF-1 response during the IGF-1 generation is diminished, whereas in the case of GH deficiency it is enhanced; in idiopathic short-stature (ISS) the responses are variable reflecting the heterogeneity in the etiology of ISS. So this child is possibly having GH deficiency and rhGH was initiated with a dose of 0.3 mg/kg/week. He gained 7 cm in height after 6 months of treatment, response again proving GH deficiency in this child.

To conclude, in our routine clinical practice the assessment of GH secretion is done primarily by pharmacologic provocation of GH release. But pharmacologic provocation alone may sometimes be misleading and the diagnosis can be missed, in such instances the IGFGT-I is useful in differentiating children from GH insensitivity and GH sensitivity.


  Acknowledgements Top


We sincerely thankful for Pfizer Company for their unconditional support in providing required growth hormone to carry out this test.

 
  References Top

1.Copeland KC, Underwood LE, Van Wyk JJ. Induction of immunoreactive somatomedin C human serum by growth hormone: Dose-response relationships and effect on chromatographic profiles. J Clin Endocrinol Metab 1980;50:690-7.  Back to cited text no. 1
[PUBMED]    
2.Rudman D, Kutner MH, Blackston RD, Cushman RA, Bain RP, Patterson JH. Children with normal-variant short stature: Treatment with human growth hormone for six months. N Engl J Med 1981;305:123-31.  Back to cited text no. 2
[PUBMED]    
3.Schwarze CP, Wollmann HA, Binder G, Ranke MB. Short-term increments of insulin-like growth factor I (IGF-I) and IGF-binding protein-3 predict the growth response to growth hormone (GH) therapy in GH-sensitive children. Acta Paediatr Suppl 1999;88:200-8.  Back to cited text no. 3
    
4.Savage MO, Blum WF, Ranke MB, Postel-Vinay MC, Cotterill AM, Hall K, et al. Clinical features and endocrine status in patients with growth hormone insensitivity (Laron syndrome). J Clin Endocrinol Metab 1993;77:1465-71.  Back to cited text no. 4
    
5.Wit JM, Camacho-Hübner C. Endocrine regulation of longitudinal bone growth. Endocr Dev 2011;21:30-41.  Back to cited text no. 5
    
6.Blum WF, Cotterill AM, Postel-Vinay MC, Ranke MB, Savage MO, Wilton P. Improvement of diagnostic criteria in growth hormone insensitivity syndrome: Solutions and pitfalls. Pharmacia study group on insulin-like growth factor I treatment in growth hormone insensitivity syndromes. Acta Paediatr Suppl 1994;399:117-24.  Back to cited text no. 6
    
7.Rosenfeld RG, Albertsson-Wikland K, Cassorla F, Frasier SD, Hasegawa Y, Hintz RL, et al. Diagnostic controversy: The diagnosis of childhood growth hormone deficiency revisited. J Clin Endocrinol Metab 1995;80:1532-40.  Back to cited text no. 7
    




 

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