Controversies in the Definition and Treatment of Idiopathic Short Stature (ISS)

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Abstract

The term idiopathic short stature (ISS) refers to short children with no identifiable disorder of the growth hormone (GH)/insulin like growth factor (IGF) axis and no other endocrine, genetic or organ system disorder. This heterogeneous group of short children without GH deficiency (GHD) includes children with constitutional delay of growth and puberty, familial short stature, or both, as well as those with subtle cartilage and bone dysplasias. In rare cases, ISS is due to IGF molecular abnormalities. In this review we tackle the major challenges in the definition and treatment of ISS.

Conflict of interest:None declared.

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Most cited references 43

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Consensus statement on the diagnosis and treatment of children with idiopathic short stature: a summary of the Growth Hormone Research Society, the Lawson Wilkins Pediatric Endocrine Society, and the European Society for Paediatric Endocrinology Workshop.

P. Cohen, A Rogol, C L Deal … (2008)

Our objective was to summarize important advances in the management of children with idiopathic short stature (ISS). Participants were 32 invited leaders in the field. Evidence was obtained by extensive literature review and from clinical experience. Participants reviewed discussion summaries, voted, and reached a majority decision on each document section. ISS is defined auxologically by a height below -2 sd score (SDS) without findings of disease as evident by a complete evaluation by a pediatric endocrinologist including stimulated GH levels. Magnetic resonance imaging is not necessary in patients with ISS. ISS may be a risk factor for psychosocial problems, but true psychopathology is rare. In the United States and seven other countries, the regulatory authorities approved GH treatment (at doses up to 53 microg/kg.d) for children shorter than -2.25 SDS, whereas in other countries, lower cutoffs are proposed. Aromatase inhibition increases predicted adult height in males with ISS, but adult-height data are not available. Psychological counseling is worthwhile to consider instead of or as an adjunct to hormone treatment. The predicted height may be inaccurate and is not an absolute criterion for GH treatment decisions. The shorter the child, the more consideration should be given to GH. Successful first-year response to GH treatment includes an increase in height SDS of more than 0.3-0.5. The mean increase in adult height in children with ISS attributable to GH therapy (average duration of 4-7 yr) is 3.5-7.5 cm. Responses are highly variable. IGF-I levels may be helpful in assessing compliance and GH sensitivity; levels that are consistently elevated (>2.5 SDS) should prompt consideration of GH dose reduction. GH therapy for children with ISS has a similar safety profile to other GH indications.

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Growth hormone insensitivity associated with a STAT5b mutation.

Vivian Hwa, Caroline K Buckway, J. Heinrich … (2003)

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The effects of insulin-like growth factors on tumorigenesis and neoplastic growth.

A Flyvbjerg, Hasnain M Khandwala, E Friend … (2000)

Several decades of basic and clinical research have demonstrated that there is an association between the insulin-like growth factors (IGFs) and neoplasia. We begin with a brief discussion of the function and regulation of expression of the IGFs, their receptors and the IGF-binding proteins (IGFBPs). A number of investigational interventional strategies targeting the GH or IGFs are then reviewed. Finally, we have assembled the available scientific knowledge about this relationship for each of the major tumor types. The tumors have been grouped together by organ system and for each of the major tumors, various key elements of the relationship between IGFs and tumor growth are discussed. Specifically these include the presence or absence of autocrine IGF-I and IGF-II production; presence or absence of IGF-I and IGF-II receptor expression; the expression and functions of the IGFBPs; in vitro and in vivo experiments involving therapeutic interventions; and available results from clinical trials evaluating the effect of GH/IGF axis down-regulation in various malignancies.

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Author and article information

Journal

Journal ID (nlm-ta): J Clin Res Pediatr Endocrinol

Journal ID (publisher-id): JCRPE

Title: Journal of Clinical Research in Pediatric Endocrinology

Publisher: Galenos Publishing

ISSN (Print): 1308-5727

ISSN (Electronic): 1308-5735

Publication date (Print): March 2009

Publication date (Electronic): 1 February 2009

Volume: 1

Issue: 3

Pages: 105-115

Affiliations

[1 ] ‘Rina Balducci’ Center of Pediatric Endocrinology, Department of Public Health and Cell Biology, Tor Vergata University, Rome, Italy

+39−06 72596178+39−06 5917415 stefano.cianfarani@ 123456uniroma2.it ‘Rina Balducci’ Center of Pediatric Endocrinology, Department of Public Health and Cell Biology, Room E−178, Tor Vergata University, Via Montpellier 1, 00133, Rome, Italy

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Publisher Item ID: 17

DOI: 10.4008/jcrpe.v1i3.53

PMC ID: 3005647

PubMed ID: 21274395

SO-VID: 6444d6b3-892a-47dd-8e71-16dfb3bb49d2

License:

This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Controversies in the Definition and Treatment of Idiopathic Short Stature (ISS)

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Karger: Endocrinology

Most cited references 43

Consensus statement on the diagnosis and treatment of children with idiopathic short stature: a summary of the Growth Hormone Research Society, the Lawson Wilkins Pediatric Endocrine Society, and the European Society for Paediatric Endocrinology Workshop.

Growth hormone insensitivity associated with a STAT5b mutation.

The effects of insulin-like growth factors on tumorigenesis and neoplastic growth.

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