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Cited by 182Growth Hormone and Insulin-like Growth FactorsPituitary Gland Disorders and TreatmentsHypothalamic control of reproductive hormones

The DOI matches its Crossref record; 43 of the 44 references it cites were found in a registry or an index.

The Usefulness of the Combined Growth Hormone (GH)-Releasing Hormone and Arginine Stimulation Test in the Diagnosis of Radiation-Induced GH Deficiency Is Dependent on the Post-Irradiation Time Interval

Darzy, K. H., Aimaretti, G., Wieringa, G., Gattamaneni, H. Rao, Ghigo, E., Shalet, S. M.·2003·The Journal of Clinical Endocrinology & Metabolism
DOI 10.1210/jc.2002-021094
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Abstract

The diagnostic usefulness of the insulin tolerance test (ITT) in patients with radiation-induced GH deficiency (GHD) is well established, whereas that of the combined GHRH plus arginine stimulation test (AST) is unproven. Both tests were undertaken in 49 adult survivors (aged 16-53.7 yr), who were previously irradiated for non-pituitary brain tumors or leukemia, and 33 age-, gender-, and BMI-matched controls. The aims of the study were to examine the impact of the time interval after irradiation on the pattern of GH responsiveness to the two provocative tests and to establish the role of the GHRH + AST in the diagnosis of radiation-induced GHD. The median (range) peak GH responses to either test were significantly lower (P < 0.0001) in the patients [GHRH + AST, 19.9 (range, 2.7-103.5) microg/liter; ITT, 5 (0.2-34.8) microg/liter] than in normals [GHRH + AST, 55 (5.7-173.5) microg/liter; ITT, 23.8 (4.2-80) microg/liter]. In patients and normal controls, the median peak GH response to the GHRH + AST was significantly greater (P < 0.0001) than the response to the ITT. However, the ratio of the peak GH response to the GHRH + AST over that achieved with the ITT (discordancy ratio) was significantly higher (P = 0.007) in the patients (median, 3.45; range, 0.8-53.5) compared with normals (median, 2; range, 0.34-18.6), consistent with dominant hypothalamic damage and relatively preserved somatotroph responsiveness. The peak GH response to the ITT fell significantly within 5 yr of irradiation with little further change over the subsequent 10 yr. In contrast, the peak GH response to the GHRH + AST barely changed within 5 yr of irradiation but subsequently declined significantly over the next 10 yr. Thus, the evolution of change in GH responsiveness to the two different stimuli over time was markedly different, resulting in a significantly raised discordancy ratio of 6 within the first 5 postirradiation years, which then normalized over the next 10 yr. The peak GH responses to the GHRH + AST and the discordancy ratio were negatively correlated with the time interval after irradiation (r = -0.40, P = 0.0037; and r = -0.4, P = 0.0046, respectively). On a practical clinical level, the discordancy between the GH test results was important; 50% of those classified as severely GHD patients by the ITT were judged normal or only GH insufficient by the GHRH + AST. In conclusion, these findings suggest that hypothalamic dysfunction occurs early and somatotroph dysfunction occurs late, following radiation damage to the hypothalamic-pituitary axis. This time dependency of somatotroph dysfunction may reflect either secondary somatotroph atrophy due to hypothalamic GHRH deficiency or delayed direct radiation-induced damage to the pituitary gland. The high false negative diagnosis rate for severe GHD makes the GHRH + AST an unreliable test in clinical practice when GH status is explored in the early years after cranial irradiation with the intention to treat.

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Crossref · 10.1210/jc.2002-021094

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Metadata

Authors
Darzy, K. H., Aimaretti, G., Wieringa, G., Gattamaneni, H. R., Ghigo, E., & Shalet, S. M.
Affiliations
  • The Christie Hospital (GB)
  • University of Turin (IT)
  • University of Manchester (GB)
ORCID
Venue
The Journal of Clinical Endocrinology & Metabolism
Publisher
The Endocrine Society
Published
2003-01
Volume
88
Issue
1
Pages
95-102
ISSN
  • 0021-972X (ISSN-L)
  • 1945-7197
DOI
10.1210/jc.2002-021094
OpenAlex
W2018480165
Semantic Scholar
917e0cda9d775dd0aaedf983619ea4393f24e7eb
Cited by
182
References
44
Citations by year
2025: 2 · 2024: 5 · 2023: 3 · 2022: 5 · 2021: 2 · 2020: 5 · 2019: 9 · 2018: 10 · 2017: 7 · 2016: 11 · 2015: 7 · 2014: 3 · 2013: 5 · 2012: 8
FWCI
6.05
Type
journal article
Language
en
Open access
closed
Locations
  • The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
  • PubMed (publishedVersion)
  • Institutional Research Information System University of Turin (University of Turin) (submittedVersion)
Topics
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Growth Hormone and Insulin-like Growth Factors
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Pituitary Gland Disorders and Treatments
  • Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
Keywords
insulin tolerance test, hypothalamic injury, brain tumor survivors, leukemia survivors, radiation-induced hypopituitarism, diagnostic test comparison, pituitary function testing
MeSH terms
Adolescent, Adult, Arginine, Deficiency Diseases, Female, Humans, Insulin, Insulin-Like Growth Factor I, Male, Middle Aged, Prolactin, Radiotherapy, Growth Hormone-Releasing Hormone, Time Factors, Human Growth Hormone

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