Diagnosing GH deficiency as a late effect of radiotherapy in childhood cancer survivors

Sfeir JG, Kittah NEN, Tamhane SU, Jasim S, Chemaitilly W, Cohen LE, Murad MH. Diagnosis of GH Deficiency as a Late Effect of Radiotherapy in Survivors of Childhood Cancers. J Clin Endocrinol Metab. 2018 Aug 1;103(8):2785-2793.

Abstract

BACKGROUND:

Limited guidance exists for selecting a laboratory method for diagnosing GH deficiency (GHD) when it occurs as a late effect of radiotherapy in childhood cancer survivors (CCSs).

METHODS:

We searched Medline, Embase, Cochrane Central Register of Controlled Trials and Database of Systematic Reviews, and Scopus for studies evaluating GHD that used IGF-1 or IGF-binding protein 3 (IGFBP-3) measurements compared with GH dynamic testing.

RESULTS:

We included 15 studies [IGF-1 (8 studies) and IGFBP-3 (7 studies)] enrolling 477 patients. Comparator tests varied widely. Overall, both IGF-1 and IGFBP-3 had suboptimal diagnostic accuracy but were strongly correlated. The use of both tests simultaneously in the same cohort did not improve the diagnostic accuracy. Despite high variability in the testing protocols, dynamic tests remained the most accurate for appropriately identifying patients with GHD. The insulin tolerance test (ITT) appears to be the most accepted reference test when used alone or in combination with arginine; however, standardized testing strategies among practice groups are absent. GHRH and arginine stimulation performed almost similarly to the ITT; however, in one study GHRH with arginine stimulation had 66% sensitivity and 88% specificity compared with the ITT. Insufficient data were available to assess the accuracy of serial GH testing (nocturnal or over 24 hours).

CONCLUSION:

The diagnostic accuracy of various dynamic tests for GHD in CCSs appears to follow the same patterns as those in non-CCSs. Interpreting GHRH stimulation is a challenge given the primarily hypothalamic dysfunction in CCSs. IGF-1 and IGFBP-3 perform poorly in this population.

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Methods

Medline, Embase, Cochrane Central Register of Controlled Trials and Database of Systematic Reviews, and Scopus were searched for studies evaluating GHD.

Studies using IGF-1 or IGFBP-3 measurements compared with GH dynamic testing were identified.

Results

Fifteen studies (IGF-1 [8 studies] and IGFBP-3 [7 studies]) enrolling 477 patients were included.

Wide variation in comparator tests was noted.

Although strongly correlated, both IGF-1 and IGFBP-3 had suboptimal diagnostic accuracy, and simultaneous use of both tests in the same cohort did not improve the diagnostic accuracy.

For appropriately identifying patients with GHD, dynamic tests remained the most accurate despite high variability in the testing protocols.

Outcomes suggest the insulin tolerance test (ITT) to be the most accepted reference test when used alone or in combination with arginine; however, among practice groups, there were no standardized testing strategies.

GHRH and arginine stimulation were almost similar to ITT regarding their performance; however, one study displayed 66% sensitivity and 88% specificity for GHRH with arginine stimulation compared with the ITT.

They identified no sufficient data assessing the accuracy of serial GH testing (nocturnal or over 24 hours).

https://www.mdlinx.com/journal-summaries/pituitary-neuroendocrinology-radiotherapy/2018/08/09/7540729?spec=neurology