Hypothalamic–Pituitary and Growth Disorders in Survivors of Childhood Cancer

An Endocrine Society Clinical Practice Guideline

Charles A. Sklar; Zoltan Antal; Wassim Chemaitilly; Laurie E. Cohen; Cecilia Follin; Lillian R. Meacham; M. Hassan Murad


J Clin Endocrinol Metab. 2018;103(8):2761-2784. 

In This Article

Commissioned Systematic Review

The Guideline Writing Committee commissioned two systematic reviews to support this guideline. The first systematic review aimed to evaluate the effect of GH treatment (GHT) in childhood cancer survivors on adult height (AH), risk of type 2 diabetes mellitus (T2DM), abnormal lipids, metabolic syndrome, quality of life, secondary tumors, and disease recurrence. Studies showed that GHT vs no GHT in this patient group was associated with a significant gain in AH and no significant association with the occurrence of secondary tumors or tumor recurrence. Studies that compared childhood cancer survivors receiving GHT to normal age- or sex-matched controls or controls with idiopathic GH deficiency (GHD) or short stature showed that GHT was associated with either improved or unchanged risk of T2DM, lipid profile, or metabolic syndrome. GHT was also associated with improvement in quality of life.

The second systematic review aimed to determine the best screening and diagnostic tests for GHD in childhood cancer survivors exposed to hypothalamic–pituitary radiation. The major challenge in this review was the lack of a "gold" standard to diagnose GHD. There was high variability in the confirmatory testing each study used. The insulin tolerance test (ITT) seems to be the most accepted reference test in the reviewed studies, either alone or in combination with arginine; although standardization of the testing dose and strategy among different practice groups is lacking. Studies included in this report spanned 4 decades; therefore, changes in clinical practice and assay methods can account for some of this variability. IGF-I and IGF-binding protein 3 had a suboptimal diagnostic accuracy, and their results were correlated. The patterns of diagnostic accuracy of all the tests evaluated suggested a similar pattern to what we see in patients who are not childhood cancer survivors.