Blunted response to a growth hormone stimulation test is associated with unfavorable cardiovascular risk factor profile in childhood cancer survivors

Abstract

Background: Childhood cancer survivors (CCS) are at risk for growth hormone (GH) deficiency. CCS are also at increased risk for early mortality from cardiovascular (CV) disease, but the association between GH levels and CV risk remains poorly understood. The goal of this study was to examine the cross-sectional association between stimulated GH levels and CV risk factors in CCS younger than 18 years.

Procedure: A total of 276 CCS (147 males, 14.4 ± 2.6 years) ≥5 years after cancer diagnosis, and 208 sibling controls (112 males, 13.6 ± 2.4 years) participated in this cross-sectional study, which included anthropometry, body composition, and metabolic studies. Blunted response (BR) was defined as peak GH level <7 µg/L after clonidine and arginine. Insulin sensitivity (M(lbm) ) was measured by euglycemic hyperinsulinemic clamp. Statistical analyses used linear and logistic regression accounting for sibling clustering, adjusted for age, sex, Tanner stage, and adiposity.

Results: Thirty-four (12%) CCS showed BR to GH stimulation. BR CCS were shorter and had a lower IGF-1 than controls; only 6 of 34 received cranial radiation therapy. CCS with normal stimulated GH response were similar to controls for CV risk factors. Conversely, BR CCS had greater adiposity, higher lipids, and lower M(lbm) than controls. Differences in lipids and M(lbm) between BR CCS and controls remained significant after adjustment for BMI or visceral fat.

Conclusions: BR to GH stimulation is prevalent in CCS youth and is associated with an unfavorable CV risk factor profile. Further studies are needed to establish the mechanisms of these associations.