Improved heart function, metabolic parameters with growth hormone replacement therapy

Growth hormone (GH) replacement therapy increased left ventricular (LV) mass and improved metabolic parameters in prepubertal children with growth hormone deficiency (GHD), according to a study from Spain.

The prospective, observational study cohort comprised 81 prepubertal children (age 7–10 years; Tanner stage I), 40 of whom had GHD (24 females; growth hormone peak ≤7.3 ng/mL), who were compared with 41 healthy children (23 females; control group). Children with GHD were given GH replacement therapy at a dose of 0.030 mg/kg/day for 6 months. All patients had blood drawn and underwent echocardiography tests at study onset with a second round of tests at 6 months in children with GHD.

At baseline, children with GHD had smaller LV mass index than children in the control group (58.73 vs 62.77 g/m²), with size significantly increasing to 68.60 g/m² following 6 months of GH replacement therapy to a comparable size between groups (p=0.143). [Front Pediatr 2018;6:174]

At baseline, children with GHD had smaller systolic and diastolic LV diameter compared with the control group (23.62 vs 25.93 mm and 37.17 vs 39.49 mm, respectively). GH replacement therapy significantly improved diastolic LV size (to 38.41 mm; p=0.007) to a level comparable with that of the control group but had no impact on systolic LV size (to 23.63 mm; p=0.976).

Brain natriuretic peptide (BNP) levels were comparable between children with GHD and control group at baseline (20.58 vs 17.54 pg/mL; p=0.231) and following GH replacement therapy (18.85 vs 17.54 pg/mL; p=0.874). Ejection fraction (67.06 percent vs 64.30 percent), E/A* relation (1.89 vs 1.93), E/E’** relation (6.54 vs 6.96), and isovolumic relaxation time (IVRT; 79.51 vs 87.66 mseg) were also comparable between children with GHD and controls at baseline, though following GH replacement therapy, ejection fraction and IVRT levels decreased (to 66.83 and 77.08 mseg, respectively; p=0.040 and 0.010 vs controls, respectively).

The lack of change in BNP levels following GH replacement suggests that ventricular dysfunction may not be present in prepubertal children with GHD, said the researchers.

Six months after GH replacement therapy, children with GHD experienced increases in glucose levels (from 4.72 to 4.94 mmol/L; p=0.011), HDL-cholesterol (from 54.38 to 59.18 mg/dL; p=0.035), insulin (from 7.33 to 8.25 μU/mL; p<0.001), HOMA-IR*** (from 1.53 to 1.80; p<0.001), QUICKI^# (from 0.36 to 0.63; p<0.001), IGFBP3^## (from 2.44 to 2.74 μg/mL; p=0.010), and IGF1^### (from 185.2 to 297.3 ng/mL; p<0.001) as well as a decrease in LDL-cholesterol (from 109.1 to 99.82 mg/dL; p=0.006).

“[C]omparing the GHD children after 6 months of replacement therapy to the control group, all parameters remained significantly elevated except LDL-cholesterol, approaching baseline values; however, values were always within the normal range for age,” said the researchers.

“Adult patients with established GHD have an increased risk of cardiovascular disease and early mortality,” said the researchers. [Lancet 2001;357:425-431] “Replacement therapy with GH has beneficial effects on [several] cardiovascular risk factors, improves ventricular function, and decreases BNP, thus suggesting that GH may be effective in reducing mortality from cardiovascular disease,” they said. [Exp Clin Endocrinol Diabetes 2010;118:172-176; Horm Metab Res 2006;38:656-661]

“[A]lterations in lipid metabolism associated with GHD are present in children with this deficiency from very early ages, and replacement therapy significantly improves their lipid parameters. [H]eart size and LV mass [also] increased, with no negative effects on diastolic function,” they added.