Children born small for gestational age treated with growth hormone therapy did not experience any negative effects on cardiometabolic health in the 5 years after stopping treatment, with researchers also observing a possible benefit on lipid profile, according to study findings reported in Lancet Diabetes & Endocrinology.
“Five years after growth hormone cessation, adults born small for gestational age and treated with growth hormone had similar systolic and diastolic blood pressures and [carotid intima media thickness] as untreated short adults born small for gestational age,” Manouk van der Steen, PhD, of the department of pediatrics at Erasmus University Hospital in Rotterdam, the Netherlands, and colleagues wrote. “These findings contradict the hypothesis that there is
a link between growth hormone treatment and vascular diseases.”
Researchers analyzed data from 199 young adults born small for gestational age who started GH therapy between ages 5 to 8 years, with a height below –2.5 SDS (mean age at start of treatment, 6 years; mean duration of therapy, 10 years). Patients received a 1 mg/m² subcutaneous injection once daily (Norditropin, Novo Nordisk), adjusted for body surface area every 3 months; treatment was discontinued at attainment of adult height. Researchers evaluated patients at cessation of therapy, and at 6 months, 2 years and 5 years, analyzing height, body weight, systolic and diastolic blood pressure, lipid profile and carotid intima media thickness (mean age at 5 years after stopping treatment, 21 years). Researchers then compared data from these patients 5 years after GH cessation with data from 285 age-matched, healthy young adults aged 18 to 24 years, including 51 untreated patients born small for gestational age with persistent short adult height, 92 patients born small for gestational age with “catch-up” growth resulting in normal adult height, and 142 patients born appropriate for gestational age with normal adult height. Primary outcomes were changes in BP, lipid concentrations and carotid intima media thickness during the 5 years after GH cessation. Secondary outcomes were BP, lipid concentrations and carotid intima media thickness for patients treated with GH therapy compared with controls.
In the 6 months after stopping GH therapy, researchers found that both systolic and diastolic BP increased, from a mean of 113 mm Hg to 116.92 mm Hg and from 62.19 mm Hg to 66.51 mm Hg, respectively; however, in the subsequent 18 months, systolic and diastolic BP decreased, and remained unchanged between 2 and 5 years. At 5 years, both systolic and diastolic BP were similar to levels at the time of GH therapy cessation, according to researchers.
In the 6 months after GH cessation, total cholesterol concentration did not change, whereas LDL concentration increased from a mean of 2.01 mmol/L to 2.1 mmol/L, and triglyceride levels decreased. In the subsequent 18 months after GH cessation, total cholesterol, triglyceride and LDL cholesterol levels all increased, but only triglyceride levels increased between 2 and 5 years. At 5 years, all lipid concentrations were higher when compared with levels at the time of GH cessation, but levels were not significant, according to researchers.
Adjustment for smoking did not change the findings. Carotid intima media thickness did not change at any time after cessation of GH therapy.
When comparing treated patients with controls, researchers did not observe any between-group differences for BP or lipid profile, with results persisting after adjustments for sex, gestational age, birth weight and birth length, socioeconomic status, smoking status and alcohol intake.
The researchers noted that, because study participants were young, they could not assess any effects of growth hormone cessation on mortality or CV event rates.
“Epidemiological data, however, indicate that a [carotid intima media thickness] of more than 1 mm at any age is associated with a significantly increased risk of myocardial infarction or cerebrovascular disease, and none of the growth hormone-treated adults born small for gestational age in our study had a [carotid intima media thickness] above 1 mm at any time during the study,” the researchers wrote. – by Regina Schaffer
Disclosures: Novo Nordisk funded this study. One of the study authors reports she received an independent research grant from Novo Nordisk.