Growth Hormone Does Not Impact Glucose Homeostasis in Turner Syndrome

Girls with Turner syndrome undergoing growth hormone (GH) treatment did not show significant changes in insulin sensitivity, insulin secretion, or beta-cell capacity to adapt to changes in insulin sensitivity, according to data from a longitudinal retrospective study published in the Journal of Clinical Endocrinology & Metabolism.

“Girls affected with Turner syndrome are nowadays treated with GH in order to improve their final height,” study researcher Giorgio Radetti, MD, of the Regional Hospital of Bolzano in Italy, told Endocrinology Advisor. “Higher doses than those usually employed in GH-deficient children are used and since GH has been reported to have some a diabetogenic activity, concern has arisen since girls with Turner syndrome very often show a tendency toward an impaired glucose tolerance, already before GH treatment.”

To further investigate the effects of GH in this patient population, the researchers assessed 104 patients with Turner syndrome receiving GH therapy. Patients underwent a yearly oral glucose tolerance test (OGTT) to determine insulin sensitivity (HOMA-S), insulin secretion, as measured through the insulinogenic index (IGI), and patients’ beta-cell capacity to adapt to changes in insulin sensitivity, as measured through the oral disposition index (ODI). Patients were aged 9.1 years at the beginning of the study and had a mean age of 14.4 at final follow-up.

“In all patients, after an overnight fast, a standard oral glucose tolerance test (1.75 g of glucose/kg body weight up to 75 g with blood samples taken at 0, 30, 60, 90, 120 min) was performed in order to evaluate glucose and insulin levels,” the researchers wrote.

Of the patients in the study, 46% (n=48) of patients were positive for thyroid autoantibodies, with 24 patients on levothyroxine. At a mean age of 13.2 years, 44% of patients (n=46) began puberty, with 41 patients needing estrogen treatment to complete pubertal development. Patients who did not begin puberty (n=58) began estrogen treatments at a median age of 15.7.

Chromosomal analysis showed that 41% patients had a 45,X karyotype, 42% of patients had an X chromosome structural abnormality, such as a short-arm deletion, long-arm deletion, ring chromosome, or isochromosome, and 17% of patients had mosaicism. There were cardiac abnormalities such as bicuspid valves, aortic coarctation, and ventricular septal hypertrophy in 22% of patients.

Overall, there was no statistical difference in mean glucose levels during OGTT at any time period during the study. Impaired glucose tolerance, defined as glucose above 7.8 mmol/L after 120 minutes but below 11.1 mmol/L, was observed in 15 girls at different time points during GH treatment. For 12 girls, this was observed only once. The percentage of patients with impaired glucose tolerance was 5.3% at baseline, 6.3% after 1 year of GH treatment, 5.5% after 2 years, 1.3% after 3 years, 3.4% after 4 years, 1.8% after 5 years, 5% after 6 years, and 10.3% after 7 years, with the researchers noting no difference in percentage of impaired glucose tolerance over time. No cases of diabetes were reported.

The researchers noted there were no significant differences in HOMA-S (0.59 vs 0.45), IGI (0.94 vs 1.2), or ODI (0.42 vs 0.42) levels between baseline and final follow-up.

In light of their results, an annual serum glucose evaluation or glycosylate hemoglobin would be sufficient for these patients and an OGTT should only be performed in borderline cases, they concluded.

“In this detailed and prolonged study we clarified eventually that treatment with GH, while significantly improving the final height of these patients, does not have any negative influence on glucose homeostasis. In particular, GH does not cause diabetes,” Dr Radetti said. “I think that this reassuring paper will be of substantial help for doctors taking care of Turner syndrome patients. Furthermore, I think that on the basis of this paper and the previous literature no other research, regarding glucose homeostasis in Turner syndrome girls treated with GH is needed.”

The study was limited by the reduced number of girls with Turner syndrome available for the final analysis, which likely decreased the power of the study.

Disclosure: The researchers report no relevant financial disclosures.

Reference

1. Baronio F, Mazzanti L, Girtler Y, et al. The influence of GH treatment on glucose homeostasis in girls with Turner Syndrome: a 7 years study. J Clin Endocrinol Metab. 2016;doi:10.1210/jc.2016-3179.