S E Franck1, A J van der Lely2, P J D Delhanty2, J O L Jørgensen2, S J C M M Neggers2. 1. Department of Internal MedicineEndocrinology Section, Pituitary Center Rotterdam, Erasmus University Medical Center Rotterdam, PO Box 2040, 3000 CA Rotterdam, The NetherlandsDepartment of Internal MedicineEndocrinology Section, Medical Research Laboratories, Aarhus University Hospital, Aarhus, Denmark s.franck@erasmusmc.nl. 2. Department of Internal MedicineEndocrinology Section, Pituitary Center Rotterdam, Erasmus University Medical Center Rotterdam, PO Box 2040, 3000 CA Rotterdam, The NetherlandsDepartment of Internal MedicineEndocrinology Section, Medical Research Laboratories, Aarhus University Hospital, Aarhus, Denmark.
Abstract
BACKGROUND: Doses of the GH receptor (GHR) antagonist pegvisomant (PEGV) that normalize insulin-like growth factor 1 (IGF1) levels vary widely among acromegaly patients. Predictors for PEGV response are baseline IGF1 levels, sex, body weight and previous radiotherapy. A GHR polymorphism lacking exon 3 (d3-GHR) is frequent in the general population. The influence of d3-GHR on PEGV responsiveness in acromegaly is unclear. OBJECTIVE: To assess the influence of d3-GHR on IGF1 levels and PEGV responsiveness in acromegaly patients using combined PEGV and long-acting somatostatin receptor ligand (LA-SRIF) treatment. DESIGN: Data were collected at the Rotterdam Pituitary Centre between 2004 and 2013. Patients with elevated IGF1 levels (>1.2 upper limit of normal; n=112) and over 6 months of high-dose LA-SRIF treatment were co-treated with PEGV. GHR genotype was assessed using genomic DNA in 104 patients. RESULTS: D3-GHR was observed in 51 (49.0%) of the patients (7.7% homozygous, 41.3% heterozygous) and was in Hardy-Weinberg equilibrium (P=0.859). Baseline characteristics were similar in d3-GHR and full-length (fl)-GHR genotypes. During PEGV/LA-SRIF treatment IGF1 levels were not different between d3-carriers and non-carriers. Similarly, no difference in PEGV dose required to normalize IGF1 (P=0.337) or PEGV serum levels (P=0.433) was observed between the two groups. However, adenoma size decreased significantly (>20% of largest diameter) in 25.6% of the fl-GHR genotype but only in 7.5% of d3-carriers (P=0.034, OR: 4.6 (CI: 1.1-18.9)). CONCLUSIONS: GHR genotype does not predict the IGF1 normalizing dose of PEGV in acromegaly patients using combination PEGV/LA-SRIF treatment. However, fewer d3-carriers showed significant reductions in adenoma size.
BACKGROUND: Doses of the GH receptor (GHR) antagonist pegvisomant (PEGV) that normalize insulin-like growth factor 1 (IGF1) levels vary widely among acromegalypatients. Predictors for PEGV response are baseline IGF1 levels, sex, body weight and previous radiotherapy. A GHR polymorphism lacking exon 3 (d3-GHR) is frequent in the general population. The influence of d3-GHR on PEGV responsiveness in acromegaly is unclear. OBJECTIVE: To assess the influence of d3-GHR on IGF1 levels and PEGV responsiveness in acromegalypatients using combined PEGV and long-acting somatostatin receptor ligand (LA-SRIF) treatment. DESIGN: Data were collected at the Rotterdam Pituitary Centre between 2004 and 2013. Patients with elevated IGF1 levels (>1.2 upper limit of normal; n=112) and over 6 months of high-dose LA-SRIF treatment were co-treated with PEGV. GHR genotype was assessed using genomic DNA in 104 patients. RESULTS: D3-GHR was observed in 51 (49.0%) of the patients (7.7% homozygous, 41.3% heterozygous) and was in Hardy-Weinberg equilibrium (P=0.859). Baseline characteristics were similar in d3-GHR and full-length (fl)-GHR genotypes. During PEGV/LA-SRIF treatment IGF1 levels were not different between d3-carriers and non-carriers. Similarly, no difference in PEGV dose required to normalize IGF1 (P=0.337) or PEGV serum levels (P=0.433) was observed between the two groups. However, adenoma size decreased significantly (>20% of largest diameter) in 25.6% of the fl-GHR genotype but only in 7.5% of d3-carriers (P=0.034, OR: 4.6 (CI: 1.1-18.9)). CONCLUSIONS:GHR genotype does not predict the IGF1 normalizing dose of PEGV in acromegalypatients using combination PEGV/LA-SRIF treatment. However, fewer d3-carriers showed significant reductions in adenoma size.
Authors: Sanne E Franck; Linda Broer; Aart Jan van der Lely; Peter Kamenicky; Ignacio Bernabéu; Elena Malchiodi; Patric J D Delhanty; Fernando Rivadeneira; Sebastian J C M M Neggers Journal: Neuroendocrinology Date: 2016-08-12 Impact factor: 4.914
Authors: A Giustina; G Arnaldi; F Bogazzi; S Cannavò; A Colao; L De Marinis; E De Menis; E Degli Uberti; F Giorgino; S Grottoli; A G Lania; P Maffei; R Pivonello; E Ghigo Journal: J Endocrinol Invest Date: 2017-02-07 Impact factor: 4.256