Background: The exon-3 deletion in the growth hormone receptor gene (d3 GHR) leads to an enhanced GH signal transduction. Acromegalic patients with the d3 GHR genotype could be expected to have more marked clinical or biochemical manifestations for a given GH level than those with the wild (fl) type GHR. We studied acromegalic patients for clinical and/or biochemical disease recurrence after surgery in relation to GHR genotype status to assess whether d3 GHR influences the relationship between GH and disease activity.
Methods: Adults with initial diagnosis between 2000 and 2009 and pituitary surgery for acromegaly at our centre, with histologically proven GH-secreting adenoma and consenting to GHR genotyping were included. GH (random or during oGTT) and IGF-1 levels were analysed during follow-up.
Results: Forty-eight patients were included. 24 were homozygous for the fl-GHR, 24 had at least one d3 GHR allele. Transsphenoidal surgery markedly decreased disease activity in all patients. 19 of them were not cured as judged clinically and by failure to reach postoperative random low (<0.4 ug/l) GH levels or GH levels suppressible to a nadir of <1 ug/l during oGTT 23 months postoperatively. 29 patients had no biochemical evidence for remaining activity and could be classified as in remission. Two of these patients subsequently developed recurrent symptoms of acromegaly during follow-up, along with an increase in IGF1. Both carried the d3 GHR genotype.
Conclusions: Despite biochemical cure as inferred from low postoperative GH levels, carriers of the d3 GHR seem to be at increased risk of recurrence. Longer follow-up periods should be monitored in a larger number of patients to find out whether a safe cut-off for postoperative nadir GH levels ought to be lower for carriers of a d3-GHR than for those with the wild (fl) type GHR.
30 Apr - 04 May 2011
European Society of Endocrinology