ECE2019 Poster Presentations Pituitary and Neuroendocrinology 3 (73 abstracts)
1Division of Endocrinology, Diabetes and Clinical Nutrition, University Hospital Zurich, 8091 Zurich, Switzerland; 2Department of Neurosurgery, Klinik Hirslanden, 8027 Zurich, Switzerland; 3Department of Neurosurgery, University Hospital Zurich, 8091 Zurich, Switzerland; 4Division of Endocrinology and Diabetes, Kantonsspital Winterthur, 8401 Winterthur, Switzerland.
Background, aims: Acromegaly is caused by excessive growth hormone (GH) secretion, usually by a pituitary adenoma. Surgical removal of the GH-producing adenoma is the most effective treatment. Drug treatment is second-line option. Earlier work suggested Soluble (s)Klotho levels to be a supplementary biomarker to IGF-1. We tested whether IGF-1 and sKlotho serum levels show a concomitant reduction under medical treatment. If yes, is the extent of reduction in serum IGF-1 and sKlotho comparable?
Methods: We determined IGF-1 and sKlotho levels (by ELISA) in serum samples of 29 patients with confirmed acromegaly treated in our hospital from 2013 onwards, before and after treatment (surgery alone or surgery and pharmacotherapy). All patients underwent transsphenoidal surgery. Patients with remnant adenomas were treated with drugs: two with cabergoline, three with lanreotide, one with octreotide LAR, and two with pegvisomant. One patient received pegvisomant before surgery to stabilise cardiomyopathy resulting from GH excess.
Results: Surgery (21 cases, 12 female) and drug treatment (eight cases, two female) decreased levels of both IGF-1 and sKlotho in the majority of cases (IGF-1, in 28, sKlotho in 29). As expected, surgery resulted in a significant decline in IGF-1 from median 841 ng/ml (interquartile range (IQR); 620994) to median 266 ng/ml (IQR 185383) with P-value <0.001. Likewise, sKlotho decreased significantly from median 4,502 pg/ml (IQR 12646677) to median 716 pg/ml (IQR 5921177) with P-value <0.001. In eight patients with pharmacotherapy, IGF-1 declined significantly from median 632 ng/ml (IQR 455.31005) to median 381 ng/ml (IQR 305438) with P-value<0.01. Similarly, sKlotho declined from median 2316 pg/ml (IQR 17554326) to median 927 pg/ml (IQR 8031203) with P-value <0.01. After surgery, there was 68% decrease in IGF-1 and 84% decrease in sKlotho. After medical treatment, IGF-1 decreased 40%and sKlotho decreased 60%. Overall, decrease in sKlotho appeared to be more pronounced than decrease in IGF-1.
Conclusion: sKlotho supplementary to IGF-1 - is a serum biomarker reliably reflecting disease activity and treatment effect (both surgery and pharmacotherapy) in patients with acromegaly.