Endocrine Abstracts

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); 620–994) to median 266 ng/ml (IQR 185–383) with P-value <0.001. Likewise, sKlotho decreased significantly from median 4,502 pg/ml (IQR 1264–6677) to median 716 pg/ml (IQR 592–1177) with P-value <0.001. In eight patients with pharmacotherapy, IGF-1 declined significantly from median 632 ng/ml (IQR 455.3–1005) to median 381 ng/ml (IQR 305–438) with P-value<0.01. Similarly, sKlotho declined from median 2316 pg/ml (IQR 1755–4326) to median 927 pg/ml (IQR 803–1203) 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.