Endocrine Abstracts

Background: It is well-known that growth hormone (GH) potently stimulates collagen turnover and it is associated with fibrosis in several tissues, but the mechanisms involved in GH-stimulated fibrosis are poorly elucidated. Fibroblast activation protein-α (FAPα) is an enzyme that can cleave collagens and is expressed almost only under pathological conditions such as fibrosis. FAPα also cleaves and inactivates fibroblast growth factor 21 (FGF21), which is a circulating hormone with pleiotropic metabolic effects. Despite their related involvements, data regarding the interaction between GH and FAPα are scarce.

Aim: To measure circulating FAPα, FGF21 components and biomarkers of collagen turnover in patients with adult-onset GH deficiency (GHD) and in patients with acromegaly before and after treatment, compared to a control group.

Methods: Serum samples obtained from 16 patients with adult-onset GHD at time of diagnosis and after GH treatment have been analyzed using immunoassays for FAPα concentration and activity, and total FGF21. Repeated serum samples obtained from 9 patients initially suspected for GHD but with a normal GH response to an insulin tolerance test serve as controls. This study is ongoing and biomarkers of collagen turnover are yet to be analyzed at time of abstract submission. Furthermore, we have obtained serum samples from 14 patients with acromegaly before and after treatment, which will be analyzed for the same parameters.

Results: Our preliminary data show that serum levels of FAPα (ng/ml) significantly increase in the GHD patients after GH treatment [135.6 (111.6-163.8) vs 168.5 (107.3-233.9), P<0.05], and FAPα activity (RFU/min) in serum likewise increase after GH treatment [719.0 (467.3-1104.2) vs 1277.8 (668.9-1609.4), P<0.05], [median (IQR)]. Total FGF21 remain unchanged after GH treatment. In the control group, FAPα concentration and activity as well as total FGF21 remain unchanged over a corresponding time period.

Conclusions: Circulating FAPα concentration and activity increase in response to GH treatment in patients with adult-onset GHD, whereas total FGF21 do not change in response to GH treatment. Further analyses in this study are ongoing, including comparable analyses in patients with acromegaly. It remains to be studied if the fibrotic and FAPα -stimulating effects of GH are causally linked.