Purpose: Although quality of life (QoL) is improved in patients with acromegaly after disease control, QoL correlates only weakly with traditional biomarkers. Our objective is to investigate a potential relation between the new serum biomarker soluble Klotho (sKlotho), GH and insulin-like growth factor 1 (IGF-1) levels, and QoL. Methods: In this prospective cohort study, we investigated 54 acromegaly patients biochemically well-controlled on combination treatment with first-generation somatostatin receptor ligands (SRLs) and pegvisomant (PEGV) at baseline and 9 months after switching to pasireotide LAR (PAS-LAR; either as monotherapy, n = 28; or in combination with PEGV, n = 26). QoL was measured by the Patient-Assessed Acromegaly Symptom Questionnaire (PASQ) and Acromegaly Quality of Life (AcroQoL) questionnaire. Results: Switching to PAS-LAR treatment significantly improved QoL without altering IGF-1 levels. QoL did not correlate with GH or IGF-1 levels, but sKlotho correlated with the observed improvements in QoL by the AcroQoL global (r = −0.35, p = 0.012) and physical subdimension (r = −0.34, p = 0.017), and with PASQ headache (r = 0.28, p = 0.048), osteoarthralgia (r = 0.46, p = 0.00080) and soft tissue swelling score (r = 0.29, p = 0.041). Parallel changes in serum sKlotho and IGF-1 (r = 0.31, p = 0.023) suggest sKlotho and IGF-1 to be similarly dependent on GH. Comparing the PAS-LAR combination therapy and the monotherapy group we did not observe a significant difference in improvement of QoL. Conclusions: Patients experienced improved QoL during PAS-LAR, either as monotherapy or in combination with PEGV. Soluble Klotho concentrations appear to be a useful marker of QoL in acromegaly patients but the underlying mechanisms remain to be investigated.

Acromegaly, Active disease, Alpha Klotho, QoL, Somatostatin receptor ligand
dx.doi.org/10.1007/s12020-020-02306-4, hdl.handle.net/1765/126679
Endocrine : International Journal of Basic and Clinical Endocrinology
Department of Internal Medicine

Coopmans, E.C. (Eva C.), El-Sayed, N. (Nour), Frystyk, J, Magnusson, N.E. (Nils E.), Jørgensen, J.O.L, van der Lely, A-J, … Neggers, S.J.C.M.M. (Sebastian J. C. M. M.). (2020). Soluble Klotho: a possible predictor of quality of life in acromegaly patients. Endocrine : International Journal of Basic and Clinical Endocrinology. doi:10.1007/s12020-020-02306-4