Abstract
PurposeAlthough 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.MethodsIn 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.ResultsSwitching 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.ConclusionsPatients 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.
Highlights
Medical treatment of acromegaly with the combination of the second-generation somatostatin receptor ligand (SRL) pasireotide long-acting release (PAS-LAR) and the GH receptor antagonist, pegvisomant (PEGV) provides control of insulin-like growth factor I (IGF-1) levels in most (77.0%) patients [1, 2]
Overall, when assessing patients with acromegaly, concomitant and parallel changes in serum soluble α-Klotho (sKlotho) and insulin-like growth factor 1 (IGF-1) were observed over time in each patient, and levels of sKlotho and IGF-1 appeared to be dependent on GH [14, 18]
The remaining 40 (74.1%) patients with elevated IGF-1 levels continued with their reduced dose of PEGV treatment, but in combination with PAS-LAR 60 mg, decreasing to 26 (48.1%) patients during 9 months of PAS-LAR treatment At baseline, the PEGV dose was significantly higher in the PASLAR combination therapy group compared with the PASLAR monotherapy group
Summary
Medical treatment of acromegaly with the combination of the second-generation somatostatin receptor ligand (SRL) pasireotide long-acting release (PAS-LAR) and the GH receptor antagonist, pegvisomant (PEGV) provides control of insulin-like growth factor I (IGF-1) levels in most (77.0%) patients [1, 2]. To this date, GH and especially GH activity, as reflected (in part) by IGF-1 concentrations in serum, are considered the ‘classical’ biomarkers to diagnose acromegaly and monitor disease activity during treatment. As sKlotho concentrations appear to reflect acromegaly disease activity [14, 15], it may potentially serve as a more integrated serum biomarker of disease-specific QoL
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