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Effects of pasireotide treatment on coagulative profile: a prospective study in patients with Cushing's disease
Mattia Barbot1, Valentina Guarnotta2, Marialuisa Zilio3
1Endocrinology Unit, Department of Medicine DIMED, University of Padova, Padova, Italy. mattiabarbot@alice.it.
Insights
Pasireotide effectively reduced cortisol in Cushing's disease (CD) patients, but did not improve blood clotting factors. Further research is needed on managing thrombotic risks during treatment.
Area of Science:
- Endocrinology
- Hematology
Background:
- Cushing's disease (CD) is associated with a procoagulative state, increasing thromboembolic risk.
- Cortisol-reducing medications may normalize coagulation, potentially mitigating these risks.
Purpose of the Study:
- To assess the impact of pasireotide treatment on coagulation factors in CD patients.
- To evaluate the effectiveness of pasireotide in managing hypercortisolism and its effect on hemostasis.
Main Methods:
- Prospective study of 21 CD patients treated with pasireotide (600 µg twice daily) for 6-12 months.
- Evaluation of biochemical, hormonal (cortisol, ACTH), and coagulation parameters (PT, aPTT, clotting factors, anticoagulants) at baseline and during therapy.
Main Results:
- Pasireotide significantly reduced urinary free cortisol (UFC) and showed partial normalization of late-night salivary cortisol (LNSC).
- No significant improvements were observed in clotting or anticoagulant factors during treatment.
- Treatment led to increased serum glucose and HbA1c, indicating worsened glucose metabolism.
Conclusions:
- Pasireotide effectively controls hypercortisolism in over half of CD patients.
- The drug did not improve coagulation parameters, possibly due to persistent CD-related factors and drug-induced metabolic changes.
- The clinical implications of persistent procoagulative state during pasireotide therapy warrant consideration.
Introduction:
Cushing's disease (CD) is characterized by procoagulative profile. Treatment with cortisol-reducing medications might normalize the coagulation impairment potentially eliminating the risk of thromboembolic complications.
Aim:
The aim of this prospective study is to evaluate the effectiveness of 6-12 months of treatment with pasireotide (Signifor®, Novartis) 600 µg twice daily on coagulative factors in 21 patients (16 females, mean age 46 ± 12.2 years) with CD. Biochemical, hormonal (urinary free cortisol, UFC; late night salivary cortisol, LNSC; ACTH) and coagulative parameters as Protrombin time (PT), aPTT, factors VIII, IX and XI, antithrombin III, protein C, protein S, fibrinogen, were evaluated at baseline and during therapy.
Results:
UFC showed a significant reduction from baseline (3.2 ± 1.8 vs. 1.0 ± 0.8, p < 0.0001) with normalization in 13/21 (61.9%) and in 7/16 (43.8%) at 6 and 12 months, respectively. On the same way LNSC returned to normal in 5/11 at 6 months, showing a trend to reduction (8.6 ± 5 vs. 4.1 ± 2.9), even though without statistical significance (p = 0.07). Throughout the treatment period there was an increase in serum glycaemia (5.5 ± 2.3 vs. 6.8 ± 2.3 mmol/L, p = 0.09), with a concomitant significant increase in HbA1c after 6 months (40.7 ± 8.4 vs. 50.7 ± 12.3 mmol/mol, p = 0.006). Regarding coagulative parameters, no differences were found neither in clotting nor in anticoagulant factors during therapy. No patients developed thrombotic complication during treatment.
Conclusions:
Pasireotide resulted an effective treatment in controlling hypercortisolism in more than half of CD patients with partial restoration also of circadian cortisol secretion. No significant improvements were observed on clotting factors; this fact might depend on persistence of typical alteration of CD, such as obesity and hypertension, and reflects also on the worsening in glucide metabolism induced by the drug. Clinical implications of persistent procoagulative impairment while on medical therapy should be considered.