Current clinical practice for thromboprophylaxis management in patients with Cushing’s syndrome across reference centers of the European Reference Network on Rare Endocrine Conditions (Endo-ERN)

Abstract

Background Cushing’s syndrome (CS) is associated with an hypercoagulable state and an increased risk of venous thromboembolism (VTE). Evidence-based guidelines on thromboprophylaxis strategies in patients with CS are currently lacking. We aimed to map the current clinical practice for thromboprophylaxis management in patients with CS across reference centers (RCs) of the European Reference Network on Rare Endocrine Conditions (Endo-ERN), which are endorsed specifically for the diagnosis and treatment of CS. Using the EU survey tool, a primary screening survey, and subsequently a secondary, more in-depth survey were developed. Results The majority of the RCs provided thromboprophylaxis to patients with CS (n = 23/25), although only one center had a standardized thromboprophylaxis protocol (n = 1/23). RCs most frequently started thromboprophylaxis from CS diagnosis onwards (n = 11/23), and the majority stopped thromboprophylaxis based on individual patient characteristics, rather than standardized treatment duration (n = 15/23). Factors influencing the initiation of thromboprophylaxis were ‘medical history of VTE’ (n = 15/23) and ‘severity of hypercortisolism’ (n = 15/23). Low-Molecular-Weight-Heparin was selected as the first-choice anticoagulant drug for thromboprophylaxis by all RCs (n = 23/23). Postoperatively, the majority of RCs reported ‘severe immobilization’ as an indication to start thromboprophylaxis in patients with CS (n = 15/25). Most RCs (n = 19/25) did not provide standardized testing for variables of hemostasis in the postoperative care of CS. Furthermore, the majority of the RCs provided preoperative medical treatment to patients with CS (n = 23/25). About half of these RCs (n = 12/23) took a previous VTE into account when starting preoperative medical treatment, and about two-thirds (n = 15/23) included ‘reduction of VTE risk’ as a goal of treatment. Conclusions There is a large practice variation regarding thromboprophylaxis management and perioperative medical treatment in patients with CS, even in Endo-ERN RCs. Randomized controlled trials are needed to establish the optimal prophylactic anticoagulant regimen, carefully balancing the increased risk of (perioperative) bleeding, and the presence of additional risk factors for thrombosis.

Mapping of the current transition of care practice for patients with pituitary disease at Endo-ERN reference centers

“…For this survey-based cross-sectional study, a survey was developed using the online EU Survey tool, as published previously ( 10 , 11 , 12 ). The representatives of the RCs within MTG6 were approached by email with a link to the survey.…”

Mineralocorticoid Receptor Activation in Vascular Insulin Resistance and Dysfunction

“…One study showed that corticosteroid therapy mismatches increased mortality by 1.5–2-fold, reducing life expectancy by 11 years in males and by 3 years in females [ 65 ]. Cushing’s syndrome is an endocrine disorder induced by increased endogenous cortisol secretion or the exogenous administration of glucocorticoids [ 66 ]. Cushing’s syndrome is not only related to increased CVD risk, such as atherosclerosis, coronary heart disease, and heart failure, but is also associated with metabolic syndromes, including obesity, glucose intolerance, insulin resistance, and diabetes [ 66 ].…”

“…Cushing’s syndrome is an endocrine disorder induced by increased endogenous cortisol secretion or the exogenous administration of glucocorticoids [ 66 ]. Cushing’s syndrome is not only related to increased CVD risk, such as atherosclerosis, coronary heart disease, and heart failure, but is also associated with metabolic syndromes, including obesity, glucose intolerance, insulin resistance, and diabetes [ 66 ]. It is accepted that Cushing’s syndrome can induce EC and VSMC dysfunction through MR signaling and lead to increased vascular inflammation, atherosclerosis, and vascular insulin resistance [ 66 ].…”

Hypercoagulability in Cushing’s syndrome: incidence, pathogenesis and need for thromboprophylaxis protocols

“…Apart from thromboprophylaxis, preoperative cortisol-lowering therapy may reduce VTE risk, although this was only shown in one retrospective study [ 6 ], whereas another retrospective study found no benefit [ 16 ]. A recent survey assessing current clinical practice of thromboprophylaxis in reference centers of the European Reference Network on Rare Endocrine Conditions (Endo-ERN) demonstrated considerable heterogeneity with respect to timing, duration and type of thromboprophylaxis [ 17 ]. Most centers started thrombophylaxis from diagnosis onwards, usually with low molecular weight heparin, but treatment duration was highly variable and often a thromboprophylaxis protocol was unavailable.…”