PMC:3724972 / 18750-21317 JSONTXT

{"project":"2_test","denotations":[{"id":"23673515-18036161-63233641","span":{"begin":165,"end":167},"obj":"18036161"},{"id":"23673515-17202453-63233641","span":{"begin":165,"end":167},"obj":"17202453"},{"id":"23673515-17659636-63233641","span":{"begin":165,"end":167},"obj":"17659636"},{"id":"23673515-17202453-63233642","span":{"begin":390,"end":392},"obj":"17202453"},{"id":"23673515-18559921-63233643","span":{"begin":916,"end":918},"obj":"18559921"},{"id":"23673515-18957506-63233644","span":{"begin":1480,"end":1482},"obj":"18957506"},{"id":"23673515-22397653-63233645","span":{"begin":1484,"end":1486},"obj":"22397653"},{"id":"23673515-15126577-63233646","span":{"begin":1488,"end":1490},"obj":"15126577"},{"id":"23673515-20497937-63233647","span":{"begin":1492,"end":1494},"obj":"20497937"},{"id":"23673515-18957500-63233648","span":{"begin":1496,"end":1498},"obj":"18957500"},{"id":"23673515-22851491-63233649","span":{"begin":1500,"end":1502},"obj":"22851491"},{"id":"23673515-18957506-63233650","span":{"begin":1679,"end":1681},"obj":"18957506"},{"id":"23673515-22397653-63233651","span":{"begin":1805,"end":1807},"obj":"22397653"},{"id":"23673515-20497937-63233652","span":{"begin":2038,"end":2040},"obj":"20497937"},{"id":"23673515-15126577-63233653","span":{"begin":2176,"end":2178},"obj":"15126577"},{"id":"23673515-18957500-63233654","span":{"begin":2180,"end":2182},"obj":"18957500"},{"id":"23673515-22851491-63233655","span":{"begin":2375,"end":2377},"obj":"22851491"}],"text":"One potential concern regarding the use of DA agonists for CD has been the association of long-term ergot derivatives with increased risk of valvular heart disease [55–57]. However, this risk was identified in studies performed in patients using DA agonists for Parkinson’s disease at doses considerably higher (often \u003e3 mg/day) than those used in CD (generally \u003c7 mg/week). Schade et al. [56] reported that the relative risk of valvular heart disease was 50.3 (95 % CI 6.6–381.4) in patients receiving \u003e3 mg/day compared to 2.6 (95 % CI 0.5–12.8) in patients receiving \u003c3 mg/day. Furthermore, a study of 78 patients receiving DA agonists (including 47 who were using cabergoline) for an average of 8 years for prolactinoma found an increased risk of aortic valve calcification and mild tricuspid regurgitation, but no increase in the risk of clinically relevant valvular heart disease compared to control patients [58]. Among patients receiving cabergoline, the mean duration of therapy was 5.2 ± 0.4 years and the mean cumulative dose was 363 ± 55 mg. There was no relation between cumulative dose of cabergoline and the presence of mild, moderate or severe valve regurgitation. Thus, the evidence suggests that valvular heart disease associated with long-term use of DA agonists is much less of a concern for patients using the doses typical of treatment regimens for CD. A summary of current prospective studies with pituitary targeted medical therapy is provided in Table 2 [40, 43, 48, 52, 53, 59].\nTable 2 Medical treatments for Cushing’s disease evaluated in prospective clinical studies\nCompound Trial Patients (N) Treatment duration Outcome\nPasireotide Boscaro et al. [40] 29 15 days 5/29 patients (17 %) achieved UFC ≤ ULN; 22/29 patients (76 %) experienced reduction in mean UFC\nColao et al. [43] 162 12 months 33/162 patients (20 %) achieved UFC ≤ ULN within 6 months without increase from randomized dose; the majority of patients experienced reduction in UFC at month 6, sustained through month 12\nCabergoline Lila et al. [52] 18 5 months 5 patients (28 %) achieved MNSC \u003c5 μg/dL or low-dose dexamethasone-suppressed serum cortisol \u003c1.8 μg/dL\nPivonello et al. [48, 53] 20 3–24 months After 3 months, 15 patients (75 %) achieved UFC ≤ ULN or ≥25 % reduction from baseline; 8 patients (40 %) maintained UFC ≤ ULN at 24 months\nRetinoic acid Pecori Girald et al. [59] 7 6–12 months 3/7 patients (43 %) achieved UFC ≤ ULN; 5/7 patients (71 %) experienced reduction in UFC\nMNSC midnight salivary cortisol, UFC urinary free cortisol, ULN upper limit of normal"}