Objective. Hair cortisol (HF) and cortisone (HE) measurements reflect tissular exposure to cortisol over months and are increased in overt Cushing’s syndrome (CS). No data is available in mild CS. We compared the diagnostic performance of HF and HE between patients with overt or mild CS. Design Single centre retrospective study Methods. HF and HE were measured by LC-MS/MS in 48 consecutive adult females with Cushing’s disease (CD), ectopic ACTH syndrome, secreting adenomas and carcinomas, and adrenal incidentalomas. All had impaired dexamethasone suppression tests. Overt CS (N=25) was diagnosed in front of specific symptoms, a mean UFC (>1.5 ULN) and increased midnight serum cortisol or salivary cortisol. Mild CS (N= 23) was diagnosed in patients lacking of specific symptoms and displaying at least one additional biological abnormality including mildly increased UFC (≤1.5 ULN), increased midnight serum cortisol or salivary cortisol and suppressed plasma ACTH in patients with adrenal tumors. 84 healthy subjects and obese patients served as controls. Results. HF and HE showed roughly similar performance in overt CS (92 and 100% sensitivity, 91 and 99% specificity, respectively). HF and HE were lower in mild CS but higher than in controls (p<0.01). HE was correlated with midnight serum cortisol (p<0.02) and volume of adrenal incidentalomas (p<0.04) but not with UFC. HF and HE had 59% and 68% sensitivity, and 79 and 94% specificity, respectively, for diagnosis of mild CS. Contrary to UFC, HF and HE was in the range of overt CS in 11/23 patients with mild CS. Patients with mild CS and increased HE required more anti-hypertensive treatments and showed worse lipid profiles than patients with normal HE. Conclusions. HF and HE measurement performed better in overt than in mild CS but is a useful adjunct to diagnose mild CS and to identify adrenocortical incidentalomas responsible for excessive cortisol exposure
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Context Prospective studies have demonstrated the efficacy of osilodrostat in Cushing's disease. No study has evaluated osilodrostat in a series of patients with paraneoplastic Cushing’s syndrome/ectopic ACTH syndrome (PNCS/EAS). Objective Evaluate in France the real-world efficacy and safety of osilodrostat in PNCS/EAS. Patients 33 patients with PNCS/EAS with intense/severe hypercortisolism. Methods Retrospective multicenter real-world study. Patients received osilodrostat between May 2019 and March 2022. Median initial dose (range) 4 mg/day (1-60); maximum dose, 20 mg/day (4-100), first, under patient- then cohort- temporary authorizations and after marketing authorization. Regimens used: titration (n = 6), block and replace (n = 16), or titration followed by block and replace (n = 11). Results In 11 patients receiving osilodrostat as first-line monotherapy, median 24h- urinary free cortisol (24h-UFC) decreased dramatically (from 26xULN [2.9-659] to 0.11xULN [0.08-14.9]; p < 0.001). In 9 of them, 24h-UFC normalization was achieved in 2 weeks (median). Thirteen additional patients were previously treated with classic steroidogenesis inhibitors but 10/13 were not controlled. In these patients, osilodrostat monotherapy, used in second line, induced a significantly decreased of 24h-UFC (from 2.6xULN [1.1-144] to 0.22xULN [0.12-0.66]; p < 0.01). Nine additional patients received osilodrostat in combination with another anticortisolic drug decreasing 24h-UFC from 11.8xULN (0.3-247) to 0.43xULN (0.33-2.4) (p < 0.01). In parallel, major clinical symptoms/comorbidities improved dramatically with improvement in blood pressure, hyperglycemia and hypokalemia, allowing the discontinuation or dose reduction of their treatments. Adrenal insufficiency (grade 3-4) was reported in 8/33 patients. Conclusions Osilodrostat is a rapidly efficient therapy for PNCS/EAS with severe/intense hypercortisolism. Osilodrostat was generally well tolerated; Adrenal insufficiency was the main side effect.
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