Peersen, Anina F

Abstract Context Salivary cortisol and cortisone provide non-invasive measures of biologically active cortisol, but their performance during dynamic testing remains incompletely defined. The utility of salivary dexamethasone to confirm exposure during dexamethasone suppression testing (DST) is unknown. Objective To compare salivary cortisol, cortisone, and dexamethasone with serum measurements during dynamic adrenal testing and to derive salivary cortisol and cortisone thresholds corresponding to clinically relevant serum cortisol concentrations. Design and Setting Cross-sectional study at a tertiary referral center. Participants Adults undergoing DST (n = 473), cosyntropin stimulation testing (CST; n = 163), or overnight metyrapone testing (OMT; n = 11). Measurements Serum cortisol was measured by immunoassay. Serum and salivary dexamethasone, salivary cortisol and cortisone were quantified by liquid chromatography–tandem mass spectrometry. Results Among 640 participants, 815 paired serum and salivary samples were analyzed. Salivary cortisol and cortisone correlated well with serum cortisol across dynamic testing, with the greatest difference following 1-mg DST (r = 0.86 vs 0.53 for cortisone and cortisol, respectively; both P < 0.001). During CST, correlations ranged from r = 0.75–0.87 for both analytes (all P < 0.001). Salivary dexamethasone correlated with serum dexamethasone (r = 0.61, P < 0.001). Salivary cortisone thresholds corresponding to prespecified clinically relevant serum cortisol concentrations of 1.8, 5, 10, and 18 µg/dL (50, 138, 276, and 497 nmol/L) were 117, 329, 585, and 1262 ng/dL (3.25, 9.13, 16.23, and 35.01 nmol/L), respectively; corresponding salivary cortisol thresholds were 16.5, 38, 80, and 278 ng/dL (0.46, 1.05, 2.21, and 7.67 nmol/L). Conclusions These findings support saliva-based dynamic adrenal testing and identify clinically relevant salivary thresholds.

Abstract Context Evidence on the evolution of cardiometabolic comorbidities following surgical remission of hypercortisolism is scarce. Objective To determine the impact of surgical remission on cardiometabolic comorbidities in patients with endogenous hypercortisolism and to identify factors associated with cardiometabolic improvement. Methods Prospective single-center cohort study (2019-2025) of adults with Cushing syndrome (CS) or mild autonomous cortisol secretion (MACS) with surgical remission of hypercortisolism. Outcomes included (1) changes in severity of hypertension, diabetes mellitus (DM), hyperlipidemia, and obesity between baseline, 3, and 12 months postremission and (2) factors associated with improvement in comorbidities. Results Among 357 patients (49% MACS, 36% pituitary CS, 10% adrenal CS, 5% ectopic CS; median age 53 years [interquartile range 42-62]; 81% women), 336 (94%) had hypertension, 241 (68%) had obesity, and 122 (35%) had DM. At a median of 12 months postsurgery, improvement in hypertension occurred in 70% (90/128) of patients with CS and 51% (60/117) of patients with MACS, DM in 90% (46/51) patients with CS and 37% (13/35) patients with MACS, and obesity in 79% (77/97) patients with CS and 20% (14/71) patients with MACS. In a multivariable analysis, higher baseline biochemical severity scores were associated with improvement in hypertension [odds ratio (OR) 1.3, 95% confidence interval (CI) 1.1-1.5), DM (OR 2.5, 95% CI 1.7-4.1), and obesity (OR 1.5, 95% CI 1.2-1.8) at a median of 12 months postremission of hypercortisolism. Conclusion Postsurgical improvement of cardiometabolic comorbidities was observed in both patients with CS and MACS. Higher baseline biochemical severity scores were associated with higher postremission improvement in comorbidities.

Abstract Context The impact of active hypercortisolism on sleep is incompletely characterized. Studies report impaired sleep in patients with Cushing syndrome (CS). Patients with mild autonomous cortisol secretion (MACS) demonstrate mild nocturnal hypercortisolism that could impact sleep. Objectives To characterize sleep abnormalities in patients with CS and MACS using the Pittsburgh Sleep Quality Index (PSQI), identify factors associated with poor sleep, and compare sleep abnormalities in patients with MACS vs referent subjects. Methods We conducted a single-center cross-sectional study of adults with active CS and MACS. Clinical and biochemical severity scores for hypercortisolism were calculated. Parallelly, we enrolled referent subjects. Quality of life was assessed using (1) the Short Form-36 (SF-36) in all participants and (2) the CushingQoL in patients with active hypercortisolism. Sleep quality was assessed using PSQI. Results PSQI was assessed in 154 patients with CS (mean 12, SD ±4.5), 194 patients with MACS (mean 11, SD 4.6), and 89 referents (mean 5, SD ±3.4). Patients with MACS exhibited shorter sleep duration, longer sleep latency, more severe daytime dysfunction, lower sleep efficiency, and a higher sleep medication use compared to referent subjects (P = <.001 for all). Age-, sex, and body mass index-adjusted analysis demonstrated no differences in PSQI or its subcomponents between patients with CS and MACS (P > .05 for all). In a multivariable analysis of patients with MACS, younger age, female sex, and higher clinical hypercortisolism severity score were associated with impaired sleep. In patients with CS, only younger age was associated with poor sleep. Conclusion Patients with MACS demonstrate sleep impairment that is similar to patients with CS. Younger women with higher clinical severity of MACS are more likely to have impaired sleep.