Worse Pituitary Adenoma Surgical Outcomes Predicted by Increasing Frailty, Not Age.

PURPOSE: Increasing patient age has been associated with worse outcomes after pituitary adenoma resection in previous studies, but the prognostic value of frailty compared with advancing age on pituitary adenoma resection outcomes has not been clearly evaluated. METHODS: The National Surgical Quality Improvement Program from 2015 to 2019 was queried for data for patients aged >18 years who underwent pituitary adenoma resection (n = 1454 identified patients). Univariate and multivariate analyses of age and frailty (5-factor modified frailty index [mFI-5]) were performed on 30-day mortality, major complications, extended length of stay (eLOS), discharge destination, and readmission and reoperation. The receiver operating characteristic curve analysis was performed to compare effect of age and mFI-5. RESULTS: On univariate analysis, increasing frailty was significantly associated with greater risk of unplanned readmission (frail: odds ratio [OR], 1.9; 95% confidence interval [CI], 1.2-3.2; severely frail: OR, 6.9; 95% CI, 2.4-19.8) and a major complication (frail: OR, 3.6; 95% CI, 2.1-6.1). Severe frailty was also associated with nonhome discharge (OR, 10.6; 95% CI, 3.2-35.8) and eLOS (OR, 4.5; 95% CI, 1.5-13.4). Increasing age was not associated with any of these outcome measures. Multivariate analysis also demonstrated similar trends. In receiver operating characteristic curve analysis, the mFI-5 score showed higher discrimination for major complications compared with age (area under the curve: 0.624 vs. 0.503; P < 0.001). CONCLUSION: Increasing frailty, and not advancing age, was an independent predictor for major complications, unplanned readmissions, eLOS, and nonhome discharge after pituitary adenoma resection, suggesting frailty to be superior to age in preoperative risk stratification in this patient population.

Decreased maximal cortisol secretion rate in patients with cirrhosis: Relation to disease severity.

BACKGROUND & AIMS: Hepatic enzymes play a major role in the metabolic elimination of cortisol, and reduced rates of cortisol clearance have been consistently observed in patients with chronic liver disease. It is less clear whether there are concomitant abnormalities of adrenocortical function in patients with cirrhosis. In the present study, we sought to assess adrenocortical function in patients with cirrhosis using measures of free cortisol appearance and elimination rates that are independent of serum concentrations of cortisol binding proteins. METHODS: Post hoc analysis used computer-assisted numerical and modelling methods with serial total and free cortisol concentration data to obtain rates of free cortisol appearance and elimination. Rate parameters were obtained in 114 patients with chronic liver disease, including Child-Pugh (CP) ≤8 (n = 53) and CP >8 (n = 61). RESULTS: Maximal cortisol secretion rate (CSRmax) was significantly decreased (p = 0.01) in patients with cirrhosis with CP >8 (0.28 nM/s; 95% CI 0.24-0.34) compared with those with CP ≤8 (0.39 nM/s; 95% CI 0.33-0.46), and CSRmax was negatively correlated with CP score (r = -0.19, p = 0.01). Free cortisol elimination rate was significantly (p = 0.04) decreased in the CP >8 group (0.16 ± 0.20 min-1) compared with that in the CP ≤8 group (0.21 ± 0.21 min-1), and free cortisol elimination rates were negatively correlated with CP score (r = -0.23, p = 0.01). A significant correlation between CSRmax and free cortisol elimination rate (r = 0.88, p <0.001) was observed. CONCLUSIONS: CSRmax and free cortisol elimination rates were significantly reduced according to severity of cirrhosis. In contrast to stimulated total cortisol concentrations, CSRmax estimates were independent of cortisol-binding protein concentrations. Results provide additional evidence of subnormal adrenocortical function in patients with cirrhosis. LAY SUMMARY: We applied numerical analytic methods to characterise adrenocortical function in patients with varying stages of chronic liver disease. We found that patients with more severe cirrhosis have decreased rate of free cortisol elimination and decreased maximal cortisol secretion rate, which is a measure of adrenocortical function. In contrast to conventional measures of adrenocortical function, those obtained using numerical methods were not affected by variation in corticosteroid binding globulin and albumin concentrations. We conclude that patients with cirrhosis demonstrate measurable abnormalities of adrenocortical function, evidence of which supports aspects of the hepatoadrenal syndrome hypothesis.

Analgesic effect of long-acting somatostatin receptor agonist pasireotide in a patient with acromegaly and intractable headaches.

A 22-year-old woman presented with worsening vision loss and headaches. A diagnosis of acromegaly was confirmed after detection of an invasive pituitary macroadenoma and biochemical testing. Despite two attempts of surgical debulking of the tumour and administration of long-acting octreotide and cabergoline, growth hormone (GH) and insulin-like growth factor 1 (IGF-1) levels were uncontrolled. The patient experienced persistent headaches despite surgery, gamma knife radiation and ventriculoperitoneal shunt placement; she was then enrolled in the ACCESS trial (ClinicalTrials.gov identifier, NCT01995734). Pasireotide (Signifor; Signifor LAR) was initiated, which led to reduced GH and IGF-1 levels and resolution of her intractable headaches. This highlights the use of monthly pasireotide in resolving headaches and improved biochemical control in a patient with acromegaly. We postulate that the headaches improved due to an analgesic and/or anti-inflammatory effect mediated by somatostatin receptors targeted by pasireotide. This may represent an additional benefit of pasireotide and requires further investigation.