Predicting malignancy in adrenal incidentaloma and evaluation of a novel risk stratification algorithm.

BACKGROUND: Incidentally discovered adrenal lesions known as adrenal incidentalomas (AI) are being encountered with increasing frequency due to the widespread use of abdominal computed tomography (CT). The aim of this study was to identify the clinical predictors of malignancy in AI and to evaluate the accuracy of a recently proposed risk stratification algorithm. METHODS: A retrospective analysis of 96 patients presenting with AI between 2004 and 2014 was undertaken; 66 patients underwent adrenalectomy, and 30 were managed non-operatively. Univariate analysis including patient demographics, CT features of tumour size, density and heterogeneity was performed. Hormonal parameters including 24-h urinary-free cortisol and serum dehydroepiandrosterone sulphate (DHEAS) were also included. A Cleveland Clinic risk stratification model utilizing adrenal size and density was evaluated. RESULTS: The overall rate of malignancy was 8%. On univariate analysis, the following preoperative variables were predictive of malignancy - tumour size on pathology (P = 0.0031) and CT (P = 0.0016), heterogeneity on CT imaging (P = 0.0036), a relative percentage washout of less than 40% (P = 0.0178), elevated 24-h urinary-free cortisol levels (P = 0.0176), elevated DHEAs (P = 0.0061) and younger age at presentation (P < 0.0001). Evaluation of the Cleveland Clinic algorithm found an area under the receiver operating characteristic curve of 0.81 (95% confidence interval 0.52-1.00). CONCLUSION: CT characteristics of tumour size, density and heterogeneity are significantly associated with malignancy in AI and applied together reliably exclude malignancy. The risk stratification algorithm utilizing size and density alone may fail to identify some smaller adrenal cancers.

TERT promoter mutations are a major indicator of recurrence and death due to papillary thyroid carcinomas.

CONTEXT: TERT promoter mutations have been associated with adverse prognosis in papillary thyroid carcinomas (PTCs). OBJECTIVE: We investigated the association between TERT promoter mutations and survival from PTC. DESIGN: Retrospective observational cohort study. PATIENTS: Eighty consecutive patients with PTC who underwent surgery between 1990 and 2003. MEASUREMENTS: TERT promoter was genotyped in DNA from 80 archival PTCs by Sanger sequencing. Median follow-up was 106 months (range 1-270). Outcomes analysis was stratified according to disease and overall survival status. For each parameter, relative risk (RR) adjusted for age at first surgery and gender was estimated. Both univariate and multivariate analyses were performed using logistic regression, Kaplan-Meier survival analysis and Cox regression models. RESULTS: PTCs from 11 patients (14%) contained either C228T or C250T TERT promoter mutation. TERT mutations were significantly associated with adverse prognostic features such as older age (P = 0·002), male gender (P = 0·01) and Stage IV disease (P = 0·03). Four patients died from PTC during follow-up: 3 patients with TERT mutations (27%) and one without (1·5%). Disease-related mortality rate with or without TERT mutations was 33·7 vs 1·6 per 1000 patient-years respectively, that is 10 (95% CI = 1·0-104·1, P = 0·05) fold higher, after adjustment for age at first surgery and gender. The combination of TERT promoter mutation and BRAF(V) (600E) significantly increased disease-related death risk (P = 0·002). TERT mutations increased expression of a reporter gene in thyroid cells containing BRAF(V) (600E) . CONCLUSIONS: TERT promoter mutations are a major indicator of death due to PTCs. Conversely, absence of TERT mutations portends better survival.

The Weight of the Resected Gland Predicts Rate of Success After Image-Guided Focused Parathyroidectomy.

BACKGROUND: A recent study of focused minimally invasive parathyroidectomy (FPTX) in sporadic primary hyperparathyroidism (pHPT) using intraoperative parathyroid hormone (ioPTH) measurements shows that inadequate ioPTH drop and multiglandular disease are more commonly found when a first gland<200 mg is resected. Our aim was to study if a resected gland that weighed <200 mg was associated with an increased persistence rate after FPTX. METHODS: This is a cohort study of FPTX for pHPT performed in the period 1998-2013. FPTX was performed in patients with pHPT where Sestamibi and Ultrasound imaging localized single-gland disease, only one gland was excised and the weight recorded. IoPTH was not used routinely. Two groups were composed according to the weight of the resected gland: Group A<200 mg and Group B≥200 mg. Persistent or recurrent disease was defined if it occurred within, or after 6 months. The primary outcome measure was the rate of persisting pHPT. RESULTS: A total of 3,511 parathyroidectomies were performed, and a total 1,745 FPTX (1,347 female) met inclusion criteria. There were 245 and 1,500 patients in groups A and B, respectively. The rate of persistent pHPT was higher in Group A, 6.1 versus 2.0% (p<0.001). Findings at re-operative surgery showed that the ipsilateral gland was diseased in 47% (7/15) of persistent cases in group A. CONCLUSION: The risk of persistent disease after MIP was higher if the resected gland weighed ≤200 mg, and this corroborates the findings of a recent study. A heightened awareness of the possibility of multigland disease should be raised, and ioPTH monitoring, identification of the ipsilateral gland or bilateral exploration may be advisable in such cases.