Thyroid cancer is the most frequent endocrine malignancy, and its incidence is increasing. A current limitation of cytological evaluation of thyroid nodules is that 20–25% are reported as indeterminate. Therefore, an important challenge for clinicians is to determine whether an indeterminate nodule is malignant, and should undergo surgery, or benign, and should be recommended to follow-up. The emergence of precision medicine has offered a valuable solution for this problem, with four tests currently available for the molecular diagnosis of indeterminate cytologies. However, efforts to critically analyze the quality of the accumulated evidence are scarce. This systematic review and meta-analysis is aimed to contribute to a better knowledge about the four available molecular tests, their technical characteristics, clinical performance, and ultimately to help clinicians to make better decisions to provide the best care options possible. For this purpose, we address three critical topics: (i) the proper theoretical accuracy, considering the intended clinical use of the test (rule-in vs rule-out) and the impact on clinical decisions; (ii) the quality of the evidence reported for each test (iii) and how accurate and effective have the tests proved to be after their clinical use. Together with the upcoming evidence, this work provides significant and useful information for healthcare system decision-makers to consider the use of molecular testing as a public health need, avoiding unnecessary surgical risks and costs.
Context
Incidentally discovered adrenal adenomas are common. Assessment for possible autonomous cortisol excess (ACS) is warranted for all adrenal adenomas given the association with increased cardiometabolic disease.
Objective
To evaluate the discriminatory capacity of three-dimensional volumetry on computed tomography (CT) to identify ACS.
Design, Setting, Patients
Two radiologists, blinded to hormonal levels, prospectively analyzed CT images on 149 adult patients with unilateral, incidentally-discovered, adrenal adenomas.
Main Outcome Measures
Diameter and volumetry of the adenoma, volumetry of the contralateral adrenal gland, and the adenoma volume-to-contralateral gland volume (AV/CV) ratio were measured. ACS was defined as cortisol≥1.8 mcg/dL after 1mg dexamethasone suppression test (DST) and a morning ACTH ≤15 pg/mL.
Results
We observed that ACS was diagnosed in 35 (23.4%) patients. Cortisol post-DST was positively correlated with adenoma diameter and volume, and inversely correlated with contralateral adrenal gland volume. Cortisol post-DST was positively correlated with the AV/CV ratio (r=0.46, p<0.001) and ACTH was inversely correlated (r=-0.28, p<0.001). The AV/CV ratio displayed the highest Odds Ratio (1.40 CI 95% 1.18-1.65) and area under curve (0.91 CI 95% 0.86-0.96) for predicting ACS. An AV/CV ratio ≥1 (48% of the cohort) had a sensitivity of 97% and a specificity of 70% to identify ACS.
Conclusions
CT volumetry of adrenal adenomas and contralateral adrenal glands has a high discriminatory capacity to identify ACS. The combination of this simple and low-cost radiological phenotyping can supplement biochemical testing to substantially improve the identification of ACS.
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