Risk Stratification of Adrenal Masses by [18F]FDG PET/CT

Changing Tactics

Betty Salgues; Carole Guerin; Vincent Amodru; François Pattou; Laurent Brunaud; Jean-Christophe Lifante; Eric Mirallié; Nicolas Sahakian; Frédéric Castinetti; Anderson Loundou; Karine Baumstarck; Fréderic Sebag; David Taïeb


Clin Endocrinol. 2021;94(2):133-140. 

In This Article


Characterization of adrenal masses is a challenging clinical scenario since a delay in malignancy diagnosis may affect the prognosis and excessive adrenalectomies (Adx) for undeterminated masses can lead to excessive resection of benign tumours with potential postoperative and endocrine morbidity. The present study aimed to evaluate the value of previously reported cut-off ratios for tumour SUVmax:liver SUVmax in an independent cohort and to build a predictive test for malignancy with two independent populations (training and validation cohorts). We also evaluated for the first time the potential role of CT-derived anthropometric parameters in this clinical setting.

The principal conclusions that can be drawn from this study include first, the previously reported performances of the cut-off values for tumour SUVmax:liver SUVmax ratio in indeterminate and/or large adrenal masses are confirmed; second, a reliable predictive model has been generated; and finally, the measurement of CT-derived anthropometric parameters did not add information.

In nononcologic patients or after complete remission of cancer, most of the malignant masses are represented by ACC: 73% in our previous study and 70% in the present series. One of the most difficulties for determining a 'universal' cut-off value for tumour SUVmax:liver SUVmax ratio mainly relies on the heterogenous nature of the ACC. In our previous prospective cohort, two malignant tumours exhibited a tumour SUVmax:liver SUVmax ratio < 1.5 and corresponded to a liposarcoma (ratio = 0.8) and an ACC (ratio = 1.4) (sensitivity of the 1.5 cut-off = 86.7%). Additionally, benign oncocytomas which are characterized by impairment of oxidative phosphorylation processes and a compensatory excessive mitochondria biogenesis, usually exhibit highly elevated uptake ratio values and represent a potential false-positive finding.

In the present cohort, 1 malignant tumour (1 renal cell cancer metastasis) had a tumour SUVmax:liver SUVmax < 1.5. Of note, during our longstanding experience (>15 years) of adrenal imaging, we have had very few cases with uptake ratio < 1.5 (none in this series). Other previous series have also reported various cut-off values for SUV-derived metabolic indices.[17–20] The main limitation of all studies on adrenal mass characterization relies on the heterogeneous nature of the population. Therefore, alternative approaches should be developed.

Since tumour size represents another powerful predictor of malignancy and may also affect [18F]FDG quantification (via partial volume effect), we have developed a model that takes into account tumour diameter and tumour SUVmax:liver SUVmax ratio, both parameters being easily measured on PET/CT examinations. The idea would be to provide a tool for clinicians that may help to calculate in a given patient the risk of malignancy and discuss the benefit-risk of Adx vs short-term imaging surveillance in each individual situations. Two models have been described, model 1 for the entire cohort and model 2 if the adrenocortical nature of the mass is known (ie steroid hormone secretion, tumour uptake of an adrenocortical tracer, metabolomics analysis and adrenal biopsy). For example, using prediction model 1, for a tumour SUVmax:liver SUVmax = 1.3 the estimated probabilities of malignancy range from 7% for 3 cm diameter to 22% for 6 cm diameter (Figure 2). As shown in our series, when estimated risk of malignancy is low, the presence of a contralateral adrenal nodule can be considered as an additional reassuring argument.

In our study, we have also measured CT-derived anthropometric parameters. Eighteen patients of our cohort had hypercortisolemia. It is well established that hypercortisolemia results in central adiposity which confers insulin resistance, dyslipidaemia and increased risk of mortality from cardiovascular disease. In overt Cushing's syndrome, CT studies demonstrated increased visceral fat.[21] In a retrospective cross-sectional analysis, CT-derived fat compartment volumes were analysed in 125 incidentalomas patients and 9 women with overt Cushing's syndrome. An increased V:TV was observed between men and women in cases with positive (serum cortisol greater than 1.8 μg/dL) vs negative low-dose dexamethasone suppression test.[22] There was no significant difference in terms of V:TV between the groups with cortisol greater than 1.8 μg/dL (1.8–2.9; 3–5, >5 μg/dL) and those with overt Cushing's syndrome. In another study, visceral fat measurements were comparable between patients with autonomous cortisol secretion compared to nonsecreting masses. However, an increased visceral fat content was observed during follow-up (3 years) in patients harbouring autonomous cortisol secretion.[23] Therefore, many factors may influence fat redistribution such as duration of exposure before diagnosis which is not easy to estimate, amount and patterns of secretion (fluctuating or permanent), individual tissue sensitivity to glucocorticoids, altered glucose metabolism. In the present study, we failed to identified any differences between benign and malignant masses in men and women. Therefore, it can be estimated that the analysis of CT-derived anthropometric parameters has very limited value in this clinical setting.

We acknowledge several limitations of the present study: the observational nature of the study, the limited sample size of the validation cohort, and the absence of pathologically proof for all masses with short follow-up CT (<12 months) in some cases.

In conclusion, although informative, it remains elusive to find a universal cut-off value for tumour SUVmax:liver SUVmax that allow diagnosis of all malignant tumours. The integration into the decision-making process of a predictive model for risk-malignancy could be an alternative approach that would enable to estimate, in a given situation, the benefit-risk of surgery vs surveillance, taking into account that Adx in experienced centres has low morbidity.