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1 2 DR FREDERIC CASTINETTI (Orcid ID : 0000-0002-1808-8800)
3 PROFESSOR DAVID TAIEB (Orcid ID : 0000-0002-0400-7600)
4 5 6 Article type : Original Article
Risk stratification of adrenal masses by [18F]FDG PET/CT: changing tactics
Running title : [18F]FDG PET/CT in adrenal tumours
Authors: Betty Salgues1, Carole Guerin2, Vincent Amodru3, François Pattou4, Laurent Brunaud5, Jean-Christophe Lifante6, Eric Mirallié7, Nicolas Shahakian1, Frédéric Castinetti3, Anderson Loundou8, Karine Baumstarck8, Fréderic Sebag2, David Taïeb1
7 8 9 10 11 12 13 14 15 16 17 Affiliations: 18 1Service de Médecine Nucléaire, Centre hospitalo-universitaire de la Timone, APHM, Centre Européen de Recherche en Imagerie Médicale, Aix Marseille Univ, France
19 20 2Service de Chirurgie Générale et Endocrinienne, Centre hospitalier Conception, APHM, Aix
21 Marseille univ, France
22 3Service d’Enodrinologie, Centre hospitalier Conception, APHM, Aix Marseille univ, France
23
4Service de Chirurgie Endocrinienne, Centre hospitalier régional universitaire de Lille, Lille,
24 France; Université Lille nord de France, INSERM, Lille, France
4Service de Chirurgie Générale et Endocrinienne, Centre hospitalier Lyon Sud, Pierre bénite
25 26 5Université de Lorraine, Service de Chirurgie digestive, hépatobiliaire et endocrinienne, Centre hospitalo-universitaire Nancy Brabois, Nancy, France
27 28 6Service de Chirurgie Générale et Endocrinienne, Centre hospitalier Lyon Sud, Pierre bénite
29 7 Chirurgie Cancérologique, Digestive et Endocrinienne, Hôtel Dieu, CHU Nantes, France 30 8 Service de Santé Publique, faculté de Médecine de la Timone, Aix Marseille Univ, France
31
32
This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as doi: 10.1111/CEN.14338
1 Correspondence
☒ 2
David Taïeb, MD, PhD
3 Service de Médecine Nucléaire
4
Centre hospitalo-universitaire de la Timone
5 Centre Européen de Recherche en Imagerie Médicale
6 Université Aix-Marseille
264, rue Saint-Pierre
7 8 13385 Marseille, France 9 david.taieb@ap-hm.fr 10 Phone/FAX: +33 (0) 4-91-38-44-06
11 12 13 14 15 16 No. of references: 23
Article type: Original article
Abstract length: 246 words
Text length: 3136 words
No. of graphics: 3 (2 tables, 1 figure)
Separate file supplied
Author contributions: All authors contributed significantly to the work, meet the criteria for authorship, provided critical review of the manuscript, and approved the final version for publication.
Conflict of interest: The authors declare that they have no conflict of interest that could be perceived as prejudicing the impartiality of the research reported.
Funding information : no funding.
Data availability statement: The data that support the findings of this study are available from the corresponding author upon reasonable request.
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1 Summary
☒ 2
3 Context: [18F]FDG PET/CT improves adrenal tumour characterization. However, there is still no consensus regarding the optimal imaging biomarkers of malignancy.
4
5 6
Objectives: To assess the performance of Tumour SUV max: Liver SUV max for malignancy-risk and to build and evaluate a prediction model.
7 8
9
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Design/Methods. The cohort consisted of consecutive patients with adrenal masses evaluated by [18F]FDG PET/CT. The gold standard for malignancy was based on histology or a multidisciplinary consensus in non-operated cases. The performance of the previously reported cutoff for Tumour SUVmax:Liver SUVmax (>1.5) was evaluated in this independent cohort. Additionally, a predictive model of malignancy was built from the training cohort (previous study) and evaluated in the validation cohort (current study).
Results. Sixty-four patients were evaluated; 28% of them had a Cushing’s syndrome. Fifty-four adrenal masses were classified as benign and 10 as malignant (including 7 adrenocortical carcinomas). Compared to benign masses, malignant lesions were larger in size, had higher unenhanced densities and higher [18F]FDG uptake. CT-derived anthropometric parameters did not differ between benign and malignant masses. A tumour SUVmax:Liver SUVmax >1.5 showed a good diagnostic performance : Se=90.0%/Sp=92.6%/PPV=69.2%/NPV=98.0% and accuracy=92.2%. A predictive model based on tumour size and tumour-to-liver uptake SUVmax ratio for malignancy-risk was validated and provides a complementary approach to the ratio.
Conclusions. Tumour SUV max: Liver SUV max uptake ratio is a useful biomarker for diagnosis of adrenal masses. Another tactic would be to calculate with the model an individual risk of malignancy and integrate this information into a shared decision-making process.
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Keywords: adrenal; [18F]FDG, computed tomography; incidentaloma; adrenocortical carcinoma
ACC
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Introduction
3 4 5 6 7 8
The adrenal glands can be affected by a variety of pathologic conditions, including hyperplasia, hemorrhage, malignant (primary or secondary) and benign tumours from cortical or medullary origin. Tumours can be hyperfunctioning, when producing an increased amount of hormones, or non-hyperfunctioning, which are characterized by normal blood hormone levels. Therefore, in some cases, these lesions can be clinically suspected of malignancy, but in most cases adrenal masses are discovered incidentally. Incidentalomas are typically found in approximately 5% of abdominal computed tomographies (CT) and are mainly benign in nature. Regardless of the mode of discovery, clinical history and physical examination, the first step relies on appropriate biochemical evaluation. Characterization of an adrenal mass by appropriate imaging investigations follows. In this setting, adrenal CT represents the first-level imaging modality for the evaluation of adrenal lesions. Several criteria have been defined on both imaging studies. High specificity for adrenocortical adenomas diagnosis was achieved using an unenhanced CT density cutoff of equal to or less than 10 Housfield units (HU) 1. Moreover, adrenocortical adenomas often exihibit a typical wash-out pattern, with an absolute enhancement washout of ≥ 60% and/or relative enhancement washout of ≥ 40% on contrast enhanced CT 2,3 or demonstrate signal loss in opposed-phased magnetic resonance imaging (MRI) 4. MRI is not superior to CT and among adrenal mass with unenhanced attenuation CT density >30 HU, 66.6% remain indeterminate after chemical shift MRI 5. Beyond these parameters, clinicians should be aware that tumour size is the best predictor of malignancy 6,7. In frequent situations, the masses remain indeterminate on radiologic imaging or are too large for accurately ruling out malignancy risk, except for typical myelolipoma, cyst or hematoma.
Several studies have shown that the assessment of metabolic activity by 18F-fluorodeoxyglucose positron emission tomography-computed tomography ([18F]FDG-PET/CT) can help to characterize large and/or indeterminate masses. The use of tumour-to-liver uptake maximum standardized uptake values (SUVmax) ratio was found to more accurate than visual analysis in the distinction between benign and malignant tumours, with an optimal threshold varying across studies 8,9. In a prospective study, we have previously shown that a ratio >1.5 (from a ROC curve) was associated with malignancy with sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of 86.7%, 86.1%, 56.5%, 96.9%, and 86.2%, respectively 10.
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2
1 Although this cutoff value is useful, it is well known that some adrenocortical cancer and even large retroperitoneal sarcomas that may mimic adrenal tumours can exhibit lower uptake values.
4
3 Considering that tumour size and tumour-to-liver uptake SUV max ratio represent predictors of malignancy, the primary goal of the study was to evaluate the performance of the previously reported tumour-to-liver uptake SUVmax ratio in a new independant cohort of 64 patients. The 5 6 secondary goals were to built a probability model for predicting malignancy based on a previously 7 reported cohort (87 patients) and validate the model in this new cohort that served as validation 8 cohort. Finally, we also evaluated whether additional parameters such as CT-derived anthropometric parameters or contralateral adrenal gland morphology could add information.
9
Accepted
1 Material and Methods
2 3 Study design
4 5
6
The inclusion criteria for validation cohort were (all criteria): 1- [18F]FDG-PET/CT performed between January 2017 and December 2019 at La Timone university hospital; 2- 18F- [18F]FDG-PET/CT performed for characterization of an adrenal mass of maximal diameter ≥ 30 mm on axial CT or ≥ 20 mm and atypical features on adrenal CT (spontaneous density ≥10 HU and slow contrast washout (absolute washout <60% and/or relative washout <40%) ; 4- absence of previous history of any type of cancer, except remission>5 yrs; 5- Available complete hormonal work-up. Cases with elevated metanephrines were excluded.
The study was approved by the local ethical committee of Aix-Marseille University. All patients gave informed consent for the use of anonymous personal data extracted from their medical records for research purposes.
Patients and tumour secretory status
Depending on their secretory status, patients were divided in four distinct categories: (1) Cushing syndrome when patients exhibited an absence of cortisol suppression (> 50 nmol/l) after a low dose dexamethasone suppression test, associated with suppressed ACTH secretion and the existence of comorbidities usually associated with hypercortisolism, (2) Subclinical hypercortisolism was defined following the ESE/ENSAT guidelines, as being likely when the cortisol after 1 mg-overnight dexamethasone suppression test was between 51 and 138nmol/L (1.9-5.0µg/dL) and certain when superior to 138 nmol/L, associated with suppressed ACTH secretion and the absence of comorbidities usually associated with hypercortisolism, (3) Other secretion defined by an increased of aldosterone/renin ratio or testosterone levels in women, (4) Non secreting, defined by normal urine and/or plasma metanephrines, normal aldosterone/renin ratio, normal mean of 2 measurements of 24-hour urinary free cortisol levels and cortisol level < 50 nmol/l following a 1 mg-overnight dexamethasone suppression test, normal testosterone in women.
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1 2 3 4
[18F]FDG-PET/CT was performed on a GE Healthcare Discovery PET/CT 710 (General Electric Healthcare) with the three-dimensionnal Time-Of-Flight mode. All patients fasted for 6 hours prior to scanning. [18F]FDG (3MBq/kg) was intravenously injected. After tracer injection, patients remained at rest and [18F]FDG-PET/CT was acquired at approximately one hour post-
5 6 injection. A whole-body imaging was perfomed from skull base to mid-thigh, corresponding to 6 to 8 steps of 2 minutes each. Slice thickness of the helical CT was 2.5 mm. The attenuation and impulsional response corrected PET was reconstructed with 3D iterative process (with 24 subsets and 2 iterations), using a CT attenuation map.
[18F]FDG-PET/CT scans were analyzed by a nuclear physician investigator blinded to the results of the other imaging and biochemical studies.
Some parameters were extracted from CT attenuation corrected PET images :
- Quantitative analysis of adrenal mass and contralateral adrenal gland uptake were assessed semi- automatically and expressed as SUVmax and tumour-to-liver SUV max uptake ratio ;
- Visual analysis (VA) of the brown adipose tissue was performed;
Other parameters were extracted from unenhanced CT images:
- Tumour size and density;
- Description of the contralateral adrenal gland as follows : 0-normal 1-hyperplasia 2-nodular;
18 19 - Analysis of liver steatosis; 20 - Measurements of total (T), visceral (V), subcutaneous (S) fat and muscle areas as follows:
21 The scan being measured was loaded into the Volume Viewer to enable the L3-L4 disc space to 22 be identified using sagittal views.
23 The single cross sectional CT image (L3-L4 disc space) was saved as a DICOM and imported into 24 25 CoreSlicer (https://coreslicer.com) 11. Attenuation range of HU was set to provide tissue areas (muscle, adipose tissue). Range of HU to select pixels was unknown by users because of the 26 proposed workflow. On the interface, the tissue area is directly selected (muscle, subcutaneous or 27 28 visceral adipose tissue, bone) and not range of HU. Automated segmentation algorithms are referenced and used in this study to provide body composition. Manual corrections was performed 29 30 31 32
to delete aberrant pixel or add others in the body segmentation. Analysis of fat and lean tissue at this area are higly correlated to corresponding whole body composition and are an important predictor of the metabolic syndrome 12-16. Total body fat mass and lean body mass have been defined using equations published by Mourtzakis et al. 13.
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1 2 3
4 5 6
Gold standard was defined from :
- Histology : 1- for adrenocortical tumours, malignant tumours was based on a Weiss score for ACCs ≥ 3; 2- for oncocytomas, malignant was based on Bisceglia scoring system: the existence of at least one major criterion defines a malignant oncocytoma. Oncocytomas with uncertain malignant potential (borderline) defined by one to four minor criteria were classified as benign.
- For non operated adrenal masses : lesions were classified as benign by a multidisciplinary staff based on imaging features on CT and CT follow-up (≥ 6 months). Stable disease was assumed when the mass remained stable or had minimal increase in size (<15%) of the tumour diameter on the last CT.
Statistical analysis
Statistical analysis was performed using IBM SPSS Statistics version 20 (IBM SPSS Inc., Chicago, IL, USA). Continuous variables are expressed as means +SD or medians with range (min, max), and categorical variables are reported as count and percentages. All the tests were two-sided. Statistical significance was defined as p<0.05.
Two different populations were defined: all the cases and the subgroup of adrenocortical tumours. For each population, comparisons of imaging findings between two groups, benign and malignant masses, were performed using student t-test or Mann-Whitney U for continuous variables and Chi-Square test (or Fisher’s exact test, as appropriate) for qualitative variables.
First, a prediction model was built from a prospective cohort (training cohort) using a logistic regression model including 2 parameters: the tumour SUVmax: liver SUV max uptake ratio and the tumour diameter. To quantify the discrimination performance of the model, the area under the receiver operating characteristic (AUC) curve was measured. Calibration plots were used to assess the calibration of this model, accompanied with a Hosmer-Lemeshow.
The prospective training cohort consisted of 87 patients from 8 French university hospitals and has been previously described 10. In the training cohort, among the 87 masses, 72 were classified as benign and 15 as malignant. Briefly, histology was obtained in 64 patients and identified 15 malignant tumours (11 ACCs, one metastasis from lung carcinoma, two leiomyosarcomas, one
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liposarcoma); 47 benign tumours including 34 ACAs and two oncocytomas with uncertain malignant potential. The remaining 23 cases remained stable on 12-months follow-up CT and were therefore considered as benign lesions.
Second, the performance of the model was tested on an independent cohort (validation cohort). The logistic regression formula from the initial cohort was applied to the validation cohort and the probability for each patient was calculated. To quantify the discrimination performance of the model, the area under the receiver operating characteristic (AUC) curve was measured. 8 Calibration plots were used to assess the calibration of this model, accompanied with a Hosmer- 9 10 11
Lemeshow chi-square test. The cutoff points were calculated from the ROC curves that maximized both sensitivity (Se) and specificity (Sp). Negative predictive value (NPV), positive predictive value (PPV), and accuracy were provided with their 95% confidence intervals.
Accepted
1 2 3 4 5 6 7
1 2 3 4 5 6
Results
Patients and tumours
During the inclusion period, 75 consecutive patients with adrenal masses were referred from endocrinologists and endocrine surgeons of our institution for [18F]FDG-PET/CT. Eleven patients 7 8 were excluded from the analysis: 5 cases due to the presence of an active cancer, 2 due to lack of information regarding their secretory status, 4 patients due to elevated metanephrines (i.e., 9 pheochromocytoma). The study population consisted of 64 patients (31 women, 33 men; mean age of 58.3 years): 35 had masses ≥ 40 mm including 18 with atypical feature on CT; 29 had masses <40 mm including 17 with atypical feature on CT. Seventeen patients had cortisol hypersecretion alone (15 overt Cushing’s syndrome, 2 subclinical Cushing’s syndrome), 1 mixed secretions (hypercortisolism and hyperaldosteronism) and 3 had isolated hyperaldosteronism.
Management
Management and therapeutic decisions were made with the knowledge of the PET/CT findings. Thirty-three patients (51%) underwent adrenalectomy.
Final diagnosis
In the validation cohort, according to the gold standard, 54 masses were classified as benign and 10 as malignant. Histology (following surgery or biopsy for two cases) was obtained in 35 patients and identified 10 malignant tumours (7 adrenocortical carcinomas-ACC, 1 metastasis from hepatocarcinoma, 1 from a renal cell carcinoma (RCC) (>5 years remission) and 1 undifferentiated carcinoma from an unknown origin), and 25 benign tumours (16 adenomas-ACA, 2 hematomas, 3 myelolipomas, 1 benign oncocytoma, 1 borderline oncocytoma of uncertain malignant potential, 2 cysts).
Overall, 29 non operated masses were classified as benign by a multidisciplinary staff. Median and mean follow-up CT were 15 months (range 6-39 months) and 18.3 months, respectively. 20/29 patients had stable disease at follow-up CT (≥ 12 months). 9/29 had stable disease at follow- up CT (6 months ≤ CT < 12 months). Among this 9 patients 4 had previous history of stable
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1 disease for more than 6 months prior PET study (>6 months to 5 years).
2 3 [18F]FDG-PET/CT findings
4 5
☒
Compared to benign lesions, malignant lesions were larger in size, had a higher spontaneaous density and higher [18F]FDG uptake values. These results were observed in the entire population (N=64), as well as in the group of histologically proven adrenocortical tumours (N=25) (Table 1).
One malignant tumour exihited a tumour SUV max: liver SUV max ratio <1.5 and corresponded to 1 adrenal metastasis from a RCC (ratio 1.2). None of the patients with malignant tumour exihibit a contralateral adrenal nodule.
Benign tumours with the highest tumour SUVmax: liver SUV max ratio corresponded to a borderline oncocytoma (ratio=13.2) and 2 adenomas with an oxyphile cells component of 50% and 10% (ratio=4.7 and 2.8, respectively).
Among the 29 non-operated benign masses: 25 had tumour SUV max: liver SUVmax ratio <1, two had a ratio=1 and the remaining 2 cases had a ratio>1 (1.4 and 1.2) but a stable disease on CT follow-up (Figure 1).
The performance of the previously reported cutoff values (based on the prospective study) for tumour SUVmax: liver SUVmax (>1.5 in the entire cohort and >1.6 adrenocortical tumours) applied to validation cohort were :
- In the entire population (n=64) using a ratio >1.5 : Se=90.0% (59.6-98.2); Sp=92.6% (82.5- 97.1), PPV= 69.2% (42.4-87.3), NPV=98.0% (89.7-99.7) and accuracy= 92.2% (83.0-96.6).
- In adrenocortical tumours (n=25) using a ratio >1.6 : Se=100% (64.6-100); Sp=77.8% (54.8- 91.0), PPV= 63.6% (35.4-84.8), NPV= 100% (78.5-100) and accuracy= 84% (65.4-93.6).
Predictors of malignancy
Two models for calculating probabilities of malignancy that takes into account both tumour size (diameter) and tumour SUV max: liver SUV max were built from a prospective cohort of patients (See materials and methods) and expressed as follows:
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1 Model 1: For the entire population
2
p
3 Logit(p) = Ln(-)Logit(p) = Ln( __ ) =- 4.088+0.043*Diameter+0.201* (tumour SUV max: liver 1-p 1-p
SUV )
max
4 5 6 Where
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z =- 4.088+0.043*Diameter+0.2* (tumour SUVmax: liver SUVmax) 9 10
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ez = Pez =P 1-p
1-p
p =
1+ez
p = ez 1+ez
Model 2: For the group of pathologically proven adrenocortical tumours (benign and malignant):
Logit(p) = Ln( -_- )Logit(p) = Ln(-) =- 5.04+0.04*Diameter+1.16* (tumour SUV max: liver 1-p 1-p
SUV max )
15 16 Where
17 18 Z =- 5.04+0.04*Diameter+1.16* (tumour SUVmax: liver SUVmax) 19 20 Where Diameter is expressed in mm and p corresponds to the probability of malignancy.
21
22 The AUC values for model 1 and 2 applied to validation cohort were 0.88 (95% CI : 0.78 to 0.95, 23 p <0.0001), and 0.91 (95% CI : 0.72 to 0.99, p <0.0001), respectively. The cutoff values of risk probability of malignancy in the model 1 was 16.1% with a sensitivity of 90% (55.5-99.7) and specificity of 74.1% (60.3-85.0). For the model 2, the cutoff was 25.8% with a sensitivity of 100% (59-100) and specificity of 83.3% (58.6-96.4).
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24 25 26 27 A graphical representation of the probabilities of malignancy according prediction model 1 is shown in Figure 2. A calculator configured to calculate individual malignancy risks with the two models is provided as supplemental file.
ez
p
1 Analysis of CT-derived anthropometric parameters
3 As shown in Table 2 and supplemental Table 1, in women and men, there were no statistical differences between benign and malignant adrenal masses for V:S ratio, V:TA ratio and total body 5 lean mass.
2 4 Accepted Article ☒
Discussion
1 2
Characterisation 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 SUV max: 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: firstly; the previously reported performances of the cutoff values for tumour SUVmax: liver SUVmax ratio in indeterminate and/or large adrenal masses are confirmed; secondly; a reliable predictive model has been generated; and finally, the measurement of CT-derived anthropometric parameters did not add information.
In non-oncologic patients or after complete remission of cancer, most of the malignant masses are represented by adrenocortical carcinomas (ACC): 73% in our previous study and 70% in the present series. One of the most difficulties for determining a “universal” cutoff value for tumour SUVmax: liver SUVmax ratio mainly relies on the heterogenous nature of the ACC. In our previous prospective cohort, two malignant tumours exihited a tumour SUV max: liver SUV max ratio <1.5 and corresponded to a liposarcoma (ratio= 0.8) and an ACC (ratio= 1.4) (Sensitivity of the 1.5 cutoff= 86.7%). Additionally, benign oncocytomas which are characterized by impairment of oxidative phosphorylation processes and a compensatory excessive mitochondria biogenesis, usually exihibit 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 yrs) 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 cutoff 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 developped a model that takes into
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1 2 3 4 5 6 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 (i.e., steroid hormone secretion, tumour uptake of an adrenocortical tracer, metabolomics analysis, adrenal biospy). For example, using prediction model 1, for a tumour SUVmax: liver SUVmax= 1.3 8 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, dyslipidemia 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 analyzed 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) versus negative low-dose dexamethasone suppresion 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 non-secreting 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 have 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.
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1 2 3 4 5 6 7
In conclusion, although informative, it remains elusive to find a universal cutoff value for tumour SUV max: liver SUV max 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 versus surveillance, taking into account that Adx in experienced centers has low morbidity.
Accepted Artige
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☒ 2
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21. Rockall AG, Sohaib SA, Evans D, et al. Computed tomography assessment of fat distribution in male and female patients with Cushing’s syndrome. Eur J Endocrinol. 2003;149(6):561-567.
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22. Debono M, Prema A, Hughes TJ, Bull M, Ross RJ, Newell-Price J. Visceral fat accumulation and postdexamethasone serum cortisol levels in patients with adrenal incidentaloma. J Clin Endocrinol Metab. 2013;98(6):2383-2391.
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1 23. Yener S, Baris M, Peker A, Demir O, Ozgen B, Secil M. Autonomous cortisol secretion in adrenal incidentalomas and increased visceral fat accumulation during follow-up. Clin Endocrinol (Oxf). 2017;87(5):425-432.
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Accepted Articl
Accepted Article
| All masses (N=64) | Adrenocortical tumours (histologically proven) (N= 25) | |||||
|---|---|---|---|---|---|---|
| Benign N= 54 | Malignant N= 10 | p | Benign N=18 | Malignant N=7 | p | |
| Age (mean) | 59.1 | 54.3 | 0.373 | 56.0 | 50.7 | 0.437 |
| Female (%) | 50.0 | 40.0 | 0.734 | 55.6 | 57.1 | 0.999 |
| Hypercortisolism (including subclinical) (%) | 22.2 | 60.0 | 0.024 | 44.4 | 85.7 | 0.090 |
| Tumour size (mm) (mean + SD) | 44.8 ± 22.2 | 88.2 ± 43.0 | 0.011 | 39.4 ± 16.2 | 91.9 ± 46.6 | 0.024 |
| Median (Min-Max) | 38.5 (20.0-110.0) | 81.5 (39.0-180) | 31.5 (22.0-73.0) | 83.0 (50.0-180.0) | ||
| Unenhanced HU (mean ± SD) | 18.8 ± 33.8 | 37.9 ± 7.2 | 0.002 | 16.4 ± 17.2 | 36.3 ±6.3 | 0.004 |
| Median (Min-Max) | 16.5 (-90-140) | 37 (25-52) | 17 (-14-45) | 36 (25-45) | ||
| Atypical feature on CT (%) | 46.3 | 100 | 0.001 | 55.5 | 100 | 0.057 |
| Tumour uptake ratio (mean + SD) | 1.1 ± 1.8 | 2.9 ± 1.2 | 0.004 | 1.9 ± 3.0 | 3.1 ± 1 | 0.008 |
| Median (Min-Max) | 0.7 (0.1-13.3) | 2.7 (1.2-4.4) | 1.0 (0.5-13.3) | 2.8 (1.7-4.4) | ||
| Tumour uptake (mean ± SD) | 4.8 ± 8.2 | 12 ± 5.4 | <0.001 | 8.6 ± 13.5 | 12.5 ± 5.3 | 0.008 |
| Median (Min-Max) | 3.3 (0.4-58.5) | 9.9 (6.2 .- 21.5) | 3.7 (2.3-58.5) | 10.0 (7.2-21.5) | ||
| Contralateral adrenal uptake (mean + SD) | 2.2 ± 0.8 | 1.8 ± 0.6 | 0.229 | 2.0 ± 0.8 | 1.8 ± 0.7 | 0.804 |
| Median (Min-Max) | 2.2 (0.7-3.9) | 2.2 (0.7-2.5) | 2.1 (0.7-3.6) | 2.2 (0.7-2.5) | ||
| Contralateral adrenal uptake ratio (mean + SD) | 0.5 ± 0.2 | 0.5 ± 0.2 | 0.559 | 0.5 ± 0.2 | 0.5 ± 0.2 | 0.901 |
| Median (Min-Max) | 0.5 (0.2-0.9) | 0.5 (0.2-0.7) | 0.4 (0.2-0.8) | 0.5 (0.2-0.7) | ||
| Contralateral gland morphology, nodular feature | 11/52 | 0/10 | 0.185 | 3/17 | 0/7 | <0.001 |
| (%) | (21.1%) | (0%) | (17.6%) | (0%) | ||
HU : Hounsfield units ; CT : computerized tomography ; SD: standard deviation ; Bold values: p<0.05
Accepted Article
| Women (all) N=31 | Men (all) N=33 | |||||
|---|---|---|---|---|---|---|
| Benign N= 27 | Malignant N= 4 | p | Benign N=27 | Malignant N=6 | p | |
| V:S ratio (mean + SD) | 49.8 ± 25.5 | 57.9 ±21.3 | 0.441 | 117.2 ± 133.7 | 95.7 ± 75.7 | 0.803 |
| Median (Min-Max) | 46.2 (17.1-128.2) | 58.4 (34-81) | 79.5 (12.8-725.0) | 83.6 (6.3-215.5) | ||
| V:TA ratio (mean + SD) | 18.6 ± 6.7 | 13.5 ± 10.3 | 0.193 | 26.8 ± 14.3 | 26.3 ± 16.0 | 0.982 |
| Median (Min-Max) | 17.9 (5.5-29.4) | 11.5 (3.3-27.8) | 26.2 (3.5-54.3) | 25.8 (2.1-44.9) | ||
| Total body fat mass (meantSD) | 28.5 ± 8.0 | 22.1 ± 9.7 | 0.154 | 30.5 ± 10.6 | 32.8 ± 8.5 | 0.424 |
| Median (Min-Max) | 26.9 (15.8-47.8) | 20.1 (12.8-35.4) | 29.3 (15.7-57.2) | 32.5 (24.0-47.5) | ||
| Total body lean mass (mean + SD) | 43.0 ± 7.7 | 40.9 ± 5.1 | 0.798 | 57.7 ± 9.0 | 62.4 ± 12.7 | 0.424 |
| Median (Min-Max) | 43.0 (30.4-62.5) | 41.9 (34-45.7) | 57.1 (44.8-76.3) | 60.7 (46.3-82.0) | ||
| BMI (Kg/m2) (mean + SD) | 28.3 ± 7.7 | 26.3 ± 4.5 | 0.977 | 27.9 ± 5.4 | 27.8 ± 6.1 | 0.699 |
| Median (Min-Max) | 26.0 (21.0-53.0) | 27.5 (20.0-30.0) | 26 (22.0-44.0) | 25.0 (22.0-37.0) | ||
| Diabetes (%) (including pre-diabetes) | 3/27 | 0/4 | 0.999 | 4/27 | 0/6 | 0.999 |
| 11.1 | 0 | 14.8 | 0 | |||
V:S ratio: ratio of visceral fat to subcutaneous fat ; V:TA ratio: ratio of visceral fat to total area ; BMI: body mass index ; SD: standard deviation ; Bold values: p<0.05
rticle
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Tumour SUVmax
Tumour SUVmax: Liver SUVmax
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For readibility, the tumor with the highest uptake values corresponding to an oncocytoma with uncertain malignant potential (classified as benign) (SUVmax= 58.5 and SUVmax ratio= 13.3) is not represented in the figure.
Accepted
Tumour SUVmax: Liver SUVmax
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0.999
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0.997
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0.98
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0.85
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Probability of malignancy
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0.65
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0.55
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0.45
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0.35
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0.985
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Tumour diameter (mm)
Each line represents a probability of malignancy. For a tumour SUVmax: liver SUVmax ratio = 1.3 the estimated probabilities of malignancy range from 7% for 30mm diameter to 22% for 60mm diameter (red arrows). The use of calculator simplifies the estimation of individual malignancy risk (supplied as supplemental file).
Accepted Article