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


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 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 and 4 patients due to elevated metanephrines (ie 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 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 haematomas, 3 myelolipomas, 1 benign oncocytoma, 1 borderline oncocytoma of uncertain malignant potential, 2 cysts).

Overall, 29 nonoperated 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 disease for more than 6 months prior PET study (>6 months to 5 years).

[18F]FDG-PET/CT Findings

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 exhibited a tumour SUVmax: liver SUVmax ratio < 1.5 and corresponded to 1 adrenal metastasis from a RCC (ratio 1.2). None of the patients with malignant tumour exhibit a contralateral adrenal nodule.

Benign tumours with the highest tumour SUVmax: liver SUVmax 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 nonoperated benign masses: 25 had tumour SUVmax: 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).

Figure 1.

Tumour SUVmax and tumour SUVmax: liver SUVmax ratio in benign and malignant tumours. For readability, the tumour 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. SUV, standardized uptake value

The performance of the previously reported cut-off 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 SUVmax: liver SUVmax were built from a prospective cohort of patients (see Section 2) and expressed as follows:

Model 1: For the entire population


Model 2: For the group of pathologically proven adrenocortical tumours (benign and malignant):


where Diameter is expressed in mm and p corresponds to the probability of malignancy.

The AUC values for models 1 and 2 applied to validation cohort were 0.88 (95% CI: 0.78–0.95, P < .0001) and 0.91 (95% CI: 0.72–0.99, P < .0001), respectively. The cut-off 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 cut-off was 25.8% with a sensitivity of 100% (59–100) and specificity of 83.3% (58.6–96.4).

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 File S1.

Figure 2.

Graphical representation of the probabilities of malignancy according to the model 1 (tumour size and the tumour SUVmax: liver SUVmax ratio). 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 30 mm diameter to 22% for 60 mm diameter (red arrows). The use of calculator simplifies the estimation of individual malignancy risk (supplied as File S1). SUV, standardized uptake value [Colour figure can be viewed at wileyonlinelibrary.com]

Analysis of CT-derived Anthropometric Parameters

As shown in Table 2 and Table S1, 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 lean mass.