Functional imaging with 11C-metomidate PET for subtype diagnosis in primary aldosteronism

Abstract

Objective: Endocrine Society guidelines recommend adrenal venous sampling (AVS) in primary aldosteronism (PA) if adrenalectomy is considered. We tested whether functional imaging of adrenal cortex with 11C-metomidate (11C-MTO) could offer a noninvasive alternative to AVS in the subtype classification of PA.

Design: We prospectively recruited 58 patients with confirmed PA who were eligible for adrenal surgery.

Methods: Subjects underwent AVS and 11C-MTO-PET without dexamethasone pretreatment in random order. The lateralization of 11C-MTO-PET and adrenal CT were compared with AVS in all subjects and in a prespecified adrenalectomy subgroup in which the diagnosis was confirmed with immunohistochemical staining for CYP11B2.

Results: In the whole study population, the concordance of AVS and 11C-MTO-PET was 51% and did not differ from that of AVS and adrenal CT (53%). The concordance of AVS and 11C-MTO-PET was 55% in unilateral and 44% in bilateral PA. In receiver operating characteristics analysis, the maximum standardized uptake value ratio of 1.16 in 11C-MTO-PET had an AUC of 0.507 (P = n.s.) to predict allocation to adrenalectomy or medical therapy with sensitivity of 55% and specificity of 44%. In the prespecified adrenalectomy subgroup, AVS and 11C-MTO-PET were concordant in 10 of 19 subjects with CYP11B2-positive adenoma and in 6 of 10 with CYP11B2-positivity without an adenoma.

Conclusions: The concordance of 11C-MTO-PET with AVS was clinically suboptimal, and did not outperform adrenal CT. In a subgroup with CYP11B2-positive adenoma, 11C-MTO-PET identified 53% of cases. 11C-MTO-PET appeared to be inferior to AVS for subtype classification of PA.

Figure 1

Patient selection, excluded subjects, and allocation to adrenalectomy or medical therapy. AVS, adrenal venous sampling; ¹¹C-MTO-PET, ¹¹C-metomidate positron emission tomography; LI, lateralization index.

Figure 2

CYP11B2-based categorization of adrenal gland samples.

Figure 3

Receiver operating characteristics (ROC) analysis. Pairs of sensitivity and specificity were calculated using ¹¹C-metomidate positron emission tomography (¹¹C-MTO-PET) SUV_max ratio (AUC = 0.507, P = 0.939), Lateralization index (LI) for adrenal venous sampling (AVS) (AUC = 0.990, P < 0.001), and adrenal computed tomography radiology report (lateralizing or bilateral/no findings, AUC = 0.542, P = 0.63) to predict subject allocation to adrenalectomy vs medical therapy groups (n = 48). SUV, standardized uptake value.

Figure 4

Study subjects divided into those with lateralizing (lateralization index, LI ≥ 4) or non-lateralizing adrenal venous sampling (AVS) result. The middle row shows the ¹¹C-metomidate positron emission tomography (¹¹C-MTO-PET) outcome and the lower row the adrenal CT outcome. Of all subjects, 15 demonstrated concordance uniformly in AVS, ¹¹C-MTO-PET, and CT. Numbers or percentages are given for each possible outcome.

Figure 5

Two patients who underwent right adrenalectomy with complete biochemical cure. In both cases, the operation was based on adrenal venous sampling (AVS) lateralizing to the right. In the upper panel (Case A) the ¹¹C-metomidate positron emission tomography (¹¹C-MTO-PET) was discordant with AVS showing increased activity in the left (L) adrenal, whereas the AVS lateralized to the right. After adrenalectomy, immunohistochemistry revealed multiple small CYP11B2-positive focuses. In the lower panel (Case B), ¹¹C-MTO-PET was concordant with AVS lateralization to the right (R) adrenal. In a histological examination of the right adrenal, the H&E stain revealed a cortical adenoma that was confirmed as an APA with CYP11B2-immunostain.