The Latest Developments of Functional Molecular Imaging in the Diagnosis of Primary Aldosteronism

Abstract

Differentiation of unilateral from bilateral aldosterone hypersecretion is the essential step in the clinical practice of primary aldosteronism (PA). Although adrenal venous sampling (AVS) has been established as the most standard test recommended by the guideline, its invasive and technically difficult nature has facilitated the approach to develop non-invasive functioning imaging as an alternative test. Compared to the conventional adrenocortical scintigraphy with cholesterol derivatives as tracer, the first-generation imaging, both of C-MTO/PET andI-IMTO/SPECT/CT, the second-generation imaging, bind with high specificity and affinity to CYP11B enzymes and have advantages in shortening the time for obtaining specific images, reducing the radiation exposure to the patient, and resolution of the images. Because of very short half-life of C-MTO,I-IMTO has a potential for a wider application than C-MTO. Sensitivity of identifying an adenoma smaller than 1 cm in diameter is still a common limitation of these new functional imaging methods. The new functional imaging could be supplementary to AVS in lateralization of PA when the results of AVS are not conclusive. To be a substitute for AVS, however, it should fulfill various conditions including high selectivity and binding affinity to CYP11B2, high sensitivity in detecting small adenoma, high resolution image, reduction of radiation exposure, and general versatility. Considering the potential number of patients, cost-effectiveness of the subtype testing in the clinical practice of PA could be one of the issues of the medical expenses. Thus, development of a new non-invasive functional imaging will have a significant impact on the clinical practice of PA and hypertension.

Prevalence, diagnosis and outcomes of treatment for primary aldosteronism

“…Positron emission tomography (PET)-CT using radiotracer 11 Cmetomidate, an inhibitor of 11β-hydroxylase and aldosterone synthase, was demonstrated as a potential non-invasive alternative to AVS [103]. The high specificity and affinity of 11 C-metomidate to CYP11B enzymes permit distinguishing cortical masses from medullary masses, and dexamethasone prior to imaging increased the difference of maximum standardised uptake values between tumour and normal adrenal by 25.6% (P < 0.01) which was absent in BAH, thereby differentiating unilateral from bilateral PA [104,105]. A recent study reported that a treatment decision based on 11 C-metomidate PET-CT achieved biochemical cure in of 4 patients with PA [106].…”

Classification of microadenomas in patients with primary aldosteronism by steroid profiling

“…In another study on patients with unilateral APA (diagnosed by AVS) with follow-up data, 36% of patients who were biochemically cured after adrenalectomy would have been misdiagnosed on the basis of CT results [40]. Thus, neither CT nor AVS are completely reliable and strong interest focusses on approaches to improve the performance and accessibility of subtype differentiation in PA [[12], [13], [14], [15], [16], [17]]. The potential utility of adrenal steroids in discriminating different subtypes of PA has been investigated in numerous studies with attention centering on the hybrid steroids 18-oxocortisol and 18-hydroxycortisol in urine or plasma [42].…”

“…The sensitivity of CT imaging is often insufficient for the identification of APAs less than 10 mm in diameter, while AVS displays high sensitivity and specificity (95% and 100%, respectively) to distinguish unilateral from bilateral PA [9,10]. AVS is a technically-demanding and invasive procedure with non-standardized protocols and variable interpretation of results, and alternative approaches to reduce or even replace AVS for subtype differentiation in PA are currently sought [[11], [12], [13], [14], [15], [16]].…”

Hormone and Metabolic Research: 50 Years of Research

“…Within the last couple of years, a special focus was given to endocrine tumors, e. g. of the neuroendocrine system including pituitary tumors and pheochromocytoma / paraganglioma. In addition, three issues were published on primary hyperaldosteronism focusing on the genetic cause of the disease as well as diagnostic and therapeutic options [2][3][4][5][6][7][8][9][10][11][12][13][14][15].…”