By Katrina R. Rodriguez-Asuncion, MD
Primary aldosteronism (PA) stands as the predominant cause of secondary hypertension, impacting around 6% of all hypertensive patients and a significant 20% of those with resistant hypertension. Besides inducing hypertension through sodium retention and subsequent volume expansion, elevated serum aldosterone levels provoke inflammatory and fibrotic changes in the heart, blood vessels, and kidneys. This not only heightens the risk of morbidity and mortality but also increases the likelihood of stroke, renal damage, and cardiovascular disease among PA patients (Quencer, 2021).
Despite the potential of surgical adrenalectomy to cure primary aldosteronism (PA) and lower the risk of cardiovascular disease, fewer than 1% of PA patients undergo this procedure. This low rate is primarily due to the invasive and technically demanding nature of adrenal venous sampling (AVS), which is the gold standard for differentiating between aldosterone-producing adenoma (APA) and idiopathic hyperaldosteronism (IHA). The success rate of adrenal venous sampling (AVS) varies significantly, ranging from 30–60% in some centers to nearly 80% in specialized centers (Puar, 2022).The invasiveness, complexity, and limited availability of AVS restrict its widespread adoption, underscoring the need for noninvasive and simplified alternatives (Wu, 2023).
Molecular imaging holds potential as a non-invasive method for detecting aldosterone-producing adenoma. Recent advances have improved non-invasive imaging techniques for identifying lateralizing primary aldosteronism. (Cardenas, 2020) Over the years, there has been consistent progress in the development and evaluation of PET tracers for determining subtypes in PA. Given the challenges and limited availability of AVS for most clinicians, the recent innovations and focused research in this area are highly commendable and invaluable. (Vaidya, 2024) Metomidate, a methyl analog of the anesthetic etomidate, acts as an inhibitor of CYP11B1 (11β-hydroxylase) and CYP11B2 (aldosterone synthase), the enzymes responsible for the final steps in cortisol and aldosterone synthesis. When labeled with 11CH3, Metomidate becomes a PET radiotracer that, combined with high-resolution CT, can detect adrenocortical tumors expressing these enzymes. (Wu, 2023)
In a study by Wu et al. (2023), pretreatment with dexamethasone prior to 11C- Metomidate PET-CT scanning was shown to suppress adrenal CYP11B1 (but not CYP11B2) protein expression. This selectivity allows for the detection of focal adrenal lesions with high 11C-metomidate uptake due to CYP11B2 expression, effectively distinguishing them from normal adrenal tissue. Patients were administered dexamethasone 0.5 mg orally every 6 hours for 72 hours before the scheduled Metomidate PET-CT. Non-contrast CT images of the adrenal glands were obtained, followed by an intravenous injection of 11C- Metomidate. Dynamic PET images were then captured for 30 minutes starting 30 minutes post-administration. In their prospective study, 11C-metomidate PET CT demonstrated an accuracy of 72.7% in predicting biochemical success and 65.4% in predicting clinical success following surgery. When compared to AVS, which had accuracies of 63.6% for biochemical success and 61.5% for clinical success, Metomidate PET CT was not superior but showed comparable results. Therefore, it can serve as a non-invasive alternative to AVS for diagnosing unilateral PA. (Wu, 2023)
Paur et al. (2022) conducted a study demonstrating that 11C-metomidate PET CT is also comparable to AVS in subtyping primary aldosteronism. Among the 25 patients who underwent surgery, 20 achieved biochemical cure. In the subset of 20 patients diagnosed with unilateral primary aldosteronism, 12 demonstrated lateralization on PET combined with AVS, four solely through PET, and three solely through AVS. One patient initially lacked lateralization with either PET or initial AVS, but subsequent AVS without cosyntropin indicated lateralization. This research, the first of its kind in Asia, shows promise. The authors propose that due to its high specificity and noninvasive nature, 11C-Metomidate PET-CT could replace AVS as the initial subtype test, with AVS reserved for cases where PET lateralization is inconclusive, thereby improving the identification of unilateral primary aldosteronism. Another advantage is that 11C-Metomidate can provide both qualitative and quantitative information through lateralization and uptake of tracer within the adenoma. However, 11C – Metomidate requires that the center has its cyclotron since the molecule has a short half-life of 20 minutes.
In Asia, particularly in low-middle-income countries, aldosterone-renin ratio screening is widely practiced, but confirmatory testing is restricted due to resource limitations such as facility availability, local assay capabilities, and financial constraints. Adrenal vein sampling (AVS) is not commonly performed, impacting a population of 442 million due to inadequate radiological facilities, a shortage of trained personnel, and high costs. (Sukor, 2024)
If this technology were available in the Philippines, it could provide a non-invasive and potentially more accessible alternative to AVS. Despite potential costs, its wider availability could significantly improve APA diagnosis and treatment, benefiting many patients and avoiding the expenses and challenges of invasive procedures in a country with limited access to specialized healthcare professionals.
References:
Vaidya, A. (2024) The Promise of Nuclear Imaging as an Alternative to Adrenal Venous Sampling for the Detection of Aldosterone-producing Adenomas. The Journal of Clinical Endocrinology & Metabolism. 109( 4). pp. e1363–e1364. Available at: https://doi.org/10.1210/clinem/dgad542
(Accessed 29 June 2024)
Wu, X., Senanayake, R., Goodchild, E. et al. (2023) [11C]metomidate PET-CT versus adrenal vein sampling for diagnosing surgically curable primary aldosteronism: a prospective, within-patient trial. Nat Med. 29. pp. 190–202. Available at: https://doi.org/10.1038/s41591-022-02114-5 (Accessed 29 June 2024)
Chen Cardenas, SM. and Santhanam, P. (2020) 11C-metomidate PET in the diagnosis of adrenal masses and primary aldosteronism: a review of the literature. Endocrine. 70(3). pp. 479-487. Available at doi: 10.1007/s12020-020-02474-3. (Accessed 1 July 2024)
Puar, T. H.a,b, Khoo, C.M., Tan, C.J., Tong, A.K, Tan, M.C. et al. (2022) 11C-Metomidate PET-CT versus adrenal vein sampling to subtype primary aldosteronism: a prospective clinical trial. Journal of Hypertension. 40(6). pp. 1179-1188. Available at DOI: 10.1097/HJH.0000000000003132 (Accessed 1 July 2024)
Quencer, K.B. (2021) Adrenal vein sampling: technique and protocol, a systematic review. CVIR Endovasc. 4, 38. Available at: https://doi.org/10.1186/s42155-021-00220-y (Accessed 29 June 2024)
Sukor, N., Sunthornyothin, S., Tran, T., Tarigan, T.J., Mercado-Asis, L.B., Sum, S., et. al. (2024) Health Care Challenges in the Management of Primary Aldosteronism in Southeast Asia. The Journal of Clinical Endocrinology & Metabolism. 109(7). pp. 1718-1725. Available at : https://doi.org/10.1210/clinem/dgae039 (Accessed 1 July 2024)
