Published today in Nature Medicine, the research solves a 60-year problem of how to detect the hormone-producing nodules without a difficult catheter study that is available in only a handful of hospitals, and often fails. The research also found that, when combined with a urine test, the scan detects a group of patients who come off all their blood pressure medicines after treatment.
More information: Morris Brown, [11C]metomidate PET-CT versus adrenal vein sampling for diagnosing surgically curable primary aldosteronism: a prospective, within-patient trial, Nature Medicine (2023). DOI: 10.1038/s41591-022-02114-5. www.nature.com/articles/s41591-022-02114-5
Hypertension is a major cause of deaths from stroke, coronary heart disease, heart failure and renal failure. The most common single cause of hypertension is primary aldosteronism (PA), accounting for 5–14% of all cases and 20–25% of treatment-resistant hypertension 1,2,3,4. The cardiometabolic consequences of hypertension are approximately twice as likely in individuals with PA compared with age- and sex-matched individuals with essential hypertension 5,6,7,8.
Although recent studies point to a continuum of disease between unilateral and bilateral subtypes, their distinction underpins the binary clinical decision of whether to remove one adrenal gland, and drives the investigations required to make this decision 9,10. Current consensus is that patients with unilateral APAs should be offered laparoscopic surgical removal of that adrenal gland and those with IHA should be treated with aldosterone antagonist drugs 11.
Despite the prevalence and penalty of PA, currently, fewer than 1% of patients are identified and fully investigated12. Many reasons exist for this shortfall in clinical care, including: low levels of clinical suspicion; time-consuming and imperfect confirmatory biochemical tests that require discontinuation of many commonly prescribed antihypertensive drugs; difficulties with patient selection for surgical intervention; and uncertainty about outcomes in patients hoping for surgical cure. The paradoxical consequence is patient and physician reluctance to embark on a diagnostic and therapeutic process with a high likelihood of major clinical benefit, and that often sub-optimal medical treatment remains the default for the overwhelming majority of patients 7,11.
Molecular imaging has the potential to increase the number of patients with PA who can be fully investigated. The current criterion standard used to distinguish patients with APA from those with IHA is adrenal vein sampling (AVS)—an invasive, technically demanding procedure with restricted availability. Metomidate—a methyl analog of the anesthetic agent etomidate—is a potent inhibitor of CYP11B1 (11β-hydroxylase) and CYP11B2 (aldosterone synthase), the final two enzymes involved in cortisol and aldosterone synthesis, respectively. Metomidate can be 11CH3 labeled and used as a positron emission tomography (PET) radiotracer in combination with high-resolution computed tomography (CT) to detect adrenocortical tumors expressing these enzymes.
A previous proof-of-concept study indicated that pre-treatment with dexamethasone for 3 d before [11C]metomidate PET-CT (MTO) scanning suppresses adrenal CYP11B1 (but not CYP11B2) protein expression, thus achieving in vivo selectivity13. This selectivity facilitates the detection of focal adrenal lesions with high [11C]metomidate uptake due to CYP11B2 expression and separates them from normal adrenal tissue. International guidelines for the management of PA acknowledge the potential for molecular imaging in the subtyping of PA11, but prospective outcomes-based data are needed to influence clinical practice.
The primary aim of this study, which we have termed MATCH (Is Metomidate superior to AVS in predicting ouTComes from adrenalectomy in primary Hyperaldosteronism), was to compare the accuracy of AVS and MTO in predicting the outcome from adrenalectomy in patients with PA (Fig. 1a).
The diagnosis of PA, the protocol for and interpretation of AVS, and the biochemical and clinical outcomes after surgery were all assessed and conducted according to international consensus guidelines and/or statements (Fig. 1b and Supplementary Table 1)11,14,15. MTO scanning was performed as previously described13, and interpreted and graded before, and in ignorance of, the information provided by AVS. The design of the study also permitted the inclusion of a number of mechanistic secondary endpoints that have the potential to refine patient selection for surgery.
These mechanistic endpoints included: a trial of aldosterone antagonist therapy (spironolactone or eplerenone) in predicting surgical cure; the influence of ethnicity and tumor genotype on surgical outcome; and the consequences of surgical and medical intervention on indices of cardiac injury and function, as determined by changes in amino (N)-terminal prohormone of brain natriuretic peptide (NT-pro BNP) levels and cardiac chamber dimensions on MRI.
