ESPEYB20 6. Adrenals Clinical Trials – New Treatments (2 abstracts)
6.7. [11C]metomidate PET-CT versus adrenal vein sampling for diagnosing surgically curable primary aldosteronism: A prospective, within-patient trial
Wu X , Senanayake R , Goodchild E , Bashari WA , Salsbury J , Cabrera CP , Argentesi G , O’Toole SM , Matson M , Koo B , Parvanta L , Hilliard N , Kosmoliaptsis V , Marker A , Berney DM , Tan W , Foo R , Mein CA , Wozniak E , Savage E , Sahdev A , Bird N , Laycock K , Boros I , Hader S , Warnes V , Gillett D , Dawnay A , Adeyeye E , Prete A , Taylor AE , Arlt W , Bhuva AN , Aigbirhio F , Manisty C , McIntosh A , McConnachie A , Cruickshank JK , Cheow H , Gurnell M , Drake WM & Brown MJ
Nat Med. 2023; 29(1):190–202.PMID: 36646800. https://pubmed.ncbi.nlm.nih.gov/36646800/
Brief summary: This study validates dexamethasone-suppressed [11C]metomidate positron emission tomography computed tomography (MTO) scanning as a CYP11B2-selective investigation for lateralizing PA.
Primary aldosteronism (PA) is the most common single cause of hypertension, accounting for 5–14% of all cases and 20–25% of treatment-resistant hypertension (1, 2). Traditionally, patients with PA are divided equally into those in whom aldosterone excess is due to a unilateral aldosterone-producing adrenal adenoma (APA), in whom surgical cure is possible, and those with bilateral production (often termed idiopathic hyperaldosteronism (IHA), who require long-term medical therapy. 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 (3). 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 days before [11C]metomidate PET-CT (MTO) scanning suppresses adrenal CYP11B1 (but not CYP11B2) protein expression, thus achieving in vivo selectivity (4). 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 objective of this prospective study of 143 patients with PA (NCT02945904) was to compare the accuracy of a non-invasive test, [11C]metomidate positron emission tomography computed tomography (MTO) scanning, with adrenal vein sampling (AVS) in predicting the biochemical remission of PA and the resolution of hypertension after surgery. A total of 128 patients reached 6- to 9-month follow-up, with 78 (61%) treated surgically and 50 (39%) managed medically. Of the 78 patients receiving surgery, 77 achieved one or more PA surgical outcome criterion for success. The accuracies of MTO at predicting biochemical and clinical success following adrenalectomy were, respectively, 72.7% and 65.4%. For AVS, the accuracies were 63.6 and 61.5%. MTO was not significantly superior, but the differences of 9.1% (95% confidence interval =−6.5 to 24.1%) and 3.8% (95% confidence interval =−11.9 to 9.4) lay within the pre-specified −17% margin for non-inferiority (P=0.00055 and P=0.0077, respectively). Of 24 serious adverse events, none was considered related to either investigation and 22 were fully resolved.
These findings indicate that MTO following pre-treatment with dexamethasone enables non-invasive detection of unilateral APAs and is at least as accurate in the prediction of outcomes from adrenalectomy as the standard, invasive investigation, AVS. Therefore, it will now be possible to diagnose unilateral APAs when AVS is either unavailable, unsuccessful or not desired by the patient. Unlike AVS, MTO is quick, safe and reliable.
References: 1. Käyser SC, et al. Study heterogeneity and estimation of prevalence of primary aldosteronism: a systematic review and meta-regression analysis. J. Clin. Endocrinol. Metab. 2016; 101:2826–2835. 2. Libianto R, et al. Detecting primary aldosteronism in Australian primary care: a prospective study. Med. J. Aust. 2022; 216:408–412. 3. Funder JW, et al. The management of primary aldosteronism: case detection, diagnosis, and treatment: an endocrine society clinical practice guideline. J. Clin. Endocrinol. Metab. 2016; 101:1889–1916. 4. Burton TJ, et al. Evaluation of the sensitivity and specificity of 11C-metomidate positron emission tomography (PET)-CT for lateralizing aldosterone secretion by Conn’s adenomas. J. Clin. Endocrinol. Metab. 2012; 97:100–109.
Volume 20
Article tools
My recent searches
My recently viewed abstracts
Authors
ESPE Yearbook of Paediatric Endocrinology
ISSN 1662-4009 (Online)
© Bioscientifica 2024 |
Privacy policy |
Cookie settings
BiosciAbstracts
Bioscientifica Abstracts is the gateway to a series of products that provide a permanent, citable record of abstracts for biomedical and life science conferences.
Find out more