Adrenal vein sampling versus CT scanning in primary aldosteronism – Authors' reply

We thank John Funder and Gian Paolo Rossi for their detailed comments, but they do not seem to fully appreciate the fact that our study was a pragmatic, randomised controlled trial. Pragmatic, in the sense that we included patients in whom a clinically suspected primary aldosteronism as underlying cause of hypertension was confirmed by a salt-loading test.1Funder JW Carey RM Mantero F et al.The management of primary aldosteronism: case detection, diagnosis, and treatment: an Endocrine Society Clinical Practice guideline.J Clin Endocrinol Metab. 2016; 101: 1889-1916Crossref PubMed Scopus (1461) Google Scholar Patients included in our study are typical patients in daily clinical practice in whom distinguishing between unilateral adenoma and bilateral hyperplasia is needed. Although Funder and Rossi suggest that we selected the most severe patients with primary aldosteronism, we note that neither the literature nor the recommendations of the guideline make a distinction between severe and non-severe primary aldosteronism. But even a relatively severe form of primary aldosteronism in our patients does not invalidate the results and conclusions of our study. Our study is also pragmatic in the sense that it is consistent with the intention-to-diagnose principle. In the primary analysis, contrary to what Funder and Rossi state, we included the four patients in whom adrenal vein sampling (AVS) failed in the AVS group, not in the CT group. Also, as described in the paper, the results of the per-protocol analysis, in which the four patients who had AVS that failed were excluded from the AVS cohort, did not differ from the results of the intention-to-diagnose analysis. The comment about difficulties with CT diagnoses is well taken, but if this has affected our study, one would have expected inferior clinical results in the CT group as compared with the AVS group. Funder and Rossi claim, based on a post-hoc power analysis of a subgroup, that the study is underpowered for patients who had had adrenalectomy. This comment overlooks the fact that the study was designed to address the clinical problem of how to select patients for adrenalectomy from the whole group of primary aldosteronism. Methodologically, and for external validity, it is not correct to do a power analysis on the subgroup of patients who had adrenalectomy because a clinician, when presented with a patient with primary aldosteronism, does not know the result of subtyping and thus if adrenalectomy is the appropriate treatment. Therefore, to base the power analysis and outcome assessment on all patients with primary aldosteronism is appropriate. As clearly acknowledged in our paper, simultaneous AVS without cosyntropin stimulation might not yield the same results as sequential AVS with cosyntropin stimulation. However, many large referral centres do AVS by sequential sampling with cosyntropin stimulation.2Rossi GP Barisa M Allolio B et al.The Adrenal Vein Sampling International Study (AVIS) for identifying the major subtypes of primary aldosteronism.J Clin Endocrinol Metab. 2012; 97: 1606-1614Crossref PubMed Scopus (249) Google Scholar Finally, our study is also pragmatic in its selection of intensity of antihypertensive treatment as a clinically relevant endpoint. This is the first study in this field that is fully compliant with the rigorous standards for evaluating diagnostic tests as defined by the GRADE Working Group.3Schunemann HJ Oxman AD Brozek J et al.Grading quality of evidence and strength of recommendations for diagnostic tests and strategies.BMJ. 2008; 336: 1106-1110Crossref PubMed Google Scholar We therefore disagree with the contention that the results of small retrospective studies and of one prospective study, in which AVS was assumed to represent the gold standard,1Funder JW Carey RM Mantero F et al.The management of primary aldosteronism: case detection, diagnosis, and treatment: an Endocrine Society Clinical Practice guideline.J Clin Endocrinol Metab. 2016; 101: 1889-1916Crossref PubMed Scopus (1461) Google Scholar constitute “the weight of considerable evidence” in favour of recommending AVS in all patients with primary aldosteronism. We do agree that, from a theoretical perspective, AVS would seem to be the preferred option. However, the results from our trial allow only one conclusion: CT and AVS are both imperfect tests, but each for its own, as yet not fully understood, reasons. Therefore, we agree with the comment by Troy Puar and colleagues, stating that our findings should urge us to critically rethink our current, perhaps overly simple, and binary classification of primary aldosteronism into unilateral adenoma and bilateral hyperplasia. We declare no competing interests. Adrenal vein sampling versus CT scan to determine treatment in primary aldosteronism: an outcome-based randomised diagnostic trialTreatment of primary aldosteronism based on CT or AVS did not show significant differences in intensity of antihypertensive medication or clinical benefits for patients after 1 year of follow-up. This finding challenges the current recommendation to perform AVS in all patients with primary aldosteronism. Full-Text PDF Adrenal vein sampling versus CT scanning in primary aldosteronismWe read with great interest the SPARTACUS study,1 which showed that the use of either adrenal CT scanning or adrenal vein sampling (AVS) to differentiate unilateral aldosterone-producing adenoma from bilateral adrenal hyperplasia led to similar blood pressure improvement in patients with primary hyperaldosteronism. Full-Text PDF Adrenal vein sampling versus CT scanning in primary aldosteronismTanja Dekkers and colleagues are to be congratulated on completing the SPARTACUS trial1 in patients with primary aldosteronism randomly assigned to adrenal vein sampling (AVS)-based or CT-based treatment. Surprisingly, they found no significant differences in outcomes between the groups in mean defined daily doses of antihypertensives or health-related quality of life (RAND-36 questionnaire score) one year after intervention. The authors conclude that the additional cost of adrenal vein sampling is unjustified and that neither CT nor AVS (in their study) accurately predicted unilateral hyperaldosteronism. Full-Text PDF