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Adrenal vein sampling: is there now a consensus?

Primary aldosteronism (PA) is now accepted to be the commonest secondary cause of hypertension. Its exact prevalence remains variable and controversial; however, most recent studies demonstrate a prevalence of 10% amongst unselected hypertensives and up to 20% in those with resistant hypertension. With the introduction of more reliable biochemical assays for the measurement of plasma aldosterone and renin (either as plasma renin activity or plasma renin concentration), making a diagnosis of PA has become more straightforward and is guided by the American Endocrine Society Clinical Practice Guideline on this topic, published in 2008. However, the issue of PA subtype differentiation remains a diagnostic problem. The two commonest causes of PA include bilateral adrenal hyperplasia (BAH), which is best treated with medications that block the effects of excess mineralocorticoid (e.g. spironolactone), or a unilateral aldosterone-producing adenoma (APA), which can potentially be cured by surgical removal of the abnormal gland. Therefore, given that each subtype is treated differently, it is important that a robust and accurate method for subtype identification exists. Currently, in most cases, it is unhelpful to rely solely on adrenal imaging due to its lack of sensitivity in identifying small APA (hence, false negatives) and the possibility of co-incidental nonfunctioning adrenal adenomas (hence, false positives), the likelihood of which increases significantly with age. Accordingly, current clinical practice guidelines recommend the use of adrenal vein sampling (AVS) as the ‘gold standard’ method of identifying unilateral aldosterone excess and, in most cases, is a prerequisite before recommending surgical removal of the affected adrenal. However, there is a perception that AVS is technically difficult and challenging to interpret and thus performed less frequently than is clinically indicated. This was supported by the Adrenal Vein Sampling International Study (AVIS) which explored AVS practice in 20 centres from Asia, Australia, USA and continental Europe (not UK). This important study confirmed that AVS was under-utilized with marked variation in techniques and interpretation of results and therefore highlighted a clear need for definitive guidelines on the use and interpretation of AVS in identifying unilateral aldosterone excess. This requirement has been addressed by the recent publication of an expert consensus statement on the use of AVS by Rossi and co-authors published in hypertension in 2014. This statement has been written by the principal investigator of the AVIS study as well as other investigators with international reputations as experts in the field of PA, all of whom work in centres where AVS is practised to a high standard. Their personal expertise, as well as careful review of all relevant literature, has resulted in the publication of a very useful statement with evidence levels graded according to American Heart Association standards. Some aspects of the guideline (careful patient selection, requirement for multidisciplinary team discussion and involvement) simply represent good generic clinical practice but its major strength is in its reviews and recommendations of exact methodologies employed in AVS. The AVIS study revealed no consensus amongst centres as to the optimal technique for AVS, in particular, whether contemporaneous use of cortiotrophin (ACTH) stimulation is required and whether adrenal veins should be sampled simultaneously or sequentially. There are good arguments for and against use of ACTH in this setting with some suggestion that it improves the gradient between peripheral and central cortisol measurements leading to greater confidence in successful sampling and increases aldosterone secretion from APA. However, there is no conclusive evidence that use of ACTH increases the likelihood of successful AVS. Similarly, given the pulsatile pattern of aldosterone and cortisol secretion, simultaneous sampling from adrenal veins is theoretically preferred over sequential techniques, however, again there are no outcome data directly comparing the two techniques. Therefore, the pragmatic recommendation of the consensus statement is that ACTH stimulation should be used if sequential adrenal vein sampling is performed (this occurred in 2/3 of centres in the AVIS study) and not required if simultaneous sampling is performed (as occurs in 1/3 of AVIS centres).