Unilateral primary aldosteronism considerations about the diagnostic criteria, adrenalectomy, and short and long time biochemical and clinical evaluation

The study by Yan and co-workers1 sought to review the literature reports on diagnostic criteria and biochemical and clinical success after surgery in patients with unilateral hyperaldosteronism. Primary aldosteronism is a syndrome, that includes various pathologies that have certain signs and symptoms in common. Since the discovery of the disease, many studies have tried to establish the criteria for diagnosis and operability of unilateral forms. With the availability of computerized tomography (CT) and magnetic resonance (MRI) and with the advance in methods to evaluate selective aldosterone secretion in the adrenal veins (AVS), the criteria have been refined and numerous guidelines have beenmadeby various societies. The initial guidelines of the Endocrine Society and the Japan Endocrine Society2,3 recommend AVS in all patients diagnosedwith primary aldosteronismwho are willing to have surgerywhen necessary. Subsequently, new guidelines considered that in some cases catheterizationwas not necessary if an adenoma was evident in a young patient with low serum potassium.4 The modification of the guidelines demonstrates that many points remain unclear and may influence the follow-up after unilateral adrenalectomy. The difficulty to create homogeneous guidelines is probably related to the fact that primary aldosteronism is a syndrome and not a defined disease with numerous underlying factors (genetic, autoimmune, family, etc.).5 The Primary Aldosteronism Surgical Outcome (PASO) study6 emphasized that thedurationof hypertension is a key factor in both the outcome of the intervention of future cardiovascular risk. Establishing


GENERAL CONSIDERATIONS
The study by Yan and co-workers 1   had their blood pressure measured and the aldosterone to renin ratio evaluated before they first noticed blood pressure was high. This point is important because we must always consider that increased aldosterone can cause permanent damage to the arteries and metabolic complications, and thus be a negative prognostic factor after unilateral adrenalectomy. It is true that the aldosterone to renin ratio often normalizes, but possible vascular damage and cardiovascular risk is a con- in identifying unilateral forms The parameters were higher considering patients with age < 40 years (71 and 79%). The study concluded that CT/MRI are not efficient tests as an alternative to AVS even in young patients, 7 but the literature studies are non-homogeneous. 8,9 An important consideration in the evaluation of the studies in the literature is that usually CT/MRI and AVS are performed in the same patient and sometimes the decision to do AVS is made just based on the CT image. Most of the centers prefer to perform surgery even in cases where the CT scan does not show an adenoma and the AVS shows lateralization, but in these cases, we believe to be preferable to perform the therapy with aldosterone receptors blockers and reserve another AVS later especially if the patient is not well controlled with the therapy. Given that in these cases hypertension often persists even after surgery, sometimes associated with persistent increase of aldosterone to renin ratio, it would be more appropriate to first treat the patient with anti-aldosterone therapy and then reconsider the possibility of surgery.
Normalization of blood pressure and serum potassium during aldosterone receptor blockers before surgery can sometimes be a criterion for the presumption of complete clinical and biochemical recovery.
Both the persistence of hyperaldosteronism due to incorrect interpretation of biochemical and morphological tests, and the persistence of hypertension even in the presence of resolution of primary aldosteronism should be evaluated in relation to the future risk not only of cardiovascular accidents, but also metabolic ones, such as diabetes.
The authors have reported correctly that the prognosis after adrenalectomy guided by CT versus AVS is heterogeneous consistent with the opportunity of a more accurate assessment prior to intervention with presumption of both clinical and biochemical success.
Therapy including anti-aldosterone drugs even in some cases not operated could be appropriate considering the classic Pitt studies 12 that have shown that such therapy protects from the risk of cardiovascular relapse regardless of the pressure and aldosterone values.
It is known that aldosterone is a factor that exacerbates cardiovascular risk because of its proinflammatory and profibrotic actions. 13 Hundemer and collaborators 14

CONCLUSIVE REMARKS
Clinical and biochemical success is not a sufficient criterion to understand the future of these patients, as pointed in the reference study. 1 Most of the guidelines have focused on biochemical or clinical parameters assessment after surgery, but future studies will need to assess subsequent long-term cardiovascular risk comparing the long-term effects of adrenalectomy and those of chronic therapy with aldosterone receptors blockers combined with other hypotensive agents.
These studies should consider that about 60% of operated patients are hypertensive after surgery 1 and that sometimes primary aldosteronism can persist even after surgery in cases that were not correctly evaluated.

FUNDING
The authors declare that there are no funders for this work.