Response to Adrenocorticotropic Hormone Stimulation During Adrenal Vein Sampling
Tanemoto et al1 raised several interesting hypotheses that are herein addressed.
Diagnosis of Aldosterone-Producing Adenoma, Bilateral Aldosterone Excess, and Undetection of Small Aldosterone-Producing Adenoma Contralateral to the Adrenalectomy Side.
We agree that the reduction of plasma aldosterone concentration (PAC) postadrenalectomy does not exclude bilateral aldosterone excess, per se, because unilateral adrenalectomy might also lower PAC in cases with bilateral hyperaldosteronism. However, Tanemoto et al1 should have noticed that the “4-corner criteria” that we exploited for diagnosing aldosterone-producing adenoma (APA) require not just PAC lowering but also correction of the primary aldosteronism.2 This means not only a clear-cut reduction of BP or a cure for arterial hypertension but also correction of the hypokalemia when present, normalization of a suppressed renin, and thereby normalization of the aldosterone:renin ratio. Had the hyperaldosteronism persisted after unilateral adrenalectomy because of bilateral APA, none of the latter would have conceivably occurred.
APAs can certainly be small and hard to detect at imaging, but in the largest prospective study on the prevalence of primary aldosteronism, only 17% of the APAs were <10 mm in size.3 The contention that a small APA in the adrenal gland contralateral to the resected side would sustain hyperaldosteronism, with ensuing poor BP reduction after unilateral adrenalectomy in our study, is, however, untenable. The PAC values occasionally slightly higher than 12.1 ng/dL that were recorded postadrenalectomy likely reflect, in our view, the normal response of the contralateral adrenal gland to correction of the hypervolemic state attributed to the hyperaldosteronism. Nonetheless, the normalization of renin, serum K+, and the aldosterone:renin ratio in all of the cases does not indicate, by any means, that there was persistent hyperaldosteronism.
Thus, because our series included no cases of bilateral APA and no contralateral small APA sustaining hyperaldosteronism postadrenalectomy, the contention that the cases in which the correct identification of the APA side was lowered by ACTH entail those cases with bilateral aldosterone excess does not apply to our findings.
Misleading Effect of ACTH on Lateralization of Aldosterone Excess.
By dividing the patients into those with correct and incorrect lateralization post-ACTH, the lateralization index remained unchanged in the former and decreased in the latter group (Figure). This is exactly the opposite of what Tanemoto et al1 hypothesized. They also suggested that a poorer reduction of BP and PAC postadrenalectomy in the cases with rather than without a lowered identification post-ACTH would support use of the ACTH stimulation for the identification of lateralized aldosterone excess in primary aldosteronism. This hypothesis is again unsupported by the data: both the decrease of PAC (data not shown) and the fall of BP postadrenalectomy did not differ between groups (Figure).
Thus, the main conclusion of our study, that an effective ACTH dose is more confounding than useful for an accurate diagnosis of surgically curable hyperaldosteronism, remains unchallenged.
Sources of Funding
This study was supported by FORICA, the S.I.I.A. and research grants 60% of the University of Padua to G.P.R. and T.M.S.
Tanemoto M, Mishima E, Takeuchi Y, Abe T. Adrenocorticotropic hormone stimulation during adrenal vein sampling. Hypertension. 2009; 54: e23.
Seccia TM, Miotto D, De Toni R, Pitter G, Mantero F, Pessina AC, Rossi GP. Adrenocorticotropic hormone stimulation during adrenal vein sampling for identifying surgically curable subtypes of primary aldosteronism: comparison of 3 different protocols. Hypertension. 2009; 53: 761–766.
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