Identification of aldosterone production sites in primary aldosteronism

Abstract

It is important to identify the sites of aldosterone biosynthesis in the adrenal glands, especially those involved in primary aldosteronism (PA). CYP11B2 catalyzes the last step of aldosterone biosynthesis but its close similarity to CYP11B1 has made it difficult to generate specific antibodies that distinguish between these two highly homologous cytochromes. We have recently produced specific monoclonal antibodies against CYP11B2. In addition, we have also produced the specific antibodies against 3BHSD 1/2, which is also the pivotal step in aldosterone biosynthesis. In 3BHSD, type 1 is the predominant form in idiopathic hyperaldosteronism (IHA) with diffuse glomerulosa hyperplasia but type 2 dominant in aldosterone producing adenoma (APA). Many of micro APA expressed 3BHSD2 and CYP11B2 with the absence of c17 and CYP11B1, which could explain the cause of hyperaldosteronism despite the small size of the lesions. In addition, many of the adrenals manifesting PA without discernible lesions demonstrated multiple clusters or nodules of cortical cells demonstrating the similar enzyme expression patterns as in micro APA. These results indicated that UMN or unilateral multiple nodules cases resulting in APA are much higher than previously considered.