CYP11B2 expression patterns in primary aldosteronism: Assessment of cortisol co-secretion and the B2 ratio criteria

Primary aldosteronism (PA) is the most common form of endocrine hypertension, with a prevalence of 5-15 %. Unilateral PA accounts for approximately 30 % of PA and has been associated with excellent post-operative results. Introduction of CYP11B2 immunostain led to the histopathology of primary aldosteronism (HISTALDO) consensus and the classification into classical and non-classical histology. We retrospectively reviewed 62 consecutive adrenalectomy cases of PA from routine clinical practice, including 46 with PA-only and 16 with cortisol cosecretion (PA-C). We also examined 3 adrenals from non-PA patients. We found that aldosterone-producing micronodules (APM/MAPM) were commonly present in the background adrenal of PA patients (59/62) and non-PA related adrenal cortex (3/3). Therefore, regardless of the presence of APM/MAPM, the presence of a solitary APA or APN was defined as classical histology, and the remaining CYP11B2-positive patterns were classified as non-classical histology (mHISTALDO). PA patients with classical histology were significantly associated with smaller APM/MAPM compared to those with non-classical histology. We validated that classical histology was significantly associated with more complete clinical and biochemical responses. We found that the PA-only group was significantly associated with smaller tumors, classical histology, more complete clinical response, and reduction in antihypertensive medication, compared to PA-C. We also explored a recently proposed criterion, the B2R (size ratio of the largest to the second largest CYP11B2-positive lesion), for defining classical and non-classical histology, which was relatively easy to use, yielding a consistent classification rate of 90.3 % (56/62) and similar associations and trends with clinical and biochemical outcomes, compared to the mHISTALDO. In summary, we validated that classical histology was associated with better outcomes by both mHISTALDO and B2R. APM/MAPM were commonly seen in the adrenal cortex. In the presence of a large solitary APA or APN, APM/MAPM should not change the classical histology classification.