Polymorphic variation of CYP11B2 predicts postoperative resolution of hypertension in patients undergoing adrenalectomy for aldosterone‐producing adenomas

Abstract

Abbreviations & Acronyms APA = aldosterone-producing adenoma ARR = aldosterone-to-renin ratio BP = blood pressure CI = confidence interval CT = computed tomography DBP = diastolic blood pressure PCR = polymerase chain reaction PHA = primary hyperaldosteronism SBP = systolic blood pressure SF-1 = steroidogenic factor-1 Objectives: The surgical cure rate of patients with aldosterone-producing adenoma varies widely, and causes of persistent hypertension are not completely established. The objective of this study was to assess the blood pressure outcome in patients after retroperitoneoscopic adrenalectomy, and to analyze the CYP11B2 344 C/T polymorphism and any factors associated with the outcome. Methods: Between 2002 and 2009, 82 patients with unilateral aldosterone-producing adenoma underwent retroperitoneoscopic adrenalectomy. Clinical and biochemical data were reviewed retrospectively. Patients were investigated to assess the association of the CYP11B2 344 C/T polymorphism with resistant hypertension after surgery. Results: Adrenalectomy cured hypertension in 44 patients (53.7%), and 27 patients (32.9%) had persistent hypertension that was much easier to control after surgery, whereas 11 patients (13.4%) had continued hypertension and poor blood pressure control. Multivariate regression analysis showed that the main determinants of postoperative cure were duration of hypertension less than 5 years (OR 4.515, 95% CI 1.978-10.293), number of antihypertensive medications Յ2 (OR 2.639, 95% CI 1.154-6.035), preoperative response to spironolactone (OR 3.105,) and the TT genotype of the CYP11B2 gene (344 C/T; OR 2.765, 95% CI 1.261-6.064). Correspondence Conclusions:The 344 C/T polymorphism of the CYP11B2 gene predicts resolution of hypertension in patients undergoing adrnelactomy for aldosterone-producing adenoma. Duration of hypertension, number of antihypertensive medications, and preoperative response to spironolactone also represents predictive factors that need to be considered for the identification of patients with continued postoperative hypertension requiring long-term monitoring and treatment.

Management of hypertension in primary aldosteronism

“…Recently, in a large series, Zhang et al [65] showed by multivariate regression that shorter duration of hypertension and lower serum aldosterone level were predictive of resolution of hypertension after adrenalectomy. Furthermore, several studies have linked the TT genotype of CYP11B2 gene encoding aldosterone synthase to successful outcomes after adrenalectomy for PA [66][67][68] .…”

Aldosterone-producing Adenoma in Primary Aldosteronism: CT-guided Radiofrequency Ablation—Long-term Results and Recurrence Rate

“…The underlying causes that accounted for persistent hypertension were controversial. In addition to the possibility of essential hypertension (30), a number of potential causative factors had been postulated (26,(31)(32)(33)(34)(35)(36)(37)(38)(39)(40)(41). These included preoperative duration of hypertension greater than or equal to 5 years (31)(32)(33)(34), preoperative need of greater than two antihypertensive medications (32)(33)(34)(35), male sex (32,36), high body mass index (32,37), advanced age (31,36,(38)(39), family history of hypertension (35), preoperative response to spironolactone (38,40), elevated serum creatinine (33), and variation in CY-P11B2 gene polymorphism (34,41).…”

Editorial Comment from Dr Fang to Polymorphic variation of CYP11B2 predicts postoperative resolution of hypertension in patients undergoing adrenalectomy for aldosterone‐producing adenomas

“…It is of great interest to evaluate if there is any correlation between the outcome of control of hypertension in patients with APA after surgery and the polymorphism of the promoter region (344 C/T) of CYP11B2. In the present issue of the journal, the team from Guangzhou General Hospital of Guangzhou Military Command in China analyzed 82 patients with APA, and found that patients with the CC and TC genotype of CYP11B2 presented with more negative preoperative responses to spironolactone, higher postoperative blood pressure and took a higher number of antihypertensive drugs than those with the TT genotype 17 . This study highlights the possible beneficial effect of the T allele of CYP11B2 on patients with APA in regard of control of blood pressure after surgery.…”