Prognostic Value of Contralateral Suppression for Remission After Surgery in Patients With Primary Aldosteronism

Sara Mørup; Nathalie Voss; Caroline Clausen; Claus Larsen Feltoft; Mikkel Andreassen; Jesper Krogh

Disclosures

Clin Endocrinol. 2022;96(6):793-802. 

In This Article

Abstract and Introduction

Abstract

Objective: Primary aldosteronism (PA) is the most common cause of endocrine hypertension and adrenalectomy is the firstline treatment for unilateral PA. Suppression of aldosterone secretion of the nondominant adrenal gland at adrenal venous sampling (AVS), that is, contralateral suppression (CLS) has been suggested as a marker of disease severity. However, whether factors such as CLS, age, gender or comorbidities are associated with remission after surgery is controversial. The objective of this study is to investigate the prognostic value of CLS, age, gender, aldosterone-to-renin ratio, antihypertensives and comorbidities for clinical and biochemical remission following unilateral adrenalectomy in patients with PA.

Design and Patients: A retrospective study of patients with PA referred for AVS at Rigshospitalet from May 2011 to September 2020, who subsequently underwent adrenalectomy. Clinical remission was defined according to the PA surgical outcome criteria, whereas complete biochemical remission was defined as normalization of hypokalaemia without potassium substitution.

Results: Eighty-four patients were available for analysis of primary outcome. Among patients with CLS, 28/58 (48.3%) obtained complete clinical remission after surgery compared with 10/26 (38.5%) without CLS (p = .40). Complete biochemical remission was obtained in 55/58 (94.8%) of patients with CLS compared with 25/28 (89.3%) without CLS (p = .44). Female gender and lower number of antihypertensives at baseline were associated with higher odds for complete clinical remission, whereas none of the investigated variables were associated with biochemical remission.

Conclusion: CLS was not significantly associated with complete clinical or biochemical remission in this cohort. Our results confirmed that female gender and lower number of antihypertensives were predictors of clinical remission.

Introduction

Primary aldosteronism (PA) is characterized by an excessive autonomous aldosterone production independent of renin, resulting in hypertension and, in severe cases, hypokalaemia. It is the most common cause of endocrine hypertension with a prevalence of 5%–15% in hypertensive patients.[1–3] PA is associated with higher cardiovascular morbidity and mortality relative to age- and sex-matched patients with essential hypertension, as well as deleterious effects on cerebrovascular and renal function, including increased risk of atrial fibrillation, myocardial infarction, strokes and chronic kidney disease.[4–6] The most common cause of PA is a unilateral aldosterone-producing adrenal adenoma (APA).[7] Surgery has shown to be superior to medical treatment in patients with unilateral disease and is therefore recommended as firstline treatment in guidelines.[3,8] Complete biochemical response, defined as correction of hypokalaemia, has been reported in up to 94% of patients after adrenalectomy and clinical benefit, defined as improvement of hypertensive status, in ~80% of patients.[8] However, only 16%–72% of surgically treated patients obtain complete clinical remission after adrenalectomy.[8–13] Thus, identification of variables that can predict remission after surgery would be helpful in informing patient choice regarding surgery versus medical therapy.

In cases of bilateral disease, medical treatment with spironolactone—a mineralocorticoid receptor antagonist—is the firstline treatment and can decrease mean blood pressure (BP) (studies report a 25% systolic and a 22% diastolic reduction) but does not result in complete clinical response in all cases.[3]

To differentiate between unilateral and bilateral PA, an adrenal venous sampling (AVS) can be performed. From these results, calculations of the lateralization index (LI)—the degree of lateralization—and the contralateral suppression index (CLSI)—the degree of contralateral suppression (CLS)—can be obtained.

In previous studies, female gender, low defined daily dose (DDD) of antihypertensives and shorter duration of hypertension before surgery have been identified as the most reliable predictors for complete or partial clinical and/or biochemical remission after adrenalectomy in patients with PA.[9,12,14–16]

However, studies show variable results regarding other potential predictors, for example, plasma potassium (p-potassium), body mass index (BMI), LI, CLSI, age and comorbidity,[12,14,16] indicating that more comprehensive studies are necessary to fully determine the effect of these factors. It has been suggested that the LI or the CLSI are indicators of disease severity. This relies on the assumption that excess of aldosterone production in the dominant adrenal gland results in suppression of renin secretion, leading to a compensatory suppression of aldosterone secretion from the contralateral (CL), healthy adrenal gland. The more aldosterone secreted by the dominant gland, the more suppressed the CL gland will be. This association between the presence of CLS and outcome from surgery have been examined in six studies. The largest studies by Monticone et al.,[17] Yang et al.[13] and Dominguez et al.[7] found no association between CLS and clinical and biochemical outcomes from surgery. By contrast, three smaller studies all found CLS to be associated with clinical remission.[16,18,19] These contradictory findings suggest that further investigation is needed to fully understand the influence of CLS on surgery outcome. Moreover, whether the preoperative degree of the CLSI and LI can be used as reliable indicators for surgery outcome in patients treated for PA with unilateral adrenalectomy remains uncertain.

The primary purpose of this study was to examine the prognostic value of CLS for clinical and biochemical remission after adrenalectomy in patients with PA. Secondary aims were to assess the association between variables previously known to be related with remission, including gender, BMI, aldosterone-to-renin ratio (ARR), diabetes, p-potassium level and LI with clinical and biochemical response.

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