One of the most important clinical outcomes in treatment of hyperaldosteronism is to control hypertension that is frequently severe and associated with end-organ damage. In the present study of patients who underwent adrenalectomy for hyperaldosteronism caused by unilateral hypersecretion of aldosterone, we found that the main clinical outcome was better control of hypertension. Nevertheless, not all patients were able to discontinue their use of all antihypertensive medication after surgery. Uncured hypertension likely resulted from coexisting irreversible vascular changes that were induced by hypertension itself and/or by direct long-standing exposure to aldosterone. [15, 16]
In our cohort, 83% of surgically treated patients achieved hypertension control, as indicated by an overall reduction of DDD. Only 24% of patients achieved clinical cure (DDD of 0). Other published studies have described hypertension cure rates ranging between 15.3% and 55%, as defined by a blood pressure of < 140/90 mmHg without the use of antihypertensive drugs. [17, 18, 19, 20] Within our cohort, 59% of patients exhibited partial clinical success, with improved blood pressure control and reduction of DDD. Previous studies have shown that this important group includes an average of 47% of patients (range, 35–66%). [21]
The number of antihypertensive drug classes themselves does not accurately reflect the total consumption of antihypertensive drugs used to control blood pressure. Thus, the defined daily dose (DDD) has been adopted to enable analysis of the consumption of many prescribed, in the present study, antihypertensive drugs. [22] Use of the DDD allows clinicians to better counsel patients with primary aldosteronism regarding the predicted postoperative change in antihypertensive drug consumption. Our present investigation is one of only a few studies to adopt the DDD concept. [23] Antihypertensive therapy defined by the DDD was reduced from a DDD of 5.4 before to 3.0 after surgery, i.e. our cohort showed a mean postoperative decrease of 2.4 DDD.
A laparoscopic or retroperitoneoscopic approach is the surgical method of choice. Compared to open adrenalectomy, laparoscopic adrenalectomy is associated with shorter hospital stays and potentially fewer complications. [2] In this study, all patients were treated laparoscopically, and no serious adverse events were observed.
Previous studies have reported the following independent factors affecting the persistence of hypertension after adrenalectomy: male sex, advanced age, increased BMI, hypertension duration of > 6 years, preoperative use of > 3 types of antihypertensive drugs, and adrenal gland size. [24, 25, 26, 27, 28, 29, 30] Zarnegar et al. proposed a scoring system to predict the benefits of adrenalectomy for patients, which combines four independent factors: the number of antihypertensive medications used, BMI, hypertension duration, and female gender. [31]
In our study, hypertension reversal was independently associated with female gender, absence of diabetes mellitus, and use of less powerful antihypertensive treatment (DDD < 4). Notably, hypertension resolution or improvement was the most important clinical outcome of the surgery. Contrary, the most accurate indicator of successful surgical treatment was the change in ARR, which we found to be normalized in 71% of the participating patients.
In cases of hyperaldosteronism, adrenalectomy should only be indicated in cases with clearly demonstrated unilateral aldosterone hypersecretion. If the preoperative algorithm for localization of hypersecretion exclusively relies on imaging methods, it is likely that up to 25% of patients will not be correctly identified. Our present data confirmed these findings, showing that 25.3% of our patients undergoing adrenalectomy had AVS-confirmed unilateral aldosterone secretion but had normal findings according to adrenal imaging. [11] AVS is the only method that can conclusively distinguish unilateral from bilateral aldosterone hypersecretion. Therefore, AVS is commonly considered a necessary prerequisite for adrenalectomy in all patients with primary hyperaldosteronism, regardless of the apparent findings on CT or MRI scans. [10, 12]
The importance of AVS appears to be particularly significant in elderly patients, who also show a greater incidence of non-functional adenomas. Additionally, young patients (age < 35 years), and cases of unilateral adrenal lesions with radiological features consistent with cortical adenoma seen on a CT scan, may not require AVS before proceeding to unilateral adrenalectomy. [12]
Notably, if both adrenal veins are not successfully catheterized, it may be necessary to repeat AVS, treat a patient medically, or consider surgery based on the findings of alternative diagnostic tests. [2] For 17 patients in the present study, we had to repeat AVS to obtain conclusive results.
Microscopic differentiation between an adenoma and adrenal hyperplasia may prove to be rather challenging. In cases of nodular hyperplasia, more nodules may be found, and the adrenal cortex surrounding these nodules will appear hyperplastic. In contrast, the histology of adenomas usually presents with extranodular atrophy. [32, 33] In our study, histological examinations were performed by several different histopathologists, therefore, it was practically impossible to clearly distinguish between the various forms of hyperplasia. Cortical adenoma can occur simultaneously with adrenal hyperplasia, but it has generally been reported that adrenal adenoma is the most common cause of unilateral aldosterone hypersecretion. However, a greater proportion of adrenal hyperplasia has been reported among patients with unilateral hypersecretion accurately diagnosed based on AVS. [34] In the present study, clinical outcomes were identical between patients with histological evidence of hyperplasia versus patients with evidence of an adenoma. This fact is consistent with studies that have reported unilateral adrenal hyperplasia to be far more frequent than previously thought. [35, 36, 37, 38, 39, 40]
A limitation of our present study is the small number of included patients, since the studied condition is rather rare. A strength of our study is the use of the DDD concept to enable analysis of the usage of combinations of multiple drugs.