To analyze the individual response to the intervention, we defined a responder as one who either stopped or reduced antihypertensive medications after the interventional procedure. The number (percentage) of responders in each group was 58 (89.2%), 10 (100%), and 6 (100%), in groups A, B, and C (P=0.762), respectively. Similarly, a serum potassium responder was defined as a subject with preoperative hypokalemia who returned to eukalemia postoperatively. Thus, the number (percentage) of serum potassium responder was 45/49 (91.8%), 7/8 (87.5%), and 5/5 (100.0%) (P=0.705), respectively, in groups A, B, and C. In general, regardless of the NP-59 finding, most of the patients with adrenal adenoma proven by pathology show significantly improved blood pressure and serum potassium levels after adrenalectomy or ablation (preoperative SBP 161.1±23.4 mmHg vs. postoperative SBP 129.9±12.6 mmHg, P<0.001; preoperative diastolic blood pressure 96.9±15.8 mmHg vs. postoperative diastolic blood pressure 81.6±8.6 mmHg, P<0.001; preoperative potassium 2.9±0.8 mmol/l vs. postoperative potassium 4.3±0.5 mmol/l, P<0.001, Fig. 3).
Pathologic reports confirmed the existence of adrenal adenoma in 60 (92.3%), 7 (70.0%), and 5 (83.3%) patients of groups A, B, and C (P=0.077), with gross tumor size ranging 2.1±0.7, 1.8±0.8, and 1.1±0.2 cm (P=0.008), respectively. Therefore, were able to analyze the sensitivity and accuracy of NP-59 adrenal scintigraphy to detect APA in this cohort. Our result showed that the sensitivity of NP-59 scintigraphy was 83.3%; specificity was 44.4%; and positive predictive value was 92.3% (Table 2). A total of 25 cases received NP-59 adrenal scintigraphy in combination with SPECT/CT before surgical intervention after SPECT/CT was available in this institute in 2012. The sensitivity, specificity, and positive predictive value of APA detection by NP-59 scintigraphy in combination with SPECT/CT scan was 85.0, 60.0, and 89.5%, respectively (Table 2).
The estimated prevalence of PA in hypertensive populations has increased from less than 1% to about 10% in western countries 6,13,14. Surgery is a potential curative treatment for unilateral disease, such as APA and less frequently for carcinomas or selected unilateral nodular idiopathic adrenal hyperplasia. However, medical therapy remains the standard treatment for BAH 15, unless it has become medically intractable 16. The establishment of a precise lateralizing imaging system is thus a critical step towards improved management of PA.
Typically, bilateral symmetrical adrenal uptake of radioactive tracer suggests BAH according to the interpretation of NP-59 results 26,27. In certain conditions, bilateral asymmetric uptake of NP-59 provides limited ability to distinguish adenoma from partially suppressed normal contralateral adrenal gland or asymmetrically expanded adrenal glands in bilateral hyperplasia 27. This was the case in our series, with two of the 10 patients in the bilateral visualization group presenting asymmetric uptake, which was eventually proven adenomas postoperatively. The other eight patients showed bilateral symmetric visualization at day 3–5 after injection of the tracer; these proved to be five adenomas, one hyperplasia, one vascular leiomyoma, and one hemorrhagic pseudocyst.
Because of the resolution limit of NP-59 planar imaging, lesions smaller than 1.5 cm in diameter may not be visible on planar scintigraphy 14. In agreement, we also found poorer NP-59 scintigraphy uptake in lesions smaller than 1.5 cm (the number of patients with tumors sized less than 1.5 cm were 9 of 65, 6 of 10, and 5 of 6 in groups A, B, and C, respectively). Thus, the diagnostic odds ratio (95% confidence interval) of APA detection by NP-59 adrenal scintigraphy was 1.93 (1.15–3.24) fold for each millimeter increase in tumor size (P=0.013).
We tried to find out the correlation between aldosterone/renin levels in patients with different NP-59 scintigraphy findings, since a higher PAC and a lower DRC has been reported in patients with APA relative to those with BAH 28. Our results showed no significant differences in PAC (P=0.221) or DRC (P=0.552) in APA patients with different (unilateral, bilateral, and negative) radioactive tracer uptake.
Our study had some limitations. First, our PA patients were retrospectively collected from the patient lists of those who had ever had NP-59 adrenal scintigraphy performed and their condition pathologically proven. Second, the nature of retrospective analysis resulted in inevitable missing data. Furthermore, some of the blood tests were done while patients were taking medications such as calcium channel blockers, angiotensin-receptor blockers, and spirolactone. Lastly, bias may exist in the specificity and false negative rate of NP-59 adrenal scintigraphy because of the small number of patients in this study.
The authors thank Dr Jen-Der Lin (Department of Endocrinology and Metabolism, CGMH) and Dr Vincent Wu (Department of Nephrology, NTUH) for their kind support and valuable suggestions. Thy also express their appreciation to Dr C. Hsueh (Division of Pathology, CGMH) for her expert review of the surgical samples. And they also thank Chang Gung Memorial Hospital (CMRPG3D1813) for financially supporting this research.
There are no conflicts of interest.
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