2023 年 70 巻 9 号 p. 917-924
Hyperkalemia is developed in a part of patients with aldosterone-producing adenoma (APA) after adrenalectomy, suspected to be due to the insufficiency of aldosterone secretion. The purpose of this study is to determine the frequency and characteristics of prolonged postoperative hypoaldosteronism (PPHA) using chemiluminescent enzyme immunoassay (CLEIA). We studied 58 patients with APA with long time after adrenalectomy and whose PAC was measured using a CLEIA kit. The PAC value measured using CLEIA was significantly lower than that of using RIA between two consecutive visits before and after the shift of measuring method of PAC (median [interquantile range], 123.0 [99.8–164.0] vs. 39.5 [15.8–64.2] pg/mL, p < 0.01). PAC was below the minimum limit of quantification (4.0 pg/mL) of the CLEIA kit at least once in nine patients (15.5%) who had PPHA. The PPHA group were older (mean ± standard deviation, 61.3 ± 8.5 vs. 50.5 ± 10.1 years, p < 0.01) and had lower eGFR (60.3 ± 14.0 vs. 82.3 ± 22.8 mL/min/1.73 m2, p < 0.01) than the non-PPHA group. The frequency of postoperative hyperkalemia (maximum serum potassium >5.5 mEq/L) was higher in the PPHA group than in the non-PPHA group (55.6% vs. 8.2%, p < 0.01). In conclusion, a few patients with APA long time after adrenalectomy had unmeasurable PAC using CLEIA. PPHA is likely to develop in patients with APA after adrenalectomy who are older and have impaired renal function. Additionally, PPHA is related to the occurrence of postoperative hyperkalemia.
PRIMARY ALDOSTERONISM (PA) generally has two subtypes: aldosterone-producing adenoma (APA) and idiopathic hyperaldosteronism (IHA) [1]. APA is often present in a unilateral adrenal gland, which indicates unilateral adrenalectomy. Adrenalectomy in patients of unilateral APA is expected to be biochemically and clinically curative and to reduce cardiovascular complications [2]. In contrast, some patients with APA develop hyperkalemia after adrenalectomy [3-8]. Although postoperative hyperkalemia may have been caused by the insufficiency of aldosterone secretion from the zona glomerulosa of the adrenal cortex, few studies had examined plasma aldosterone concentration (PAC) in patients with postoperative hyperkalemia in detail [8, 9]. Fischer et al. reported that 6 of 110 patients with PA after adrenalectomy had persistent hyperkalemia, and all of them had unmeasurable PAC levels (<35 pg/mL). They defined postoperative hypoaldosteronism as PAC <35 pg/mL. Herein, PAC was measured using RIA kit with the minimum limit of quantification (LOQ) at 35 pg/mL.
PAC is conventionally measured using radioimmunoassay (RIA), which results in inappropriately high plasma aldosterone value due to the low specificity of antibodies [10]. Recently, chemiluminescent enzyme immunoassay (CLEIA) kits used to measure renin and aldosterone concentrations in the blood have become available in Japan [11, 12]. After April 2021, the supply of the RIA kit that had been generally used for aldosterone measurement was terminated in Japan. Aldosterone concentrations in the blood measured using CLEIA kits have been reportedly almost identical to those measured using liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS), which is the most reliable method for measuring aldosterone [12]. To date, no study has evaluated the postoperative PAC using LC-MS/MS or CLEIA in comparison with RIA.
In our hospital, the method of measuring PAC had been switched from RIA to CLEIA since May 2020. In this study, PAC levels were measured using a CLEIA kit in patients with APA who had undergone adrenalectomy. We aimed to investigate the frequency of postoperative hypoaldosteronism (PPHA) defined as CLEIA-measured PAC levels below the minimum LOQ of the CLEIA kit in patients least 1 year after adrenalectomy, and to examine the characteristics of patients with PPHA.
We investigated the patients with PA who underwent unilateral adrenalectomy and were pathologically diagnosed with APA between August 2007 and September 2019 at Sapporo City General Hospital. The procedures for diagnosis of PA were generally made in accordance with the guidelines of the Japan Endocrine Society [13] and the Japanese Society of Hypertension [14], and indications for unilateral total adrenalectomy and unilateral partial adrenalectomy were determined based on adrenal vein sampling (AVS) and results of computed tomography (CT). The patients were followed up for more than 1 year after surgery.
Diagnosis of PAScreening for PA was performed after changing from potentially interfering antihypertensive drugs to calcium channel blockers and/or to α-blockers, where applicable. Screening was determined based on the ratio of PAC (pg/mL) to plasma renin activity (PRA; ng/mL/h) (aldosterone to renin ratio [ARR]) >200 pg/mL/ng/mL/h, using RIA kits both for renin and aldosterone. Diagnosis of PA was established by at least one positive result of confirmatory testing, captopril challenge test, furosemide-upright test, saline infusion test, and oral salt loading test [13, 14].
Adrenal vein samplingThe procedure of AVS was described elsewhere [15]. Briefly, blood samples were generally obtained via AVS before and 30 min after administration of 0.25 mg cosyntropin from both adrenal veins and the inferior vena cava (IVC) at a point distal to the renal vein. AVS was determined to be successful when selectivity index (the ratio of cortisol in the adrenal vein relative to that in the IVC) was >2 before and >5 after ACTH stimulation. Unilateral disease on AVS was defined as LI (ratio of aldosterone/cortisol in the dominant adrenal vein relative to that in the non-dominant adrenal vein) >2 before and >4 after ACTH stimulation, as well as the ratio between aldosterone/cortisol in the non-dominant adrenal vein and aldosterone/cortisol in the IVC (contralateral ratio; CR) <1. The laterality diagnosis was decided for each patient according to AVS results mainly after ACTH stimulation.
Assay methodsBefore May 2020, PAC was measured using the commercially available RIA kit (SPAC-S Aldosterone Kit; Fuji Rebio, Co., Ltd, Tokyo, Japan; reference range in supine position, 30–159 pg/mL; minimum LOQ, 25.0 pg/mL). PRA was also measured using the commercially available RIA kit (Renin activity FR; Fuji Rebio, Co., Ltd, Tokyo, Japan; reference range in supine position, 0.2–2.7 ng/mL/h) [11]. After May 2020, PAC and active renin concentration (ARC) were measured using commercially available CLEIA kits, Lumipulse Presto aldosterone kit (Fuji Rebio, Co., Ltd, Tokyo, Japan; reference range, 3.0–82.1 pg/mL; minimum LOQ, 4.0 pg/mL), and Lumipulse Presto renin kit (Fuji Rebio, Co., Ltd, Tokyo, Japan; reference range, 2.21–39.49 pg/mL; minimum LOQ, 0.20 pg/mL) [11].
AnalysisIn the present study, we included patients with PA diagnosed by measuring renin and aldosterone using the RIA kits before May 2020 and those who visited the outpatient clinic in our hospital more than 1 year after surgery and had complete data on renin and aldosterone levels measured using the CLEIA kits.
Prolonged postoperative hypoaldosteronism (PPHA) was defined as PAC <4.0 pg/mL which was the minimum LOQ of the CLEIA kit more than 1 year after adrenalectomy.
To examine the characteristics of PPHA, we compared each parameter between patients with PPHA and without PPHA at diagnosis of PA and at the time of the first CLEIA measurement of PAC and examined the relationship between PPHA and postoperative hyperkalemia.
This study was approved by the Ethics Committee of Sapporo City General Hospital (R5-063-1016).
StatisticsData were analyzed and compared using BellCurve for Excel (Social Survey Research Information Co., Ltd., Tokyo, Japan). T-test or Mann-Whitney U-test was performed to analyze continuous variables, and Fisher’s exact test to compare the frequency between the two groups. Logistic regression analysis was used to determine the risk factors of PPHA. Statistical significance was achieved when p-value was <0.05.
A total of 58 patients with PA who underwent adrenalectomy were analyzed. PA was diagnosed between July 2007 and July 2019, and adrenalectomy was performed between August 2007 and September 2019. Patient characteristics at the time of diagnosis of PA are shown in Table 1. Of the 58 patients, 31 (53.4%) were female, and 50 (86.2%) had hypokalemia. Based on CT scan results, adrenal tumors on the right side were detected in 31 patients; on the left side, in 21 patients; and on the bilateral side, in four patients; no tumor was detected in two patients. Adrenalectomy was performed on the right side in 31 patients and on the left side in 27 patients. A partial adrenalectomy was conducted on the right side in four patients and on the left side in two patients. The remaining patients underwent a unilateral total adrenalectomy. Supplemental Table 1 shows the relationship between the side of adrenalectomy and the laterality on CT. In four patients with bilateral lesions and two patients with bilateral normal on CT, the side of surgery was determined based on AVS. In three patients, surgery was done on the opposite side of the lesion on CT in accordance with the results of AVS. Based on pathological findings, all patients were diagnosed with adrenocortical adenoma.
| Gender | Male 27 (46.6%), Female 31 (53.4%) |
| Age (years) | 52.2 ± 10.5 |
| Duration of hypertension (years) | 9.6 ± 7.6 |
| Antihypertensive drugs (DDD) | 2.07 ± 1.26 |
| Systemic blood pressure (mmHg) | 137.4 ± 18.1 |
| Diastolic blood pressure (mmHg) | 79.1 ± 12.0 |
| Serum potassium (mEq/L) | 3.2 ± 0.5 |
| eGFR (mL/min/1.73 m2) | 78.9 ± 23.0 |
| Plasma renin activity (ng/mL/h) | 0.1 [0.1–0.3] |
| Plasma aldosterone concentration (pg/mL) | 333.5 [227.25–483.25] |
| Aldosterone to renin ratio (pg/mL/ng/mL/h) | 1,762 [1,083–2,554] |
| Laterality of adrenal tumor on CT scan | Left 21 (36.2%), right 31 (51.7%), bilateral 4 (6.9%), bilateral normal 2 (3.4%) |
| Tumor size on CT scan (mm) | 14.5 ± 4.1 |
| Tumor size on resected specimen (mm) | 13.0 ± 4.8 |
Data are expressed as mean ± standard deviation (SD), median (interquartile range), and number (percentage); eGFR, estimated glomerular filtration ratio; DDD, defined daily dose; CT, computed tomography.
Before May 2020, PAC and PRA were measured using RIA kits. In all measurements of PAC using the RIA kit, there were no PAC values below the minimum LOQ of the RIA kit (25.0 pg/mL). After May 2020, PAC and ARC were measured using CLEIA kits. The interval from surgery to the first measurement of PAC using the CLEIA kit was 78 ± 44 months (mean ± standard deviation). Fig. 1 shows the comparison of PAC values between two consecutive visits before and after switching the PAC measurement methods. CLEIA-measured PAC value at first visit after the switch of the measuring method for PAC was significantly lower than RIA-measured PAC value at previous visit (median [interquartile range], 123.0 [99.8–164.0] pg/mL vs. 39.5 [15.8–64.2] pg/mL, p < 0.01). In eight patients, PAC measured using CLEIA for the first time was below the minimum LOQ (4.0 pg/mL); in particular, one patient had PAC of 4.6 pg/mL, which decreased below the minimum LOQ during a subsequent outpatient visit. In 49 patients, after multiple measurements for PAC, the results were not below the minimum LOQ. Nine patients with PAC below the minimum LOQ at least once during outpatient visits more than 1 year after adrenalectomy were considered to have PPHA. In the 9 patients with PPHA, the PAC levels from the last measurement using the RIA kit before changing the method ranged 60.0–103.0 pg/mL.
Comparison of PAC values at consecutive two visits before and after switching of method of measuring PAC from RIA to CLEIA
PAC, plasma aldosterone concentration; RIA, radioimmunoassay; CLEIA, chemiluminescent enzyme immunoassay.
Table 2 shows the comparison of the parameters at diagnosis of PA between the PPHA group and non-PPHA group (Table 2). Age was significantly higher in the PPHA group (p < 0.01). Moreover, the PPHA group had longer duration of hypertension and greater define daily dose of antihypertensive drugs than the non-PPHA group but without statistical significance. While the estimated glomerular filtration ratio (eGFR) [16] was significantly lower in the PPHA group (p < 0.01), the systolic blood pressure, diastolic blood pressure, serum potassium, PRA, PAC, and ARR measured using RIA were not significantly different between the two groups. The positive rates of confirmatory tests were not significantly different between the two groups (Supplemental Table 2). Tumor diameter measured on CT image and measured using surgical specimens tended to be larger in the PPHA group than in the non-PPHA group but without significant difference. The contralateral ratio after ACTH stimulation in AVS tended to be lower in the PPHA group, but without significant difference. In the non-PPHA group, 13 of 49 patients (26.5%) showed <10 mm in diameter of tumor using surgical specimen; by contrast, in the PPHA group, none of the nine patients had tumors less than 10 mm in diameter. Mineralocorticoid receptor antagonists (MRAs) were preoperatively administered in 7 of 9 patients (77.8%) in the PPHA group and in 29 of 49 patients (59.2%) in the non-PPHA group (p = 0.46).
| PPHA group (n = 9) | Non-PPHA group (n = 49) | p-value | |
|---|---|---|---|
| Gender | Male 4 (44.4%), Female 5(55.6%) | Male 23 (46.9%), Female 26 (53.1%) | 1.00 |
| Age (years) | 61 ± 8.5 | 50.5 ± 10.1 | <0.01 |
| Duration of hypertension (years) | 14.4 ± 6.7 | 8.8 ± 7.5 | 0.05 |
| Antihypertensive drugs (DDD) | 2.64 ± 1.12 | 1.97 ± 1.27 | 0.15 |
| Systemic blood pressure (mmHg) | 137.9 ± 16.5 | 137.3 ± 18.5 | 0.93 |
| Diastolic blood pressure (mmHg) | 76.3 ± 9.3 | 76.9 ± 12.4 | 0.46 |
| Serum potassium (mEq/L) | 3.4 ± 0.5 | 3.2 ± 0.5 | 0.28 |
| eGFR (mL/min/1.73 m2) | 60.3 ± 14.0 | 82.3 ± 22.8 | <0.01 |
| Plasma renin activity (ng/mL/h) | 0.2 [0.1–0.2] | 0.2 [0.1–0.3] | 0.32 |
| Plasma aldosterone concentration (pg/mL) | 247 [172–315] | 341 [228–488] | 0.19 |
| Aldosterone renin ratio (pg/mL/ng/mL/h) | 1,575 [1,340–2,470] | 1,840 [1,065–2,580] | 0.99 |
| Laterality of adrenal tumor on CT scan | Left 4 (44.4%), right 5 (55.6%) | Left 17 (34.7%), right 26 (53.1%), bilateral 4 (8.2), bilateral normal 2 (4.1%) |
1.00 |
| Tumor size on CT scan (mm) | 15.0 ± 4.5 | 14.4 ± 4.1 | 0.35 |
| Tumor size on resected specimen (mm) | 15.3 ± 3.4 | 12.5 ± 4.9 | 0.10 |
| Contralateral ratio in AVS | 0.30 ± 0.23 | 0.76 ± 1.36 | 0.69 |
Data are expressed as mean ± standard deviation (SD), median (interquartile range), and number (percentage); PPHA, prolonged postoperative hypoaldosteronism; DDD, defined daily dose; eGFR, estimated glomerular filtration ratio; CT, computed tomography; AVS, adrenal vein sampling.
At the first outpatient visit after the switch to CLEIA kits to measure renin and aldosterone levels in the blood, the parameters were compared between the PPHA group and the non-PPHA group (Table 3). The PPHA group had a significantly older age, significantly lower DBP, significantly higher serum potassium levels, significantly lower eGFR, and significantly lower PAC and ARR using CLEIA kits than the non-PPHA group. There was no significant difference in ARC between the two groups after using CLEIA kits. However, logistic regression analysis results could not show with statistical significance the risk factors for developing PPHA at the time of diagnosis of PA and at the first follow-up intended to measure PAC using CLEIA.
| PPHA group (n = 9) | Non-PPHA group (n = 49) | p-value | |
|---|---|---|---|
| Age at the first visit after changing to CLEIA | 68.1 ± 9.7 | 57.3 ± 11.7 | 0.01 |
| Interval from adrenalectomy (months) | 75 ± 40 | 79 ± 45 | 0.82 |
| Antihypertensive drugs (DDD) | 1.83 ± 1.05 | 1.14 ± 1.46 | 0.18 |
| Systemic blood pressure (mmHg) | 129.7 ± 18.5 | 125.0 ± 13.4 | 0.37 |
| Diastolic blood pressure (mmHg) | 71.9 ± 9.9 | 80.0 ± 10.0 | 0.03 |
| Serum potassium (mEq/L) | 4.7 ± 0.4 | 4.3 ± 0.4 | <0.01 |
| eGFR (mL/min/1.73 m2) | 36.7 ± 11.1 | 64.5 ± 17.8 | <0.01 |
| Active renin concentration (pg/mL) | 4.1 [0.6–7.4] | 6.8 [3.8–12.2] | 0.22 |
| Plasma aldosterone concentration (pg/mL) | 4 [4–4] | 42.3 [26.8–68.9] | <0.01 |
| Aldosterone to renin ratio | 1.05 [0.54–6.67] | 6.08 [3.65–11.80] | 0.02 |
PPHA, prolonged postoperative hypoaldosteronism; CLEIA, chemiluminescent enzyme immunoassay; DDD, defined daily dose; eGFR, estimated glomerular filtration ratio.
Drug use during the first outpatient visit after changing the measurement method for renin and aldosterone to the CLEIA kits was also investigated. There was no significant difference in the frequency of the patients who took antihypertensive drugs between the two groups. Angiotensin II receptor blockers (ARBs) were taken by a significantly higher number of patients in the PPHA group than that in the non-PPHA group (p < 0.01). MRAs were taken by only 8 of 49 patients in the non-PPHA group, which was not significantly different with the proportion of the patients in the PPHA group. Fludrocortisone was taken by only 2 of 9 patients in the PPHA group, which was significantly higher than that in the non-PPHA group (p < 0.01) (Table 4).
| PPHA group (n = 9) | Non-PPHA group (n = 49) | p-value | |
|---|---|---|---|
| Taking antihypertensive drugs | 7 (77.8%) | 30 (61.2%) | 0.46 |
| Taking ARBs | 6 (66.7%) | 7 (14.3%) | <0.01 |
| Taking MRAs | 0 (0%) | 8 (16.3%) | 0.33 |
| Taking fludrocortisone | 2 (22.2%) | 0 (0%) | <0.01 |
| Maximum serum potassium (mEq/L) | 5.6 ± 0.6 | 4.9 ± 0.5 | <0.01 |
| Maximum serum potassium >5.5 mEq/L | 5 (55.6%) | 4 (8.2%) | <0.01 |
| Maximum serum potassium >5.0 mEq/L | 7 (77.8%) | 14 (28.6%) | <0.01 |
Data are expressed as mean ± standard deviation (SD), median (interquartile range), and number (percentage); CLEIA, chemiluminescent enzyme immunoassay; PPHA, prolonged postoperative hypoaldosteronism; ARB, angiotensin II receptor blocker; MRA, mineralocorticoid receptor antagonist.
Serum potassium concentrations had been investigated in all courses after surgery. When hyperkalemia was defined as a maximum postoperative serum potassium level >5.5 mEq/L, the prevalence of hyperkalemia was significantly higher in the PPHA group than that in the non-PPHA group (55.6% vs. 8.2%, p < 0.01). When hyperkalemia was defined as a maximum postoperative serum potassium level >5.0 mEq/L, the prevalence of hyperkalemia was also significantly higher in the PPHA group than that in non-PPHA group (77.8% vs. 28.6%, p < 0.01) (Table 4).
Hyperkalemia is an important complication of adrenalectomy for PA. It is generally rare and transient and presents shortly after surgery [3-8]. Hyperkalemia is thought to be caused by hypoaldosteronism resulting from the removal of APA.
In large cohort studies of PA after adrenalectomy, the frequencies of postoperative hyperkalemia ranged 6.3%–29.1% [9, 17-20]. Three studies found no difference in the PAC after adrenalectomy, measured using RIA, between hyperkalemic group and normokalemic group [17-19]. In another study, PAC in patients with postoperative hyperkalemia was not discussed [20]. In contrast, Fischer et al. reported that 5.5% of patients with PA who underwent adrenalectomy had persistent hyperkalemia. PAC measured using the RIA kit (Coat-a-Count-RIA, Biermann DPC, Bad Nauheim, Germany) in all patients with persistent hyperkalemia were below the minimum LOQ (35 pg/mL) [9], suggesting that postoperative hyperkalemia was closely related to low PAC value below the minimum LOQ. In that study, PAC was measured by the RIA kit which had a high minimum LOQ. If a more accurate measurement method had been used, the results might be different.
In the present study, PAC was measured patients with APA more than 1 year after adrenalectomy using CLEIA kits. Approximately 15.5% of patients had PAC values below the minimum LOQ (4.0 pg/mL).
By analogy with the postoperative course of ACTH-independent Cushing’s syndrome, hypoaldosteronism is thought to be most frequently seen immediately after surgery and is thought to precede hyperkalemia and impaired renal function. In the patients with PPHA found in this study, hypoaldosteronism is thought to be developed immediately after surgery, and persisted even after a long period from surgery.
PAC values measured using CLEIA kits developed recently in Japan are apparently lower than that measured using the RIA kit. The Japan Endocrine Society formed a committee for the standardization of measuring aldosterone levels to examine the compatibility of the commercial kits available in Japan in 2020. When LC-MS/MS was used as a control measurement method for aldosterone, the values of aldosterone measured by the RIA kit was clearly high, and the measured value by the CLEIA kits were almost equivalent to that by LC-MS/MS. The regression equation for aldosterone values between the RIA kit used in the present study and LC-MS/MS was reported as aldosterone (RIA) = 1.217 × aldosterone (LC-MS/MS) + 61.0 pg/mL, and PAC was evaluated as inappropriately high when evaluated using the RIA kit, especially in patients with lower plasma aldosterone concentration. In contrast, the regression equation for aldosterone values between the CLEIA kit used in the present study and LC-MS/MS was as follows: aldosterone (CLEIA) = 1.053 × aldosterone (LC-MS/MS) –1.1 pg/mL [12]. Additionally, the minimum LOQ for PAC is lower in the CLEIA kit than that in the RIA kit, which were both used in the present study (4.0 pg/mL vs. 25.0 pg/mL) [12]. If the minimum LOQ of the CLEIA kit is used as the cut-off value for diagnosing hypoaldosteronism, it is a sufficiently strict value and can diagnose hypoaldosteronism with high specificity.
In the present study, patients in the PPHA group were older at diagnosis and had impaired renal function than patients in the non-PPHA group. Moreover, the PPHA group had longer duration of hypertension, higher number and defined daily dose of antihypertensive drugs, and lower contralateral ratio in AVS than the non-PHA group, although there were no significant differences. These findings suggest that long-term suppression of aldosterone secretion from the zona glomerulosa of the normal adrenal gland surrounding APA in PPHA patients irreversibly impairs aldosterone secretion from the residual adrenal glands even after surgery. The impaired renal function may be due to the longer duration of PA and aging. Meanwhile, the diameter of tumors in resected specimens was not significantly different between the PPHA group and the non-PPHA group. However, there were no cases with the diameter of tumor less than 10 mm in the PPHA group, but 26.5% of the cases in the non-PPHA group had the diameter of tumor with less than 10 mm. This suggests that the properties of APA are different between groups and that the patients with micro-APA may unlikely develop PPHA. In addition, PPHA was not thought to be caused by the postoperative suppression of renin, because there was not significant difference in the active renin concentration after surgery between the PPHA and non-PPHA groups.
Regarding the involvement of drugs, the frequency of preoperative MR antagonists’ use was not significantly different between the PPHA group and the non-PPHA group, but the postoperative frequency of ARBs’ use was significantly higher in the PPHA group. The use of RAS system inhibitors after surgery may be involved in development of PPHA. Two patients in the PPHA group had received fludrocortisone for several years after adrenalectomy; both renin and aldosterone levels were suppressed in these patients. In these patients, the administration of fludrocortisone was started because of marked hyperkalemia and decreased renal function in the early postoperative period. Therefore, fludrocortisone administration does not appear to be the main cause of hypoaldosteronism.
In the present study, the prevalence of postoperative hyperkalemia during the entire course after surgery was significantly higher in the PPHA group than in the non-PPHA group, regardless of whether the cut-off value of serum potassium was 5.0 mEq/L or 5.5 mEq/L. However, the onset of PPHA was not completely consistent with the onset of postoperative hyperkalemia. The cut-off values for the diagnosis of these pathological conditions and the timing of diagnosis might have affected these findings. In addition, factors other than PAC may be involved in the development of postoperative hyperkalemia.
There are some limitations in the present study. First, this was a single-center, retrospective, observational study, which might be prone to selection bias and the number of patients was too small to determine the risk factors for developing PPHA. Since this was a retrospective study, the types of preoperative and postoperative antihypertensive drugs were not standardized. Therefore, serum potassium level as well as PAC might have been affected by the antihypertensive drugs. Second, the method of measuring renin and aldosterone was changed during the postoperative follow-up, and the course could not be followed-up with a single method of measurement. Since the blood samples were not stored, it was not possible to compare the PAC values of both assays using the same sample. Third, we did not study genetic mutations in the resected adrenal adenomas. Further studies are needed to investigate the relationship between the likelihood of postoperative hypoaldosteronism and gene mutations in APA.
In conclusion, a few patients with APA long time after adrenalectomy had unmeasurable PAC using the newly available CLEIA kit in Japan. PPHA is likely to develop in patients with APA after adrenalectomy who are older and have impaired renal function. Additionally, PPHA is related to the occurrence of postoperative hyperkalemia.
The authors have nothing to disclose.
| Laterality of adrenal lesion on CT scan | Left adrenalectomy (n = 27) | Right adrenalectomy (n = 31) | Total (n = 58) |
|---|---|---|---|
| Left tumor | 21 (77.8%) | 0 (0%) | 21 (36.2%) |
| Right tumor | 3 (11.1%) | 28 (90.3%) | 31 (51.7%) |
| Bilateral tumors | 1 (3.7%) | 3 (9.6%) | 4 (6.9%) |
| Bilaterally normal | 2 (7.4%) | 0 (0%) | 2 (3.4%) |
Data are expressed as number (percentage). CT, computed tomography.
| PPHA group (n = 9) | Non-PPHA group (n = 49) | p-value | |
|---|---|---|---|
| Captopril challenge test | 9/9 (100%) | 45/48 (93.8%) | 1.00 |
| Furosemide upright test | 4/4 (100%) | 23/23 (100%) | 1.00 |
| Saline infusion test | 1/1 (100%) | 4/4 (100%) | 1.00 |
Data are expressed as number (positive/investigated) and percentage. PPHA, prolonged postoperative hypoaldosteronism.
