Accumulating evidence has shown the adverse effect of long-term hyperaldosteronism on cardiovascular morbidity that is independent of blood pressure. However, the diagnosis of primary aldosteronism (PA) remains a challenge for patients who present with subtle or atypical features or have chronic kidney disease (CKD). SPECT/CT has proven valuable in the diagnosis of a number of conditions. The aim of this study was to determine the usefulness of I-131 NP-59 SPECT/CT in patients with atypical presentations of PA and in those with CKD. The records of 15 patients with PA were retrospectively analyzed. NP-59 SPECT/CT was able to identify adrenal lesion(s) in CKD patients with suspected PA. Patients using NP-59 SPECT/CT imaging, compared with those not performing this procedure, significantly featured nearly normal serum potassium levels, normal aldosterone-renin ratio, and smaller adrenal size on CT and pathological examination and tended to feature stage 1 hypertension and non-suppressed plasma renin activity. These findings show that noninvasive NP-59 SPECT/CT is a useful tool for diagnosis in patients with subclinical or atypical features of PA and those with CKD.
Primary aldosteronism (PA) is the most common cause of surgically curable secondary hypertension and affects more than 10% of the general hypertensive population [
It has been reported that an increased serum aldosterone level in normotensive individuals leads to the development of sustained hypertension in the future [
The common modalities used for subtype identification of PA also have limitations. Adrenal CT scan is considered the initial diagnostic modality for the identification of adrenal nodules; however, its diagnostic sensitivity is estimated to be 50% [
Single photon emission computed tomography (SPECT)/CT imaging is a significant technical innovation that simultaneously provides anatomic and functional information to allow for better localization of tracer activity and to enhance diagnostic accuracy and sensitivity [
The records of 14 patients with PA (5 males, 10 females) with a median age of 55.9 years (range, 27–72 years) who underwent adrenalectomy at our institution from April 2007 to April 2010 were retrospectively reviewed. Patients were followed until October 2010. One patient who did not undergo adrenalectomy because of clinically confirmed bilateral adrenal hyperplasia was also included in the analysis. Therefore, the study included 15 patients, 14 with pathologically confirmed PA, and one with clinically confirmed PA. Of the 15 patients, 6 who received NP-59 SPECT/CT imaging served as the SPECT/CT group, and the other 9 who did not receive NP-59 SPECT/CT imaging served as the control group. The complete data of these 15 patients are presented in Tables 1 and
Qualitative analysis of Tables
We collected clinical data including age, gender, systolic and diastolic BP at admission, chief complaints, laboratory results (serum potassium [K], plasma aldosterone concentration [PAC], plasma renin activity [PRA], aldosterone-renin-ratio [ARR], and transtubular potassium gradient [TTKG]) or 24-hour urinary potassium excretion, and confirmatory tests results (including saline loading test or/and captopril test) if done, followup outcomes, and imaging and pathological data. PAC and PRA were measured by commercial RIA kits (ALDOCTK, #P2714, Diasorin Inc., MN, USA, and GAMMACOAT PLASMA RENIN ACTIVITY, #CA-1533, Diasorin Inc., MN, USA, resp.). Normal ranges for PAC and PRA are 3.7–24 ng/dL and 0.15–2.33 ng/mL/h, respectively.
The definition of hypertension stage was based on the JNC 7 classifications [
A dexamethasone suppression regimen (1 mg orally 4 times daily) was initiated 7 days before tracer injection and this was continued throughout the imaging procedure and for 5 days postinjection [
CT images with fine cuts (3 mm) were obtained and interpreted by a well-experienced radiologist. The NP-59 planar, SPECT, and SPECT/CT images were interpreted by 2 nuclear medicine specialists. Aldosteronism on the affected side(s) was considered if there was early visualization of the tracer on imaging before the fifth postinjection day and intense uptake greater than that in the liver [
Of the 15 patients, 14 underwent laparoscopic adrenalectomy by an experienced surgeon. The histopathological examinations of the surgical specimens were performed by an experienced pathologist.
All data are expressed as median (range). The differences between the SPECT/CT group and the control group were compared by Fisher’s exact test for categorical variables, or by Mann-Whitney
Pathological examination showed that 12 of 15 patients had unilateral adenomas, 1 had a micronodule, and 1 had unilateral focal nodular hyperplasia (Table
A 27-year-old woman (patient 15) who had stage 4 CKD presented with stage 1 hypertension alone due to bilateral adrenal hyperplasia, whose PAC was elevated, but whose serum potassium level was normal, whose PRA was nonsuppressive, whose ARR was negative, whose confirmatory testing was negative, whose bilateral adrenal lesions had normal appearing on CT (a) and faint uptakes on planar imaging (b) but true positive on SPECT (c) and coronal SPECT/CT (d) imaging. After treatment with 25 mg of spironolactone, her BP and PAC were normalized.
Demographic and clinical data of study subjects.
Patient | Age (y) | Gender | BP (mm Hg) at admission | HTN* stage | Chief complaint | Laboratory tests | Confirmatory tests | ||||||
SBP | DBP | Serum K (mEq/L) | PAC# (ng/dL) | PRA# (ng/mL/h) | ARR | TTKG | Test | Result | |||||
Control group ( | |||||||||||||
1 | 50 | F | 230 | 130 | 2 | HTN | 2.2 | 60.08 | 0.13 | 462 | — | Captopril | Positive |
2 | 34 | F | 186 | 105 | 2 | Weakness | 1.6 | 45.80 | 0.13 | 352 | 4.5 | Saline loading | Positive |
3 | 58 | F | 220 | 120 | 2 | HTN | 2.69 | 29.28 | 0.13 | 225 | — | Captopril | Positive |
4 | 32 | F | 182 | 121 | 2 | HTN | 2.87 | 40.00 | 1.71 | 23 | — | — | — |
5 | 71 | F | 146 | 94 | 1 | Weakness | 2.61 | 32.10 | 0.05 | 642 | 6.2 | — | — |
6 | 59 | M | 152 | 71 | 1 | HTN | 3.49 | 25.55 | 0.45 | 57 | — | Saline loading | Positive |
7 | 60 | F | 160 | 90 | 2 | Weakness | 1.74 | 110.70 | 0.18 | 615 | 11.9 | — | — |
8 | 72 | M | 180 | 117 | 2 | Weakness | 1.96 | 31.80 | 0.06 | 122 | — | — | — |
9 | 56 | F | 154 | 83 | 1 | Weakness | 2.76 | 21.70 | 0.53 | 41 | 6.1 | — | — |
SPECT/CT group ( | |||||||||||||
10 | 55 | F | 140 | 90 | 1 | Accidentally palpable Irregular pulse | 3.24 | 31.9 | 2.52 | 13 | 8.8 | Saline loading Captopril | Negative |
11 | 48 | F | 145 | 80 | 1 | HTN | 4.01 | 26.8 | 0.06 | 447 | — | Saline loading Captopril | Negative |
12† | 57 | M | 170 | 100 | 2 | HTN | 2.79 | 37.2 | 0.32 | 116 | 72.1 mEq/d! | Saline loading | Negative |
13 | 56 | M | 144 | 90 | 1 | — | 4.14 | 25.3 | 1.31 | 12 | — | — | — |
14 | 39 | M | 206 | 115 | 2 | HTN | 2.2 | 27.5 | 1.68 | 16 | 8.2 | — | — |
15† | 27 | F | 150 | 88 | 1 | HTN | 4.32 | 29.3 | 1.62 | 18 | — | Captopril | Negative |
Abbreviations: SBP: systolic blood pressure; DBP: diastolic blood pressure; HTN: hypertension; S/S: symptom/sign; K: potassium; PAC: plasma aldosterone concentration; PRA: plasma renin activity; ARR: aldosterone-renin ratio; TTKG: transtubular potassium gradient; F: female; M: male.
#Normal range of PAC, PRA, and serum K is 3.7–24 ng/dL, 0.15–2.33 ng/mL/h, and 3.5 to 5.0 mEq/L, respectively.
*HTN stage according to JNC 7 report.
† Patients 12 and 15 had stages 3 and 4 chronic kidney disease with serum creatinine level of 2.2 mg/dL (eGFR 32.9 mL/min/1.73 m2) and 2.5 mg/dL (eGFR 24.6 mL/min/1.73 m2), respectively.
!24-hour urine excretion of potassium.
Imaging and pathological data of study subjects.
Patient | Age (y) | Gender | CT result | NP-59 result | Pathological result | Followup improvement | ||||
Appearance (side) | Size (mm) | Planar | SPECT | SPECT/CT | Finding | Size (mm) | ||||
Control group ( | ||||||||||
1 | 50 | F | Nodule (L) | 20 | — | — | — | Adenoma | 21 | PAC, PRA, K |
2 | 34 | F | Nodule (L) | 18 | — | — | — | Adenoma | 16 | PAC, PRA, K, BP |
3 | 58 | F | Nodule (R) | 17 | — | — | — | Adenoma | 17 | PAC, PRA, K |
4 | 32 | F | Nodule (L) | 20 | — | — | — | Adenoma | 20 | PAC, K, BP |
5 | 71 | F | Nodule (L) | 17 | — | — | — | Adenoma | 25 | PAC, PRA, K, BP |
6 | 59 | M | Nodule (L) | 11 | — | — | — | Adenoma | 10 | PAC, BP |
7 | 60 | F | Nodule (R) | 21 | — | — | — | Adenoma | 20 | PAC, K |
8 | 72 | M | Nodule (R) | 22 | — | — | — | Adenoma | 20 | PAC, PRA, K, BP |
9 | 56 | F | Nodule (L) | 17 | — | — | — | Adenoma | 17 | PAC, K, BP |
SPECT/CT group ( | ||||||||||
10 | 55 | F | Normal | — | N | R | R | Micronodule | 0.8 | PAC, K, BP |
11 | 48 | F | Nodule (L) | 17 | L | L | L | Adenoma | 17 | PAC, PRA, K, BP |
12† | 57 | M | Enlarge (L) | 9 (in thickness) | N | L | L | Focal nodular hyperplasia | 6 | PAC, PRA, K, BP |
13 | 56 | M | Nodule (L) | 12 | N | L | L | Adenoma | 10 | PAC, BP |
14 | 39 | M | Nodule (R) | 14 | N | R | R | Adenoma | 12 | PAC, K, BP |
15† | 27 | F | Normal | — | Faint | Bil | Bil | —# | —# | PAC, BP |
Abbreviations: CT: computed tomography; L: left; R: right; Bil: bilateral; other abbreviations are the same as Table
†Patients 12 and 15 had stages 3 and 4 chronic kidney disease with serum creatinine level of 2.2 and 2.5 mg/dL, respectively.
#Patient 15 did not undergo adrenalectomy because of bilateral adrenal hyperplasia.
In the control group (
In the control group (
CT produced 9 (100%) true positive results in the control group. CT produced 2 (33%) false negative and 4 (67%) true positive results in the SPECT/CT group. NP-59 planar imaging produced 2 (33%) true positive and 4 (67%) false negative results. NP-59 SPECT and SPECT/CT produced 6 (100%) true positive results, indicating 100% sensitivity.
We divided all 15 patients into 4 categories based on the severity of hypertension and hypokalemia: category 1 (stage 2 hypertension and hypokalemia;
NP-59 SPECT/CT correctly identified 3 adenomas (median size, 12 mm; range 10–17 mm), 1 micronodule (0.8 mm in size), 1 focal nodular hyperplasia (with the largest micronodule 6 mm in size), and 1 bilateral adrenal hyperplasia (Figure
Comparison of variables between the control and SPECT/CT groups.
Variable | Control group ( | SPECT/CT group ( | |
---|---|---|---|
Age (y)† | 58 (32–72) | 51 (27–57) | .157 |
Male gender ( | 2 (22%) | 3 (50%) | .329 |
Systolic BP (mm Hg)† | 180 (146–230) | 147 (144–206) | .077 |
Diastolic BP (mm Hg)† | 105 (71–130) | 90 (80–115) | .237 |
Serum potassium (mEq/L)† | 2.6 (1.6–3.49) | 3.6 (2.2–4.32) | .029 |
PAC (ng/dL)† | 32.1 (21.7–110.7) | 28.4 (25.3–37.2) | .239 |
PRA (ng/mL/h)† | 0.06 (0.05–0.53) | 1.47 (0.06–2.52) | .058 |
Aldosterone-renin ratio (ARR)† | 352.3 (23–642) | 18.7 (13–447) | .025 |
CT size (mm)† | 18 (11–22) | 10.5# (9–17#) | .007 |
Pathological size (mm)† | 20 (10–25) | 10* (0.8–17*) | .015 |
Abbreviations are the same as Tables
†Data are expressed as median (range).
#
*
‡
The median level of serum potassium was significantly higher in the SPECT/CT group than in the control group (3.6 versus 2.6 mEq/L, resp.,
This is the first study to report the use of NP-59 SPECT/CT in patients with normal renal function and those with CKD who are clinically suspected to have PA but have subtle clinical symptoms, atypical results on screening tests, negative confirmatory tests, or negative CT findings. This study adds novel data to existing knowledge of PA by qualitatively analyzing the associations between clinical symptoms and screening tests (Figure
The first part of this study qualitatively analyzed the application of NP-59 SPECT/CT in patients suspected of having PA, but clinically not confirmed, as shown in Figure
In addition, it is worth noting that 2 patients with CKD (patients 12 and 15) were diagnosed with PA by means of NP-59 SPECT/CT in this study. The diagnosis of PA in patients with CKD is difficult and easily missed, and only 2 cases have been reported in the English literature [
The second part of our study analyzed the differences in clinical and pathological parameters between the 2 groups, as shown in Table
The Framingham offspring study has shown that an excess of circulating aldosterone in normotensive individuals results in the development of sustained hypertension [
The present study has some limitations. First, this was a retrospective study, and confirmatory testing and NP-59 SPECT/CT were not performed in all patients. Second, the specificity and diagnostic accuracy of NP-59 SPECT/CT cannot be established because of the small number of cases. Third, all patients did not undergo adrenal vein sampling.
In summary, our findings demonstrated that NP-59 SPECT/CT could be a reliable and non-invasive tool for an early diagnosis of PA in patients with subclinical or atypical features of PA and in CKD patients with suspected PA. NP-59 SPECT/CT imaging may transform the diagnostic process and lead to early identification and prompt management of these patients to achieve the cure of hypertension.
The authors have no conflict of interests.
The authors would like to thank Professor Shih-Hua Lin, the Chief of Division of Nephrology, Department of Internal Medicine, Tri-Service General Hospital, Taipei, Taiwan, and Professor Shang-Jyh Hwang, Division of Nephrology, Department of Internal Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan, to challenge us to complete this study.