Differential Diagnosis Of Primary Aldosteronism Research Articles

Diagnosis and therapy of primary aldosteronism: new aspects

Primary aldosteronism represents the most frequent cause of endocrine hypertension. It is associated with a higher morbidity and mortality compared to essential hypertension. Early identification of the affected patients is crucial, as the adequate therapy leads to an excellent long-term prognosis, especially after unilateral adrenalectomy. Diagnosis consists of three steps: diagnosis, confirmation test and subtype differentiation. The 2 most frequent causes of primary aldosteronism are aldosterone producing adenoma, which can be cured by surgery, and idiopathic bilateral adrenal hyperplasia, which is treated with mineralocorticoid receptor antagonists.Screening by aldosterone-to-renin ratio is recommended in designed risk populations. As the aldosterone-to-renin ratio displays a limited sensitivity and specificity, confirmatory testing is recommended in most patients with positive screening test. Prediction scores allow to skip confirmatory testing under certain circumstances. Adrenal vein sampling still represents the gold standard in subtype differentiation of primary aldosteronism. Steroid profiling could possibly make dispensable adrenal vein sampling in patients with bilateral hyperplasia. Different studies investigate the potential of functional imaging for differential diagnosis of primary aldosteronism.

The Diagnostic Value of Captopril Challenge Test for Primary Aldosteronism

To investigate the diagnostic value of different captopril challenge test (CCT) diagnostic criteria for diagnosing primary aldosteronism (PA). We collected the clinical data of 184 patients with hypertension retrospectively in West China Hospital of Sichuan University. Receiver operating characteristic (ROC) curves were used to analyze the post-CCT efficacy of aldosterone renin activity ratio (ARR), plasma aldosterone concentration (PAC), plasma renin activity (PRA) and PAC suppression rate for PA diagnosis. This study included 125 cases of primary aldehyde (PA group) and 59 cases of essential hypertension (EH group), and there were 38 normal renin primary hypertension (NREH group) and 21 low renin primary hypertension (LREH group) in EH group. The post-CCT PAC suppression rate (median (P 25, P 75)) of EH and PA group were 0.190 (0.083, 0.351) and 0.125 (0.024, 0.237), respectively. Compared with the NREH group, the basic and post-CCT PRA of LREH group were lower ( P<0.001), and there were no significant differences compared with the PA group ( P>0.05). We found significant overlap of post-CCT PRA and ARR between PA group and LREH group, while the overlap of post-CCT PAC between the two groups was small. In differential diagnosis of PA and EH, the areas under ROC curve of the post-CCT ARR, PAC, PRA and PAC suppression rate were 0.860 (95% confidence interval ( CI): 0.800-0.907), 0.881 (95% CI: 0.825-0.924), 0.771 (95% CI: 0.703-0.831) and 0.632 (95% CI: 0.558-0.701), respectively. There was no significant difference between the first two indexes ( Z=0.443, P=0.658), and both of them were higher than the latter two ( P<0.05). The optimal post-CCT cut-off values for ARR and PAC in differential diagnosis of PA and EH were 19.24 ng·dL -1 with a sensitivity of 78.4% and a specificity of 88.1%, and 32.47 (ng·dL -1)/(ng·mL -1·h -1) with a sensitivity of 84.17% and a specificity of 72.41%. Both ARR and PAC have higher diagnostic value than the post-CCT PAC suppression rate, post-CCT PAC is especially suitable as a confirmatory testing criterion of PA.

The Value of Serum Potassium and Ratio of Sodium to Potassium after Saline Infusion Test in Differential Diagnosis of Primary Hyperaldosteronism

To explore the electrolyte characteristics between different types of primary aldosteronism (PA), especially the value of serum potassium and the ratio of sodium to potassium after saline infusion test (SIT) in differential diagnosis of PA. The clinical data was collected from 135 patients who received screening for the causes of hypertension from Jan. 2009 to Dec. 2018 in West China Hospital. The patients were divided into two groups: essential hypertension group (EH group, 34 patients) and primary aldosteronism group (PA group, 101 patients). PA patients were divided into aldosterone-producing adenoma group (APA group, 60 patients) and idiopathic hyperaldosteronism group (IHA group, 41 patients). To analyze the value of serum potassium and the ratio of sodium to potassium after SIT in the differential diagnosis of PA with receiver operating characteristic (ROC) curve. Compared with EH group, the serum potassium level of APA group was lower either before or after SIT ( P<0.01). The ratio of sodium to potassium before and after SIT in APA group were higher than that in EH group ( P<0.05). There were no differences between APA group and IHA group in the level of serum potassium and the ratio of sodium to potassium before SIT. The level of serum potassium after SIT in APA group was lower than that in IHA group ( P<0.01), and the ratio of sodium to potassium was higher ( P<0.05). The area under ROC curve ( AUC) of serum potassium level and the ratio of sodium to potassium after SIT were 0.641 and 0.646, respectively, while the AUC of aldosterone level was 0.788. The optimal cut-off value of serum sodium level was 3.56 mmol/L, with a sensitivity and specificity of 46.7% and 85.4%. The optimal cut-off value of ratio of sodium to potassium was 39.09, with 53.3% and 80.5% in sensitivity and specificity. The serum potassium and the ratio of sodium to potassium after SIT has limited diagnostic value for its low sensitivity in differential diagnosis of PA.

Метод сравнительного селективного забора крови из надпочечниковых вен в дифференциальной диагностике первичного гиперальдостеронизма на примере клинического случая

Метод сравнительного селективного забора крови из надпочечниковых вен в дифференциальной диагностике первичного гиперальдостеронизма на примере клинического случая

Urine steroid metabolomics as a diagnostic tool in primary aldosteronism

Introduction: The regular diagnostic workup for primary aldosteronism (PA) can be very demanding and involves multiple invasive as well as time and cost intensive diagnostic tests. Here we have explored the value of urinary steroid metabolome analysis in the diagnosis and differential diagnosis of PA. Previously, urinary 3α,5β-tetrahydroaldosterone (THAldo) has been suggested as a reliable screening test for PA and serum 18-oxocortisol and 18-hydroxycortisol have been reported as diagnostic markers with the potential to distinguish unilateral aldosterone-producing adenomas (APA) from bilateral adrenal hyperplasia (BAH). Patients and methods: We studied 180 PA patients (103 APA, 71 BAH) in whom PA had been confirmed by saline infusion test followed by adrenal vein sampling for subtype differentiation. We carried out targeted sequencing for disease-causing somatic mutations in the KCNJ5, CACNA1D, ATP1A1 and ATP2B3 genes in tumour tissue obtained by unilateral adrenalectomy, which was available in 75/103 APA patients. The urine steroid metabolome was analysed by gas chromatography-mass spectrometry comprising the quantification of 38 distinct steroids including metabolites of aldosterone, deoxycorticosterone, corticosterone as well as 18OH-cortisol (18OH-F) and 18-oxo-tetrahydrocortisol (18oxo-THF). Results: As expected, urinary excretion of mineralocorticoids (p 69 μg/24h, with significantly higher THAldo in APAs compared to BAH (p=0.0082). Similarly, APAs had significantly higher excretion of 18OH-F (p=0.0171) and 18oxo-THF (p=0.0005). Genetic analysis of APA tissue revealed mutations in KCNJ5 (n=29), ATPases (n=12) and CACNA1D (n=6) while in 28 patients no known mutation was identified. Patients with KCNJ5 mutations had significantly increased excretion of both 18OH-F (p=0.0002) and 18oxo-THF (p<0.0001) as compared to the other mutation groups. Conclusion: Urine steroid metabolomics is a promising approach for the diagnosis and differential diagnosis of PA.

A prospective evaluation of postural stimulation testing, computed tomography and adrenal vein sampling in the differential diagnosis of primary aldosteronism

In primary aldosteronism (PA), discriminating unilateral from bilateral disease is crucial because adrenalectomy is frequently curative in the former case but rarely helps in the latter. Various series have reported the utility of postural stimulation testing (PST), cross-sectional imaging and adrenal vein sampling (AVS) in the assessment of PA, but most of these studies were retrospective. To prospectively determine the diagnostic utility of PST, AVS and computed tomography (CT) using a radiological scoring system in the assessment of PA in a tertiary centre, as well as to document the incidence of autonomous cortisol cosecretion. Fifty consecutive patients with PA underwent PST, CT, AVS and a low-dose dexamethasone suppression test with measurement of serum cortisol at 48 h. For patients who underwent surgery, histological confirmation, and a normal postoperative serum aldosterone concentration and plasma renin activity were taken as evidence for unilateral disease. For other patients, results from successful adrenal vein sampling were the diagnostic evidence against which CT and PST were assessed. Postural stimulation testing had a sensitivity and specificity of 44-56% and 71-75%, respectively. CT had an overall sensitivity and specificity of 77% and 80%, respectively, rising to 100% sensitivity and specificity if there was a single, discrete macronodule with an unequivocally normal contralateral gland. Evidence of cosecretion of cortisol occurred in 14% of patients. Preliminary experience is presented of an objective radiological scoring system for selecting patients with PA for AVS. PST provides little, if any, useful additional information. A significant minority of patients with PA exhibit evidence of cortisol cosecretion, which may have implications for perioperative management.

Adrenal vein sampling using rapid cortisol assays in primary aldosteronism is useful in centers with low success rates

Adrenal vein sampling (AVS) is considered the gold standard in the differential diagnosis of primary aldosteronism (PA), but success rates vary between centers. We hypothesized that rapid (intraprocedure) cortisol measurement can improve performance in a center with initially low AVS success rate. We analyzed 46 patients with confirmed PA studied between 2008 and 2010. Forty-seven PA patients studied between 2004 and 2008 identified by retrospective chart review served as controls. All patients were treated at a single tertiary care university hospital. Starting in 2008, rapid cortisol assays (RCA) were performed in all patients during the AVS procedure. A cortisol gradient of ≥2.0 between adrenal vein and a femoral vein sample was used as success criterion. Up to two repeat samples were drawn if adrenal vein cortisol was below this threshold. Results During the control period 26 of 47 AVS were successful (55%). After introduction of RCA, 39 out of 46 AVS (85%) were successful (P=0.003). In 21 of the 46 cases (46%) a resampling was necessary. The increase in overall success was due to an increase in successful right AVS (85 vs 62% before introduction of RCA; P=0.02) and a training effect (P=0.024 for trend). RCA during AVS are useful in centers with an initially low AVS success rate.

Endosonographie—eine zusätzliche diagnostische Möglichkeit bei der Differenzierung der beiden häufigsten Formen des primären Hyperaldosteronismus

Background: Primary aldosteronism is an important and one of the few potentially curable forms of secondary hypertension. The distinction between aldosterone-producing adenoma (APA) and idiopathic adrenal hyperplasia (IHA) may be difficult, but establishing the correct diagnosis is essential because surgery is only effective in patients with adrenal adenoma. Case Report: The case of a 65-year-old man with long-term hypertension due to an APA is reported. The routine laboratory tests displayed an elevated plasma aldosterone/renin quotient as well as an elevated 24-h urinary excretion of aldosterone and its metabolites. The serum aldosterone concentration did not decrease normally in the saline suppression test. The posture testing demonstrated an increase in aldosterone. These facts might lead to the conclusion of an IHA. Magnetic resonance imaging (MRI) of the adrenal glands revealed no abnormalities. Because of the unusual combination of laboratory findings and radiologic results an endosonographic examination of the adrenal glands was performed which yielded a unilateral adrenal adenoma. With establishing this diagnosis, curative surgery became possible. Conclusion: This case demonstrates that in the differential diagnosis of primary aldosteronism, endosonography is more important than previously discussed. It may be helpful in the differentiation of an unusual constellation of laboratory and radiologic findings.

Evaluation of Diagnostic Tests in the Differential Diagnosis of Primary Aldosteronism: Unilateral Adenoma Versus Bilateral Micronodular Hyperplasia

Effective management of primary aldosteronism is dependent upon correct localization of excessive aldosterone production. We report our results of localization studies in patients with biochemically and pathologically confirmed primary aldosteronism. Retrospective chart review identified 69 patients with unilateral adrenal adenoma and 11 with adrenal hyperplasia. Correct unilateral versus bilateral localization of excessive aldosterone production was predicted in 70% versus 71%, respectively, by adrenal venography, 100% versus 63% by adrenal vein hormone sampling, 46% versus 56% by adrenal nuclear scanning and 69% versus 13% by anomalous postural decline of aldosterone. Adrenal computerized tomography appeared to localize correctly 86% versus 80% of the lesions. Unilateral adrenalectomy normalized blood pressure in 79% of the patients with unilateral adenomas versus only 18% of those with adrenal hyperplasia. Once primary aldosteronism is confirmed, localization by adrenal vein sampling, adrenal venography and adrenal computerized tomography is most effective in directing antihypertensive therapy.

The unique steroidogenesis of the aldosteronoma in the differential diagnosis of primary aldosteronism.

18-Hydroxycortisol and 18-oxocortisol have been isolated from the urine of patients with aldosterone producing adrenocortical adenomas, but not from those with idiopathic hyperaldosteronism associated with bilateral adrenal hyperplasia. These C-18 oxygenated cortisols are biosynthesized by the substitution of cortisol for the normal substrate, corticosterone, in the terminal oxidase system required for the biosynthesis of 18-hydroxycorticosterone and aldosterone. To make use of this biochemical difference between the two groups in the preoperative diagnosis of primary aldosteronism, we have developed and utilized a specific primary standard analytical method, stable isotope dilution mass fragmentography, for quantifying 18-hydroxycortisol and the tetrahydro metabolite of 18-oxocortisol in 24-h urine samples. The normal range by this technique of 4.6 +/- 1.8 micrograms/day tetrahydro 18-oxocortisol and 43 +/- 23 micrograms/day 18-hydroxycortisol in urine was lower and narrower than previous estimates using other methods. Excretion of the 18-oxocortisol metabolite ranged from 2-12 micrograms/day in bilateral hyperplasia and 17-1203 micrograms/day in typical adenomas. 18-Hydroxycortisol excretion similarly separated bilateral hyperplasia (23-59 micrograms/day) from typical adenomas (60-2750 micrograms/day). The cortisol C-18 oxidation pathway describes a unique steroidogenic mechanism in the aldosteronoma not present in idiopathic aldosteronism due to bilateral adrenal hyperplasia and as such provides a basis for the biochemical classification of primary aldosteronism and the differentiation of these two groups. This unique biochemistry was also observed in unilateral hyperplasia but not in the renin-dependent aldosteronoma.

The unique steroidogenesis of the aldosteronoma in the differential diagnosis of primary aldosteronism

The unique steroidogenesis of the aldosteronoma in the differential diagnosis of primary aldosteronism

A radioimmunoassay for 18-hydroxycortisol in plasma and urine.

Increased excretion of 18-hydroxycortisol has been proposed as a specific biochemical marker for differential diagnosis of primary aldosteronism. We describe the development of a direct RIA with an 125I label that permits measurement of the steroid in less than or equal to 0.5 microL of urine or less than or equal to 25 microL of plasma. For control subjects, the mean concentrations of 18-hydroxycortisol in urine and plasma were 310 (SD 178) nmol/24 h (n = 32) and 2.27 (SD 0.80) nmol/L (n = 37), respectively; patients with Conn's adenoma or glucocorticoid-remediable aldosteronism had values for urine in the range 1084 to 6534 nmol/24 h and concentrations in plasma ranging from 6.49 to 31.20 nmol/L. Patients with idiopathic zona glomerulosa hyperplasia had values for urine and plasma ranging from 353 to 734 nmol/24 h and from 0.26 to 6.60 nmol/L, respectively. Concentrations of 18-hydroxycortisol in urine clearly discriminate patients with idiopathic hyperplasia from those with other forms of primary aldosteronism, but further work is required to assess the diagnostic accuracy of determinations in plasma.

Changes in plasma renin activity after administration of spironolactone.

Spironolactone, a potent aldosterone-blocking agent, was administered to 34 subjects including 4 patients with primary aldosteronism, and changes in plasma renin activity and electrolytes were followed up. Plasma renin activity was found to elevate during the medication in all subjects except 4, who were suffering from primary aldosteronism. In the latter subjects there was no increase in the renin activity. A possibility was suggested with regard to the differential diagnosis of primary aldosteronism from other mimicking hypertensions using this spironolactone test.