cosyntropin and Hyperaldosteronism

Notwithstanding the high prevalence of primary aldosteronism (PA), probably the most common form of secondary hypertension, the diagnosis of PA is often neglected or delayed, thus precluding target treatment, which is curative in many cases. For selection of the most appropriate treatment, a fundamental step is the distinction between a lateralized form, mainly aldosterone-producing adenoma (APA), and bilateral adrenocortical hyperplasia (BAH), also known as idiopathic hyperaldosteronism (IHA). To this aim all current guidelines recommend adrenal vein sampling (AVS), a technically challenging procedure that often fails, particularly in non-experienced hands. Cosyntropin (synthetic ACTH) is administered in the attempt to maximize adrenal cortisol secretion and avoid pulsatile adrenocortical hormone secretion in about 40% of the referral centres around the world. However, the Endocrine Society guidelines do not advise about the use or not of cosyntropin as stimulus during AVS, as there are arguments in favour and against its use. These arguments are presented in this debate article reflecting the views of groups that currently use and do not use cosyntropin.

Topics: Adrenal Glands; Aldosterone; Cosyntropin; Hormones; Humans; Hyperaldosteronism; Phlebotomy

Aldosterone producing adenoma and bilateral adrenal hyperplasia are the two most common subtypes of primary aldosteronism (PA) that require targeted and distinct therapeutic approaches: unilateral adrenalectomy or lifelong medical therapy with mineralocorticoid receptor antagonists. According to the 2016 Endocrine Society Guideline, adrenal venous sampling (AVS) is the gold standard test to distinguish between unilateral and bilateral aldosterone overproduction and therefore, to safely refer patients with PA to surgery. Despite significant advances in the optimization of the AVS procedure and the interpretation of hormonal data, a standardized protocol across centers is still lacking. Alternative methods are sought to either localize an aldosterone producing adenoma or to predict the presence of unilateral disease and thereby substantially reduce the number of patients with PA who proceed to AVS. In this review, we summarize the recent advances in subtyping PA for the diagnosis of unilateral and bilateral disease. We focus on the developments in the AVS procedure, the interpretation criteria, and comparisons of the performance of AVS with the alternative methods that are currently available.

Topics: Adrenal Glands; Animals; Biopsy; Cosyntropin; Diagnosis, Differential; Humans; Hyperaldosteronism; Magnetic Resonance Imaging; Reproducibility of Results; Sensitivity and Specificity; Tomography, X-Ray Computed; Veins

During the last two decades, primary aldosteronism has emerged as the most common cause of secondary hypertension, and advances in the diagnosis and treatment of this condition have improved patient care substantially. A major stumbling block in the evaluation and management of these patients, which ultimately guides treatment and prognosis, is answering the question, "Which adrenal gland(s) produce aldosterone?" Adrenal vein sampling has emerged as the only reliable method to determine the answer to this question; however, the methodology and criteria for lateralization have been determined empirically with little prospective data. The major remaining controversies surrounding adrenal vein sampling include: who should perform and who should undergo the procedure; what criteria should be used to define a successful study and lateralization of aldosterone production; whether cosyntropin should be infused during the procedure and how; and what to do when results are ambiguous? This article reviews some of the advances in the execution of this procedure, the variations in procedure, the data that fuel the controversies, and the issues that need to be resolved in the future.

Topics: Adrenal Glands; Blood Specimen Collection; Cosyntropin; Diagnostic Techniques, Endocrine; Dissent and Disputes; Humans; Hyperaldosteronism; Veins

Adrenocorticotropic hormone (ACTH) can contribute to aldosterone excess in primary aldosteronism (PA) via increased melanocortin type 2 receptor expression. Dynamic manipulation of the hypothalamic-pituitary-adrenal (HPA) axis could assist PA subtyping, but a direct comparison of dynamic tests is lacking.. To investigate plasma steroid differences between aldosterone-producing adenoma (APA) and bilateral PA (BPA) relative to ACTH variations.. We conducted comprehensive dynamic testing in 80 patients: 40 with APA and 40 with BPA. Peripheral plasma was collected from each patient at 6 time points: morning; midnight; after 1 mg dexamethasone suppression; and 15, 30, and 60 minutes after ACTH stimulation. We quantified 17 steroids by mass spectrometry in response to ACTH variations in all patients and compared their discriminative power between the 2 PA subtypes.. Patients with APA had higher morning and midnight concentrations of 18-hydroxycortisol, 18-oxocortisol, aldosterone, and 18-hydroxycorticosterone than those with BPA (P < 0.001 for all). In response to cosyntropin stimulation, the APA group had larger increments of aldosterone, 18-oxocortisol, 11-deoxycorticosterone, corticosterone, and 11-deoxycortisol (P < 0.05 for all). Following dexamethasone suppression, the APA group had larger decrements of aldosterone, 18-hydroxycortisol, and 18-oxocortisol (P < 0.05 for all), but their concentrations remained higher than in the BPA group (P < 0.01 for all). The highest discriminatory performance between the PA subtypes was achieved using steroids measured 15 minutes post-ACTH stimulation (area under receiver operating characteristic curve 0.957).. Steroid differences between APA and BPA are enhanced by dynamic HPA testing; such noninvasive tests could circumvent the need for adrenal vein sampling in a subset of patients with PA.

Topics: Adrenocorticotropic Hormone; Adult; Aged; Aldosterone; Cosyntropin; Diagnostic Techniques, Endocrine; Female; Humans; Hydrocortisone; Hyperaldosteronism; Male; Middle Aged; Predictive Value of Tests; Steroids; Stimulation, Chemical

Differentiating unilateral form from bilateral is a critical diagnostic step in primary aldosteronism (PA), for which adrenal vein sampling (AVS) is accepted to be the most reliable. However, variance of corticotropin could affect the diagnosis in AVS.. We conducted simultaneous bilateral AVS on ten biochemically diagnosed PA cases, and used the aldosterone-to-cortisol ratio (A/C) of the samples for the diagnosis. The diagnosis by AVS after a low-dose (0.1 microg) ACTH stimulation, which can provoke maximum-physiologic corticotropic response, was compared with those before the stimulation and after the standard-dose (250 microg) ACTH stimulation.. In half of the cases, the low-dose pre-stimulation affected the diagnosis. In four out of ten cases, the side-to-side ratios of A/C were changed in the basal/low-dose/standard-dose AVS as 6.62/2.46/0.63, 2.13/0.41/0.14, 1.88/2.38/2.40, and 1.96/2.27/1.90 respectively. In three out of ten cases, the adrenal vein to the matching inferior vena cava ratio of A/C was also changed across 1, the cut-off to indicate suppression of aldosterone secretion. Additionally, the confirmation of successful sampling was difficult in five out of ten and two out of ten cases of the basal and low-dose AVS respectively, whereas it was easy in all the cases of the standard-dose AVS.. The diagnosis in the basal AVS could be affected by the physiologic fluctuation of ACTH at relatively high prevalence. The basal AVS would be unreliable to differentiate two forms of PA.

Topics: Adrenal Glands; Adrenocorticotropic Hormone; Adult; Aged; Aldosterone; Cosyntropin; Diagnostic Techniques, Endocrine; Female; Hormones; Humans; Hydrocortisone; Hyperaldosteronism; Male; Middle Aged; Reproducibility of Results; Veins; Vena Cava, Inferior

An institutional study previously demonstrated that cosyntropin stimulation testing on postoperative day 1 (POD1-CST) identified patients at risk for adrenal insufficiency (AI) following unilateral adrenalectomy (UA) for adrenal-dependent hypercortisolism (HC) and primary aldosteronism (PA), allowing for selective glucocorticoid replacement (GR).. This study re-evaluates the need for GR following UA for patients with HC and PA in a larger cohort.. A prospective database identified 108 patients who underwent UA for mild autonomous cortisol excess (MACE) (n = 47), overt hypercortisolism (OH) (n = 27), PA (n = 22), and concurrent PA/HC (n = 12) from September 2014 to October 2020; all underwent preoperative evaluation for HC. MACE was defined by the 1 mg dexamethasone suppression test (cortisol >1.8 μg/dL), with ≥5 defined as OH. GR was initiated for basal cortisol ≤5 or stimulated cortisol ≤14 (≤18 prior to April 2017) on POD1-CST.. Fifty-one (47%) patients had an abnormal POD1-CST; 54 (50%) were discharged on GR (27 MACE, 20 OH, 1 PA, 6 PA/HC). Median duration of GR was OH: 6.0 months, MACE: 2.1 months, PA: 1 month, PA/HC: 0.8 months. Overall, 26% (n = 7) of patients with OH and 43% (n = 20) of patients with MACE did not require GR. Two (2%) patients with OH had normal POD1-CST but developed AI several weeks postoperatively requiring GR. None experienced life-threatening AI.. POD1-CST identifies patients with HC at risk for AI after UA, allowing for selective GR. One-quarter of patients with OH and nearly half of patients with MACE can forgo GR after UA. Patients with PA do not require evaluation for AI if concurrent HC has been excluded preoperatively.

Topics: Adrenal Glands; Adrenal Insufficiency; Adrenalectomy; Aged; Cosyntropin; Cushing Syndrome; Female; Glucocorticoids; Hormone Replacement Therapy; Humans; Hyperaldosteronism; Male; Middle Aged; Postoperative Complications; Postoperative Period; Prospective Studies; Retrospective Studies; Risk Assessment

We examined if measurement of adrenal androgens adds to subtype diagnostics of primary aldosteronism (PA) under cosyntropin-stimulated adrenal venous sampling (AVS).. A prospective pre-specified secondary endpoint analysis of 49 patients with confirmed PA, of whom 29 underwent unilateral adrenalectomy with long-term follow-up.. Concentrations of androstenedione, dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulphate (DHEAS) were measured during AVS in addition to aldosterone and cortisol. Subjects with lateralisation index (LI) of ≥4 were treated with unilateral adrenalectomy, and the immunohistochemical subtype was determined with CYP11B2 and CYP11B1 stains. The performance of adrenal androgens was evaluated by receiver operating characteristics (ROC) curve analyses in adrenalectomy and medical therapy groups.. During AVS, the correlations between cortisol and androstenedione, DHEA and DHEAS for LI and selectivity index (SI) were highly significant. The right and left side SIs for androstenedione and DHEA were higher (p < .001) than for cortisol. In ROC analysis, the optimal LI cut-off values for androstenedione, DHEA and DHEAS were 4.2, 4.5 and 4.6, respectively. The performance of these LIs for adrenal androgens did not differ from that of cortisol.. Under cosyntropin-stimulated AVS, the measurement of androstenedione and DHEA did not improve the cannulation selectivity. The performance of cortisol and adrenal androgens are confirmatory but not superior to cortisol-based results in lateralisation diagnostics of PA.

Topics: Adrenal Glands; Aldosterone; Androgens; Androstenedione; Cosyntropin; Dehydroepiandrosterone; Humans; Hydrocortisone; Hyperaldosteronism; Prospective Studies; Retrospective Studies

Topics: Adrenal Glands; Cosyntropin; Humans; Hyperaldosteronism

The reproducibility of adrenal vein sampling (AVS) is unknown.. This work aimed to determine reproducibility of biochemical results and diagnostic lateralization in patients undergoing repeat AVS.. A retrospective chart review was conducted of single-center, single-operator AVS procedures at a tertiary care center. Included were patients with confirmed primary aldosteronism (PA) undergoing repeat AVS because of concerns about technical success or discordant diagnostic results. Simultaneous AVS was performed by an experienced operator using a consistent protocol of precosyntropin and postcosyntropin infusion. Among successfully catheterized adrenal veins (selectivity index ≥ 2), the correlation of the adrenalaldosterone/cortisol (A/C) ratio was measured between the first and second AVS. The secondary outcome measure was diagnostic agreement on repeat AVS lateralization (lateralization index ≥ 3).. There were 46 sets of AVS from 23 patients at a median of 3 months apart. There was moderate correlation in A/C ratios in the adrenal veins and inferior vena cava (Spearman r = 0.49-0.59, P < .05) pre cosyntropin. Post cosyntropin, the correlation was better (Spearman r = 0.67-0.76, P < .05). In technically successful AVS, there was moderate correlation between the repeated lateralization indices (Spearman r = 0.53, P < .05). In 15 patients in whom repeat AVS was performed because of apparent lateralization discordance with computed tomography imaging, the final diagnosis was the same in the second AVS procedure. Initial failed AVS was successful 75% of the time on repeat attempt.. Repeat AVS was feasible and usually successful when an initial attempt failed. There was modest correlation between individual repeat adrenal A/C ratios and lateralization indices when AVS was performed twice. The final lateralization diagnosis was identical in all cases. This demonstrates that AVS is a reliable and reproducible localizing test in PA.

Topics: Adrenal Glands; Adult; Aged; Aged, 80 and over; Aldosterone; Blood Specimen Collection; Catheterization; Cohort Studies; Cosyntropin; Diagnostic Techniques, Endocrine; Female; Humans; Hydrocortisone; Hyperaldosteronism; Hypertension; Male; Middle Aged; Predictive Value of Tests; Reproducibility of Results; Retrospective Studies

Cortisol levels in response to stress are highly variable. Baseline and stimulated cortisol levels are commonly used to determine adrenal function following unilateral adrenalectomy. We report the results of synacthen stimulation testing following unilateral adrenalectomy in a tertiary referral center.. Data were collected retrospectively for 36 patients who underwent synacthen stimulation testing one day post unilateral adrenalectomy. None of the patients had clinical signs of hypercortisolism preoperatively. No patient received pre- or intraoperative steroids. Patients with overt Cushing's syndrome were excluded.. The median age was 58 (31-79) years. Preoperatively, 16 (44%) patients had a diagnosis of pheochromocytoma, 12 (33%) patients had primary aldosteronism and 8 (22%) patients had non-functioning adenomas with indeterminate/atypical imaging characteristics necessitating surgery. Preoperative overnight dexamethasone suppression test results revealed that 6 of 29 patients failed to suppress cortisol to <50 nmol/L. Twenty (56%) patients achieved a stimulated cortisol ≥450 nmol/L at 30 minutes and 28 (78%) at 60 minutes. None of the patients developed clinical adrenal insufficiency necessitating steroid replacement.. Synacthen stimulation testing following unilateral adrenalectomy using standard stimulated cortisol cut-off values would wrongly label many patients adrenally insufficient and may lead to inappropriate prescriptions of steroids to patients who do not need them.

Topics: Adenoma; Adrenal Gland Neoplasms; Adrenal Insufficiency; Adrenalectomy; Adult; Aged; Cosyntropin; Cushing Syndrome; Dexamethasone; Endocrinology; Female; Humans; Hydrocortisone; Hyperaldosteronism; Male; Middle Aged; Pheochromocytoma; Postoperative Period; Retrospective Studies

Adrenal venous sampling (AVS) is the key test for subtyping primary aldosteronism (PA), but its interpretation varies widely across referral centers and this can adversely affect the management of PA patients.. To investigate in a real-life study the rate of bilateral success and identification of unilateral aldosteronism and their impact on blood pressure outcomes in PA subtyped by AVS.. In a retrospective analysis of the largest international registry of individual AVS data (AVIS-2 study), we investigated how different cut-off values of the selectivity index (SI) and lateralization index (LI) affected rate of bilateral success, identification of unilateral aldosteronism, and blood pressure outcomes.. AVIS-2 recruited 1625 individual AVS studies performed between 2000 and 2015 in 19 tertiary referral centers. Under unstimulated conditions, the rate of biochemically confirmed bilateral AVS success progressively decreased with increasing SI cut-offs; furthermore, with currently used LI cut-offs, the rate of identified unilateral PA leading to adrenalectomy was as low as <25%. A within-patient pairwise comparison of 402 AVS performed both under unstimulated and cosyntropin-stimulated conditions showed that cosyntropin increased the confirmed rate of bilateral selectivity for SI cut-offs ≥ 2.0, but reduced lateralization rates (P < 0.001). Post-adrenalectomy outcomes were not improved by use of cosyntropin or more restrictive diagnostic criteria.. Commonly used SI and LI cut-offs are associated with disappointingly low rates of biochemically defined AVS success and identified unilateral PA. Evidence-based protocols entailing less restrictive interpretative cut-offs might optimize the clinical use of this costly and invasive test. (J Clin Endocrinol Metab XX: 0-0, 2020).

Topics: Adrenal Glands; Adrenalectomy; Cosyntropin; Diagnosis, Differential; Follow-Up Studies; Hormones; Humans; Hyperaldosteronism; Prognosis; Retrospective Studies; Specimen Handling

Topics: Adrenal Glands; Cosyntropin; Humans; Hyperaldosteronism; Veins

We investigated the clinical significance of ACTH stimulation during adrenal venous sampling (AVS) by surgical outcome of primary aldosteronism (PA).. Multicenter retrospective study by Japan PA study.. We allocated 314 patients with both basal and ACTH-stimulated AVS data who underwent adrenalectomy to three groups: basal lateralization index (LI) ≥2 with ACTH-stimulated LI ≥4 on the ipsilateral side (Unilateral (U) to U group, n = 245); basal LI <2 with ACTH-stimulated LI ≥4 (Bilateral (B) to U group, n = 15); and basal LI ≥2 with ACTH-stimulated LI <4 (U to B group, n = 54). We compared surgical outcomes among the groups using the Primary Aldosteronism Surgical Outcome (PASO) criteria.. Compared with U to U group, U to B group had poor clinical and biochemical outcomes and low rates of adrenal adenoma as pathological findings (P = 0.044, 0.006, and 0.048, respectively), although there were no significant differences between U to U and B to U groups. All patients in U to B group with clinical and biochemical benefits, however, had adrenal adenoma as pathological findings and could be well differentiated from those with poor surgical outcomes via basal LI (>8.3), but not ACTH-stimulated LI. These results were similar even when we defined each group based on a cut-off value of 4 for basal LI.. Although PA patients in U to B group had worse surgical outcomes than did those in U to U group, basal LI could discriminate among patients with better surgical outcomes in U to B group.

Topics: Adenoma; Adrenal Gland Neoplasms; Adrenal Glands; Adrenalectomy; Adrenocortical Adenoma; Adult; Aged; Cohort Studies; Cosyntropin; Female; Humans; Hyperaldosteronism; Male; Middle Aged; Prognosis; Registries; Retrospective Studies; Sensitivity and Specificity; Treatment Outcome

To evaluate the utility of microcatheter in adrenal venous sampling (AVS) for assessing aldosterone hypersecretion and the laterality in patients with primary aldosteronism.. This retrospective study was approved by the institutional review board of Gifu University Hospital, and written informed consent was waived. A total of 37 consecutive patients with primary aldosteronism underwent AVS by inserting a microcatheter into the right adrenal central vein (RCV), left adrenal central vein (LCV), and left adrenal common trunk (CT) followed by AVS with 5-French (5-Fr) catheter. The diagnosis of aldosterone hypersecretion was confirmed if the plasma aldosterone level after the administration of cosyntropin injection was ≥14,000 pg/ml. The laterality of aldosterone hypersecretion was determined based on the lateralized and contralateral ratios. Aldosterone hypersecretion and the laterality were diagnosed and compared based on the results obtained using 5-Fr catheter and microcatheter.. Plasma aldosterone levels were significantly higher in the RCV, LCV, and CT selected using microcatheter than in the right and left adrenal veins (LAVs) selected using 5-Fr catheter (. Microcatheter can effectively assess aldosterone hypersecretion and the laterality, especially in the LAV.. Especially for the left adrenal venous sampling, the tip of microcatheter could certainly reach the left adrenal vein orifice compared with 5-Fr catheter, therefore correct diagnosis is made and this leads to appropriate treatment.

Topics: Adrenal Glands; Adult; Aged; Catheterization, Peripheral; Cosyntropin; Equipment Design; Female; Hormones; Humans; Hyperaldosteronism; Male; Middle Aged; Radiation Dosage; Retrospective Studies; Specimen Handling; Time Factors; Vascular Access Devices

The importance of cosyntropin stimulation during adrenal vein sampling (AVS) is not fully established, partly due to insufficient AVS data relating the presence and absence of cosyntropin stimulation with postoperative outcome. Therefore, we investigated differences in AVS indices before and after cosyntropin stimulation, and determined whether unstimulated or stimulated AVS indices better correlated with treatment outcome. A retrospective study was conducted in two parts: one with 185 patients who underwent AVS and the other with 81 patients who underwent unilateral adrenalectomy for unilateral aldosterone oversecretion. The selectivity index (SI), lateralized ratio (LR), and contralateral ratio (CR) before and after cosyntropin stimulations were determined, along with blood pressure outcome 1 year after surgery. Primary aldosteronism was diagnosed according to the Japanese Endocrine Society 2009 guidelines. The percentage of AVS patients with successful catheterization, defined as unstimulated SI > 2 before and stimulated SI > 5, increased after cosyntropin stimulation from 52% to 93% and from 74% to 98% for the right and left adrenal veins, respectively. LR decreased after cosyntropin stimulation (P < 0.001). In the postoperative patients, complete and partial clinical success was achieved in 49 and 27%, respectively. Low CR (<1) and high LR (≥2.6) after cosyntropin stimulation better correlated with postoperative blood pressure outcome than those before stimulation (CR < 1 and LR ≥ 2). These data suggest that cosyntropin stimulation facilitated the judgment of catheter insertion and postcosyntropin AVS indices may be more useful for predicting treatment outcome after unilateral adrenalectomy. Further study should examine the usefulness of cosyntropin stimulation in AVS performed in other settings.

Topics: Adrenal Glands; Adrenalectomy; Adult; Aged; Catheterization; Cosyntropin; Female; Humans; Hyperaldosteronism; Male; Middle Aged; Radiography, Interventional; Retrospective Studies

Correct subtyping of primary aldosteronism (PA) is critical for guiding clinical management. Adrenal imaging is less accurate than adrenal vein sampling (AVS); nonetheless, AVS is invasive, technically challenging, and scarcely available.. To identify predictors of concordance between cross-sectional imaging and lateralized AVS in patients with PA that could help circumvent AVS in a subset of patients.. We retrospectively studied all patients with PA who underwent AVS in a tertiary referral center from 2009 to 2019. AVS was performed before and after cosyntropin stimulation. Patients with lateralized AVS in at least one condition were included. Aldosterone synthase-guided next-generation sequencing was performed on available adrenal tissue. Logistic regression was implemented to identify predictors of imaging-AVS lateralization concordance.. A total of 234 patients (62% men), age 20 to 79 years, 73% white, 23% black, and 2% Asian were included. AVS lateralization was found: 1) both pre- and post-cosyntropin (Uni/Uni) in 138 patients; 2) only at baseline (Uni/Bi) in 39 patients; 3) only after cosyntropin stimulation (Bi/Uni) in 29 patients. Catheterization partially failed in 28 patients. AVS-imaging agreement was higher in patients with KCNJ5 versus other aldosterone-driver somatic mutations (90.3% versus 64.6%; P < 0.001); in Asian and white versus black Americans (75%, 70%, and 36%, respectively); in younger patients; and those with left adrenal nodules and contralateral suppression. Conversely, AVS-imaging agreement was lowest in Uni/Bi patients (38% vs. 69% in Uni/Uni, and 62% in Bi/Uni; P = 0.007).. While AVS-imaging agreement is higher in young white and Asian patients, who have KCNJ5-mutated aldosterone producing adenomas, no predictor confers absolute imaging accuracy.

Topics: Adrenal Cortex Function Tests; Adrenal Cortex Neoplasms; Adrenal Glands; Adrenocortical Adenoma; Adult; Aged; Aldosterone; Cosyntropin; Female; G Protein-Coupled Inwardly-Rectifying Potassium Channels; Humans; Hyperaldosteronism; Male; Middle Aged; Mutation; Reproducibility of Results; Retrospective Studies; Young Adult

Cosyntropin [ACTH (1-24)] stimulation during adrenal vein (AV) sampling (AVS) enhances the confidence in the success of AV cannulation and circumvents intraprocedure hormonal fluctuations. Cosyntropin's effect on primary aldosteronism (PA) lateralization, however, is controversial.. To define the major patterns of time-dependent lateralization, and their determinants, after cosyntropin stimulation during AVS.. We retrospectively studied patients with PA who underwent AVS before, 10, and 20 minutes after cosyntropin stimulation between 2009 and 2018. Unilateral (U) or bilateral (B) PA was determined on the basis of a lateralization index (LI) value ≥4 or <4, respectively. Available adrenal tissue underwent aldosterone synthase-guided next-generation sequencing.. PA lateralization was concordant between basal and cosyntropin-stimulated AVS in 169 of 222 patients (76%; U/U, n = 110; B/B, n = 59) and discordant in 53 patients (24%; U/B, n = 32; B/U, n = 21). Peripheral and dominant AV aldosterone concentrations and LI were highest in U/U patients and progressively lower across intermediate and B/B groups. LI response to cosyntropin increased in 27% of patients, decreased in 33%, and remained stable in 40%. Baseline aldosterone concentrations predicted the LI pattern across time (P < 0.001). Mutation status was defined in 61 patients. Most patients with KCNJ5 mutations had descending LI, whereas those with ATP1A1 and ATP2B3 mutations had ascending LI after cosyntropin stimulation.. Patients with severe PA lateralized robustly regardless of cosyntropin use. Cosyntropin stimulation reveals intermediate PA subtypes; its impact on LI varies with baseline aldosterone concentrations and aldosterone-driver mutations.

Topics: Adrenal Cortex Function Tests; Adrenal Glands; Aldosterone; Catheterization; Cosyntropin; Female; Humans; Hyperaldosteronism; Male; Middle Aged; Phlebotomy; Retrospective Studies; Veins

Although saline infusion test is widely used as a confirmatory test for primary aldosteronism (PA), it is reportedly less sensitive in patients in whom aldosterone is responsive to the upright position by performing it in recumbent position. Based on a single-centre experience, seated saline infusion test (SSIT) has been reported to be highly sensitive and superior to recumbent testing in identifying both unilateral and bilateral forms of PA. However, due to limited participants number, the utility of SSIT needs to be validated in other series.. This study aimed to evaluate the accuracy of SSIT in determining the PA subtypes compared with adrenocorticotropic hormone stimulation test under dexamethasone suppression (Dex-AT).. Sixty-four patients with PA who underwent both SSIT and Dex-AT were included. Subtype diagnosis of PA was determined by adrenal venous sampling (AVS) (16 unilateral and 48 bilateral forms).. Plasma aldosterone concentrations (PACs) were measured after SSIT and Dex-AT.. The area under the receiver operating characteristic (ROC) curve for diagnosing unilateral PA was greater in SSIT than that in Dex-AT (0.907 vs. 0.755; P = .023). ROC curve analysis predicted optimal cut-off PACs of 13.1 ng/dL (sensitivity, 93.8%; specificity, 79.2%) for SSIT and 34.2 ng/dL (sensitivity, 75.0%; specificity, 68.8%) for Dex-AT.. Seated saline infusion test has superior accuracy in subtype diagnosis of PA compared with Dex-AT. SSIT can be a sensitive test for determining patients who require AVS prior to surgery.

Topics: Adrenocortical Adenoma; Adult; Aldosterone; Cosyntropin; Female; Humans; Hyperaldosteronism; Hypertension; Male; Middle Aged; Renin-Angiotensin System; ROC Curve; Saline Solution

Topics: Adrenal Glands; Adult; Aldosterone; Cosyntropin; Female; Humans; Hydrocortisone; Hyperaldosteronism; Male; Middle Aged; Veins

Cosyntropin and metoclopramide can affect the subtyping of primary aldosteronism when used with adrenal vein sampling by exerting hormone- and side-specific effects on cortisol and aldosterone secretion. We investigated how these stimuli affect the selectivity index, the relative aldosterone secretion index, and the lateralization index in consecutive primary aldosteronism patients submitted to adrenal vein sampling.. We recruited 171 patients; of these, 149 underwent adrenal vein sampling before and after stimulation with cosyntropin (250 µg intravenous bolus, n= 53, 73% with an aldosterone-producing adenoma) or with metoclopramide (10 mg intravenous bolus, n= 96, 65% aldosterone-producing adenoma), and 32 with an aldosterone-producing adenoma were investigated for the relative gene expression of dopamine, melanocortin 2, and 5-hydroxytryptamine (serotonin) 4 receptor with microarrays. Cosyntropin increased the selectivity index similarly on both sides; metoclopramide did not. Cosyntropin decreased relative aldosterone secretion index on the aldosterone-producing adenoma side but not contralaterally. Metoclopramide did not affect the selectivity index, but increased the relative aldosterone secretion index similarly on both sides. Because of these changes, cosyntropin decreased the lateralization index, while metoclopramide did not affect it. The relative gene expression of melanocortin 2, albeit heterogeneous across tumors, was 35% less (P<.0001) in aldosterone-producing adenoma than in the normal adrenal cortex, while dopamine receptor D2 and 5-hydroxytryptamine (serotonin) 4 receptors did not differ between tissues.. Cosyntropin, while facilitating ascertainment of selectivity, lessens the lateralization, likely because of a blunted melanocortin 2 expression in aldosterone-producing adenoma. The similar expression of dopamine and 5-hydroxytryptamine (serotonin) 4 receptors in aldosterone-producing adenoma and the normal adrenal cortex can explain why metoclopramide increased the relative aldosterone secretion index on both sides and, therefore, failed to increase the lateralization index.

Topics: Adrenal Glands; Adult; Aged; Biomarkers; Cosyntropin; Dopamine D2 Receptor Antagonists; Female; Hormones; Humans; Hyperaldosteronism; Injections, Intravenous; Male; Metoclopramide; Middle Aged; Retrospective Studies; Veins

Adrenal vein sampling (AVS) is intended to confirm unilateral forms of primary aldosteronism, which are amenable to surgical cure. Excessively strict AVS criteria to define lateralization may result in many patients incorrectly categorized as bilateral primary aldosteronism and opportunity for surgical cure missed.. Retrospective review of an AVS-primary aldosteronism database in which surgical cases are verified by standardized outcomes. Having used 'less strict' AVS criteria for lateralization, we examined the distribution of AVS lateralization indices in our confirmed unilateral primary aldosteronism cases both with and without cosyntropin stimulation. The proportion of proven unilateral cases that would have been missed with stricter AVS interpretation criteria was calculated. Particular focus was given to the proportion of missed cases according to use of international guidelines. False-positive lateralization with 'less strict' interpretation was also calculated.. Of 80 surgical primary aldosteronism cases, 10-23% would have been missed with AVS lateralization indices of 3 : 1 to 5 : 1, with or without cosyntropin. If strict selectivity indices (for confirmation of catheterization) were combined with strict lateralization indices, up to 70% of unilateral primary aldosteronism cases could have been missed. Use of Endocrine Society AVS guidelines would have missed 21-43% of proven unilateral cases. 'Less strict' AVS interpretation yielded one case (1.2%) of false lateralization.. Excessively strict AVS interpretation criteria will result in a high rate of missed unilateral primary aldosteronism with subsequent loss of opportunity for intervention. Use of more lenient lateralization criteria will improve the detection rate of unilateral primary aldosteronism with very low false-positive rate.

Topics: Adrenal Glands; Cosyntropin; Humans; Hyperaldosteronism; Retrospective Studies

Although corticotropin is a representative secretagogue of aldosterone, the utility of the cosyntropin stimulation test (C-ST) in diagnosing primary aldosteronism (PA) has not been elucidated. Aim of the study was to evaluate the clinical utility of C-ST for confirmatory testing and subtype classification of PA.. In this retrospective study, we identified patients with hypertension and positive case-detection results for PA who underwent C-ST and saline infusion testing (SIT) between 2006 and 2013 at eight referral centres in Japan. PA and essential hypertension (EH) were distinguished based on SIT results. PA subtype classification was determined by adrenal venous sampling (AVS). Plasma aldosterone concentration (PAC) was measured before and 30 and 60 min after intravenous cosyntropin administration. The ability of C-ST to distinguish PA from EH and to distinguish unilateral from bilateral disease was assessed by the area under the receiver operating characteristic curve.. Of 205 patients with hypertension and positive case-detection results, 139 (68%) had PA based on SIT results. Eighteen patients in whom AVS was unsuccessful were excluded from analysis. The baseline PAC before C-ST was significantly higher (P < 0·01) in patients with PA than in those with EH. However, the degree of difference in PAC between patients with PA and EH was not enhanced by the administration of cosyntropin. In addition, the administration of cosyntropin did not improve the distinction between bilateral and unilateral PA subtypes.. C-ST has no utility as a confirmatory and subtype testing of PA when the diagnosis of PA is based on the positive results in SIT.

Topics: Adult; Aged; Cosyntropin; Diagnosis, Differential; Diagnostic Techniques, Endocrine; Essential Hypertension; Female; Humans; Hyperaldosteronism; Hypertension; Male; Middle Aged; Predictive Value of Tests; Retrospective Studies; ROC Curve; Sensitivity and Specificity; Sodium Chloride

Difficulty to recognize or canulate the right adrenal vein is the most frequent cause of adrenal venous sampling (AVS) failure. We aimed to assess multinomial regression modeling (MRM) of peripheral and left adrenal vein samplings to detect lateralization of aldosterone secretion when the right AVS is missing.. Simultaneous bilateral AVS samplings were performed before (basal) and after intravenous cosyntropin injection in 188 consecutive patients between December 1989 and September 2015. Different reference standards for lateralization of aldosterone secretion were defined for basal and for postcosyntropin AVS and according to lateralization index cutoffs at least 2 and at least 4. MRMs were built to detect lateralization of aldosterone secretion according to these reference standards using only peripheral and left adrenal veins samplings (without the right AVS). Detection accuracy was assessed by the area under the receiver operating characteristic (AUROC) curves and detection sensitivities were reported for specificity at least 95%.. For basal AVS with lateralization index at least 2, AUROC were respectively 0.931 [95% confidence interval (CI) 0.894-0.968] and 0.922 (95% CI 0.882-0.962) for right and left lateralization of aldosterone secretion detection and MRM could detect respectively 65.5 and 62.7% of the right and left lateralization of aldosterone secretion. For AVS after cosyntropin with lateralization index at least 4, AUROC were respectively 0.964 (95% CI: 0.940-0.987) and 0.955 (95% CI: 0.927-0.983) for right and left lateralization of aldosterone secretion, and MRM could detect respectively 77.2 and 72.9% of the right and left lateralization of aldosterone secretion.. MRM can detect lateralization of aldosterone secretion without the right AVS in most patients and could eliminate the need for repeat AVS when right adrenal vein canulation is nonselective or impossible.

Topics: Adrenal Glands; Adult; Aged; Aged, 80 and over; Aldosterone; Area Under Curve; Cosyntropin; Female; Hormones; Humans; Hyperaldosteronism; Male; Middle Aged; Regression Analysis; Retrospective Studies; ROC Curve; Veins; Young Adult

We evaluated the influence of catheter sampling position and size on left adrenal venous sampling (AVS) in patients with primary aldosteronism (PA) and analyzed their relationship to cortisol secretion. This retrospective study included 111 patients with a diagnosis of primary aldosteronism who underwent tetracosactide-stimulated AVS. Left AVS was obtained from two catheter positions - the central adrenal vein (CAV) and the common trunk. For common trunk sampling, 5-French catheters were used in 51 patients, and microcatheters were used in 60 patients. Autonomous cortisol secretion was evaluated with a low-dose dexamethasone suppression test in 87 patients. The adrenal/inferior vena cava cortisol concentration ratio [selectivity index (SI)] was significantly lower in samples from the left common trunk than those of the left CAV and right adrenal veins, but this difference was reduced when a microcatheter was used for common trunk sampling. Sample dilution in the common trunk of the left adrenal vein can be decreased by limiting sampling speed with the use of a microcatheter. Meanwhile, there was no significant difference in SI between the left CAV and right adrenal veins. Laterality, determined according to aldosterone/cortisol ratio (A/C ratio) based criteria, showed good reproducibility regardless of sampling position, unlike the absolute aldosterone value based criteria. However, in 11 cases with autonomous cortisol co-secretion, the cortisol hypersecreting side tended to be underestimated when using A/C ratio based criteria. Left CAV sampling enables symmetrical sampling, and may be essential when using absolute aldosterone value based criteria in cases where symmetrical cortisol secretion is uncertain.

Topics: Adrenal Cortex Neoplasms; Adrenal Glands; Adrenocortical Adenoma; Aldosterone; Asymptomatic Diseases; Catheterization; Cosyntropin; Cushing Syndrome; Dexamethasone; Diagnosis, Differential; Female; Humans; Hydrocortisone; Hyperaldosteronism; Male; Middle Aged; Phlebotomy; Reproducibility of Results; Retrospective Studies; Severity of Illness Index; Veins; Vena Cava, Inferior

Adrenal venous sampling is considered to be the most reliable diagnostic procedure to lateralize aldosterone excess in primary aldosteronism (PA). However, normative criteria have not been established partially because of a lack of data in non-PA hypertensive patients. The aim of the study was to investigate aldosterone concentration and its gradient in the adrenal vein of non-PA hypertensive patients. We retrospectively studied the results of cosyntropin-stimulated adrenal venous sampling in 40 hypertensive patients who showed positive screening testing but negative results in 2 confirmatory tests/captopril challenge test and saline infusion test. Plasma aldosterone concentration, aldosterone/cortisol ratio, its higher/lower ratio (lateralization index) in the adrenal vein with cosyntropin stimulation were measured. Median plasma aldosterone concentration in the adrenal vein was 25 819 pg/mL (range, 5154-69 920) in the higher side and 12 953 (range, 1866-36 190) pg/mL in the lower side (P<0.001). There was a significant gradient in aldosterone/cortisol ratio between the higher and the lower sides (27.2 [5.4-66.0] versus 17.3 [4.0-59.0] pg/mL per μg/dL;P<0.001) with lateralization index ranging from 1.01 to 3.87. The aldosterone lateralization gradient was between 1 to 2 in 32 patients and 2 to 4 in 8 patients. None of the patients showed lateralization index ≥4. The present study demonstrated that plasma aldosterone concentration in the adrenal veins showed significant variation and lateralization gradient even in non-PA hypertensive patients. Adrenal venous sampling aldosterone lateralization gradients between 2 and 4 should be interpreted with caution in patients with PA because these gradients can be found even in patients with negative confirmatory testing for PA.

Topics: Adrenal Glands; Age Factors; Aged; Aldosterone; Cohort Studies; Cosyntropin; Female; Humans; Hyperaldosteronism; Hypertension; Japan; Male; Mass Screening; Middle Aged; Reference Values; Retrospective Studies; Severity of Illness Index; Sex Factors; Statistics, Nonparametric; Tertiary Care Centers; Veins

Steroid profiling for diagnosis of endocrine disorders featuring disordered production of steroid hormones is now possible from advances in liquid chromatography with tandem mass spectrometry (LC-MS/MS). Adrenal venous (AV) measurements of aldosterone and cortisol are a standard practice in the clinical work-up of primary aldosteronism, but do not yet take advantage of steroid profiling.. A novel LC-MS/MS based method was developed for simultaneous measurement of 15 adrenal steroids: aldosterone, corticosterone, 11-deoxycorticosterone, progesterone, pregnenolone, cortisone, cortisol, 11-deoxycortisol, 17-hydroxyprogesterone, androstenedione, dehydroepiandrosterone, dehydroepiandrosterone-sulfate, 21-deoxycortisol, 18-oxocortisol and 18-hydroxycortisol. These were compared in peripheral venous (pV) and AV plasma from 70 patients undergoing AV sampling with and without cosyntropin stimulation. Aldosterone and cortisol levels measured by LC-MS/MS were compared with those measured by immunoassay.. Reproducibility of measurements with coefficients of variation ≤10% as well as analytical sensitivity sufficient to measure low pV levels particularly of aldosterone demonstrate the utility of the assay for profiling adrenal steroids in primary aldosteronism. Method comparisons indicated assay and concentration dependent differences of cortisol and aldosterone concentrations measured by immunoassay and LC-MS/MS. Median AV/pV ratios of 11-deoxycortisol (53.0), 17-hydroxyprogesterone (33.4), pregnenolone (62.4), androstenedione (40.6) and dehydroepiandrosterone (33.3) were 2.9- to, 5.4-fold larger than those for cortisol (11.6), with additionally generally larger increases than for cortisol with than without cosyntropin stimulation.. Our LC-MS/MS assay, in addition to improvements over existing immunoassay measurements of aldosterone and cortisol, offers profiling of 13 other adrenal steroids, providing a potentially useful method for the clinical work-up of patients with primary aldosteronism. In particular, the larger AV/pV ratios of several steroids compared to cortisol suggest more sensitive alternatives to the latter for assessing positioning of AV sampling catheters.

Topics: Adrenal Glands; Adult; Aged; Chromatography, Liquid; Cosyntropin; Female; Humans; Hydrocortisone; Hyperaldosteronism; Immunoassay; Male; Middle Aged; Reproducibility of Results; Steroids; Tandem Mass Spectrometry

Adrenal venous sampling is recommended by current guidelines to identify surgically curable causes of hyperaldosteronism but remains markedly underused. Key factors contributing to the poor use of adrenal venous sampling include the prevailing perceptions that it is a technically challenging procedure, difficult to interpret, and can be complicated by adrenal vein rupture. In addition, the lack of uniformly accepted standards for the performance of adrenal venous sampling contributes to its limited use. Hence, an international panel of experts working at major referral centers was assembled to provide updated advice on how to perform and interpret adrenal venous sampling. To this end, they were asked to use the PICO (Patient or Problem, Intervention, Control or comparison, Outcome) strategy to gather relevant information from the literature and to rely on their own experience. The level of evidence/recommendation was provided according to American Heart Association gradings whenever possible. A consensus was reached on several key issues, including the selection and preparation of the patients for adrenal venous sampling, the procedure for its optimal performance, and the interpretation of its results for diagnostic purposes even in the most challenging cases.

Topics: Adrenal Glands; Catheterization; Cosyntropin; Hormones; Humans; Hyperaldosteronism; Veins

We hypothesized aldosteronoma responsiveness to cosyntropin may be a characterizing feature that could be determined in addition to standard adrenal vein sampling (AVS) data. We reviewed an AVS database from June 2005 to October 2011 including 65 patients with confirmed primary aldosteronism (PA) who underwent AVS and, if applicable, unilateral adrenalectomy. Patients were divided into confirmed lateralized and non-lateralized groups and subgrouped by histology. Plasma aldosterone in inferior vena cava (IVC) pre- and post-cosyntropin infusion during AVS was measured. Peak aldosterone and proportional change was compared between groups. Baseline and peak IVC aldosterone was higher in lateralized patients but incremental aldosterone rise was much greater in subjects with bilateral hyperplasia. From receiver operator characteristics (ROC) analysis, the optimized diagnostic cut point of peak IVC aldosterone of >649 pmol l(-1) would have a sensitivity of 94% for surgical disease although specificity of just 59%. A 250% increase in IVC aldosterone following cosyntropin would be specific enough to exclude 87% of surgical/lateralized disease. These diagnostic capabilities are similar to other results with non-AVS tests performed for diagnosis of lateralization. Although not specific enough to replace standard AVS interpretation, a marked IVC aldosterone increase after cosyntropin during AVS is a useful additional test to diagnose non-lateralizing forms of PA. Such a calculation requires no additional expense or tests.

Topics: Adrenal Cortex Neoplasms; Adrenal Glands; Adrenalectomy; Adrenocortical Adenoma; Adult; Aldosterone; Arabidopsis Proteins; Cosyntropin; Cyclophilins; Diagnosis, Differential; Female; Hormones; Humans; Hyperaldosteronism; Male; Middle Aged; Postoperative Period; Retrospective Studies; Sensitivity and Specificity; Vena Cava, Inferior

To analyze failure modes in a high-volume adrenal vein sampling (AVS) practice in an effort to identify preventable causes of nondiagnostic sampling.. A retrospective database was constructed containing 343 AVS procedures performed over a 10-year period. Each nondiagnostic AVS procedure was reviewed for failure mode and correlated with results of any repeat AVS. Data collected included selectivity index, lateralization index, adrenalectomy outcomes if performed, and details of AVS procedure. All AVS procedures were performed after cosyntropin stimulation, using sequential technique.. AVS was nondiagnostic in 12 of 343 (3.5%) primary procedures and 2 secondary procedures. Failure was right-sided in 8 (57%) procedures, left-sided in 4 (29%) procedures, bilateral in 1 procedure, and neither in 1 procedure (laboratory error). Failure modes included diluted sample from correctly identified vein (n = 7 [50%]; 3 right and 4 left), vessel misidentified as adrenal vein (n = 3 [21%]; all right), failure to locate an adrenal vein (n = 2 [14%]; both right), cosyntropin stimulation failure (n = 1 [7%]; diagnostic by nonstimulated criteria), and laboratory error (n = 1 [7%]; specimen loss). A second AVS procedure was diagnostic in three of five cases (60%), and a third AVS procedure was diagnostic in one of one case (100%). Among the eight patients in whom AVS ultimately was not diagnostic, four underwent adrenalectomy based on diluted AVS samples, and one underwent adrenalectomy based on imaging; all five experienced improvement in aldosteronism.. A substantial percentage of AVS failures occur on the left, all related to dilution. Even when technically nondiagnostic per strict criteria, some "failed" AVS procedures may be sufficient to guide therapy. Repeat AVS has a good yield.

Topics: Adrenal Glands; Adrenalectomy; Adult; Aged; Aldosterone; Biomarkers; Blood Specimen Collection; Catheterization, Peripheral; Cosyntropin; Databases, Factual; Female; Hospitals, High-Volume; Humans; Hydrocortisone; Hyperaldosteronism; Male; Middle Aged; Patient Selection; Philadelphia; Phlebography; Predictive Value of Tests; Reproducibility of Results; Retrospective Studies; Treatment Outcome; Veins

A published clinical prediction score indicated that a unilateral adrenal adenoma and either hypokalemia or an estimated glomerular filtration rate of 100 ml/min/1.73 m2 was 100% specific for unilateral primary aldosteronism. This study aimed to validate this score in a separate cohort of patients with primary aldosteronism.. A review of patients with primary aldosteronism from June 2005 to July 2013 at a single center's hypertension clinic. One hundred twelve patients with primary aldosteronism underwent successful adrenal vein sampling and the 110 patients with full data available were included in the final analysis. Adrenal vein sampling was performed all patients desiring surgery by the simultaneous collection of sample prior to and 15 minutes after a cosyntropin infusion with a 3:1 aldosterone/cortisol ratio diagnosing unilateral primary aldosteronism. The derived score was applied to the cohort. Sensitivity and specificity were calculated for clinical prediction score of ≥5 points.. There were 64 patients found to have unilateral primary aldosteronism and 48 had bilateral disease. A score ≥5 points had 64% sensitivity (95% confidence interval, 51-76) and 85% specificity (95% confidence interval, 71-94) for unilateral disease. Four patients had lateralization of primary aldosteronism to the side contralateral to the adenoma.. The 100% specificity of the score for the unilateral origin of primary aldosteronism was not validated in this cohort with a score of ≥5 points. At best, a high score in this prediction rule may be an additional tool for helping to confirm a decision to offer patients adrenal vein sampling.

Topics: Adrenal Glands; Adult; Aldosterone; Cosyntropin; Female; Glomerular Filtration Rate; Humans; Hydrocortisone; Hyperaldosteronism; Hyperkalemia; Male; Predictive Value of Tests; Reproducibility of Results; Retrospective Studies; Sensitivity and Specificity; Veins

"Successful" adrenal vein catheterization in primary aldosteronism (PA) is often defined by a ratio of >3:1 of cortisol in the adrenal vein vs the inferior vena cava. Non-use of corticotropin (ACTH) during sampling may increase the apparent failure rate of adrenal vein catheterization due to lower cortisol levels. A retrospective study was performed on all patients with confirmed unilateral PA between June 2005 and August 2011. Adrenal vein sampling (AVS) included simultaneous bilateral baseline samples with repeat sampling 15 minutes after intravenous infusion of 250 μg of Cortrosyn (ACTH-S). Successful catheter placement was judged as adrenal cortisol:IVC cortisol of >3:1, applied to both baseline and ACTH-S samples and lateralization of aldosteronism was judged as normalized aldosterone/cortisol (A/C) ratio >3 times the contralateral A/C ratio. In ACTH-S samples, 94% of right-sided catheterizations were biochemically successful with 100% success on the left. Among baseline samples, only 47% of right- and 44% of left-sided samples met the 3:1 cortisol criteria. However, 95% of apparent "failed" baseline cortisol sets still showed lateralization of A/C ratios that matched the ultimate pathology. Non-ACTH-stimulated samples may be incorrectly judged as failed catheter placement when a 3:1 ratio is used. ACTH-stimulated sampling is the preferred means to confirm catheterization during AVS.

Topics: Adrenal Glands; Adrenalectomy; Aldosterone; Catheterization, Peripheral; Cosyntropin; Female; Humans; Hydrocortisone; Hyperaldosteronism; Infusions, Intravenous; Male; Middle Aged; Predictive Value of Tests; Retrospective Studies; Vena Cava, Inferior

Adrenal vein sampling is used to establish the origins of excess production of adrenal hormones in primary aldosteronism. Correct catheter positioning is confirmed using adrenal vein measurements of cortisol, but this parameter is not always reliable. Plasma metanephrine represents an alternative parameter. The objective of our study was to determine the use of plasma metanephrine concentrations to establish correct catheter positioning during adrenal vein sampling with and without cosyntropin stimulation. We included 52 cosyntropin-stimulated and 34 nonstimulated sequential procedures. Plasma cortisol and metanephrine concentrations were measured in adrenal and peripheral venous samples. Success rates of sampling, using an adrenal to peripheral cortisol selectivity index of 3.0, were compared with success rates of metanephrine using a selectivity index determined by receiver operating characteristic curve analysis. Among procedures assessed as selective using cortisol, the adrenal to peripheral vein ratio of metanephrine was 6-fold higher than that of cortisol (94.0 versus 15.5; P<0.0001). There were significant positive relationships between adrenal to peripheral vein ratios of cortisol and metanephrine for cosyntropin-stimulated samplings but not for nonstimulated samplings. Receiver operating characteristic curve analysis indicated a plasma metanephrine selectivity index cutoff of 12. Using this cutoff, concordance in sampling success rates determined by cortisol and metanephrine was substantially higher in cosyntropin-stimulated than in nonstimulated samplings (98% versus 59%). For the latter procedures, sampling success rates determined by metanephrine were higher (P<0.01) than those determined by cortisol (91% versus 56%). In conclusion, metanephrine provides a superior analyte compared with cortisol in assessing the selectivity of adrenal vein sampling during procedures without cosyntropin stimulation.

Topics: Adrenal Glands; Adult; Aged; Aldosterone; Blood Specimen Collection; Cosyntropin; Female; Humans; Hydrocortisone; Hyperaldosteronism; Male; Metanephrine; Middle Aged; Veins

Our objective was to develop clinical practice guidelines for the diagnosis and treatment of patients with primary aldosteronism.. The Task Force comprised a chair, selected by the Clinical Guidelines Subcommittee (CGS) of The Endocrine Society, six additional experts, one methodologist, and a medical writer. The Task Force received no corporate funding or remuneration.. Systematic reviews of available evidence were used to formulate the key treatment and prevention recommendations. We used the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) group criteria to describe both the quality of evidence and the strength of recommendations. We used "recommend" for strong recommendations and "suggest" for weak recommendations.. Consensus was guided by systematic reviews of evidence and discussions during one group meeting, several conference calls, and multiple e-mail communications. The drafts prepared by the task force with the help of a medical writer were reviewed successively by The Endocrine Society's CGS, Clinical Affairs Core Committee (CACC), and Council. The version approved by the CGS and CACC was placed on The Endocrine Society's Web site for comments by members. At each stage of review, the Task Force received written comments and incorporated needed changes.. We recommend case detection of primary aldosteronism be sought in higher risk groups of hypertensive patients and those with hypokalemia by determining the aldosterone-renin ratio under standard conditions and that the condition be confirmed/excluded by one of four commonly used confirmatory tests. We recommend that all patients with primary aldosteronism undergo adrenal computed tomography as the initial study in subtype testing and to exclude adrenocortical carcinoma. We recommend the presence of a unilateral form of primary aldosteronism should be established/excluded by bilateral adrenal venous sampling by an experienced radiologist and, where present, optimally treated by laparoscopic adrenalectomy. We recommend that patients with bilateral adrenal hyperplasia, or those unsuitable for surgery, optimally be treated medically by mineralocorticoid receptor antagonists.

Topics: Algorithms; Catheterization; Combined Modality Therapy; Cosyntropin; Diagnostic Techniques, Endocrine; Eplerenone; Hormone Replacement Therapy; Humans; Hyperaldosteronism; Mineralocorticoid Receptor Antagonists; Reproducibility of Results; Spironolactone

Patients with glucocorticoid-remediable aldosteronism (GRA) possess a chimeric gene resulting from fusion of the genes encoding steroid aldosterone synthase and 11 beta-hydroxylase. In the adrenal zona fasciculata, this may lead to ectopic expression under ACTH control of aldosterone synthase activity and increased formation of cortisol C18 oxidation products. We assessed mineralocorticoid and glucocorticoid pathways in three patients with GRA. Baseline plasma progesterone, 17 alpha-hydroxyprogesterone, corticosterone, and cortisol were normal in all patients, whereas 11-deoxycorticosterone, aldosterone, and 11-deoxycortisol were above normal. The ratios of both corticosterone/11-deoxycorticosterone and cortisol/11-deoxycortisol were abnormally low, and decreased further 60 min after administration of ACTH-(1-24) (250 micrograms) as an i.v. bolus. A low corticosterone/11-deoxycorticosterone ratio is consistent with an increased aldosterone synthase activity forming aldosterone by corticosterone. Similarly, a decreased cortisol/11-deoxycortisol ratio could reflect enhanced cortisol C18 oxidation. Our findings are in agreement with a hyperfunction of the 11 beta-hydroxylase/aldosterone synthase complex in the adrenal zona fasciculata of GRA induced by the new chimeric gene.

Topics: Adrenocorticotropic Hormone; Adult; Aldosterone; Cortodoxone; Cosyntropin; Desoxycorticosterone; Female; Glucocorticoids; Humans; Hydrocortisone; Hyperaldosteronism; Male; Reference Values

Topics: Adenoma; Adrenal Gland Neoplasms; Adrenocorticotropic Hormone; Cosyntropin; Humans; Hyperaldosteronism; Male; Middle Aged

In vitro aldosterone, deoxycorticosterone, corticosterone and cortisol production of human adrenocortical cells derived from adenomas (Conn's syndrome, Cushing's syndrome), from hyperplastic adrenals (Cushing's syndrome) and from adrenals surrounding aldosteronoma are described. Cells from adenomas causing either Cushing's syndrome or Conn's syndrome harboured the highest basal and ACTH-stimulated corticosteroid production. Adrenocortical cells derived from micronodular hyperplasia causing Cushing's syndrome and cells from cortisol producing adenoma displayed predominantly cortisol and corticosterone secretion both under basal conditions and following stimulation with ACTH. Aldosteronoma cells showed highly variable aldosterone, deoxycorticosterone, corticosterone and cortisol response to ACTH. However, in aldosteronoma cell suspensions, the basal and ACTH-stimulated ratios of aldosterone to cortisol were increased when compared to ratios of steroids produced by cells from other adrenal tissues. Chronic treatment with spironolactone of patients with Conn's syndrome before surgery was associated with a decreased ratio of aldosterone to corticosterone, revealing that 18-hydroxylase in aldosteronoma cells may be inhibited during long-term therapy. Non-tumorous cells isolated from adrenals surrounding aldosteronoma displayed less aldosterone prior to and after stimulation with ACTH than aldosteronoma cells.

Topics: Adenoma; Adrenal Cortex; Adrenal Cortex Hormones; Adrenocorticotropic Hormone; Aldosterone; Corticosterone; Cosyntropin; Cushing Syndrome; Desoxycorticosterone; Humans; Hydrocortisone; Hyperaldosteronism; In Vitro Techniques

Primary cultures of dissociated parenchymal cells from Conn's adenomata causing primary hyperaldosteronism were successfully set up by a method previously used with normal adult human and rat adrenocortical tissue. In such cultures the adenomatous cells largely prevailed (making up 87% of the whole cell population), could survive for lengthy terms (at least up to 30 days), and were endowed with a spontaneous, discrete capability to proliferate. The de novo RNA- and DNA-synthetic and mitotic activities of Conn's cells were markedly stimulated in cultures exposed between 16 and 21 to daily doses of exogenous cyclic AMP, either alone or in equimolar association with cyclic GMP. A significantly weaker, though still prominent enhancement of adenomatous cell growth was elicited also by daily administrations of an equimolar mixture of ACTH1-24 and angiotensin II. In contrast, little stimulation or inhibition of growth or no effect at all could be observed when cyclic GMP, ACTH1-24, and angiotensin II were respectively administered, each by itself.

Topics: Adrenal Cortex Neoplasms; Adrenocorticotropic Hormone; Angiotensin II; Cell Division; Cosyntropin; Culture Techniques; Cyclic AMP; Cyclic GMP; Humans; Hyperaldosteronism; Time Factors

Topics: Adrenal Cortex Function Tests; Adrenal Insufficiency; Cosyntropin; Humans; Hyperaldosteronism; Hypertension; Membrane Potentials; Pituitary-Adrenal Function Tests; Potassium; Spironolactone

Parallel fluctuations of potential difference (P.D.) across oral and rectal mucosa are probably related to the activity of autonomic nerves rather than adrenal steroids. Unlike rectal mucosa, oral mucosa does not respond to exogenous or endogenous aldosterone. Therefore subtraction of oral P.D. from rectal P.D. gives a closer indication of mineralocorticoid activity than does rectal P.D. alone. In normal subjects plasma-aldosterone correlated well with subtraction P.D. (r = 0.74; P is less than 0.001). A subtraction P.D. higher than 26 mV in subjects on a normal sodium intake indicated primary or secondary hyperaldosteronism; if the level was lower than 11 mV four hours after intramuscular injection of 0.25 mg tetracosactrin this suggested mineralocorticoid deficiency. Measurement of oral and rectal P.D. permits rapid and inexpensive diagnosis of aldosterone excess and deficiency. The method may also be used in study of the mineralocorticoid effect of other adrenal steroids: as assessed with this bioassay, the plasma 18-OH-deoxycorticosterone, which is raised in some patients with essential hypertension, lacked any in vivo mineralocorticoid activity.

Topics: Action Potentials; Adrenal Insufficiency; Aldosterone; Circadian Rhythm; Cosyntropin; Desoxycorticosterone; Female; Humans; Hydrocortisone; Hyperaldosteronism; Intestinal Mucosa; Male; Mouth Mucosa; Potassium; Rectum; Sodium; Stimulation, Chemical

Topics: Adrenal Glands; Aldosterone; Angiotensin II; Corticosterone; Cosyntropin; Diet; Female; Humans; Hydrocortisone; Hyperaldosteronism; Male; Potassium; Sodium