Developments in Primary Aldosteronism Subtyping Using Steroid
                    Profiling

AbstractAdrenal venous sampling is the standard of care for identifying patients with unilateral primary aldosteronism, which is often caused by an aldosterone producing adenoma and can be cured with surgery. The numerous limitations of adrenal venous sampling, including its high cost, scarce availability, technical challenges, and lack of standardized protocols, have driven efforts to develop alternative, non-invasive tools for the diagnosis of aldosterone producing adenomas. Seminal discoveries regarding the pathogenesis of aldosterone producing adenomas made over the past decade have leveraged hypotheses-driven research of steroid phenotypes characteristic of various aldosterone producing adenomas. In parallel, the expanding availability of mass spectrometry has enabled the simultaneous quantitation of many steroids in single assays from small volume biosamples. Steroid profiling has contributed to our evolving understanding about the pathophysiology of primary aldosteronism and its subtypes. Herein, we review the current state of knowledge regarding the application of multi-steroid panels in assisting with primary aldosteronism subtyping.

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An LC–MS/MS method for steroid profiling during adrenal venous sampling for investigation of primary aldosteronism

The Journal of Steroid Biochemistry and Molecular Biology ◽

10.1016/j.jsbmb.2014.10.006 ◽

2015 ◽

Vol 145 ◽

pp. 75-84 ◽

Cited By ~ 59

Author(s):

Mirko Peitzsch ◽

Tanja Dekkers ◽

Matthias Haase ◽

Fred C.G.J. Sweep ◽

Ivo Quack ◽

...

Keyword(s):

Primary Aldosteronism ◽

Adrenal Venous Sampling ◽

Venous Sampling ◽

Steroid Profiling

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Is it Possible to Extirpate Cardiovascular Events in Primary Aldosteronism after Surgical Treatment

Japanese Clinical Medicine ◽

10.4137/jcm.s6316 ◽

2010 ◽

Vol 1 ◽

pp. JCM.S6316 ◽

Cited By ~ 8

Author(s):

Tetsuo Nishikawa ◽

Yoko Matsuzawa ◽

Jun Saito ◽

Masao Omura

Keyword(s):

Surgical Treatment ◽

Primary Aldosteronism ◽

Secondary Hypertension ◽

Adrenal Venous Sampling ◽

Venous Sampling ◽

Partial Adrenalectomy ◽

Aldosterone Producing Adenoma ◽

Idiopathic Hyperaldosteronism ◽

Micro Catheter ◽

Indication For Treatment

It is well known that primary aldosteronism (PA) due to aldosterone-producing adenoma (APA) is a surgically curable secondary hypertension. Thus, the differential diagnosis between unilateral hyperaldosteronemia due to APA and bilateral hyperaldosteronemia due to idiopathic hyperaldosteronism (IHA) is crucial to decide surgical indication for treatment in PA patients. Adrenal venous sampling (AVS) can diagnose the laterality of hypersecretion of aldosterone in those patients, while it is still impossible to differentiate bilateral hypersecretion of bilateral aldosterone-producing adenomas (Blt-APAs) from that of bilateral hyperplasia of IHA. To solve the problem, we try to develop a new method of supper-selective ACTH-stimulated adrenal venous sampling (SS-ACTH-AVS). We performed SS-ACTH-AVS by using a strip-tip type 2.2 Fr micro-catheter (Koshin Medical Inc. Japan). Adrenal effluents were sampled super-selectively at the central veins and at one or two tributaries of adrenal veins in each gland. We would like to emphasize that SS-ACTH-AVS can precisely analyze the situation of hyperfunction of steroidogenesis in each side of adrenals as well as in some tiny lesions inside the adrenal cortex which are not visible in the CT images. Moreover, we can differentiate Blt-APAs from IHA, and postulate the decision of surgical treatment, such as partial adrenalectomy. Thus, we should perform SS-ACTH-AVS especially in the case demonstrating the existence of bilateral adrenal lesions such as unilateral and bilateral tumors, or even no tumor in both sides in the patients with PA.

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ACTH Stimulation Maximizes the Accuracy of Peripheral Steroid Profiling in Primary Aldosteronism Subtyping

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/clinem/dgab420 ◽

2021 ◽

Author(s):

Yuta Tezuka ◽

Kae Ishii ◽

Lili Zhao ◽

Yuto Yamazaki ◽

Ryo Morimoto ◽

...

Keyword(s):

Primary Aldosteronism ◽

Dynamic Testing ◽

Characteristic Curve ◽

Receptor Expression ◽

Acth Stimulation ◽

Hypothalamic Pituitary Adrenal ◽

Non Invasive ◽

Steroid Profiling ◽

Aldosterone Producing Adenoma ◽

Dexamethasone Suppression

Abstract Background ACTH can contribute to aldosterone excess in primary aldosteronism (PA) via increased melanocortin type 2 receptor expression. Dynamic manipulation of the hypothalamic-pituitary-adrenal axis could assist PA subtyping, but a direct comparison of dynamic tests is lacking. Methods We conducted comprehensive dynamic testing in 80 patients: 40 with aldosterone-producing adenoma (APA) and 40 bilateral PA (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 two PA subtypes. Results 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). Conclusion Steroid differences between APA and BPA are enhanced by dynamic hypothalamic-pituitary-adrenal testing; such non-invasive tests could circumvent the need for adrenal vein sampling in a subset of patients with PA.

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Adrenal venous sampling for primary aldosteronism: laboratory medicine best practice

Journal of Clinical Pathology ◽

10.1136/jclinpath-2017-204423 ◽

2017 ◽

Vol 70 (11) ◽

pp. 911-916 ◽

Cited By ~ 6

Author(s):

Gregory Kline ◽

Daniel T Holmes

Keyword(s):

Primary Aldosteronism ◽

Best Practice ◽

Laboratory Medicine ◽

Secondary Hypertension ◽

Adrenal Venous Sampling ◽

Venous Sampling ◽

Aldosterone Antagonists ◽

Bilateral Disease ◽

Patient Preparation ◽

Aldosterone Producing Adenoma

Primary aldosteronism (PA) is the most common form of secondary hypertension and is critical to identify because when caused by an aldosterone-producing adenoma (APA) or another unilateral form, it is potentially curable, and even when caused by bilateral disease, antihypertensives more specific to PA treatment can be employed (ie, aldosterone antagonists). Identification of unilateral forms is not generally accomplished with imaging because APAs may be small and elude detection, and coincidental identification of a non-functioning incidentaloma contralateral to an APA may lead to removal of an incorrect gland. For this reason, the method of choice for identifying unilateral forms of PA is selective adrenal venous sampling (AVS) followed by aldosterone and cortisol analysis on collected samples. This procedure is technically difficult from a radiological standpoint and, from the laboratory perspective, is fraught with opportunities for preanalytical, analytical and postanalytical error. We review the process of AVS collection, analysis and reporting. Suggestions are made for patient preparation, specimen labelling practices and nomenclature, analytical dilution protocols, which numerical results to report, and the necessary subsequent calculations. We also identify and explain frequent sources of confusion in the aldosterone and cortisol results and provide an example of tabular reporting to facilitate interpretation and communication between laboratorian, radiologist and clinician.

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Adrenocorticotropic Hormone–Stimulated Adrenal Venous Sampling Underestimates Surgically Curable Primary Aldosteronism: A Retrospective Cohort Study and Review of Contemporary Studies

Hypertension ◽

10.1161/hypertensionaha.121.17248 ◽

2021 ◽

Author(s):

Nicholas Yozamp ◽

Gregory L. Hundemer ◽

Marwan Moussa ◽

Jonathan Underhill ◽

Tali Fudim ◽

...

Keyword(s):

Primary Aldosteronism ◽

Adrenocorticotropic Hormone ◽

Adrenal Venous Sampling ◽

Original Research ◽

Venous Sampling ◽

Acth Stimulation ◽

The Past ◽

Unilateral Disease ◽

The Impact ◽

Lateralization Index

Guidelines recommend adrenal venous sampling to determine disease laterality in primary aldosteronism. Adrenocorticotropic hormone (ACTH) stimulation clearly improves the likelihood of successful adrenal vein catheterization but may lead to a decrease in lateralization rates. To examine the impact of ACTH on lateralization, we performed a retrospective analysis of 340 patients with confirmed primary aldosteronism who underwent adrenal venous sampling with a single interventional radiology team using a protocol of sampling both before and after an ACTH bolus. In addition to this original research, we conducted a review of similar studies from the past 5 years to develop a consensus on the impact of ACTH on lateralization for primary aldosteronism. In the original research analysis, following a bolus of ACTH, 58% of patients had a decline in lateralization index which led to discordance between the pre-ACTH and post-ACTH classifications of lateralization in up to 26% of cases. The majority of discordant cases were due to reclassification from unilateral disease pre-ACTH to bilateral disease post-ACTH. In patients who already lateralized with unstimulated sampling, the response to ACTH did not have any impact on surgical outcomes. In a review of contemporary studies, we identified 11 similar studies in the past 5 years, of which 10 reported either no change or a decrease in lateralization index following ACTH, resulting in ≈25% discordance between unstimulated and stimulated lateralization rates. We conclude that ACTH stimulation during adrenal venous sampling can underestimate surgically remediable primary aldosteronism and recommend that the role of ACTH be limited primarily to enhancing selectivity.

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SUN-176 A Case of Aldosterone-Producing Adenoma with Preoperative Use of a Novel Mineralocorticoid Receptor Antagonist Esaxerenone

Journal of the Endocrine Society ◽

10.1210/jendso/bvaa046.1837 ◽

2020 ◽

Vol 4 (Supplement_1) ◽

Author(s):

Hiroaki Yamanami

Keyword(s):

Blood Pressure ◽

Receptor Antagonist ◽

Primary Aldosteronism ◽

Mineralocorticoid Receptor ◽

Adrenal Venous Sampling ◽

Venous Sampling ◽

Mineralocorticoid Receptor Antagonist ◽

Plasma Aldosterone Concentration ◽

Potassium Supplementation ◽

Aldosterone Producing Adenoma

Abstract Background: Esaxerenone is a novel mineralocorticoid receptor antagonist (MRA) with nonsteroidal structure and high selectivity to MR, which became clinically available in Japan in 2019. Clinical Case: A 57-year-old woman showed a left adrenal incidentaloma (15mm) on MRI. Serological tests confirmed a diagnosis of primary aldosteronism: baseline plasma aldosterone concentration (PAC) was elevated (47.3 ng/dL, n < 15.9 ng/dL), and plasma renin activity (PRA) below sensitivity. PAC after saline infusion was 43.2 ng/dL. Overnight 1mg dexamethasone suppression test was negative. Her blood pressure had been well-controlled with amlodipine 5mg daily. Despite of large amount of potassium supplementation (96 mmol/day orally and 50 mmol/day intravenously), the level of serum potassium remained low (3.2 mmol/L). Adrenal venous sampling (AVS) was performed successfully, showing laterality index of 45.8 on left. Segmental AVS supported aldosterone hypersecretion from the tumor. After diagnosis, esaxerenone was introduced and the patient became normokalemic without potassium supplementation after a week. No adverse effect occurred in a period of two months before surgery. She underwent laparoscopic left total adrenalectomy. The tumor was positive for CYP11B2, consistent with aldosterone producing adenoma (APA). She became normotensive and normokalemic without any medications. Conclusion: This case illustrates the preoperative effectiveness of esaxerenone on blood pressure and hypokalemia in patients with APA. Key words: Esaxerenone; mineralocorticoid receptor antagonist; case report; adrenal venous sampling; primary aldosteronism; aldosterone producing adenoma

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