Richard D Gordon

University of Queensland | UQ · Department of Medicine

Objective Primary aldosteronism (PA) is a common, potentially curable form of hypertension characterised by excessive, autonomous aldosterone production. In the distal renal tubule, aldosterone is involved in volume homeostasis by modulation of NaCl reabsorption via the epithelial Na+ channel (ENaC), the NaCl cotransporter (NCC) and the Cl-/HCO3- e...

Objective Aldosterone-producing adenoma (APA) accounts for ∼30% of primary aldosteronism. Based on responses of aldosterone to upright posture, APA can be divided into posture-responsive and –unresponsive forms. Somatic gene mutations in KCNJ5, CACNA1D, ATP1A1, or ATP2B3 have been reported to exist in more than 90% of APAs. We sought to compare the...

In primary aldosteronism (PA), the occurrence of K⁺ loss and hypertension suggest alterations in renal tubular transport, but the molecular basis of these alterations in humans is unclear. In this study, urinary extracellular vesicles (uEVs) isolated from patients undergoing fludrocortisone suppression testing (FST, as a means of confirming or excl...

Context and Objective Posture-responsive and -unresponsive aldosterone-producing adenomas (APAs) account for approximately 40% and 60% of APAs, respectively. Somatic gene mutations have been recently reported to exist in approximately 90% of APAs. This study was designed to characterize the biochemical, histopathologic, and genetic properties of th...

Background: Many medications (including most antihypertensives) and physiological factors affect the aldosterone/renin ratio (ARR) when screening for primary aldosteronism (PA). We sought to validate a novel equilibrium angiotensin II (eqAngII) assay and compare correlations between the aldosterone/angiotensin II ratio (AA2R) and the current ARR u...

Background In primary aldosteronism (PA), excessive, autonomous secretion of aldosterone is not suppressed by salt loading or fludrocortisone. For seated saline suppression testing (SSST), the recommended diagnostic cut-off 4-hour plasma aldosterone concentration (PAC) measured by HPLC-MS/MS is 162pmol/L. Most diagnostic laboratories, however, use...

Purpose of Review The application of advanced genetic techniques has recently begun to unravel the genetic basis for familial primary aldosteronism type 2 (FH-II). Recent Findings Whole-exome sequencing in a large family with FH-II revealed a shared rare damaging heterozygous variant in CLCN2 (chr.3: g.184075850C>T, p.Arg172Gln) in three severely...

Context Failure of plasma aldosterone suppression during fludrocortisone (FST) or saline suppression testing (SST) confirms primary aldosteronism (PA). Aldosterone is frequently higher upright than recumbent in PA; upright levels are used during FST. In a pilot study (24 PA patients), seated SST (SSST) was more sensitive than recumbent (RSST). Obj...

Context Current threshold values for primary aldosteronism (PA) diagnostic testing are based on measuring aldosterone (PAC) using immunoassays. Quantification of PAC by liquid chromatography-tandem mass spectrometry (LC-MS/MS) yields lower values. Objective To compare aldosterone measurement by radioimmunoassay (RIA) with LC-MS/MS and evaluate per...

Primary aldosteronism, a common cause of severe hypertension 1 , features constitutive production of the adrenal steroid aldosterone. We analyzed a multiplex family with familial hyperaldosteronism type II (FH-II) 2 and 80 additional probands with unsolved early-onset primary aldosteronism. Eight probands had novel heterozygous variants in CLCN2, i...

Widespread application of the plasma aldosterone/renin ratio (ARR) as a screening test has led to the recognition that primary aldosteronism (PA) is the most common specifically treatable and potentially curable form of hypertension, accounting for 5–10% of patients. Maximal detection requires accurate diagnostic approaches and awareness and contro...

Germline loss-of-function mutations in the armadillo-repeat-containing 5 (ARMC5) gene are an established cause of Cushing’s syndrome due to bilateral macronodular adrenal hyperplasia (BMAH),1, 2 and may play a role in primary aldosteronism.³ As familial hyperaldosteronism type II (FH-II) has a presumed genetic basis,⁴ we hypothesised that germline...

Obstructive sleep apnoea (OSA) is known to commonly co-exist with primary aldosteronism (PA), but it is unknown if treatment of PA improves sleep apnoea parameters in these patients. We therefore aimed to determine whether specific medical or surgical treatment of PA improves OSA, as measured by the apnoea-hypopnoea index (AHI). We recruited patien...

Background: Plasma aldosterone/renin ratio (ARR) is the most popular screening test for primary aldosteronism (PA). Because both estrogen and progesterone (including in oral contraceptive agents) affect aldosterone and renin levels, we studied effects of combined hormonal replacement therapy (HRT) on ARR, measuring renin as both direct renin conce...

Background: The most popular screening test for primary aldosteronism (PA) is the plasma aldosterone/ renin ratio (ARR). Medications, dietary sodium, posture and time of day all affect renin and aldosterone levels, and can result in false negative or positive ARRs if not controlled. Most antihypertensive medications affect the ARR and can interfer...

In the 60 years that have passed since the discovery of the mineralocorticoid hormone aldosterone, much has been learned about its synthesis (both adrenal and extraadrenal), regulation (by renin-angiotensin II, potassium, adrenocorticotrophin, and other factors), and effects (on both epithelial and nonepithelial tissues). Once thought to be rare, p...

Objective: Adrenal vein sampling (AVS) is the only reliable means to distinguish between aldosterone-producing adenoma and bilateral adrenal hyperplasia, the two most common subtypes of primary aldosteronism (PA). To distinguish between unilateral and bilateral disease is of fundamental importance because it allows to allocate patients to the corr...

Objective: Obstructive sleep apnoea (OSA) is known to commonly co-exist with primary aldosteronism (PA), but it is unknown if treatment via mineralocorticoid receptor blockade or adrenalectomy (for aldosterone producing adenoma, APA), improves sleep apnoea parameters in these patients. We therefore aimed to determine if specific medical or surgica...

Background: Distal tubular sodium retention is a potent driver of hypertension, with the thiazide sensitive sodium-chloride cotransporter (NCC) a key player. The upstream modulators of NCC are unclear, but recent evidence has revealed the kinases 'with-no-lysine kinase 4' (WNK4) and 'STE20/SPS1-related, proline alanine-rich kinase' (SPAK) to be in...

Objective: Adrenal vein sampling (AVS) is vital for determining treatment options for primary aldosteronism (PA), but is a difficult procedure. Adrenocorticotropic hormone (ACTH) infusion or bolus has been reported to improve AVS success rates by increasing cortisol secretion, but effects on aldosterone and thus lateralisation are controversial. W...

Distal tubular sodium retention is a potent driver of hypertension, and the thiazide-sensitive sodium-chloride cotransporter (NCC) has a key role in this process. In humans, factors regulating NCC are unclear, but in animal models, aldosterone is a potent regulator, possibly via effects on plasma potassium. We studied the effects of the mineralocor...

Objective: Adrenal vein sampling (AVS) is used for determining treatment options for primary aldosteronism (PA), but is a difficult procedure. Adrenocorticotropic hormone (ACTH) infusion or bolus has been reported to improve AVS success rates by increasing cortisol secretion, but effects on lateralization are controversial. We therefore assessed t...

We thank the authors for their positive and insightful comments. The close agreement between their results and ours certainly adds weight to the findings and conclusions of our study. We also thank them for their proposed explanation concerning the discrepancy in reported results of in vitro studies assessing the effects of progesterone on aldoster...

Aldosterone-producing adenoma and bilateral adrenal hyperplasia account for >90% of all primary aldosteronism cases. Distinguishing between bilateral and unilateral disease is of fundamental importance because it allows targeted therapy. Adrenal vein sampling (AVS) is the only reliable means to preoperatively differentiate between unilateral and bi...

Unlabelled: In patients with primary aldosteronism (PA) undergoing adrenal venous sampling (AVS), cortisol levels are measured to assess lateralization of aldosterone overproduction. Concomitant adrenal autonomous cortisol and aldosterone secretion therefore have the potential to confound AVS results. We describe a case where metanephrine was meas...

Primary aldosteronism (PA) accounts for 5-10 of hypertension and in a third of cases is caused by autonomous aldosterone production by adenomas (APA). Somatic mutations in the potassium channel encoded by KCNJ5 have been detected in surgically removed APAs. To better understand the role of these mutations we resequenced the KCNJ5 channel in a large...

The diagnosis of pheochromocytoma/paraganglioma (PPGL) involves detection of elevated levels of plasma and/or 24-h urine catecholamines and/or their metabolites, including metanephrines. Although these tests are reasonably sensitive, false-positive results are often encountered. Follow-up tests can provide additional information to correctly diagno...

Recent studies of renal artery stenosis (RAS) failed to demonstrate greater benefit from angioplasty in terms of blood pressure (BP) lowering than medical treatment. Not all RAS are haemodynamically significant and identification of patients likely to benefit from angioplasty remains essential. We examined whether performing renal venous renin stud...

Primary aldosteronism (PA), in which there is excessive and autonomous adrenal production of aldosterone, accounts for around 5-10% of hypertension. PA may be unilateral (usually aldosterone-producing adenoma [APA]) or bilateral (usually adrenal hyperplasia). Recently, somatic mutations in KCNJ5 (encoding a potassium channel) have been detected in...

Objective: Distal tubular sodium retention is a potent driver of hypertension, with the thiazide sensitive sodium chloride cotransporter (NCC) and its phosphorylated form (pNCC) key players. The upstream modulators of NCC expression and phosphorylation are unclear, but some evidence suggests that mineralocorticoid receptor (MR) activation by aldost...

Objective: In primary aldosteronism (PA), adrenal vein sampling (AVS) distinguishes unilateral and bilateral disease. In AVS aldosterone/cortisol ratios (A/F) correct aldosterone concentration for dilution from non-adrenal blood. Comparisons are then made between left, right and peripheral A/F ratios. Criteria for interpretation however vary widely...

Objective: Since renin and aldosterone levels vary during the menstrual cycle, and are critical criteria for interpretation of aldosterone suppression tests to confirm or exclude primary aldosteronism, outcome of testing may vary depending on the menstrual cycle phase. We assessed the effect of timing within the menstrual cycle on levels of renin,...

Objective Demonstration of unilateral aldosterone production by adrenal venous sampling (AVS) is required to select appropriate candidates for adrenalectomy in patients with primary aldosteronism (PA). During AVS, aldosterone and cortisol levels are measured to assess successful cannulation and lateralisation. In patients with aldosterone-producing...

Context: In primary aldosteronism (PA), adrenal vein sampling (AVS) distinguishes unilateral and bilateral disease by comparison of aldosterone/cortisol (A/F) ratios. There is controversy about the criteria for interpretation, however, and in particular it is not clear whether contralateral suppression (CS) (defined as A/F(adrenal) ≤ A/F(periphera...

Background Since renin and aldosterone levels vary during the menstrual cycle, and are critical criteria for interpretation of aldosterone suppression tests to confirm or exclude primary aldosteronism, outcome of testing may vary depending on the menstrual cycle phase. We assessed the effect of timing within the menstrual cycle on levels of renin,...

Structured summaryAimsHyponatraemia is one of the major adverse effects of thiazide diuretics and the leading cause of drug-induced hyponatraemia requiring hospital admission. We sought to review and analyse all published cases of this important condition.Methods Ovid Medline, Embase, Web of Science and PubMed electronic databases were searched to...

The basic clinical pathophysiology of primary aldosteronism (PAL) was described by Conn in terms of autonomous production of aldosterone, secondary suppression of renin and development of hypertension with hypokalaemic alkalosis. Conn recognised a normokalaemic form of the syndrome and suggested that it might masquerade as essential hypertension an...

Context: Bilateral macronodular adrenal hyperplasia (BMAH) is a rare form of adrenal Cushing's syndrome. Familial cases have been reported, but at the time we conducted this study, the genetic basis of BMAH was unknown. Recently, germline variants of armadillo repeat containing 5 (ARMC5) in patients with isolated BMAH and somatic, second-hit mutat...

Context: Failure of aldosterone suppression by sodium loading during fludrocortisone suppression testing (FST) or saline suppression testing (SST) confirms primary aldosteronism (PA). We previously found recumbent SST (RSST) to lack sensitivity. Aldosterone levels can be higher upright (e.g. seated) than recumbent in patients with PA and upright l...

Because of change in the accepted meaning of the term primary aldosteronism (PA), and in the methods used to screen for and diagnose it, the perceived prevalence of PA (and hence the epidemiology of PA) has undergone and is still undergoing progressive change since the first description of PA. As well, methodology for measuring renin and aldosteron...

The major role of the aldosterone/renin ratio (ARR) test is in screening hypertensive patients for primary aldosteronism (PA). Although currently the most reliable and popular approach, the value of this screening test depends on an appreciation of factors (such as antihypertensive and other medications, posture, time of day, age, gender, phase of...

As originally defined, the term familial hyperaldosteronism type II (FH-II) refers to the occurrence in families of at least two members with primary aldosteronism (PA) that is not glucocorticoid suppressible and not associated with the hybrid CYP11B1/2 gene mutation responsible for familial hyperaldosteronism type I (FH-I, glucocorticoid-remediabl...

Primary aldosteronism (autonomous aldosterone production with suppressed renin) plays an important pathophysiological role in what has been previously labeled as essential hypertension. Besides the recently described germline mutations in the KCNJ5 potassium channel associated with familial primary aldosteronism, somatic mutations in the same chann...

Background/aim: Reninomas are rare juxtaglomerular tumours which can cause severe hypertension and hypokalaemia. Diagnosis can be problematic and these tumours can be difficult to locate on imaging. In this report we aim to demonstrate the value of carefully performed renal vein renin ratios (RVRRs) to assist in locating these tumours. Method/res...

The study of families with rare inherited forms of hypo- and hypertension has been one of the most successful strategies to probe the molecular pathophysiology of blood pressure control and has revealed dysregulation of distal nephron sodium reabsorption to be a common mechanism. Familial Hyperkalaemic Hypertension (FHHt, Gordon Syndrome) is a salt...

In primary aldosteronism, adrenal vein sampling (AVS) suggests unilateral aldosterone-producing adenoma (APA) when the aldosterone/cortisol (A/F) ratio is less than or equal to peripheral on one side and at least two times peripheral on the other. When A/F ratios are lower bilaterally than peripheral despite adequate samples (adrenal venous cortiso...

The growing realisation since the early 1990s that primary aldosteronism (PA) is a much more common cause of hypertension than previously thought, and that aldosterone excess has adverse effects that are at least partly independent of blood pressure, have been the main driving forces for a renaissance in clinical and research interest in PA. This h...

Background: Obstructive sleep apnea (OSA) is a strong and independent risk factor for the development of hypertension, particularly resistant hypertension, and cardiovascular diseases. Patients with resistant hypertension have a high prevalence of OSA in association with elevated aldosterone levels, high salt intake, and salt-sensitive BP. The obj...

Primary aldosteronism (PA) is the commonest specifically treatable and sometimes curable cause of hypertension, and delay in diagnosis is associated with cardiovascular morbidity not explained by hypertension alone. Controversy is high regarding screening, diagnostic and sub-typing tests, and especially their "cut-off" points. This is not surprisin...

Background: Adrenal vein sampling (AVS) distinguishes unilateral from bilateral primary aldosteronism (PA). Unilateral aldosterone-producing adenoma (APA) is suggested by aldosterone/cortisol (A/F) ratios <= peripheral on one side (contralateral suppression) and >=2 times peripheral on the other. Occasionally, despite adequate samples (adrenal veno...

Background: Primary aldosteronism (PA) may account for 5-10% of patients with hypertension. Recently, a family with florid PA and marked zona fasciculata (ZF) hyperplasia was reported to have a germ-line mutation within KCNJ5 (encodes a potassium channel) [1]. Somatic mutations were also identified in eight of 22 large, apparently sporadic aldoster...

Background: Obstructive sleep apnea (OSA) is a strong and independent risk factor for hypertension. Aldosterone excess may play a pathophysiological role in the relationship between hypertension and OSA. Objectives: To determine the prevalence of OSA among patients with primary aldosteronism (PA) and possible mechanisms linking aldosterone and OSA....

Introduction: Accurate measurement of aldosterone and cortisol is crucial for diagnosis of primary aldosteronism (PA), but current assays lack specificity and precision. A semi-automated, simultaneous HPLC-tandem mass spectrometry (HPLC-MS/MS) method for aldosterone and cortisol was applied to fludrocortisone suppression testing (FST) and adrenal v...

Clinical studies have shown that aldosterone and salt are independently related to hypertension, cardiovascular morbidity and mortality. More recently, studies in humans have demonstrated that, similarly to animals, endogenous aldosterone and dietary salt intake have not only separate, but also combined effects to accelerate target-organ deteriorat...

In patients who seek surgical cure of primary aldosteronism (PA), The Endocrine Society Guidelines recommend the use of adrenal vein sampling (AVS), which is invasive, technically challenging, difficult to interpret, and commonly held to be risky. The aim of this study was to determine the complication rate of AVS and the ways in which it is perfor...

Primary hyperaldosteronism, one cause of which is aldosterone-producing adenomas (APAs), may account for ≤5% to 10% of cases of essential hypertension. Germline mutations have been identified in 2 rare familial forms of primary hyperaldosteronism, but it has been reported recently that somatic mutations of the KCNJ5 gene, which encodes a potassium...