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Context: Primary aldosteronism (PA) is one of the most common causes of secondary hypertension, but the comparative outcomes of targeted treatment remain unclear. Objective: To compare the clinical outcomes in patients treated for primary aldosteronism over time. Methods: Medline and EMBASE were searched. Original studies reporting the incidence of mortality, major adverse cardiovascular outcomes (MACE), progression to chronic kidney disease, or diabetes following adrenalectomy vs medical therapy were selected. Two reviewers independently abstracted data and assessed study quality. Standard meta-analyses were conducted using random-effects models to estimate relative differences. Time to benefit meta-analyses were conducted by fitting Weibull survival curves to estimate absolute risk differences and pooled using random-effects models. Results: 15 541 patients (16 studies) with PA were included. Surgery was consistently associated with an overall lower risk of death (hazard ratio [HR] 0.34, 95% CI 0.22-0.54) and MACE (HR 0.55, 95% CI 0.36-0.84) compared with medical therapy. Surgery was associated with a significantly lower risk of hospitalization for heart failure (HR 0.48 95% CI 0.34-0.70) and progression to chronic kidney disease (HR 0.62 95% CI 0.39-0.98), and nonsignificant reductions in myocardial infarction and stroke. In absolute terms, 200 patients would need to be treated with surgery instead of medical therapy to prevent 1 death after 12.3 (95% CI 3.1-48.7) months. Conclusion: Surgery is associated with lower all-cause mortality and MACE than medical therapy for PA. For most patients, the long-term surgical benefits outweigh the short-term perioperative risks. [ABSTRACT FROM AUTHOR]

Primary aldosteronism (PA) is an endocrinopathy characterized by dysregulated aldosterone production that occurs despite suppression of renin and angiotensin II, and that is non-suppressible by volume and sodium loading. The effectiveness of surgical adrenalectomy for patients with lateralizing PA is characterized by the attenuation of excess aldosterone production leading to blood pressure reduction, correction of hypokalemia, and increases in renin—biomarkers that collectively indicate a reversal of PA pathophysiology and restoration of normal physiology. Even though the vast majority of patients with PA will ultimately be treated medically rather than surgically, there is a lack of guidance on how to optimize medical therapy and on key metrics of success. Herein, we review the evidence justifying approaches to medical management of PA and biomarkers that reflect endocrine principles of restoring normal physiology. We review the current arsenal of medical therapies, including dietary sodium restriction, steroidal and nonsteroidal mineralocorticoid receptor antagonists, epithelial sodium channel inhibitors, and aldosterone synthase inhibitors. It is crucial that clinicians recognize that multimodal medical treatment for PA can be highly effective at reducing the risk for adverse cardiovascular and kidney outcomes when titrated with intention. The key biomarkers reflective of optimized medical therapy are unsurprisingly similar to the physiologic expectations following surgical adrenalectomy: control of blood pressure with the fewest number of antihypertensive agents, normalization of serum potassium without supplementation, and a rise in renin. Pragmatic approaches to achieve these objectives while mitigating adverse effects are reviewed. [ABSTRACT FROM AUTHOR]

Optimal duration of bisphosphonate therapy was unknown until the FLEX study was published in 2006 showing a 5‐year course to be adequate for most women. In 2008, a link between long‐term bisphosphonate and atypical femoral fractures was reported and confirmed in later studies. We hypothesized these landmark observations should have led to a decrease in use of bisphosphonates for >5 or 10 years, from 2010 onward. The Manitoba Bone Mineral Density (BMD) Registry with linkage to provincial pharmacy data was used to determine the percentage of long‐ and very long‐term bisphosphonate users from therapy start. The cohort comprised women aged >50 years with BMD between 1995 and 2018 with oral bisphosphonate first prescribed for >90 days with adherence >75% in the first year. For each calendar year of continued therapy, the percentage of patients and medication possession rate was tabulated. The percentage of users beyond 5 years was compared among patients who started therapy in 1998–2004 (those taking 5 years of therapy still finish before 2010) versus 2005–2012 (all new therapy starts overlap 2010 in those taking ≥5 years of treatment). The cohort included 2991 women with mean follow‐up 8.8 (1.3) years, 64.9% of whom took continuous oral bisphosphonate for >5 years and 41.9% for >10 years. In the earlier versus later era, there were 74.4% versus 70.2% who completed 5 years. With respect to longer treatment, there were 68.0% and 60.5% of patients treated for 6 or more years (p < 0.0001) and 46.6% versus 33.5% treated for >10 years (p = 0.08). Medication possession rate was >79% in every year of therapy. Landmark studies leading to more limited bisphosphonate courses may have slightly reduced longer‐term treatment, but up to one‐third of adherent patients in the modern era still receive continuous bisphosphonate therapy for >10 years. © 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR). [ABSTRACT FROM AUTHOR]

BACKGROUND Hypertension plus obstructive sleep apnea (OSA) is recommended in some guidelines as an indication to screen for primary aldosteronism (PA), yet prior data has brought the validity of this recommendation into question. Given this context, it remains unknown whether this screening recommendation is being implemented into clinical practice. METHODS We conducted a population-based retrospective cohort study of all adult Ontario (Canada) residents with hypertension plus OSA from 2009 to 2020 with follow-up through 2021 utilizing provincial health administrative data. We measured the proportion of individuals who underwent PA screening via the aldosterone-to-renin ratio by year. We further examined screening rates among patients with hypertension plus OSA by the presence of concurrent hypokalemia and resistant hypertension. Clinical predictors associated with screening were assessed via Cox regression modeling. RESULTS The study cohort included 53,130 adults with both hypertension and OSA, of which only 634 (1.2%) underwent PA screening. Among patients with hypertension, OSA, and hypokalemia, the proportion of eligible patients screened increased to 2.8%. Among patients ≥65 years with hypertension, OSA, and prescription of ≥4 antihypertensive medications, the proportion of eligible patients screened was 1.8%. Older age was associated with a decreased likelihood of screening while hypokalemia and subspecialty care with internal medicine, cardiology, endocrinology, or nephrology were associated with an increased likelihood of screening. No associations with screening were identified with sex, rural residence, cardiovascular disease, diabetes, or respirology subspecialty care. CONCLUSIONS The population-level uptake of the guideline recommendation to screen all patients with hypertension plus OSA for PA is exceedingly low. [ABSTRACT FROM AUTHOR]

Denosumab is a widely used medication for the treatment of osteoporosis. It has been observed in recent years that abruptly stopping denosumab leads to an increase in bone turnover markers, a decrease in bone mineral density, and a higher incidence of vertebral fractures. We present the case of a 53-year-old woman with few comorbidities and no prior fragility fractures who experienced 4 spontaneous and severely debilitating vertebral fractures 5-months post denosumab discontinuation. At the time of her fractures, she was found to have markedly elevated bone turnover markers, despite bone mineral density that was not significantly changed from measurements done while on denosumab treatment. She went on to be treated with an alternative antiresorptive agent, risedronate, and had substantial declines in her bone turnover markers, along with clinical improvement in her back pain. She experienced no further fractures while on treatment. Abrupt discontinuation of denosumab without starting an alternative antiresorptive agent can lead to spontaneous vertebral fractures. These fractures can occur in young patients with no prior history of fragility fractures and can be severely debilitating. An alternative antiresorptive agent should be started in the case of denosumab discontinuation. [ABSTRACT FROM AUTHOR]

Context: FRAX® estimates 10-year fracture probability from osteoporosis-specific risk factors. Medical comorbidity indicators are associated with fracture risk but whether these are independent from those in FRAX is uncertain. Objective: We hypothesized Johns Hopkins Aggregated Diagnosis Groups (ADG®) score or recent hospitalization number may be independently associated with increased risk for fractures. Methods: This retrospective cohort study included women and men age =40 in the Manitoba BMD Registry (1996-2016) with at least 3 years prior health care data and used linked administrative databases to construct ADG scores along with number of hospitalizations for each individual. Incident Major Osteoporotic Fracture and Hip Fracture was ascertained during average follow-up of 9 years; Cox regression analysis determined the association between increasing ADG score or number of hospitalizations and fractures. Results: Separately, hospitalizations and ADG score independently increased the hazard ratio for fracture at all levels of comorbidity (hazard range 1.2-1.8, all P<0.05), irrespective of adjustment for FRAX, BMD, and competing mortality. Taken together, there was still a higher than predicted rate of fracture at all levels of increased comorbidity, independent of FRAX and BMD but attenuated by competing mortality. Using an intervention threshold of major fracture risk >20%, application of the comorbidity hazard ratio multiplier to the patient population FRAX scores would increase the number of treatment candidates from 8.6% to 14.4%. Conclusion: Both complex and simple measures of medical comorbidity may be used to modify FRAX-based risk estimates to capture the increased fracture risk associated with multiple comorbid conditions in older patients. [ABSTRACT FROM AUTHOR]

Context: Medication may be considered when bone mineral density (BMD) loss is reported as "excessive." Objective: We hypothesized that the rate of BMD change between 2 serial tests demonstrates higher random variability at shorter vs longer intervals, misclassifying some women as "rapid losers." Methods: This retrospective observational cohort study in Manitoba, Canada included women aged > 55 years without osteoporosis medications or glucocorticoids. Using paired baseline (1998-2016) and repeat (2001-2018) BMD measurements, we estimated the distribution of annualized change (first to second BMD) at spine, hip, and femoral neck stratified by testing interval (2-2.9, 3-3.9,...9-9.9, ≥ 10.0 years). "Rapid annual bone loss" was defined as exceeding the 95th percentile for decreases from all measurement pairs. Odds ratios (OR) for rapid loss were estimated using regression models adjusted for age and clinical covariates. Results: From 7126 paired BMD measurements, mean annualized change was constant yet standard deviations in BMD change were > 2-fold greater with intervals of 2 to 2.9 years vs ≥ 10 years(P < 0.001). "Rapid annual loss" was seen in ~10% of short-interval tests vs < 1% of long-interval tests. ORs for "rapid loss" progressively declined with increasing testing interval (spine 15.3 [4.8-48.9], total hip 9.3 [4.4-19.5], femoral neck 18.7 [6.8-51.3] for a 2- to 2.9-year testing interval; referent ≥ 10 years). Conclusion: There is a wider apparent range in annualized BMD loss with short-interval testing which greatly attenuates over longer intervals. BMD reports of "rapid loss" across shorter testing intervals likely reflect an artifact of BMD measurement error and should not be used as an indication for antifracture medication initiation. [ABSTRACT FROM AUTHOR]

BACKGROUND Targeted treatment of primary aldosteronism (PA) is informed by adrenal vein sampling (AVS), which remains limited to specialized centers. Clinical prediction models have been developed to help select patients who would most likely benefit from AVS. Our aim was to assess the performance of these models for PA subtyping. METHODS This external validation study evaluated consecutive patients referred for PA who underwent AVS at a tertiary care referral center in Alberta, Canada during 2006–2018. In alignment with the original study designs and intended uses of the clinical prediction models, the primary outcome was the presence of lateralization on AVS. Model discrimination was evaluated using the C -statistic. Model calibration was assessed by comparing the observed vs. predicted probability of lateralization in the external validation cohort. RESULTS The validation cohort included 342 PA patients who underwent AVS (mean age, 52.1 years [SD, 11.5]; 201 [58.8%] male; 186 [54.4%] with lateralization). Six published models were assessed. All models demonstrated low-to-moderate discrimination in the validation set (C -statistics; range, 0.60–0.72), representing a marked decrease compared with the derivation sets (range, 0.80–0.87). Comparison of observed and predicted probabilities of unilateral PA revealed significant miscalibration. Calibration-in-the-large for every model was >0 (range, 0.35–1.67), signifying systematic underprediction of lateralizing disease. Calibration slopes were consistently <1 (range, 0.35–0.87), indicating poor performance at the extremes of risk. CONCLUSIONS Overall, clinical prediction models did not accurately predict AVS lateralization in this large cohort. These models cannot be reliably used to inform the decision to pursue AVS for most patients. [ABSTRACT FROM AUTHOR]

Context: Fracture on therapy should motivate better antifracture medication adherence. Objective: This study aimed to describe osteoporosis medication adherence in women before and following a fracture. Methods: This retrospective cohort analysis of antifracture medication possession ratios (MPR) among women in the Manitoba BMD Registry (1996-2013) included menopausal women who started antifracture drug therapy after a dual-energy x-ray absorptiometry (DXA)-BMD assessment with follow-up for 5 years during which a nontraumatic fracture occurred at least 1 year after starting treatment. Linked prescription records determined medication adherence (estimated by MPR) in 1-year intervals. The variable of interest was MPR in the year before and after the year in which the fracture occurred, with subgroup analyses according to duration of treatment pre-fracture. We chose an MPR of ≥ 0.50 to indicate minimum adherence needed for drug efficacy. Results: There were 585 women with fracture on therapy, 193 (33%) had hip or vertebral fracture. Bisphosphonates accounted for 82.2% of therapies. Median MPR the year prior to fracture was 0.89 (IQR, 0.49-1.0) and 0.69 (IQR, 0.07-0.96) the year following the year of fracture (P < 0.0001). The percentage of women with MPR ≥ 0.5 pre-fracture was 73.8%, dropping to 57.3% post-fracture (P < 0.0001); when restricted to hip/vertebral fracture, results were similar (58.2% to 33.3%; P < 0.002). Among those with pre-fracture MPR < 0.5, only 21.7% achieved a post-fracture MPR ≥ 0.5. Conclusions: Although fracture on therapy may motivate sustained/improved adherence, MPR remains low or even declines after fracture in many. This could reflect natural decline in MPR with time but is paradoxical to expectations. Fracture on therapy represents an important opportunity for clinicians to reemphasize treatment adherence. [ABSTRACT FROM AUTHOR]

Context: Adrenal gland imaging is recommended by the current guidelines for the workup of primary aldosteronism (PA). However, its diagnostic performance has not been established in large, multiethnic cohorts of patients who undergo adrenal vein sampling (AVS) and adrenalectomy.Objective: This work aims to assess the diagnostic accuracy of cross-sectional adrenal imaging.Methods: This international multicenter study took place in tertiary referral centers. A total of 1625 PA patients seeking surgical cure were enrolled in an international study involving 19 centers in North America, Europe, Asia, and Australia. Of these, 1311 (81%) had imaging data available and 369 (23%), who received a final diagnosis of surgically cured unilateral PA, were examined. Patients underwent AVS and imaging by computed tomography and/or magnetic resonance imaging. The accuracy of detection of unilateral PA at imaging was estimated by the area under the receiver operator characteristics curve using cure (biochemical and/or full clinical success) as the reference at follow-up after unilateral adrenalectomy.Results: In the cohort of 1311 patients with imaging data available, 34% and 7% of cases showed no detectable or bilateral nodules, respectively. Imaging did not detect the culprit adrenal in 28% of the surgically cured unilateral PA patients. Moreover, the clinical outcome did not differ significantly between the imaging-positive and imaging-negative patients.Conclusion: Cross-sectional imaging did not identify a lateralized cause of disease in around 40% of PA patients and failed to identify the culprit adrenal in more than one-fourth of patients with unilateral PA. [ABSTRACT FROM AUTHOR]

Context: The value of serial bone mineral density (BMD) monitoring while on osteoporosis therapy is controversial.Objective: We determined the percentage of women classified as suboptimal responders to therapy with antiresorptive medications according to 2 definitions of serial BMD change.Methods: This was a cohort study using administrative databases at a single-payer government health system in Manitoba, Canada. Participants were postmenopausal women aged 40 years or older receiving antiresorptive medications and having 3 sequential BMD measures. Women stopping or switching therapies were excluded. The percentage of women whose spine or hip BMD decreased significantly during the first or second interval of monitoring by BMD was determined. Suboptimal responder status was defined as BMD decrease during both monitoring intervals or BMD decreased from baseline to final BMD.Results: There were 1369 women in the analytic cohort. Mean BMD monitoring intervals were 3.0 (0.8) and 3.2 (0.8) years. In the first interval, 3.2% and 6.5% of women had a decrease in spine or hip BMD; 8.0% and 16.9% had decreases in the second monitoring interval; but only 1.4% showed repeated losses in both intervals. Considering the entire treatment interval, only 3.2% and 7.4% showed BMD loss at spine or hip. Results may not apply to situations of poor adherence to antiresorptive medication or anabolic therapy use.Conclusion: Among women highly adherent to antiresorptive therapy for osteoporosis, a very small percentage sustained BMD losses on repeated measures. The value of multiple serial BMD monitoring to detect persistent suboptimal responders should be questioned. [ABSTRACT FROM AUTHOR]

The role of mid‐treatment monitoring dual‐energy X‐ray absorptiometry–bone mineral density (DXA‐BMD) for bisphosphonate‐treated patients with osteoporosis remains unsettled. A common reason for such monitoring is to encourage ongoing medication adherence. We sought to determine if a DXA‐BMD treatment monitoring test was associated with improved medication adherence and whether improved adherence after a DXA‐BMD treatment monitoring test was associated with subsequent reduction in fracture rates. Using linked administrative databases within Manitoba, Canada, we performed a retrospective cohort study of women starting and continuing antiresorptive therapy in whom a mid‐treatment DXA‐BMD monitoring test was performed. From the provincial pharmacy database, we estimated medication adherence by calculating annual medication possession ratio (MPR) and determining the change in MPR with respect to change (stable/decrease) in the DXA‐BMD monitoring test, in addition to fracture rates before and after the test. The cohort comprised 3418 women, 90.7% treated with oral bisphosphonate, with pharmacy data for the 3 years before and after the mid‐treatment DXA‐BMD. Median (interquartile range) MPR was 0.84 (0.49–0.99) in the year before DXA‐BMD and 0.84 (0.48–0.99) in the year after DXA‐BMD (p = 0.37). Among those whose DXA‐BMD declined, MPR in the prior year was 0.54 (0.04–0.92) but improved to 0.70 (0.31–0.92) in the year after DXA‐BMD (p < 0.001). Among those whose DXA‐BMD monitoring test was stable/improved, the fracture rate before the monitoring DXA‐BMD was 10.1 per 1000 person‐years and in those whose DXA‐BMD monitoring test showed a decrease, the rate was 23.7 per 1000 person‐years (p < 0.001). Despite improved adherence in those with DXA‐BMD decline, the post DXA‐BMD fracture rate was 22.4 per 1000 person‐years versus 12.9 per 1000 person‐years in those who had stable DXA‐BMD (p < 0.001). A mid‐treatment DXA‐BMD reassessment strategy may be useful to focus attention upon adherence, but for optimal fracture outcomes, treatment adherence should be specifically addressed at the commencement of therapy. © 2021 American Society for Bone and Mineral Research (ASBMR). [ABSTRACT FROM AUTHOR]

Context: The aldosterone to renin ratio (ARR) is the guideline-recommended screening test for primary aldosteronism. However, there are limited data in regard to the diagnostic performance of the ARR.Objective: To evaluate the sensitivity and specificity of the ARR as a screening test for primary aldosteronism.Methods: We searched the MEDLINE, Embase, and Cochrane databases until February 2020. Observational studies assessing ARR diagnostic performance as a screening test for primary aldosteronism were selected. To limit verification bias, only studies where dynamic confirmatory testing was implemented as a reference standard regardless of the ARR result were included. Study-level data were extracted and risk of bias and applicability were assessed using the QUADAS-2 tool.Results: Ten studies, involving a total of 4110 participants, were included. Potential risk of bias related to patient selection was common and present in half of the included studies. The population base, ARR positivity threshold, laboratory assay, and reference standard for confirmatory testing varied substantially between studies. The reported ARR sensitivity and specificity varied widely with sensitivity ranging from 10% to 100% and specificity ranging from 70% to 100%. Notably, 3 of the 10 studies reported an ARR sensitivity of <50%, suggesting a limited ability of the ARR to adequately identify patients with primary aldosteronism.Conclusions: ARR performance varied widely based on patient population and diagnostic criteria, especially with respect to sensitivity. Therefore, no single ARR threshold for interpretation could be recommended. Limitations in accuracy and reliability of the ARR must be recognized in order to appropriately inform clinical decision-making. [ABSTRACT FROM AUTHOR]

Context: False-positive results are common for pheochromocytoma/paraganglioma (PPGL) real-world screening.Objective: Determine the correlation between screening urine and seated plasma metanephrines in outpatients where PPGL was absent, compared to meticulously prepared and supine-collected plasma metanephrines with age-adjusted references.Design: Retrospective cohort study.Setting: Databases from a single-provider provincial laboratory (2012-2018), a validated PPGL registry, and a manual chart review from a specialized endocrine testing unit.Patients: PPGL registry data excluded known PPGL cases from the laboratory database. Outpatients having both urine and plasma metanephrines <90 days apart.Methods: The correlation between urine and seated plasma measures along with the total positivity rate. All cases of plasma metanephrines drawn in the endocrine unit were reviewed for test indication and test positivity rate.Results: There were 810 non-PPGL pairs of urine and plasma metanephrines in the laboratory database; 46.1% of urine metanephrines were reported high. Of seated outpatient plasma metanephrines drawn a median of 5.9 days later, 19.2% were also high (r = 0.33 and 0.50 for normetanephrine and metanephrine, respectively). In contrast, the meticulously prepared and supine collected patients (n = 139, 51% prior high urine metanephrines) had <3% rate of abnormal high results in patients without known PPGL/adrenal mass.Conclusions: There was a poor-to-moderate correlation between urine and seated plasma metanephrines. Up to 20% of those with high urine measures also had high seated plasma metanephrines in the absence of PPGL. Properly prepared and collected supine plasma metanephrines had a false-positive rate of <3% in the absence of known PPGL/adrenal mass. [ABSTRACT FROM AUTHOR]

Context: The reproducibility of adrenal vein sampling (AVS) is unknown.Objective: This work aimed to determine reproducibility of biochemical results and diagnostic lateralization in patients undergoing repeat AVS.Methods: 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).Results: 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.Conclusion: 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. [ABSTRACT FROM AUTHOR]

Objective: Despite the significant morbidity and mortality associated with pheochromocytoma and paraganglioma, little is known about their epidemiology. The primary objective was to determine the incidence of pheochromocytoma and paraganglioma in an ethnically diverse population. A secondary objective was to develop and validate algorithms for case detection using laboratory and administrative data. Design: Population-based cohort study in Alberta, Canada from 2012 to 2 019. Methods: Patients with pheochromocytoma or paraganglioma were identified using linked administrative databases and clinical records. Annual incidence rates per 100 000 people were calculated and stratified according to age and sex. Algorithms to identify pheochromocytoma and paraganglioma, based on laboratory and administrative data, were evaluated. Results: A total of 239 patients with pheochromocytoma or paraganglioma (collectively with 251 tumors) were identified from a population of 5 196 368 people over a period of 7 years. The overall incidence of pheochromocytoma or paraganglioma was 0.66 cases per 100 000 people per year. The frequency of pheochromocytoma and paraganglioma increased with age and was highest in individuals aged 60-79 years (8.85 and 14.68 cases per 100 000 people per year for males and females, respectively). An algori thm based on laboratory data (metanephrine >two-fold or normetanephrine >three-fold higher than the upper limit of normal) closely appro ximated the true frequency of pheochromocytoma and paraganglioma with an estimated incidence of 0.54 cases per 100 000 people per year. Conslusion: The incidence of pheochromocytoma and paraganglioma in an unsel ected population of western Canada was unexpectedly higher than rates reported from other areas of the world. [ABSTRACT FROM AUTHOR]

Context: Unilateral aldosteronomas should suppress renin and contralate ral aldosterone secretion. Complete aldosterone suppression in contralateral adrenal vein sample (A VS) could predict surgical outcomes. Objectives: To retrospectively evaluate the prevalence of basal contralate ral suppression using Aldosterone (A)contralateral(CL)/Aperipheral(P) as compared to (A/Cortisol(C)CL)/(A/C)P ratio in primary aldosteronism (PA) patients studied in two Canadian centers. To determine the best cut-off to predict c linical and biochemical surgical cure. To compare the accuracy of ACL/AP to the basal and post-ACTH lateralization index (LI) in predic ting surgical cure. Methods: In total, 330 patients with PA and successful AVS were include d; 124 lateralizing patients underwent surgery. Clinical and biochemical cure at 3 and 12 months were evaluated using the PASO criteria. Results: Using ACL/AP and (A/C)CL/(A/C)P at the cut-off of 1, the prevalence of contralateral suppressio n was 6 and 45%, respectively. Using ROC curves, the ACL/AP ratio is associated with clinical cure at 3 and 12 months and biochemical cure at 12 months. (A/C)CL/(A/C)P is associated with biochemical cure only. The cut-offs for ACL/AP offering the best sensitivity (Se) and specificity (Sp) for clinical and biochemic al cures at 12 months are 2.15 (Se: 63% and Sp: 71%) and 6.15 (Se: 84% and Sp: 77%), respectively. Basal LI and post-ACT H LI are associated with clinical cure but only the post- ACTH LI is associated with biochemical cure. Conclusions: In lateralized PA, basal contralateral suppression defined by ACL/AP is rare and incomplete compared to the (A/C)CL/(A/C)P ratio and is associated with clinical and biochemical postoper ative outcome, but with modest accuracy. [ABSTRACT FROM AUTHOR]

Objective: Determine rate of high plasma normetanephrine or metanephrine (PNM-PMN) in a large sample of patients according to PNM-PMN posture and age-adjusted references. Design: Retrospective re-analysis of PNM-PMN from a Canadian reference laboratory (n = 5452), 2011-2015; most were in seated position (n = 5112) rather than supine (n = 340). An international PPGL database demonstrated expected distribution of supine PNM-PMN in PPGL patients. Methods: All PNM-PMN from a tertiary referral laboratory were reviewed. Any PNM-PMN result greater than 2× upper reference limit (URL) was considered likely true PPGL. Results 1-2× URL were uncertain, requiring additional testing/follow-up despite most being false positive given the r arity of PPGL. The rate of results in the 1-2× URL category were calculated for each group according to collection posture and differing published URL: seated, supine or supine age adjusted. Results: When collected and interpreted by seated URL, 19.6% of PNM req uired additional testing; only 4.6% being >2× URL. For patients over age 50 years, the abnormal rate was 24. 9%. When collected supine, interpreted by supine age-adjusted URL, only 5.3% of PNM were mildly elevated. Possible false positives may be even lower when considering PMN or plasma methoxytyramine which were commonly h igh in true PPGL despite mild PNM elevations. Conclusions: In a general medical population, seated PNM has a high rate of abnormal results, far exceeding expected prevalence. Supine measurement with supine, age-adjusted interpretation is strongly preferred prior to costly or invasive PPGL investigations. Summary: Review of 5452 plasma normetanephrine measurements showed 20% to be high, likely false positives for most. Supine, age-adjusted measures were half as likely to be elevated. [ABSTRACT FROM AUTHOR]

Published by Bioscientifica Ltd. Printed in Great Britain © 2021 European Society of Endocrinology https://eje.bioscientifica.com https://doi.org/10.1530/EJE-21-0258 European Journal of Endocrinology 184:5 L21-L23 A A Leung and others Pheochromocytoma at high altitude Incidence of pheochromocytoma and paraganglioma varies according to altitude: meta-regression analysis Alexander A Leung 1,2, Martin D Hyrcza 3,4, Janice L Pasieka 5 and Gregory A Kline 1 1 Division of Endocrinology and Metabolism, Department of Medicine, 2 Department of Community Health Sciences, 3 Department of Pathology and Laboratory Medicine, University of Calgary, Calgary, Alberta, Canada, 4 Alberta Precision Laboratories, Alberta Health Services, Calgary, Alberta, Canada, and 5 Department of Surgery, University of Calgary, Calgary, Alberta, Canada We thank Drs Patel and Mihai for their interest in our article where we described the incidence of pheochromocytoma and paraganglioma in Alberta, Canada (1). The findings of the meta-regression analysis indicate that the incidence of pheochromocytoma and paraganglioma varies according to altitude, as is consistent with previous studies suggesting that hypoxia mediates tumorigenesis (3, 14). [Extracted from the article]

Endocrine hypertension, particularly primary aldosteronism (PA), was previously considered to account for less than 1% of all hypertension and was suspected only when patients presented with spontaneous hypokalemia. However, the last 20 years of PA research has now clearly shown that PA is not a rarity, but rather, may account for up to 13% of unselected hypertensive individuals and between 10% and 20% of those with resistant hypertension. Most of these patients do not have spontaneous hypokalemia. The population prevalence of PA likely far exceeds actual detection rates in routine clinical care. As PA represents one of the most common, potentially reversible causes of hypertension, and is associated with significant cardiovascular complications over the long term, it is clear that a pragmatic strategy for targeted case detection in primary care is needed. [ABSTRACT FROM AUTHOR]