Keeping primary aldosteronism in mind: Deficiencies in screening at-risk hypertensives

doi:10.1016/j.surg.2018.05.085

Surgery

Volume 165, Issue 1, January 2019, Pages 221-227

https://doi.org/10.1016/j.surg.2018.05.085 Get rights and content

Abstract

Background

Primary aldosteronism is a common but underdiagnosed cause of hypertension. Patients with this disorder have worse morbidity compared with those with essential hypertension, but with timely diagnosis and appropriate intervention these patients are potentially cured and may have reversal of target organ damage. The goal of this study was to determine if hypertensive patients considered high risk were checked for primary aldosteronism.

Methods

We reviewed electronic health records to identify patients age 18 years or older with coexisting hypertension and hypokalemia or hypertension and sleep apnea, then determined if they had been investigated with measurement of aldosterone or renin. We built regression models to identify explanatory variables for screening in these 2 high-risk groups.

Results

Of nearly 37,000 patients with hypertension and hypokalemia, only 2.7% were ever screened for primary aldosteronism. Most opportunities for case detection were during inpatient hospitalizations, yet in this setting, patients were less likely than clinic patients be screened. Similarly, 3.0% of hypertensive patients with sleep apnea were screened since the inclusion of this group in case detection recommendations.

Conclusion

Uptake of practice guidelines by hospital physicians, fueled by support from their specialty societies, may help to identify many more patients with unrecognized primary aldosteronism.

Introduction

Primary aldosteronism is estimated to affect between 5% and 12% of hypertensive patients and has gained recognition as a major public health problem.1, 2 Many physicians are taught in medical school that high blood pressure and hypokalemia are necessary for diagnosis. Although hypertension in primary aldosteronism is associated with lower potassium levels, only a quarter of all cases of primary aldosteronism have hypokalemia at presentation, and these are likely patients with more severe disease.³ One of the major clinical challenges over the years has been identifying patients with primary aldosteronism from among the many patients with essential hypertension.

The most common subtypes of this disease are aldosterone-producing adenoma and adrenal hyperplasia. In centers where adrenal vein sampling is routinely performed, the prevalence of adrenal adenomas among patients with primary aldosteronism ranges from 28% to 50%.³ For patients with a unilateral cause of primary aldosteronism, surgery can be curative. However, early diagnosis and appropriate treatment is key. Delays or failures to diagnose primary aldosteronism lead to significant damage to the cardiovascular and renal systems, greater than what is observed in patients with high blood pressure alone.⁴ Timely surgical intervention not only produces clinical and biochemical success in the majority of patients, but can reverse target organ injury.5, 6, 7, 8 Despite knowledge that adrenalectomy may cure hyperaldosteronism in patients with some subtypes of primary aldosteronism, it still remains a largely unrecognized and untreated disease.9, 10

The Endocrine Society recently updated their clinical practice guidelines on the screening, diagnosis, and treatment of primary aldosteronism.¹¹ Screening tests are recommended for several groups of patients considered high risk for this disease, comprising about half of all patients with high blood pressure.⁹ Included in this strategy are hypertensive patients with sleep apnea. Although sleep apnea is a known cause of secondary hypertension, more recent evidence suggests sleep apnea may manifest from primary aldosteronism, possibly owing to fluid retention in the neck leading to an increase in airway resistance.¹² The principle goal of this study was to determine if physicians were appropriately recognizing those considered to have a higher probability of primary aldosteronism. First, we identified hypertensive patients having hypokalemia and explored screening patterns within this group. Next, we searched for patients with hypertension and sleep apnea and looked at their frequency of screening since the release of these expanded screening guidelines. With both strategies, we discovered a marked deficiency in screening for primary aldosteronism.

Section snippets

Methods

This study was deemed exempt by the University of Chicago Institutional Review Board because all data were deidentified. To identify qualifying patient encounters, we queried electronic health records stored in the clinical research database warehouse using a cohort discovery program. This database contains patient information in electronic health records from our tertiary care center, including outpatient, inpatient, and emergency department encounters. We selected all patients from the age of

Results

From February 16, 1999 to December 15, 2017, there were 116,929 patients at least 18 years of age with a diagnosis of essential hypertension based on ICD-9/10 codes at this institution. Within this cohort, 36,979 patients (32%) had laboratory evidence of hypokalemia with documentation of a onetime serum potassium level less than 3.5 mEq/L (Fig. 1). This included 64,858 separate clinical encounters, comprising outpatient, inpatient, and emergency department visits. Similar to all patients with

Discussion

Screening for primary aldosteronism is recommended for hypertensive patients with hypokalemia and other high-risk hypertensive patients, including those with severe or resistant hypertension, an incidental adrenal mass, or obstructive sleep apnea.¹¹ We discovered that screening tests were not performed on 97% of patients with hypertension and hypokalemia. These findings are dramatic but parallel results from similar studies. In 1 recent cross-sectional study, less than 10% of general

Conflicts of interest

Funding for this study was provided by the Department of Surgery at the University of Chicago.

The authors indicate that they have no other conflicts of interest regarding the content of this article.

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Increased diagnosis of primary aldosteronism, including surgically correctable forms, in centers from five continents
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Long-term renal outcomes in patients with primary aldosteronism
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Cited by (50)

Development of a risk-prediction model for primary aldosteronism in veterans with hypertension
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Rates of screening for primary aldosteronism in patients who meet the criteria are exceedingly low (1%–3%). To help clinicians prioritize screening in patients most likely to benefit, we developed a risk-prediction model.
Using national Veterans Health Administration data, we identified patients who met the criteria for primary aldosteronism screening between 2000 and 2019. We performed multivariable logistic regression to identify characteristics associated with positive primary aldosteronism testing before generating a risk-scoring system based on the coefficients (0< β < 0.5 = 1 pt, 0.5 ≤ β < 1 = 2 pts, 1 ≤ β < 1.5 = 3 pts) and then tested the system performance using an internal validation cohort.
We identified 502,190 patients who met primary aldosteronism screening criteria, of whom 1.6% were screened and 15% tested positive. Based on the regression model, we generated a risk-scoring system based on a total of 9 possible points in which age under 50, absence of smoking history, and resistant hypertension each scored 1 point; elevated serum sodium 2 points; and hypokalemia 3 points. Rates of positive screening increased with risk score, with 5.6% to 6.7% of those scoring 0 points testing positive; 7.9% to 9.0% 1 point; 8.6% to 10% 2 points; 13% to 14% 3 points; 21% 4 points; 22% to 38% 5 points; 27% to 38% 6 points; 42% to 49% 7 points; and 50% to 51% ≥8 points.
In hypertensive patients who meet the criteria for primary aldosteronism screening, rates of positive screening range from 5.6% to 51%. Use of our risk-predication model incorporating these factors can identify patients most likely to benefit from testing.
Underdiagnosis of Primary Aldosteronism: A Review of Screening and Detection
2023, American Journal of Kidney Diseases
A clinical condition may be missed due to its higher-than-recognized prevalence or inadequate diagnostic screening. Both factors apply to primary aldosteronism, which is woefully underdiagnosed as a cause of hypertension and end-organ damage. Screening tests should be strongly considered for diseases that pose significant morbidity or mortality if left untreated, that have a high prevalence, and that have treatments that lead to improvement or cure. In this review we present the evidence for each of these points. We outline studies that estimate the prevalence of primary aldosteronism in different at-risk populations and how its recognition has changed over time. We also evaluate myriad studies of screening rates for primary aldosteronism and what factors do and do not influence current screening practices. We discuss the ideal conditions for screening, measuring the aldosterone to renin ratio in different populations that use plasma renin activity or direct renin concentration, and the steps for diagnostic workup of primary aldosteronism. Finally, we conclude with potential strategies to implement higher rates of screening and diagnosis of this common, consequential, and treatable disease.
Personalized Treatment of Patients With Primary Aldosteronism
2023, Endocrine Practice
Primary aldosteronism (PA) is a highly prevalent yet underdiagnosed secondary cause of hypertension. PA is associated with increased cardiovascular and renal morbidity compared with patients with primary hypertension. Thus, prompt identification and targeted therapy of PA are essential to reduce cardiovascular and renal morbidity and mortality in a large population with hypertension. Unilateral adrenalectomy is preferred for lateralized PA as the only potentially curative therapy. Surgery also mitigates the risk of cardiovascular and renal complications associated with PA. Targeted medical therapy, commonly including a mineralocorticoid receptor antagonist, is offered to patients with bilateral PA and those who are not surgical candidates. Novel therapies, including nonsteroidal mineralocorticoid receptor antagonists and aldosterone synthase inhibitors, are being developed as alternative options for PA treatment. In this review article, we discuss how to best individualize therapy for patients with PA.
Impact of an endocrine hypertension unit on the diagnosis of primary aldosteronism
2023, Endocrinologia, Diabetes y Nutricion
Implementation of a formal sleep center–based screening protocol for primary aldosteronism in patients with obstructive sleep apnea
2023, Surgery (United States)
Citation Excerpt :
Still, Conroy et al18 reported that only 3.4% of eligible OSA patients were screened for PA after the 2016 guidelines were instated. Similarly, Ruhle et al31 found only 3% of hypertensive patients with OSA were screened since inclusion of this group in screening recommendations. The higher screening rate in our study may be partly explained by more recent data collection, allowing more time for providers to adjust their clinical practice to include screening patients with OSA and HTN.
There is a bidirectional association between primary aldosteronism and obstructive sleep apnea, with evidence suggesting that the treatment of primary aldosteronism can reduce obstructive sleep apnea severity. Current guidelines recommend screening for primary aldosteronism in patients with comorbid hypertension and obstructive sleep apnea, identifying potential candidates for treatment. However, emerging data suggest current screening practices are unsatisfactory. Moreover, data regarding the true incidence of primary aldosteronism among this population are limited. This study aimed to assess the primary aldosteronism screening rate among patients with obstructive sleep apnea and hypertension at our institution and estimate the prevalence of primary aldosteronism among this population.
Sleep studies conducted at our institution between January and September 2021 were retrospectively reviewed. Adult patients with a sleep study diagnostic of obstructive sleep apnea (respiratory disturbance index ≥5) and a diagnosis of hypertension were included. Patient medical records were reviewed and laboratory data of those with biochemical screening for primary aldosteronism were assessed by an experienced endocrinologist. Screening rates were compared before and after initiation of a screening protocol in accordance with the 2016 Endocrine Society guidelines.
A total of 1,005 patients undergoing sleep studies were reviewed; 354 patients had comorbid obstructive sleep apnea and hypertension. Patients were predominantly male (67%), with a mean age of 58 years (standard deviation = 12.9) and mean body mass index of 34 (standard deviation = 8.1). The screening rate for primary aldosteronism among included patients was 19% (n = 67). The screening rate was significantly higher after initiation of a dedicated primary aldosteronism screening protocol (23% vs 12% prior; P = .01). Fourteen screens (21%) were positive for primary aldosteronism, whereas 45 (67%) were negative and 8 (12%) were indeterminate. Four had prior abdominal cross-sectional imaging, with 3 revealing an adrenal adenoma. Compared with patients without primary aldosteronism, patients with positive primary aldosteronism screens were more likely to have a history of hypokalemia (36% vs 4.4%; P = .002). The frequency of hyperlipidemia, diabetes mellitus, and left ventricular hypertrophy did not differ between patients with positive versus negative screens.
Current screening practices for primary aldosteronism among patients with comorbid obstructive sleep apnea and hypertension are suboptimal. Patients evaluated at sleep centers may represent an optimal population for screening, as the prevalence of primary aldosteronism among this cohort appears high.
Impact of dedicated multidisciplinary service on patient selection and outcomes for surgical treatment of primary aldosteronism
2022, Surgery (United States)
Primary aldosteronism is the most common surgically curable cause of endocrine hypertension. Management of the unilateral subtype of primary aldosteronism with adrenalectomy requires multidisciplinary input. It is unclear if a dedicated endocrine hypertension service confers better outcomes compared to standard care offered by individual clinicians.
In this retrospective study, patients from the Monash University Endocrine Surgery Database were divided into either the endocrine hypertension service group, where patients were managed by a dedicated multidisciplinary team, or the standard group, where patients were managed by individual clinicians. The comparisons included patient selection for surgery, perioperative blood pressure control, and surgical cure rate.
Despite similar perioperative blood pressure, patients in the endocrine hypertension service group (n = 41) were on fewer antihypertensive medications (1 vs 2, P = .011) compared to the standard group (n = 55). A larger proportion of patients in the endocrine hypertension service group had either bilateral adrenal nodules or no adrenal lesions on computed tomography (41% vs 18%, P = .013). Patients in the standard group had larger adrenal lesions on computed tomography (median 15 mm vs 10 mm, P = .032). Postoperatively, the biochemical cure rate was higher in the endocrine hypertension service group at 6 to 12 months (97% vs 76%, P = .021).
Patients managed by endocrine hypertension service were more likely to be diagnosed with surgically curable primary aldosteronism without a unilateral adrenal adenoma on imaging, required fewer medications for perioperative blood pressure control, and experienced superior postoperative outcomes. Referral to a dedicated endocrine hypertension service is recommended for patients with primary aldosteronism who wish to pursue a surgical cure.

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: Presented at the 39th annual meeting of the American Association of Endocrine Surgeons in Durham, North Carolina, May 6–8, 2018.

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Keeping primary aldosteronism in mind: Deficiencies in screening at-risk hypertensives

Abstract

Background

Methods

Results

Conclusion

Introduction

Section snippets

Methods

Results

Discussion

Conflicts of interest

Lancet

J Am Coll Cardiol

Lancet Diabetes Endocrinol

Lancet Diabetes Endocrinol

Lancet (London, England)

Increased diagnosis of primary aldosteronism, including surgically correctable forms, in centers from five continents

J Clin Endocrinol Metab

Long-term renal outcomes in patients with primary aldosteronism

JAMA

Rapid reversal of left ventricular hypertrophy and intracardiac volume overload in patients with resistant hypertension and hyperaldosteronism: a prospective clinical study

Hypertens (Dallas, Tex 1979)

Cardiovascular outcomes in patients with primary aldosteronism after treatment

Arch Intern Med

Is primary aldosteronism still largely unrecognized

Horm Metab Res