Diagnostic Delay and Disease Burden in Primary Aldosteronism: An International Patient Survey
Abstract
BACKGROUND:
Primary aldosteronism (PA) is a common but underdiagnosed cause of hypertension. Many patients experience preventable end-organ injury due to delayed or missed diagnosis but data on the experience of patients are limited.
METHODS:
We evaluated the lived experience of PA and determines factors associated with diagnostic delay through an international anonymous online cross-sectional survey, codesigned by researchers and PA consumers. We distributed the survey through academic medical centers, Amazon Mechanical Turk, Twitter, PA patient advocacy groups, and hypertension support groups on Facebook between March 21 and June 5, 2022.
RESULTS:
Of 684 eligible respondents, 66.5% were women. Diagnostic delay (defined as ≥5 years between the diagnosis of hypertension and PA) was reported in 35.6%. Delay was more likely in women than in men (odds ratio, 1.55 [95% CI, 1.10–2.20]) and respondents with ≥3 comorbidities versus none (odds ratio, 1.77 [95% CI, 1.05–3.02]), ≥10 symptoms versus none (odds ratio, 2.73 [95% CI, 1.74–4.44]), and on ≥4 antihypertensive medications versus none (odds ratio, 18.23 [95% CI, 6.24–77.72]). Three-quarters of patients (74.4%) experienced reduced symptom burden following targeted PA treatment. Quality of life improved in 62.3% of patients, and greater improvement was associated with being a woman (odds ratio, 1.42, [95% CI, 1.02–1.97]), receiving adrenalectomy (odds ratio, 2.36 [95% CI, 1.67–3.35]), and taking fewer antihypertensive medications following diagnosis (odds ratio, 5.28 [95% CI, 3.55–7.90]).
CONCLUSIONS:
One-third of patients with PA experienced prolonged diagnostic delays. Targeted treatment led to reduced symptom burden and improved quality of life. Gender differences in diagnostic delay and symptom burden are prominent. These findings suggest that routine screening for PA at the onset of hypertension may reduce diagnostic delay and facilitate timely diagnosis.
Graphical Abstract
NOVELTY AND RELEVANCE
What Is New?
This is the largest survey of people with primary aldosteronism recruited from 6 continents, providing a robust representation of affected patients. We described the lived experience of patients with primary aldosteronism (PA) and determined factors associated with diagnostic delay.
What Is Relevant?
Diagnostic delay of PA is associated with being a woman, having more comorbidities, having more nonspecific symptoms, and taking multiple antihypertensive medications.
Gender differences in diagnostic delay and disease burden associated with PA were prominent. Women were more likely to report their hypertension being dismissed by doctors despite having better hypertension knowledge and awareness.
Respondents reported a wide range of symptoms that have not been formally attributed to primary aldosteronism. Patient-reported benefits of disease-specific treatment for primary aldosteronism were characterized by reduced symptom burden and improved quality of life.
Clinical/Pathophysiological Implications?
Patients with PA experienced a prolonged diagnostic delay. Targeted treatment led to reduced symptom burden and improved quality of life. These findings suggest that routine screening for PA at the onset of hypertension, irrespective of age and gender, may reduce diagnostic delay and facilitate timely diagnosis.
Primary aldosteronism (PA) is the most common endocrine cause of hypertension. It is characterized by aldosterone excess due to renin-independent aldosterone production.1,2 While previously considered rare, emerging research has shown that PA affects 5% to 15% of people with hypertension and up to 29% of those with resistant hypertension.3–7 PA can be surgically cured by unilateral adrenalectomy or treated with targeted medical therapy. Individuals with PA are at increased risk of adverse cardiovascular and renal outcomes if left untreated.8–10
Despite the high disease prevalence and availability of targeted treatment, PA is rarely diagnosed in routine clinical practice. In a population-based cohort study from Alberta, Canada, only 0.7% of 1.1 million adults with hypertension were screened for PA.11 Even among people with clinical characteristics strongly suggestive of PA, such as those with hypertension and hypokalemia or resistant hypertension, <3% were screened in tertiary care settings in the United States.12–15
Patients with PA often experience preventable end-organ injury due to diagnostic delay or misdiagnosis.10,14,16 At a hypertension service in Australia, 61% of patients with PA had hypertension for over 10 years and 42% had end-organ damage by the time of referral.16 Missing the diagnosis of secondary hypertension is a key contributor to unacceptably poor blood pressure (BP) control globally.17 Much can be gained, in terms of BP control and cardiovascular risk reduction, by improving the diagnostic pathway for patients with PA.
One strategy for improvement is through the understanding of patient experiences, which can provide unique insights into patient outcomes and inform methods to optimize patient care.18,19 There is, however, limited literature reporting the experience of patients with PA.20,21 In this study, we aimed to quantitatively evaluate the lived experience of patients with PA through an international survey. The main objective is to determine factors associated with diagnostic delay, PA-related clinical symptoms, disease burden, self-perceived quality of life (QoL), and treatment outcomes.
METHODS
Data Availability
The data that support the findings of this study are available from the corresponding author upon reasonable request only.
Study Design and Population
This was an international online cross-sectional survey conducted between March 21 and June 5, 2022. Responses were obtained from people with a self-reported diagnosis of PA using a range of platforms and approaches: invitations from PA specialists (academic medical centers), Amazon Mechanical Turk (mTurk), PA patient advocacy groups (the Primary Aldosteronism Foundation and the Conn syndrome/hyperaldosteronism support group on Facebook), hypertension support groups on Facebook, email invitations from the Queensland Hypertension Association in Australia, and Twitter. Each participant could only complete the survey once. Amazon mTurk is a Web-based platform with >500 000 registered users worldwide, which allows researchers to recruit respondents to complete a task or survey for compensation. Amazon mTurk is broadly used in health research as it allows the recruitment of a diverse population and has comparable reliability to conventional survey recruitment methods.22,23 The distribution/sharing of Facebook and Twitter posts was facilitated by respondents and health care professionals through a snowball sampling effect. With the exception of the Amazon mTurk respondents who received $0.01, all other respondents did not receive incentives for completing the survey.
Eligible respondents were aged ≥18 years, able to read and understand a survey written in English, and able to provide informed consent and had a self-reported diagnosis of PA. The study was approved by the Monash Health Human Research Ethics Committee (QA/75921/MonH-2021-265695[v1]). This study was reported based on the Consensus-Based Checklist for Reporting of Survey Studies.24
Survey Instrument
A survey was developed on the Qualtrics Insight platform (Qualtrics XM; https://www.qualtrics.com), and a link to the online survey was made available to potential respondents through emails or social media. The survey was evaluated for wording and content by a panel of patients from PA patient advocacy and support groups, endocrinologists, general practitioners, and survey specialists. The survey included 6 primary domains: sociodemographic characteristics, hypertension knowledge, perception and attitude toward hypertension screening, diagnostic experience, symptoms related to PA, and treatment experience.
An explanatory statement at the beginning of the anonymous survey advised respondents that survey completion would serve as informed consent. Respondents were allowed to withdraw at any stage before submitting the survey. No response review and revision were possible after survey submission.
Outcomes
The primary outcome was the prevalence of perceived diagnostic delay and associated factors, while secondary outcomes included the factors influencing disease burden and QoL following PA treatment.
Respondents were asked to report the time between hypertension and PA diagnosis using 5 categories: <1, 1 to 3, 3 to 5, 5 to 10, and >10 years. A free-text numerical response was allowed for respondents who answered >10 years. PA diagnosis was considered delayed if the time between the initial diagnosis of hypertension and PA diagnosis was ≥5 years. Disease burden was represented by the number of clinical symptoms and assessed at 2 time points, before and after PA treatment. Respondents were provided with a list of 36 symptoms based on discussion from the PA Foundation and Facebook support group, of which ≥1 could be selected. Self-perceived QoL improvement was assessed by the perception of the well-being of respondents following PA diagnosis and treatment. Respondents were provided with a 5-point Likert scale to respond to the statement: “I have noticed an improvement in my QoL after receiving treatment for primary aldosteronism”.
Statistical Analysis
Data were analyzed using descriptive analysis and regression models using R, version 4.0.2. Continuous outcomes were expressed as mean and SD for normally distributed data or median with 25th and 75th percentiles (interquartile range) for skewed data, while categorical data were summarized as frequencies with percentages. Clinical characteristics were compared between men and women, and across 3 main geographic regions (North America/Europe/Australia and New Zealand) using the t test or 1-way ANOVA for continuous variables or the χ2 test for categorical variables. Missingness was assumed to be random, and no missing data imputation was conducted as there were <5% missing data in all variables.
Logistic regression was used to identify factors associated with the diagnostic delay of PA. Negative binomial regression was performed to identify factors associated with the number of clinical symptoms before PA treatment using the R package pscl. Negative binomial regression was chosen as the variance of number of symptoms (96.23) was greater than the mean (10). A 95% CI was reported for all regression estimates. Ordinal logistic regression was used to examine factors associated with self-perceived QoL improvement following PA treatment using the R package MASS. The QoL Likert scale was combined into a 3-level outcome variable: strongly agree and agree into improved, neither agree nor disagree into unchanged, and strongly disagree and disagree into declined. Missing data refer to expected data that were not provided by respondents, while respondents who selected not applicable were excluded from this analysis. The Brant test was performed to check the proportional odds assumption for all variables in the regression models using the R package brant. α=0.05 was used to determine statistical significance.
RESULTS
Characteristics of Respondents
The survey was completed by 684 eligible respondents. Respondents (Table 1) had a mean age of 43.6 years at survey completion (SD, 13.3; range, 20–84), two-thirds were women (n=455; 66.5%), three-quarters had undergraduate or postgraduate education (n=531; 77.6%), one-fifth were from rural areas (n=146; 21.3%), one-third were current smokers (n=238; 34.8%) and most had access to a national medical insurance scheme (n=588; 86.0%). One-third of respondents received surgical PA treatment (n=246; 36.0%). Women were older than men at survey completion, but there were no gender differences in educational attainment and location of residence. Before PA diagnosis, more men had comorbidities and hypokalemia, while more women required ≥4 antihypertensive medications.
| Characteristic | All respondents (N=684) | By gender | Comparison between gender (P value) | |
|---|---|---|---|---|
| Men (n=225) | Women (n=455) | |||
| Age at survey completion, y; mean, SD | 43.63 (13.30) | 40.92 (13.15) | 44.99 (13.18) | <0.001 |
| Highest education, n (%) | ||||
| Bachelor’s degree and above | 531 (77.6) | 180 (80.0) | 350 (76.9) | 0.417 |
| Region of residences, n (%) | 0.001 | |||
| North America | 472 (69.0) | 167 (74.2) | 303 (66.6) | |
| Europe | 108 (15.8) | 33 (14.7) | 74 (16.3) | |
| Australia and New Zealand | 65 (9.5) | 7 (3.1) | 58 (12.7) | |
| Asia | 25 (3.7) | 11 (4.9) | 13 (2.9) | |
| Africa | 6 (0.9) | 3 (1.3) | 3 (0.7) | |
| Middle East | 4 (0.6) | 1 (0.4) | 3 (0.7) | |
| South America | 4 (0.6) | 3 (1.3) | 1 (0.2) | |
| Rural area, n (%) | 146 (21.3) | 50 (22.4) | 95 (21.1) | 0.772 |
| Smoking status, n (%) | <0.001 | |||
| Never smoker | 311 (45.5) | 69 (30.7) | 241 (53.0) | |
| Ex-smoker | 135 (19.7) | 30 (13.3) | 1004 (22.8) | |
| Current smoker | 238 (34.8) | 126 (56.0) | 110 (24.2) | |
| Survey source, n (%) | <0.001 | |||
| Facebook PA support group | 395 (57.7) | 72 (32.0) | 320 (70.3) | |
| Other survey sources | 289 (42.3) | 153 (68.0) | 135 (29.7) | |
| No. of comorbidities, % | 0.003 | |||
| None | 94 (13.7) | 17 (7.6) | 77 (17.2) | |
| 1–2 | 397 (58.0) | 140 (62.2) | 254 (56.7) | |
| ≥3 | 186 (27.2) | 68 (30.2) | 117 (26.1) | |
| Hypokalemia before diagnosis, n (%) | 568 (83.0) | 199 (91.7) | 366 (85.3) | 0.029 |
| Has access to the national medical insurance scheme, n (%) | 588 (86.0) | 193 (92.2) | 393 (88.7) | 0.100 |
| No. of ED visits before PA diagnosis, n (%) | <0.001 | |||
| Never | 170 (24.9) | 29 (12.9) | 139 (30.5) | |
| Once | 143 (20.9) | 56 (24.9) | 86 (18.9) | |
| 2–3 times | 196 (28.7) | 79 (35.1) | 116 (25.5) | |
| ≥4 times | 175 (25.6) | 61 (27.1) | 114 (25.1) | |
| Admitted to the hospital with high BP before being diagnosed with PA, n (%) | 386 (56.4) | 165 (74.7) | 219 (49.1) | <0.001 |
| No. of symptoms reported before PA diagnosis, n (%) | <0.001 | |||
| None | 107 (15.6) | 33 (14.7) | 73 (16.0) | |
| 1–4 | 197 (28.8) | 107 (47.6) | 87 (19.1) | |
| 5–9 | 90 (13.2) | 35 (15.6) | 55 (12.1) | |
| ≥10 | 290 (42.4) | 50 (22.2) | 240 (52.7) | |
| No. of different antihypertensive medications before PA diagnosis, n (%) | <0.001 | |||
| None | 33 (4.8) | 1 (0.4) | 32 (7.0) | |
| 1–3 | 428 (62.6) | 169 (75.1) | 256 (56.3) | |
| ≥4 | 223 (32.6) | 55 (24.4) | 167 (36.7) | |
| Had surgical PA treatment | 246 (36.0) | 98 (43.6) | 147 (32.3) | 0.005 |
| Perceptions of respondents about their doctors and hypertension, n (%) | ||||
| For a long time, I was told by my doctors that my high BP was just the way it is and to live with it. | 0.031 | |||
| Disagree/strongly disagree | 137 (21.0) | 41 (18.9) | 96 (22.2) | |
| Agree/strongly agree | 409 (62.6) | 129 (59.4) | 278 (64.2) | |
| Neither agree nor disagree | 107 (16.4) | 47 (21.7) | 59 (13.6) | |
| I felt my doctors did not know how to diagnose primary aldosteronism. | 0.030 | |||
| Disagree/strongly disagree | 195 (29.1) | 58 (26.4) | 134 (30.1) | |
| Agree/strongly agree | 362 (54.1) | 113 (51.4) | 248 (55.7) | |
| Neither agree nor disagree | 112 (16.7) | 49 (22.3) | 63 (14.2) | |
| My doctors did not look for a root cause of my high BP. | <0.001 | |||
| Disagree/strongly disagree | 138 (20.5) | 47 (21.3) | 91 (20.3) | |
| Agree/strongly agree | 443 (65.8) | 123 (55.7) | 316 (70.5) | |
| Neither agree nor disagree | 92 (13.7) | 51 (23.1) | 41 (9.2) | |
| High BP is a serious health problem for me. | 0.016 | |||
| Disagree/strongly disagree | 20 (2.9) | 7 (3.1) | 13 (2.9) | |
| Agree/strongly agree | 606 (88.6) | 189 (84.0) | 413 (90.8) | |
| Neither agree nor disagree | 58 (8.5) | 29 (12.9) | 29 (6.4) | |
| If I do not feel unwell, I do not worry about BP. | <0.001 | |||
| Disagree/strongly disagree | 386 (56.5) | 76 (33.9) | 307 (67.5) | |
| Agree/strongly agree | 212 (31.0) | 106 (47.3) | 105 (23.1) | |
| Neither agree nor disagree | 85 (12.4) | 42 (18.8) | 43 (9.5) | |
| Quality of life improvement following PA treatment, n (%) | 0.087 | |||
| Improve | 426 (62.3) | 128 (59.3) | 295 (68.0) | |
| Unchanged | 143 (20.9) | 56 (25.9) | 86 (19.8) | |
| Deteriorate | 85 (12.4) | 32 (14.8) | 53 (12.2) | |
| Time between hypertension diagnosis and PA diagnosis, n (%) | 0.002 | |||
| <1, y | 89 (13.0) | 20 (8.9) | 68 (14.9) | |
| 1–3, y | 216 (31.6) | 90 (40.0) | 125 (27.5) | |
| 3–5, y | 136 (19.9) | 50 (22.2) | 86 (18.9) | |
| 5–10, y | 86 (12.6) | 23 (10.2) | 62 (13.6) | |
| >10, y | 157 (23.0) | 42 (18.7) | 114 (25.1) | |
BP indicates blood pressure; ED, emergency department; and PA, primary aldosteronism.
Respondents originated from a range of recruitment platforms: the hyperaldosteronism/Conn syndrome support group (n=395; 57.7%), Amazon mTurk (n=170; 24.9%), medical specialists (n=53; 7.7%), PA Foundation (n=17; 2.5%), general practitioners (n=16; 2.3%), personal research (n=14; 2.1%), Twitter (n=8; 1.2%), Queensland Hypertension Association (n=3; 0.4), and others/unspecified platforms (n=8; 1.2%).
At survey completion, most respondents were residing in North America (n=472; 69.0%), Europe (n=108; 15.8%), and Australia and New Zealand (n=65; 9.5%), with few from Asia, Middle East, Africa, and South America. North Americans were younger than Europeans, Australians, and New Zealanders, but Australians and New Zealanders were less likely than Europeans or North Americans to have had hypokalemia, emergency department presentations, or hospitalizations with hypertension before PA diagnosis (Table S1).
Diagnostic Delay and Associated Factors
Over one-tenth of respondents (n=89, 13%) were diagnosed with PA within 1 year of hypertension diagnosis. PA diagnosis was delayed by at least 5 years in 35.6% of respondents, while 23.0% of respondents waited for >10 years for PA diagnosis with the longest delay reported as 38 years.
A delay in PA diagnosis was more likely in women than men, never smokers than current smokers, respondents with ≥3 comorbidities than those with none, and respondents on ≥4 antihypertensive medications than those on ≤3 medications (Table 2). Educational attainment, normokalemia, residing in rural areas, or access to national medical insurance schemes did not have significant relationships with diagnostic delay. The odds of diagnostic delay differed by the perception of respondents about their doctors. Diagnostic delay was more likely in respondents who felt that their doctors did not evaluate them for an underlying cause of their hypertension. Respondents who were on more antihypertensive medications before PA diagnosis were more likely to report poor perception and experience with their doctors in the testing process but had good hypertension awareness (Table S2). Women had better knowledge and awareness about hypertension, but they reported receiving insufficient workup for hypertension more often than men. When respondents were divided into the PA Facebook support group and other survey sources, men in the Facebook group were more likely to describe a delayed PA diagnosis (Table S3). However, due to the relatively small number of men in the Facebook support group, this result did not have a significant impact on the pooled sample, which still demonstrated that women were more likely to experience diagnostic delay overall (Table S4).
| Characteristics | Experiencing diagnostic delay | Relationship with respondent characteristics | ||
|---|---|---|---|---|
| n, % | OR | 95% CI | P value | |
| Age at survey completion, y | … | 1.08 | 1.07–1.10 | <0.001 |
| Gender | ||||
| Men | 65 (28.9) | Ref | ||
| Women | 176 (38.7) | 1.55 | 1.10–2.20 | 0.012 |
| Highest education | ||||
| Other | 64 (41.8) | Ref | ||
| Bachelor’s degree and above | 179 (33.7) | 0.71 | 0.49–1.02 | 0.065 |
| Place of residence | ||||
| Rural area | 55 (37.7) | Ref | ||
| City/urban/town/suburban | 186 (35.0) | 0.89 | 0.61–1.31 | 0.555 |
| Region of residence | ||||
| North America | 155 (32.8) | Ref | ||
| Europe | 54 (50.0) | 2.05 | 1.34–3.13 | <0.001 |
| Australia and New Zealand | 26 (40.0) | 1.36 | 0.79–2.31 | 0.254 |
| Other regions | 8 (20.5) | 0.53 | 0.22–1.12 | 0.118 |
| Survey sources | ||||
| Other survey sources | 42 (14.5) | Ref | ||
| Facebook PA support group | 201 (50.9) | 6.09 | 4.19–9.02 | <0.001 |
| Smoking history | ||||
| Never smoker | 140 (45.0) | Ref | ||
| Ex-smoker | 71 (52.6) | 1.36 | 0.90–2.03 | 0.142 |
| Current smoker | 32 (13.4) | 0.19 | 0.12–0.29 | <0.001 |
| Hypokalemia before PA diagnosis (ie, have you ever been told you have low potassium on a blood test?) | ||||
| No | 26 (31.7) | Ref | ||
| Yes | 211 (37.1) | 1.27 | 0.78–2.12 | 0.339 |
| Has access to the national medical insurance scheme | ||||
| No | 24 (36.4) | Ref | ||
| Yes | 212 (36.1) | 0.99 | 0.59–1.70 | 0.960 |
| No. of ED visits prior to diagnosis | ||||
| Never | 82 (48.2)) | Ref | ||
| Once | 41 (28.8) | 0.43 | 0.27–0.69 | <0.001 |
| 2–3 times | 40 (20.4) | 0.28 | 0.17–0.43 | <0.001 |
| >3 times | 80 (45.7) | 0.90 | 0.59–1.38 | 0.639 |
| Admitted to the hospital with high BP before being diagnosed with PA | ||||
| No | 135 (47.4) | Ref | ||
| Yes | 106 (27.5) | 0.42 | 0.30–0.58 | <0.001 |
| No. of comorbidities | ||||
| None | 29 (30.9) | Ref | ||
| 1–2 | 130 (32.7) | 1.09 | 0.68–1.79 | 0.724 |
| ≥3 | 82 (44.1) | 1.77 | 1.05–3.02 | 0.033 |
| No. of symptoms reported before PA diagnosis | ||||
| None | 34 (31.8) | Ref | ||
| 1–4 | 20 (10.2) | 0.24 | 0.13–0.45 | <0.001 |
| 5–9 | 26 (28.9) | 0.87 | 0.47–1.60 | 0.661 |
| ≥10 | 163 (56.2) | 2.73 | 1.74–4.44 | <0.001 |
| No. of different types of antihypertensive medications at the time of PA diagnosis | ||||
| None | 3 (9.1) | Ref | ||
| 1–3 | 96 (22.4) | 2.89 | 1.00–12.24 | 0.085 |
| ≥4 | 144 (64.6) | 18.23 | 6.24–77.72 | <0.001 |
| Had surgical PA treatment | ||||
| No | 184 (42.0) | Ref | ||
| Yes | 59 (24.0) | 0.44 | 0.31–0.62 | <0.001 |
| Perceptions of respondents about their doctors and hypertension, n (%) | ||||
| For a long time, I was told by my doctors that my high BP was just the way it is and to live with it. | ||||
| Disagree/strongly disagree | 37 (27.0) | Ref | ||
| Agree/strongly agree | 178 (43.5) | 2.08 | 1.37–3.22 | <0.001 |
| Neither agree nor disagree | 19 (17.8) | 0.58 | 0.31–1.08 | 0.090 |
| I felt my doctors did not know how to diagnose primary aldosteronism. | ||||
| Disagree/strongly disagree | 54 (27.7) | Ref | ||
| Agree/strongly agree | 152 (42.0) | 1.89 | 1.30–2.77 | <0.001 |
| Neither agree nor disagree | 32 (28.6) | 1.04 | 0.62–1.74 | 0.869 |
| My doctors did not look for a root cause of my high BP. | ||||
| Disagree/strongly disagree | 27 (19.6) | Ref | ||
| Agree/strongly agree | 204 (46.0) | 3.51 | 2.24–5.65 | <0.001 |
| Neither agree nor disagree | 9 (9.8) | 0.45 | 0.19–0.97 | 0.050 |
| High BP is a serious health problem for me. | ||||
| Disagree/strongly disagree | 8 (40.0) | Ref | ||
| Agree/strongly agree | 221 (36.5) | 0.86 | 0.35–2.23 | 0.747 |
| Neither agree nor disagree | 14 (24.1) | 0.48 | 0.16–1.43 | 0.179 |
| If I do not feel unwell, I do not worry about BP. | ||||
| Disagree/strongly disagree | 202 (52.3) | Ref | ||
| Agree/strongly agree | 25 (11.8) | 0.12 | 0.08–0.19 | <0.001 |
| Neither agree nor disagree | 16 (18.8) | 0.21 | 0.11–0.37 | <0.001 |
BP indicates blood pressure; ED, emergency department; OR, odds ratio; PA, primary aldosteronism; and Ref, reference group.
*
That is, the time between hypertension diagnosis and PA diagnosis is ≥5 y—all respondents combined.
Disease Burden
The majority (84.4%) of respondents were symptomatic before PA diagnosis and reported an average of 10 (SD, 9.81) symptoms (Table 1). The 10 most common symptoms reported were body aches (45.9%), anxiety (45.5%), exhaustion (43.0%), headaches (36.1%), palpitations (35.1%), poor concentration (32.7%), muscle cramping (31.1%), blurred vision (30.7%), nocturia (30.7%), and chest tightness (29.8%; Table S5). Following the commencement of PA treatment, the percentage of symptomatic respondents decreased to 47.7%, with the largest decrease observed for those presenting with nocturia, polyuria, muscle cramping, lightheadedness, or hypertensive crises (Figure). Three-quarters (74.4%) of respondents experienced a reduced symptom burden following targeted PA treatment. Decreased symptom burden was associated with being a woman, having normokalemia, having no history of hospital admission for hypertension, and being on targeted medical therapy (Table S6).
Several factors were found to be associated with the number of PA symptoms at baseline (Table 3). Those of an older age, women, or from the Facebook PA Support Group experienced more symptoms related to PA. Respondents who had hypokalemia or were hospitalized with hypertension before PA diagnosis reported fewer symptoms. Educational attainment, geographic location, and hypertension knowledge did not influence symptom burden.
| Characteristics | Relative risk ratios | 95% CI | P value |
|---|---|---|---|
| Age at survey completion, y | 1.03 | 1.03–1.04 | <0.001 |
| Gender | |||
| Men | Ref | ||
| Women | 2.23 | 1.86–2.67 | <0.001 |
| Education | |||
| Other | Ref | ||
| Bachelor’s degree and above | 0.81 | 0.65–1.00 | 0.052 |
| Location | |||
| Rural areas | Ref | ||
| Urban/town/suburbans | 0.85 | 0.69–1.05 | 0.138 |
| Region of residence | |||
| North America | Ref | ||
| Europe | 1.52 | 1.20–1.93 | <0.001 |
| Australia and New Zealand | 1.59 | 1.17–2.16 | 0.003 |
| Other regions | 0.38 | 0.26–0.55 | <0.001 |
| Survey source | |||
| Other survey sources | Ref | ||
| Facebook PA support group | 4.00 | 3.46–4.62 | <0.001 |
| Smoking | |||
| Never smoker | Ref | ||
| Ex-smoker | 1.06 | 0.87–1.28 | 0.574 |
| Current smoker | 0.30 | 0.25–0.35 | <0.001 |
| Comorbidities | |||
| None | Ref | ||
| 1–2 | 0.67 | 0.50–0.89 | 0.006 |
| ≥3 | 0.91 | 0.67–1.24 | 0.558 |
| No. of antihypertensive medications before PA diagnosis | |||
| None | Ref | ||
| 1–3 | 0.57 | 0.39–0.83 | 0.003 |
| ≥4 | 1.21 | 0.82–1.79 | 0.326 |
| No. of ED visits prior to diagnosis | |||
| None | Ref | ||
| Once | 0.66 | 0.50–0.86 | 0.002 |
| 2–3 | 0.64 | 0.50–0.82 | <0.001 |
| ≥4 | 1.01 | 0.79–1.30 | 0.910 |
| No. of doctor visits | |||
| 1–5 | Ref | ||
| ≥6 | 1.69 | 1.38–2.06 | <0.001 |
| Admitted to the hospital with high BP before PA diagnosis | |||
| No | Ref | ||
| Yes | 0.64 | 0.53–0.76 | <0.001 |
| High BP is a serious health problem for me. | |||
| Disagree/strongly disagree | Ref | ||
| Agree/strongly agree | 0.93 | 0.56–1.55 | 0.795 |
| Neither agree nor disagree | 0.56 | 0.31–1.03 | 0.063 |
| Hypokalemia before diagnosis | |||
| No | Ref | ||
| Yes | 0.71 | 0.52–0.96 | 0.025 |
| Quality of life following PA treatment | |||
| Deteriorate | Ref | ||
| Unchanged | 0.88 | 0.61–1.21 | 0.381 |
| Improved | 0.94 | 0.69–1.26 | 0.661 |
BP indicates blood pressure; ED, emergency department; PA, primary aldosteronism; and Ref, reference group.
QoL Improvement
Most respondents (62.3%) self-reported improved QoL following the commencement of PA treatment, while 20.9% and 12.4% of respondents reported unchanged and deteriorated QoL respectively.
Several factors were associated with QoL improvement following PA treatment (Table 4), including being women, receiving surgical treatment, being a member of the Facebook group, and taking fewer antihypertensive medications following PA diagnosis. Improvement in QoL was not significantly associated with the age of respondents, educational attainment, locations and regions of residences, diagnostic delay, comorbidities, or baseline hypokalemia. The number of symptoms at baseline was not associated with QoL improvement following treatment (Table 3). Respondents who had adrenalectomy were more likely to report QoL improvement but were less likely to have reduced symptom burden than those on targeted medical therapy (Table S7).
| Characteristics | Experiencing QoL improvement, n (row%) | Relationship with respondent characteristics | ||||
|---|---|---|---|---|---|---|
| Improved | Unchanged | Deteriorate | OR | 95% CI | P value | |
| Age at survey completion, y† | … | 1.00 | 0.99–1.01 | 0.862 | ||
| Gender† | ||||||
| Men | 128 (59.3) | 56 (25.9) | 32 (14.8) | Ref | ||
| Women | 295 (68.0) | 86 (19.8) | 53 (12.2) | 1.42 | 1.02–1.97 | 0.037 |
| Highest education† | ||||||
| Other | 92 (63.4) | 35 (24.1) | 18 (12.4) | Ref | ||
| Bachelor’s degree and above | 334 (65.6) | 108 (21.2) | 67 (13.2) | 1.07 | 0.73–1.55 | 0.724 |
| Smoking status† | ||||||
| Never smoker | 202 (68.0) | 57 (19.2) | 32 (12.8) | Ref | ||
| Ex-smoker | 86 (67.7) | 25 (19.7) | 16 (12.6) | 0.99 | 0.64 | 0.969 |
| Current smoker | 138 (60.0) | 61 (26.5) | 31 (13.5) | 0.74 | 0.52–1.05 | 0.095 |
| Hypokalemia before diagnosis (ie, have you ever been told you have low potassium on a blood test?)† | ||||||
| No | 43 (57.3) | 18 (24.0) | 14 (18.7) | Ref | ||
| Yes | 360 (66.1) | 117 (21.5) | 68 (12.5) | 1.48 | 0.91–2.37 | 0.104 |
| Place of residence† | ||||||
| Rural area | 91 (65.9) | 31 (22.5) | 16 (11.6) | Ref | ||
| City/urban/town/suburban | 331 (65.0) | 111 (21.8) | 67 (13.2) | 0.94 | 0.64–1.39 | 0.775 |
| Region of residence† | ||||||
| North America | 293 (64.4) | 103 (22.6) | 59 (13.0) | Ref | ||
| Europe | 69 (67.6) | 17 (16.7) | 16 (15.7) | 1.09 | 0.70–1.72 | 0.722 |
| Australia and New Zealand | 41 (69.5) | 12 (20.3) | 6 (10.2) | 1.27 | 0.72–2.31 | 0.424 |
| Other regions | 23 (59.0) | 11 (28.2) | 4 (10.3) | 0.91 | 0.48–1.78 | 0.769 |
| Survey source† | ||||||
| Other survey sources | 163 (58.6) | 74 (26.6) | 41 (14.7) | Ref | ||
| Facebook PA support group | 263 (69.9) | 69 (18.4) | 44 (11.7) | 1.58 | 1.15–2.17 | <0.001 |
| Experienced diagnosis delay† | ||||||
| No | 281 (66.4) | 92 (21.7) | 50 (11.8) | Ref | ||
| Yes | 145 (62.8) | 51 (22.1) | 35 (15.2) | 0.83 | 0.60–1.16 | 0.274 |
| No. of comorbidities† | ||||||
| None | 57 (65.5) | 18 (20.7) | 12 (13.8) | Ref | ||
| 1–2 | 250 (66.1) | 84 (22.2) | 44 (11.6) | 1.06 | 0.65–1.70 | 0.824 |
| ≥3 | 116 (63.4) | 39 (21.3) | 28 (15.3) | 0.90 | 0.53–1.52 | 0.709 |
| Had surgical PA treatment† | ||||||
| No | 240 (58.7) | 97 (23.7) | 72 (17.6) | Ref | ||
| Yes | 186 (75.9) | 46 (18.8) | 13 (5.3) | 2.36 | 1.67–3.35 | <0.001 |
| Perception of respondents about their doctors’ attitude towards BP | ||||||
| For a long time, I was told by my doctors that my high BP was just the way it is and to live with it.† | ||||||
| Disagree/strongly disagree | 73 (57.5) | 21 (16.5) | 33 (26.0) | Ref | ||
| Agree/strongly agree | 305 (77.2) | 59 (14.9) | 31 (7.8) | 2.99 | 1.95–4.56 | <0.001 |
| Neither agree nor disagree | 34 (32.1) | 58 (54.7) | 14 (13.2) | 0.64 | 0.39–1.03 | 0.065 |
| If I do not feel unwell, I do not worry about BP.† | ||||||
| Disagree/strongly disagree | 247 (67.9) | 69 (19.0) | 48 (13.2) | Ref | ||
| Agree/strongly agree | 132 (64.7) | 48 (23.5) | 24 (11.8) | 0.91 | 0.64–1.29 | 0.587 |
| Neither agree nor disagree | 46 (54.1) | 26 (30.6) | 13 (15.3) | 0.61 | 0.39–0.97 | 0.033 |
| Medication-related adverse reactions | ||||||
| I experience more side effects from my medications now.† | ||||||
| Lesser | 148 (67.0) | 51 (23.1) | 22 (10.0) | Ref | ||
| More | 163 (66.0) | 44 (17.8) | 40 (16.2) | 0.88 | 0.60–1.28 | 0.504 |
| Unchanged | 82 (54.7) | 46 (30.7) | 2 (14.7) | 0.62 | 0.41–0.93 | 0.021 |
| Less stressed about BP | ||||||
| I am less stressed about my BP now.† | ||||||
| Less stress | 300 (79.6) | 55 (14.6) | 22 (5.8) | Ref | ||
| More stress | 48 (37.5) | 39 (30.5) | 41 (32.0) | 0.14 | 0.09–0.21 | <0.001 |
| Unchanged | 69 (52.3) | 45 (34.1) | 18 (13.6) | 0.30 | 0.20–0.45 | <0.001 |
| Ongoing potassium tablets requirement | ||||||
| I still take potassium tablets to maintain a normal blood potassium level.† | ||||||
| No | 156 (65.3) | 40 (16.7) | 43 (18.0) | Ref | ||
| Yes | 170 (72.0) | 46 (19.5) | 20 (8.5) | 1.51 | 1.03–2.22 | 0.037 |
| Not applicable | 52 (52.0) | 37 (37.0) | 11 (11.0) | 0.73 | 0.46–1.14 | 0.163 |
| No. of medications following PA diagnosis | ||||||
| I take fewer medications now for the treatment of my BP.† | ||||||
| Less | 265 (78.4) | 53 (15.7) | 20 (5.9) | Ref | ||
| More | 69 (43.9) | 42 (26.8) | 46 (29.3) | 0.19 | 0.13–0.28 | <0.001 |
| Unchanged | 60 (50.8) | 45 (38.1) | 13 (11.0) | 0.32 | 0.21–0.49 | <0.001 |
BP indicates blood pressure; OR, odds ratio; PA, primary aldosteronism; QoL, quality of life; and Ref, reference group.
*
Responses to the question: I have noticed an improvement in my quality of life after receiving treatment for primary aldosteronism—all respondents combined.
†
Proportional odds assumption was proven to hold for this variable by the Brant test.
DISCUSSION
To the best of our knowledge, this study represents the largest international survey of people with PA. We found that at least one-third of respondents had a delayed PA diagnosis by at least 5 years, one-quarter of respondents had a delayed diagnosis by at least 10 years, and three-quarters of respondents experienced a significant symptom burden, irrespective of their geographic location. Symptom resolution and improved QoL were reported by the majority of the participants following PA treatment. Respondents who had adrenalectomy were 2.4× more likely to report QoL improvement than those who received targeted medical therapy. Lived experiences of respondents of PA were not associated with socioeconomic status, including educational attainment and location of residences, but were strongly associated with gender, number of comorbidities, and perceptions of the attitudes of their doctors toward hypertension.
Our respondents reported a significant time delay between their diagnosis of hypertension and the recognition of PA, with over half reporting a delay of at least 3 years, one-third reporting a delay of at least 5 years, and 23% reporting a delay of at least 10 years. As there is no standard definition for diagnostic delay, a 5-year cutoff was selected for our analysis although any delay beyond 1 year may be considered unacceptable. While time is required to escalate antihypertensive medications, which is consistent with our finding that diagnostic delay was most likely in people who took at least 4 antihypertensives, it is also possible that people on multiple agents were less likely to be screened.25 Furthermore, diagnosis may be delayed due to false negative screening test results caused by commonly used antihypertensive medications.26 In our study, these respondents were more likely to report poor perceptions and experiences with their doctors for the diagnostic process of PA despite having better hypertension awareness, highlighting the importance of implementing further strategies to increase the awareness and utilization of PA screening among clinicians. Our finding that people on multiple antihypertensive were 18.2× more likely to have a delayed diagnosis suggests that earlier screening, before patients are initiated on antihypertensive drugs, maybe a feasible strategy to reduce diagnostic delay. Such a strategy led to the diagnosis of PA in 14% of treatment-naive patients with hypertension in an Australian primary care setting7 and has been reported to be cost-effective in China and Australia.27,28
A gender difference was prominent in the likelihood of diagnostic delay with women being 1.6× more likely to report a delay of over 5 years. Women were more likely to report their hypertension being dismissed by their doctors despite having better hypertension knowledge and awareness.29 Suboptimal cardiovascular preventative care for women has previously been documented.30–32 In the context of PA, the lower BP in premenopausal women may contribute to a time lag before hypertension reaches a degree of severity that warrants PA testing based on current guidelines.33 Furthermore, the confounding effects of menstrual cycle and hormonal contraception on plasma renin and aldosterone concentration may also deter primary care physicians from screening premenopausal women for PA.34–37 Additional factors that may have contributed to the gender difference in diagnostic delay include fewer hypertension-related emergency presentations and hospital admissions, less comorbidities, being on more antihypertensives, and higher frequency of symptoms not specifically attributed to PA among women.
Another factor that may have contributed to diagnostic delay is the wide range of patient-reported symptoms that have not been formally established as associated with PA. More than 50% of survey respondents reported experiencing ≥5 symptoms before diagnosis. The top 5 symptoms were body aches, anxiety, exhaustion, headaches, and palpitations, which improved with targeted treatment in the majority of respondents. While the symptoms may seem nonspecific, some may be directly mediated by aldosterone-induced MR (mineralocorticoid receptor) activation. Hypokalemia could cause myalgias and fatigue; elevated BP could cause headaches.38,39 Respondents with a delayed diagnosis were more likely to have a higher number of symptoms that may reflect underlying end-organ injury.16 Palpitations and impaired physical endurance may be related to the increased incidence of arrhythmias or heart failure associated with PA, while nocturia and polyuria could be associated with renal tubular effects of MR activation.40,41 Our finding that symptom burden was associated with diagnostic delay suggests the potential influence of diagnostic distractions on the decision of clinicians to screen patients for PA.42 Importantly, 74.4% of respondents experienced a reduction in their symptom burden following targeted treatment. However, PA-related symptoms persisted in nearly half of respondents despite targeted medical therapy, possibly due to inadequate MR antagonist therapy or high salt intake.43 Respondents who had adrenalectomy were more likely to report QoL improvement but were less likely to have reduced symptom burden than those on targeted medical therapy. It is unclear why surgically treated patients had a higher number of residual symptoms than medically treated patients. It may relate to the severity of their disease, as reflected by more hospital admissions and hypokalemia before diagnosis, which means that symptoms take longer to resolve, or they may have persistent symptoms with reduced intensity, which were not explored in this survey. These findings support the notion that routine screening for PA in all patients with recently diagnosed hypertension, irrespective of symptoms, may be most effective at identifying the disease and improving patient outcomes.44
STRENGTHS AND LIMITATIONS
In addition to the large sample size, a key strength of our study was its focus on the lived experiences of patients with PA. This survey was codesigned by consumer advocates who have lived with PA, as well as clinicians and researchers with a focused interest in PA. Furthermore, we utilized diverse survey dissemination methods and recruited over 600 participants from 6 continents, providing a robust representation of the PA lived experience that supplements a recent qualitative study of 25 respondents.20 There were <5% missing data across all variables.
Our findings can, to some extent, be generalized to other populations and care settings but require consideration of the limitations of online survey research. The calculation of the survey response rate was not possible as the number of respondents who were exposed to email invitations and online posting of our survey was unknown. Eligible respondents were recruited based on self-reported diagnosis of PA. Recall bias may affect the accuracy of reported years of delayed diagnosis and the number of symptoms, especially in respondents who received their diagnosis long before the survey. A categorical variable was used to minimize the effect of recall bias on diagnostic delay but may also underestimate its true burden. To ascertain symptoms related to PA, a 36-item symptom list was developed from discussions with PA consumers. However, the use of a predetermined symptom list carries the risk of a suggestion effect. Furthermore, it is not possible to conclude that these symptoms are unique to people with PA without a comparative study with essential hypertension. Another limitation relates to potential sampling bias. Although various survey dissemination methods were used, most respondents were recruited from a crowdsourcing platform and patient support group. The respondents from the support group were mainly represented by women, and members were more likely to experience diagnostic delay perhaps reflecting dissatisfaction with their diagnostic or treatment processes, distinct from other survey respondents. However, the support group is founded and maintained by patients, and it is the very purpose of our survey to understand their experiences that can then be used to drive change in practice. Diagnostic delay may, in fact, be underestimated as respondents from the support group are likely more well-informed about PA in contrast to the less informed general public, which may be harboring undiagnosed PA. Furthermore, the high prevalence of hypokalemia, hospital admissions, and multiple emergency department presentations suggest that survey participants had more severe diseases. It could equally suggest that people with PA but normokalemia and mild hypertension may be left undiagnosed in the community and, therefore, not able to participate in this survey. Another limitation was the use of simple QoL questions instead of standardized metrics to measure QoL as a way to limit the length of our survey. Moreover, the inclusion of standardized QoL metrics may increase the risk of recall bias as respondents had to recall QoL before and after adrenalectomy or targeted medical therapy. However, taken together with the reduction in symptoms, the reported improvement in QoL in a large proportion of the patients was credible.
PERSPECTIVES
This study provides a comprehensive view of the lived experiences of people with PA. Most respondents experienced delayed diagnosis of PA, with one-third experiencing delayed diagnosis by at least 5 years and one-quarter by at least 10 years. The delay was more prominent among women and those with more comorbidities, more antihypertensive medications, and a greater number of symptoms. QoL improvement and reduced symptom burden were observed in most respondents following targeted PA treatment. These findings suggest that routine screening for PA at the onset of hypertension, irrespective of gender, age, and symptoms, is likely required to address the factors associated with diagnostic delay and facilitate timely targeted treatment for this common disease.
ARTICLE INFORMATION
Author Contributions
R.A. Ananda performed literature search, survey design, and data collection. All co-authors modified and refined the survey. R.A. Ananda and S.M. Gwini conducted statistical analysis. R.A. Ananda wrote the article. All co-authors contributed to data interpretation and revised the article. J. Yang supervised all steps of the study. All authors had access to all the data and had final responsibility for the decision to submit for publication.
Source of Funding
This research was supported by the National Health and Medical Research Council. This is an investigator-led study in which the funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the article; and decision to submit the article for publication.
Acknowledgments
The authors are grateful to the following individuals, all of whom were consumers from primary aldosteronism (PA) advocacy and support groups: PA Foundation (Marianne Leenaerts, Deborah Kelly, Mike McGowan, and Rene Moreno), hyperaldosteronism/Conn syndrome support group on Facebook (John M. Clark and Erin Consuegra), and other PA consumers (Fran Williams and John Malios); all PA consumers had provided assistance with the development of survey instrument and its dissemination to the PA community and review of the results.
Footnote
Nonstandard Abbreviations and Acronyms
- BP
- blood pressure
- mTurk
- Mechanical Turk
- PA
- primary aldosteronism
- QoL
- quality of life
Supplemental Material
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© 2023 American Heart Association, Inc.
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Received: 24 August 2023
Accepted: 14 November 2023
Published online: 14 December 2023
Published in print: February 2024
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- Things We Do for No Reason: Failing to consider primary aldosteronism in the initial evaluation of hypertension, hypertensive urgency, and hypertensive emergency, Journal of Hospital Medicine, (2025).https://doi.org/10.1002/jhm.70035
- High prevalence of primary aldosteronism in a tertiary care hospital in Lebanon, Medicine, 104, 6, (e41384), (2025).https://doi.org/10.1097/MD.0000000000041384
- Analysis of clinical and biochemical characteristics and left ventricular hypertrophy in patients with indeterminate saline infusion test results, Frontiers in Endocrinology, 15, (2024).https://doi.org/10.3389/fendo.2024.1506814
- Challenges in Diagnosing and Managing the Spectrum of Primary Aldosteronism, Journal of the Endocrine Society, 8, 7, (2024).https://doi.org/10.1210/jendso/bvae109
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