Primary Aldosteronism Screening and Diagnosis in Primary Health Care

Arterial hypertension is a very common disorder. In most cases the cause is unknown and therefore classified as essential or primary hypertension. Primary aldosteronism (PA), characterized by an inappropriate aldosterone secretion, has traditionally been estimated to account for approximately 1 % of all hypertensive cases. By using the aldosterone to renin ratio (ARR) as a screening tool, the detection of patients with PA has been facilitated. Recent international screening studies have found a high prevalence of the disease accounting for up to 10 % of hypertensive individuals. Thus, PA is recognized to be the most common cause of secondary hypertension. However, the prevalence of PA varies between study populations and the frequency among hypertensive patients in primary health care remains uncertain. When we planned these studies, no studies had previously been done in Swedish primary health care.
Confirmatory tests are necessary in the evaluation of patients with increased ARR.
The fludrocortisone suppression test (FST) is considered to be a reliable method for the
diagnosis of PA since it confirms an autonomous aldosterone production. However, the
investigational procedure varies between centres. The cut off level for aldosterone depends
on the analytical methods applied and there is no consensus on supplementation with NaCl.
Furthermore, the optimal duration of the test is unknown. The test is somewhat cumbersome
for the patients, and has traditionally been performed as an in-patient procedure. It is not
without risks, especially due to the accumulation of extracellular fluid and hypokalemia.
The oral captopril suppression test has less side effects compared to the FST, and could
potentially be useful as a confirmatory test for PA, especially in primary health
care. The evaluation of the test has previously been based on decreasing concentrations of
aldosterone. However, the evaluation of the test with the ARR for the diagnosis of PA has not
been assessed. Moreover, the reliability of the captopril suppression test for the diagnosis of
PA remains uncertain.

The general aim of this thesis is to estimate the prevalence of PA among patients with
hypertension in a Swedish primary care setting, and to evaluate the performance of
confirmatory tests in the diagnosis of PA, using modern methods for the analysis of serum
aldosterone and plasma renin. Reference values for different confirmatory diagnostic tests for
PA were obtained as part of the research project.

In paper I and IV hypertensive patients were screened for PA by the aldosterone to renin ratio (ARR). Patients with a high ARR were referred for confirmatory testing. In paper I, 17 of 200 patients (8.5%) with previously diagnosed and medically treated hypertension were found to have PA. In paper IV, 11 of 200 newly diagnosed and untreated hypertensive patients (5.5%), were diagnosed with PA. Thus, both screening investigations confirmed a high prevalence of the disease.

In paper II, reference values for aldosterone and renin were obtained for the FST in healthy subjects. The cut off value for S-aldosterone was 225 pmol/L after four days with FST or 305 pmol/L if the test was restricted to three days. Furthermore, the investigation showed that FST can be shortened to three days and that a 500 mg NaCl supplementation equivalent to the obligatory daily losses is sufficient for a reliable outcome for the test. The specific time during the day for blood sampling was not of particular importance.

In paper III, reference values for a 25 mg Captopril test for aldosterone, renin and ARR were obtained in healthy subjects. The results were then applied in hypertensive patients screened for PA with a high ARR. The evaluation showed that the captopril test is not reliable as a confirmatory test in the diagnosis of PA. The specificity for the discrimination between PA and patients with primary hypertension was very low, especially for patients with alterations in the renin angiotensin regulatory system. In the clinical setting, the post captopril ARR is only marginally better for the diagnosis of PA, compared to the basal ARR. However, an ARR at 120 min within the normal range strongly argues against PA. On the other hand, a high ARR (> 130 pmol/mIU) after the captopril test not only supports the diagnosis of PA, but also suggests the possibility of an aldosterone secreting adrenal adenoma.

In conclusion, the prevalence of PA among hypertensive patients in a Swedish primary health care area is higher than previously known. Thus, the family practitioner should consider incorporating ARR screening for PA in the evaluation of patients with hypertension, not only among those with traditional signs for PA, but especially in patients who have been newly diagnosed.