Studies of diagnosis and differential diagnosis in primary aldosteronism

Abstract

This thesis comprises three studies with the general aim to improve our knowledge on the prevalence and diagnostics in primary aldosteronism (PA). PA is a hypertensive disorder with an estimated prevalence of 5-18 % in the hypertensive population. In PA there is an autonomous hypersecretion of the hormone aldosterone from one or both adrenals, which causes hypertension. Renin, which normally regulates aldosterone, is suppressed by feed-back mechanisms. It is important to detect and treat PA since aldosterone excess causes cardiovascular complications per se.

By using the aldosterone to renin ratio (ARR) as a screening tool, it has become easier to detect PA. The prevalence rates vary between study populations and the frequency among hypertensive patients in primary care remains uncertain. In Study I we screened 178 patients with hypertension in primary care for PA by using the ARR, with their ongoing antihypertensive medication. The prevalence found was 1.1-3.8 %. This may represent the true estimate. However, we found that several antihypertensive agents had a suppressive effect on the ARR which could lead to false negative ratios. On the basis of the low prevalence of PA found in our study, we cannot support general screening in the antihypertensive population.

A correct subtype classification of PA is essential as unilateral forms may be treated by surgery while bilateral forms are treated pharmacologically. Adrenocortical scintigraphy with SPECT with the radiopharmaceutical tracer NP-59 may be used to detect lateralized aldosterone secretion. The role for scintigraphy with SPECT has not been sufficiently evaluated, though. In study II 47 patients with PA were examined with NP-59 scintigraphy with SPECT. The side of aldosterone hypersecretion was correctly localized in 76%. The positive predictive value for scintigraphic lateralization was 93 % and the sensitivity 83 %. With the limited sensitivity for scintigraphy with SPECT in this study, this imaging technique cannot be recommended as a first line diagnostic procedure. As the accuracy for a lateralized uptake was high, scintigraphy may be used if the gold standard procedure, adrenal venous sampling, is inconclusive or not possible to perform.

Subtype classification, even the histopathologic examination, can be uncertain. Unilateral adenoma and bilateral hyperplasia are the most common subtypes. With in situ hybridization, expression of the gene CYP 11B2 encoding for enzymes involved in aldosterone synthesis can be visualized in adrenal tissue and indicates aldosterone secretion. In study III histopathological data and results from long-term follow-up in 27 patients with PA were compared to the expression of CYP 11B2 in adrenal tissue. In cases not cured of PA with uncertain histopathologic diagnosis, aldosterone secretion was detected in small nodules indicating hyperplasia. In some cases with ambiguous histopathologic findings, aldosterone secretion was seen only in a dominant nodule indicating the presence of an aldosterone producing adenoma. The localization of aldosterone secretion in adrenal tissue by using in situ hybridization may play an additional role in the postoperative follow-up.