The genetic background of primary aldosteronism

One of the most frequent causes of secondary hypertension is primary aldosteronism. The disease is caused by the autonomous aldosterone production of the adrenal cortex leading to elevated aldosterone levels causing hyperten-sion and often hypokalemia, and if untreated, could lead to a plethora of pathophysiological issues. The diagnosis and treatment of primary aldosteronism is of paramount significance, since depending on its subtype, surgical or pharma-ceutical intervention can lead to the full recovery of the patient. However, due to the difficulties in diagnosis, the illness often remains underdiagnosed. The two most common causes of primary aldosteronism are unilateral aldos-terone producing adenoma and bilateral adrenal hyperplasia. The majority of cases are sporadic, but hereditary forms are also known, namely, familiar hyperaldosteronism types I-IV and primary aldosteronism with seizures and neuro-logical abnormalities syndrome. Familiar hyperaldosteronism type I is caused by the unequal crossing-over of two genes coding for the enzymes catalyzing the last steps in cortisol and aldosterone biosynthesis, while the other types of hereditary aldosteronisms are caused by mutations in genes coding ion channels. In a significant portion of spo-radic aldosterone producing adenomas, somatic mutations can be diagnosed in genes that are also affected by germ -line mutations in the hereditary forms of primary aldosteronism. The overlap in genes involved in the hereditary and sporadic forms of the disease underlines the common pathomechanisms in these two disease entities. In our review, we present the genetic background of primary aldosteronism, the genes involved in both hereditary and sporadic forms and their mutations, with an outlook on their scientific, therapeutic and diagnostic significance.

Automated summary

One of the most common causes of secondary hypertension is primary aldosteronism, which is caused by autonomous aldosterone production of the adrenal cortex. The disease leads to elevated aldosterone levels, hypertension, and hypokalemia, and if untreated, can result in various pathophysiological complications. The diagnosis and treatment of primary aldosteronism are crucial, as intervention can lead to patient recovery, but the illness often remains underdiagnosed due to diagnostic difficulties.