Mass Spectrometry PAPA

Morphological and genetic studies suggest that abnormal steroid secretion is a feature of primary aldosteronism. Steroid excess parallels gross changes in adrenal cortex architecture and size. The underlying pathways initiating and maintaining abnormal steroid secretion and adrenal growth are currently studied. Phenotypically, some clinical features of primary aldosteronism are similar to other steroid excess syndromes, such as cortisol excess or Cushing’s syndrome. For example, many patients with primary aldosteronism have metabolic syndrome, osteoporosis, and suffer from depression and anxiety. Indeed, in a recent study, we confirmed glucocorticoid co-secretion as a hallmark of primary aldosteronism quantifying 38 distinct adrenal derived steroids using gas chromatography/mass spectrometry in 24-h urine samples.

Additional studies using liquid chromatography mass spectrometry (LC-MS) we detected steroid fingerprints associated with the mutational status of aldosterone producing adenomas (KCNJ5, ATP1A1/ATP2B3, CACNA1D). A striking finding was significant glucocorticoid and hybrid steroid excess production in the whole group of primary aldosteronism patients. It is the hypothesis of this ERC proposal that analysis of steroidobolomic fingerprints in liquid biopsies will provide a window to the pathophysiology of primary aldosteronism. In addition, it will pave the way to new diagnostic and therapeutic procedures facilitating treatment.