Uncovering the origins of primary aldosteronism using single cell technology (Dr Kate Laycock)

Aldosterone-producing adrenal adenomas (APAs) are the most common surgically curable cause of hypertension, but individual prediction of postoperative outcome is challenging. Emerging data suggest that outcomes are influenced by APA genotype.

In our prospective MATCH study, 16/20 (80%) patients with GNA11/Q+CTNNB1 and KCNJ5 mutant APAs were completely cured compared to 3/19 (16%) with CACNA1D mutations. The histopathology of these APAs also differs.

GNA11/Q+CTNNB1 and KCNJ5-mutant APAs have surrounding zona glomerulosa hyperplasia, but other APAs characteristically have adjacent aldosterone-producing micronodules. Human adrenal cells, from which APAs arise, have a high mutation rate.

We hypothesise that single nuclei analysis of the adjacent adrenal cortex may help to identify different precursor cells in APAs with each somatic mutation.

This may explain why CACNA1D mutations can be multiple whilst KCNJ5 mutations are solitary, and hence offer a scientific basis for expecting outcomes to differ among somatic genotypes.