Ins and Outs of Aldosterone-Producing Adenomas of the Adrenal

Genetic and Molecular Aspects of Hypertension

“…Downloaded from http://ahajournals.org by on April 27, 2019 aldosterone secretion in the absence of angiotensin II or hyperkalemia causes primary aldosteronism, which is present in ≈2% of the general population, 10% of hypertension in referral centers, and possibly 20% to 25% of resistant hypertension. 12,65 Primary aldosteronism most commonly results from bilateral adrenal hyperplasia and other less common causes include unilateral adrenal hyperplasia, APA, and ≈5% of individuals have Mendelian forms of primary aldosteronism. 66,67 Individuals with primary aldosteronism constitutively produce aldosterone from the adrenal gland, resulting in hypertension with variable hypokalemia and a suppressed circulating renin.…”

Recent Findings in the Genetics of Blood Pressure: How to Apply in Practice or Is a Moonshot Required?

“…Mutations in three other genes, encoding the α-subunit of Na + -K + -ATPase itself; the ATP2B3 , a plasma membrane Ca 2+ -ATPase homologous to the sarcoplasmic endoplasmic reticulum Ca 2+ -ATPases (SERCA); and CACNA1D , encoding an L-type Ca 2+ channel CaV1.3, are observed in ~ 7% of the cases [ 13 ]. Whereas APAs in adrenal zona glomerulosa cells harbour gain-of-function mutations in genes important for the regulation of Na + and Ca 2+ -, ATP1A1 and CACNA1D , respectively, KCNJ5 mutations are common in APAs resembling cortisol-secreting cells of the adrenal zona fasciculata [ 14 ••]. Adenomas with KCNJ5 mutations are typical of Conn’s adenoma and tend to be larger than other tumours with fasciculata-like features by histopathology and gene expression analysis, whilst CACNA1D and ATP1A1 mutations appear to be associated with a glomerulosa-like phenotype and are more likely to be diagnosed in older men with resistant hypertension [ 15 , 16 ].…”

“…Adenomas with KCNJ5 mutations are typical of Conn’s adenoma and tend to be larger than other tumours with fasciculata-like features by histopathology and gene expression analysis, whilst CACNA1D and ATP1A1 mutations appear to be associated with a glomerulosa-like phenotype and are more likely to be diagnosed in older men with resistant hypertension [ 15 , 16 ]. The case of APAs brings to focus a paradox in genomics medicine, the availability of a specific and cheap pharmacologic antagonist of aldosterone, spironolactone, and benign nature of APAs, create a hurdle to embarking on the expensive investigations and surgery, which at best offers 30 to 60% likelihood of curing hypertension [ 14 ••].…”