Exp Clin Endocrinol Diabetes 2014; 122 - OP5_20
DOI: 10.1055/s-0034-1371995

Prevalence and clinical correlates of CACNA1D mutations in primary aldosteronism

A Riester 1, A Osswald 1, E Fischer 1, TM Strom 2, F Beuschlein 1, M Reincke 1
  • 1Medizinische Klinik und Poliklinik IV, LMU München, Munich, Germany
  • 2Institute of Human Genetics, Helmholtz Zentrum München, Munich, Germany

Primary aldosteronism is the most common form of secondary arterial hypertension. In aldosterone producing adenomas (APAs) somatic mutations as the cause of autonomous aldosterone secretion have been described in the KCNJ5 and ATPases genes, and more recently in the CACNA1D gene coding for a calcium channel.

As data on the prevalence of this mutation and clinical correlation are still missing we investigated 93 patients with APAs diagnosed according to the German Conn Registry in a single institution. CACNA1D sequencing was performed on DNA extracted from frozen (n = 82) or paraffin embedded (n = 11) APA samples. In addition to previously described mutations in Exon 6, 8, 16, 23 and 32, additionally mutations were identified with whole exome-sequencing in Exon 15 (Leu675Pro) and 28 (Val1171Phe). Overall, 7 somatic mutations in 4 different exons of the CACNA1D gene could be found (8%), whereas in 34% of the APAs a KCNJ5 and in 11% an ATPase mutation was detected.

By comparison of the four groups including KCNJ5- ATPase-, CACNA1D- mutation carriers and patients with none of these mutations only gender (P < 0.01), age (P < 0.01), minimal potassium (P < 0.05) and preoperative microalbuminuria (P < 0.05) were found to be significantly different: CACNA1D mutations carriers were preferable male (71%), had a higher minimal potassium (median 3.1 mmol/l) and had a median age of 59 years at initial diagnosis. In contrast, no differences were detectable in aldosterone, renin, pre-operative blood pressure, adenoma size or postoperative outcome. Also lateralisation index in AVS showed no significant differences.

In summary, this is the first description of prevalence of CACNA1D mutations in a large patient cohort. According to our data distinguishing between different mutations carriers on the basis of clinical data is difficult. Nevertheless, patients with a CACNA1D mutation in APAs are mostly male at higher age and a milder phenotype regarding hypokalaemia.