Endocrine Abstracts

Adrenal vein sampling (AVS) is a technically demanding procedure required for identification of suitable candidates for unilateral adrenalectomy in primary aldosteronism. Recently, somatic mutations in aldosterone producing adenomas (APA) have become a focus of research. We identified KCNJ5 K⁺-channel mutations in 34% of APAs, and more recently mutations in 2 ATPase family members in 11 and 6%. However, it is unclear whether steroid gradients during the AVS are influenced by the mutation status of the APA. This might have impact on final diagnosis and treatment.

To analyse the influence of somatic mutations on gradients in AVS, 39 patients with APAs diagnosed according to the German Conn Registry standard were studied. All subjects underwent technically successful AVS (with a selectivity index >2) and had a mutation analysis in tumor tissue. The mutation status of the APAs was: 11 KCNJ5 mutations (6 G151R, 5 L168R), 8 ATPase mutations (5 ATP1A1, 3 ATP2B3) and 20 with none of these mutations.

Patients with ATPase mutations showed higher blood pressure and lower potassium levels than those with KCNJ5 mutation or no mutation. Lateralization indexes of ATPase mutation carriers were 55.8±23.4 compared to 27.8±11.6 in KCNJ5 mutation carriers and 27.7±9.1 in KCNJ5/ATPase negative patients (P=ns). Contralateral suppression (ratio of plasma aldosterone to cortisol of the contralateral side and aldosterone to cortisol in the periphery) was most distinct in ATPase mutated patients with marginal significance (ATPase 0.2±0.1, KCNJ5 0.6±0.2, KCNJ5/ATPase non-mutated 0.8±0.2, P=0.065).

In summary, ATPase mutations seem to be associated with a higher lateralization of aldosterone production. In contrast to prior findings we did not confirm higher lateralization indexes in KCNJ5 mutated patients. However, further studies with a higher number of patients being included are required.