Double CYP11B1/CYP11B2 Immunohistochemistry and Detection of KCNJ5 Mutations in Primary Aldosteronism.

Context: The search for somatic mutations in adrenals resected from patients with primary aldosteronism (PA) is performed by Sanger sequencing, often implemented with immunohistochemistry (IHC)-guidance focused on aldosterone-producing (CYP11B2-positive) areas.

Objective: To investigate the impact of double IHC for CYP11B1 and CYP11B2 on Sanger and next-generation sequencing (NGS).

Methods: We investigated 127 consecutive adrenal aldosterone-producing adenomas from consenting surgically cured PA patients using double IHC for CYP11B1 and CYP11B2, by Sanger sequencing and NGS.

Endothelin-1 Drives Epithelial-Mesenchymal Transition in Hypertensive Nephroangiosclerosis.

Background: Tubulointerstitial fibrosis, the final outcome of most kidney diseases, involves activation of epithelial mesenchymal transition (EMT). Endothelin-1 (ET-1) activates EMT in cancer cells, but it is not known whether it drives EMT in the kidney. We therefore tested the hypothesis that tubulointerstitial fibrosis involves EMT driven by ET-1.

Normoaldosteronemic aldosterone-producing adenoma: immunochemical characterization and diagnostic implications.

Background: A high aldosterone-renin ratio (ARR) is commonly used to identify primary aldosteronism, but the ARR is high when renin is low, even if plasma aldosterone concentration values are normal, suggesting the existence of 'normoaldosteronemic' primary aldosteronism. However, most such cases did not undergo adrenalectomy; moreover, because of the lack of antibody for the human CYP11B2 (aldosterone synthase), conclusive demonstration of a normoaldosteronemic aldosterone-producing adenoma was not possible thus far.

Method: In 2003, a lady presented with severe hypertension a right adrenal nodule, low renin, high ARR, but normal plasma aldosterone concentration.

GPER-1 and estrogen receptor-β ligands modulate aldosterone synthesis.

Fertile women have lower blood pressure and cardiovascular risk than age-matched men, which suggests that estrogens exert cardiovascular protective effects. However, whether 17 β-estradiol (E2) blunts aldosterone secretion, and thereby affects the gender dimorphism of blood pressure, is unknown. We therefore sought for the estrogen receptor (ER) subtypes in human adrenocortical tissues ex vivo by performing gene and protein expression studies.

A novel KCNJ5-insT149 somatic mutation close to, but outside, the selectivity filter causes resistant hypertension by loss of selectivity for potassium.

Context: Understanding the function of the KCNJ5 potassium channel through characterization of naturally occurring novel mutations is key for dissecting the mechanism(s) of autonomous aldosterone secretion in primary aldosteronism.

Objective: We sought for such novel KCNJ5 channel mutations in a large database of patients with aldosterone-producing adenomas (APAs).

Methods: We discovered a novel somatic c.