Endocrine Surgery Unit, Department of Surgery, Oncology, and Gastroenterology (F.T., M.I.).
ARHYVAB PhD program in Arterial Hypertension and Vascular Biology, Department of Medicine (F.T., F.B.R., I.C., B.C., E.K., T.M.S., M.I., G.-P.R.).
Hypertension. 2024 Dec;81(12):2468-2478. doi: 10.1161/HYPERTENSIONAHA.124.23700. Epub 2024 Oct 2.
Primary aldosteronism (PA), the most common curable salt-dependent form of arterial hypertension, features renal K loss and enhanced Na reabsorption. We investigated whether the electrolyte, water, and TonEBP (tonicity-responsive enhancer binding protein)/ (nuclear factor of activated T cells 5) content is altered in the skin of patients with PA and corrected by surgical cure.
We obtained skin biopsies from 80 subjects: 49 consecutive patients with PA, optimally treated with a mineralocorticoid receptor antagonist; 6 essential hypertensives; and 25 normotensive controls. We measured Na, K, water content with atomic absorption spectroscopy after ashing, and mRNA with digital droplet polymerase chain reaction. The patients with PA were retested after adrenalectomy.
We discovered a higher dry weight of the skin biopsy specimen at surgery than at follow-up (<0.001) and a direct correlation with electrolyte and water content (all <0.01), indicating the need for dry weight adjustment of electrolyte and water data. Surgical cure of PA markedly increased skin dry weight-adjusted K (from 1.14±0.1 to 2.81±0.27 µg/mg; <0.001) and water content (from 2.92±1.4 to 3.85±0.23 mg/mg; <0.001), but left dry weight-adjusted skin Na content unaffected. In patients with PA at baseline, mRNA was higher (=0.031) than in normotensive controls and decreased after surgery (=0.035).
Despite mineralocorticoid receptor antagonist treatment ensuring normokalemia, the patients with PA had a skin cell K depletion that was corrected by adrenalectomy. The activated /TonEBP pathway during mineralocorticoid receptor antagonist administration suggests enhanced skin Na lymphatic drainage and can explain the lack of overt skin Na accumulation in patients with PA. Its deactivation after surgical cure can account for the lack of skin Na decrease postadrenalectomy.
URL: https://www.clinicaltrials.gov; Unique identifier: NCT06090617.
原发性醛固酮增多症（PA）是最常见的可治愈的盐依赖性动脉高血压形式，其特征为肾脏钾丢失和钠重吸收增强。我们研究了 PA 患者的皮肤是否存在电解质、水和 TonEBP（渗透压反应增强结合蛋白）/（激活 T 细胞核因子 5）含量的改变，以及这些改变是否可以通过手术治愈得到纠正。
我们从 80 名受试者中获得了皮肤活检样本：49 名连续的 PA 患者，经过最优的盐皮质激素受体拮抗剂治疗；6 名原发性高血压患者；和 25 名血压正常的对照组。我们通过原子吸收光谱法在灰化后测量了钠、钾和水的含量，并通过数字液滴聚合酶链反应测量了 mRNA 的含量。PA 患者在肾上腺切除术后进行了复测。
我们发现手术时皮肤活检标本的干重高于随访时（<0.001），并且与电解质和水含量呈直接相关（均<0.01），这表明需要对电解质和水数据进行干重调整。PA 的手术治愈显著增加了皮肤干重校正后的钾（从 1.14±0.1 增加到 2.81±0.27 µg/mg；<0.001）和水含量（从 2.92±1.4 增加到 3.85±0.23 mg/mg；<0.001），但对皮肤干重校正后的钠含量没有影响。在基线时的 PA 患者中， mRNA 高于正常血压对照组（=0.031），并在手术后降低（=0.035）。
尽管盐皮质激素受体拮抗剂治疗确保了正常血钾，但 PA 患者仍存在皮肤细胞钾耗竭，这种耗竭在肾上腺切除术后得到纠正。在盐皮质激素受体拮抗剂治疗期间，激活的 /TonEBP 通路表明增强了皮肤钠的淋巴引流，这可以解释 PA 患者中没有明显的皮肤钠积累。手术后该通路的失活可以解释肾上腺切除术后皮肤钠减少。
