Anti-Aldosterone Monoclonal antibody, clone BMEP

Introduction Hyperparathyroidism (HPT) is associated with mortality and cardiovascular disease (CVD) in dialysis patients. However, its mechanism is still unclear. It is suspected that parathyroid hormone (PTH) is associated with the renin-angiotensin-aldosterone system (RAAS) as a possible mechanism. Thus, we examined their hormonal interaction in hemodialysis patients with secondary HPT. Materials and methods Seventeen hemodialysis patients with HPT were included. All patients underwent total parathyroidectomy (PTx). Serum intact PTH (iPTH), calcium and phosphate levels, plasma renin activity (PRA), and plasma aldosterone levels (ALD) were measured pre- and post-PTx. Results Pre-serum iPTH tended to be correlated with pre-PRA and were significantly correlated with pre-ALD (pre-PRA:r = 0.44,p = 0.07, pre-ALD:r = 0.49,p < 0.05). With the reduction in serum iPTH after PTx, PRA and ALD significantly decreased after PTx. Additionally, the change in serum iPTH tended to be correlated with the changes in PRA and ALD (PRA;r = 0.46,p = 0.05, ALD;r = 0.45,p = 0.06). Conclusion Our results suggest that PTH could be interrelated with RAAS in hemodialysis patients with secondary HPT.

This review reports the main molecular alterations leading to development of benign cortisol- and/or aldosterone-secreting adrenal tumors. Causes of adrenal Cushing syndrome can be divided in 2 groups: multiple bilateral tumors or adenomas secreting cortisol. Bilateral causes are mainly primary pigmented nodular adrenocortical disease, most of the time due to PRKAR1A germline-inactivating mutations, and primary bilateral macronodular adrenal hyperplasia that can be caused in some rare syndromic cases by germline-inactivating mutations of MEN1, APC, and FH and of ARMC5 in isolated forms. PRKACA somatic-activating mutations are the main alterations in unilateral cortisol-producing adenomas. In primary hyperaldosteronism (PA), familial forms were identified in 1% to 5% of cases: familial hyperaldosteronism type I (FH-I) due to a chimeric CYP11B1/CYP11B2 hybrid gene, FII-II due to CLCN-2 germline mutations, FII-III due to KCNJ5 germline mutations, FII-IV due to CACNA1H germline mutations and PA, and seizures and neurological abnormalities syndrome due to CACNAID germline mutations. Several somatic mutations have been found in aldosterone-producing adenomas in KCNJ5, ATP1A1, ATP2B3, CACNA1D, and CTNNB1 genes. In addition to these genetic alterations, genome-wide approaches identified several new alterations in transcriptome, methylome, and miRnome studies, highlighting new pathways involved in steroid dysregulation. (C) Endocrine Society 2020.