Center for Adrenal Disorders, Boston, MA 02115, United States.
Division of Endocrinology, Diabetes, and Hypertension, Boston, MA 02115, United States.
Eur J Endocrinol. 2024 Aug 5;191(2):241-250. doi: 10.1093/ejendo/lvae099.
Extracellular calcium critically regulates physiologic aldosterone production. Moreover, abnormal calcium flux and signaling are involved in the pathogenesis of the majority of primary aldosteronism cases.
We investigated the influence of the saline suppression test (SST) on calcium homeostasis in prospectively recruited participants (n = 86).
During SST, 100% of participants had decreases in serum calcium, with 48% developing frank hypocalcemia. Serum calcium declined from 2.30 ± 0.08 mmol/L to 2.13 ± 0.08 mmol/L (P < .001) with parallel increases in parathyroid hormone from 6.06 ± 2.39 pmol/L to 8.13 ± 2.42 pmol/L (P < .001). In contrast, serum potassium and bicarbonate did not change, whereas eGFR increased and serum glucose decreased (P < .001). Lower body surface area (translating to greater effective circulating volume expansion during SST) was associated with greater reductions in (β = .33, P = .001), and absolutely lower, serum calcium levels (β = .25, P = .001). When evaluating clinically-relevant diagnostic thresholds, participants with post-SST aldosterone levels <138 pmol/L had lower post-SST calcium and 25-hydroxyvitamin D levels (P < .05), and higher post-SST parathyroid hormone levels (P < .05) compared with those with post-SST aldosterone levels >277 pmol/L.
SST uniformly decreases serum calcium, which is likely to be due to the combination of variable dilution, increased renal clearance, and vitamin D status. These acute reductions in bioavailable calcium are associated with lower post-SST aldosterone. Given the critical role of extracellular calcium in regulating aldosterone production, these findings warrant renewed inquiry into the validity of SST interpretations for excluding primary aldosteronism.
细胞外钙对生理醛固酮的产生具有关键调节作用。此外，异常的钙流和信号转导参与了大多数原发性醛固酮增多症病例的发病机制。
我们前瞻性地招募了参与者（n=86），研究了盐水抑制试验（SST）对钙稳态的影响。
在 SST 期间，100%的参与者血清钙下降，其中 48%出现明显低钙血症。血清钙从 2.30±0.08mmol/L 降至 2.13±0.08mmol/L（P<0.001），同时甲状旁腺激素从 6.06±2.39pmol/L 增至 8.13±2.42pmol/L（P<0.001）。相比之下，血清钾和碳酸氢盐没有变化，而 eGFR 增加，血糖降低（P<0.001）。较低的体表面积（在 SST 期间转化为更大的有效循环容量扩张）与血清钙水平的更大降低相关（β=0.33，P=0.001），并且血清钙水平绝对较低（β=0.25，P=0.001）。当评估临床相关的诊断阈值时，SST 后醛固酮水平<138pmol/L 的患者 SST 后钙和 25-羟维生素 D 水平较低（P<0.05），SST 后甲状旁腺激素水平较高（P<0.05），而 SST 后醛固酮水平>277pmol/L 的患者则较低。
SST 一致降低血清钙，这可能是由于稀释、肾清除率增加和维生素 D 状态的变化。这些生物利用钙的急性减少与 SST 后醛固酮降低有关。鉴于细胞外钙在调节醛固酮产生中的关键作用，这些发现值得重新探讨 SST 解释排除原发性醛固酮增多症的有效性。
