Garibaldi Luigi R, Sastry Shruti, McPhaul Michael J, March Christine A
Division of Pediatric Endocrinology, UPMC Children's Hospital of Pittsburgh, Pittsburgh, PA, USA.
Department of Pediatrics, 6614 University of Pittsburgh , Pittsburgh, PA, USA.
J Pediatr Endocrinol Metab. 2025 May 23. doi: 10.1515/jpem-2025-0046.
Hypotonic polyuria, also known as the polyuria-polydipsia syndrome (PPS), caused by primary polydipsia (PP), arginine vasopressin deficiency (AVP-D or central diabetes insipidus), or uncommonly by AVP resistance (AVP-R), is diagnostically challenging due to overlapping symptoms and the need to conclusively diagnose or exclude AVP-D caused by serious organic lesions of the central nervous system. Diagnostic tests that stimulate AVP secretion by increasing plasma osmolality include the water deprivation test (WDT) and the hypertonic saline test (HST). The WDT, considered the gold standard for evaluating PPS in children, has suboptimal diagnostic accuracy, is burdensome, and requires hospitalization. The HST has been used rarely in children due to safety concerns and need for intensive monitoring. The finding that some anterior pituitary stimulating agents also stimulate the posterior pituitary, and the availability of a robust serum/plasma assay for copeptin as a reliable surrogate of AVP, has allowed development of nonosmotic, copeptin/AVP stimulation tests. In the present review, we focus on these new copeptin stimulation tests, which include single stimuli with intravenous (IV) arginine, IV insulin, intramuscular glucagon, oral levodopa, and double stimuli (IV arginine-insulin or AITT; IV arginine and oral Levodopa/carbidopa or ALD-ST), which we have previously shown to induce very robust copeptin secretion. Specifically, the ALD-ST differentiated AVP-D from PP in 20 children with high diagnostic accuracy at a cutoff stimulated copeptin of 9.3 pmol/L. We propose the utilization of the outpatient ALD-ST in the early stages of PPS evaluation in children, given its safety, cost-effectiveness, and limited side effects.
低渗性多尿症，也称为多尿-多饮综合征（PPS），由原发性烦渴（PP）、精氨酸血管加压素缺乏（AVP-D或中枢性尿崩症）或罕见的AVP抵抗（AVP-R）引起，由于症状重叠以及需要明确诊断或排除由中枢神经系统严重器质性病变导致的AVP-D，其诊断具有挑战性。通过增加血浆渗透压来刺激AVP分泌的诊断测试包括禁水试验（WDT）和高渗盐水试验（HST）。WDT被认为是评估儿童PPS的金标准，但其诊断准确性欠佳、操作繁琐且需要住院治疗。由于安全问题和需要密切监测，HST在儿童中很少使用。一些垂体前叶刺激剂也能刺激垂体后叶，以及可获得用于可靠替代AVP的copeptin的强大血清/血浆检测方法，使得非渗透性copeptin/AVP刺激试验得以发展。在本综述中，我们重点关注这些新的copeptin刺激试验，包括静脉注射（IV）精氨酸、IV胰岛素、肌肉注射胰高血糖素、口服左旋多巴的单一刺激，以及双重刺激（IV精氨酸-胰岛素或AITT；IV精氨酸与口服左旋多巴/卡比多巴或ALD-ST），我们之前已证明这些刺激能诱导非常强烈的copeptin分泌。具体而言，在20名儿童中，ALD-ST以刺激后copeptin 9.3 pmol/L的截断值，以高诊断准确性区分了AVP-D和PP。鉴于其安全性、成本效益和有限的副作用，我们建议在儿童PPS评估的早期阶段使用门诊ALD-ST。
