Calcium Metabolism and Osteoporosis Program, World Health Organization (WHO) Collaborating Center (CC) for Metabolic Bone Disorders, Division of Endocrinology, American University of Beirut, Beirut, Lebanon.
Department of Clinical, Internal, Anaesthesiologic and Cardiovascular Sciences, 'Sapienza', Rome University, Rome, Italy.
J Bone Miner Res. 2022 Nov;37(11):2330-2350. doi: 10.1002/jbmr.4679. Epub 2022 Oct 17.
This narrative review summarizes data on classical and nonclassical manifestations of primary hyperparathyroidism (PHPT). It is based on a rigorous literature search, inclusive of a Medline search for systematic reviews from 1940 to December 2020, coupled with a targeted search for original publications, covering four databases, from January 2013-December 2020, and relevant articles from authors' libraries. We present the most recent information, identify knowledge gaps, and suggest a research agenda. The shift in the presentation of PHPT from a predominantly symptomatic to an asymptomatic disease, with its varied manifestations, has presented several challenges. Subclinical nephrolithiasis and vertebral fractures are common in patients with asymptomatic disease. The natural history of asymptomatic PHPT with no end organ damage at diagnosis is unclear. Some observational and cross-sectional studies continue to show associations between PHPT and cardiovascular and neuropsychological abnormalities, among the different disease phenotypes. Their causal relationship is uncertain. Limited new data are available on the natural history of skeletal, renal, cardiovascular, neuropsychological, and neuromuscular manifestations and quality of life. Normocalcemic PHPT (NPHPT) is often diagnosed without the fulfillment of rigorous criteria. Randomized clinical trials have not demonstrated a consistent long-term benefit of parathyroidectomy (PTX) versus observation on nonclassical manifestations. We propose further refining the definition of asymptomatic disease, into two phenotypes: one without and one with evidence of target organ involvement, upon the standard evaluation detailed in our recommendations. Each of these phenotypes can present with or without non-classical manifestations. We propose multiple albumin-adjusted serum calcium determinations (albumin-adjusted and ionized) and exclusion of all secondary causes of high parathyroid hormone (PTH) when establishing the diagnosis of NPHPT. Refining the definition of asymptomatic disease into the phenotypes proposed will afford insights into their natural history and response to interventions. This would also pave the way for the development of evidence-based guidance and recommendations. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).
这篇叙述性综述总结了原发性甲状旁腺功能亢进症 (PHPT) 的经典和非经典表现的数据。它基于严格的文献检索，包括从 1940 年到 2020 年 12 月的 Medline 系统评价搜索，以及从 2013 年 1 月至 2020 年 12 月的四个数据库的原始出版物的针对性搜索，以及作者图书馆的相关文章。我们呈现了最新的信息，确定了知识空白，并提出了一个研究议程。PHPT 的表现从以症状为主转变为无症状疾病，其表现多种多样，这带来了一些挑战。亚临床肾结石和椎骨骨折在无症状疾病患者中很常见。在诊断时没有终末器官损害的无症状 PHPT 的自然史尚不清楚。一些观察性和横断面研究继续显示 PHPT 与心血管和神经心理异常之间的关联，以及不同疾病表型之间的关联。它们的因果关系尚不确定。关于骨骼、肾脏、心血管、神经心理和神经肌肉表现以及生活质量的自然史的新数据有限。正常血钙甲状旁腺功能亢进症 (NPHPT) 通常在没有满足严格标准的情况下被诊断出来。随机临床试验并未证明甲状旁腺切除术 (PTX) 与观察对非经典表现的长期益处。我们建议进一步细化无症状疾病的定义，将其分为两种表型：一种没有，一种有靶器官受累的证据，在我们建议中详细的标准评估基础上。这些表型中的每一种都可以有或没有非经典表现。我们建议进行多次白蛋白校正血清钙测定（白蛋白校正和离子化），并排除所有继发性甲状旁腺激素 (PTH) 升高的原因，以建立 NPHPT 的诊断。将无症状疾病的定义细化为所提出的表型将深入了解其自然史和对干预的反应。这也将为制定基于证据的指导和建议铺平道路。
