Endocrinol Metab.  2021 Jun;36(3):525-535. 10.3803/EnM.2021.1061.

Normocalcemic Primary Hyperparathyroidism: Need for a Standardized Clinical Approach

• Zavatta G
• Clarke BL

• KMID: 2517641
• DOI: http://doi.org/10.3803/EnM.2021.1061

Abstract

Since normocalcemic primary hyperparathyroidism (NHPT) was first defined at the Third International Workshop on the Management of Asymptomatic Primary Hyperparathyroidism in 2008, many papers have been published describing its prevalence and possible complications. Guidelines for the management of this condition are still lacking, and making the diagnosis requires fulfillment of strict criteria. Recent studies have shown that intermittent oscillations of serum calcium just below and slightly above the normal limits are very frequent, therefore challenging the assumption that serum calcium must be consistently normal to make the diagnosis. There is debate if these variations in serum calcium outside the normal range should be included under the rubric of NHPT or, rather, a milder form of classical primary hyperparathyroidism. Innovative approaches to define NHPT have been proposed that still need to be validated in prospective studies. Non-classical complications, especially cardiovascular complications, have been associated with NHPT, indicating that hyperparathyroidism may be a cardiovascular risk factor. New associations between parathyroid hormone (PTH) and several other comorbidities have also been reported from observational studies, suggesting that excessive PTH secretion might cause tissue dysfunction independent of serum calcium. Heterogeneous studies using different definitions of NHPT, however, make it difficult to draw definitive conclusions regarding the role of PTH excess when complications other than osteoporosis or kidney stones are described. This review will focus on clinical aspects and suggest an approach to NHPT.

Keyword

Hyperparathyroidism; Osteoporosis; Nephrolithiasis; Parathyroid surgery; Calcium; Parathyroid hormone

Figure

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  Fig. 1 Ambulatory patients with normocalcemic primary hyperparathyroidism (NHPT) typically present with upper-normal serum calcium levels, which may be occasionally be slightly above the upper limit of the normal range if biochemical measurements are collected serially over time. It is not yet clear whether this biochemical pattern is associated with classical or non-classical complications, or whether parathyroidectomy reduces the risk of bone loss or kidney stones. Prospective studies are needed to clarify these issues. The green bar on the right represents the proposed method [13] to identify patients with NHPT, which requires that albumin-adjusted serum calcium be normal and remain within the least significant change (LSC) over 3 to 6 months. This proposed definition of NHPT contrasts with that of the Fourth International Workshop on the Management of Asymptomatic Primary Hyperparathyroidism, in which serum calcium levels must remain persistently within normal limits. 25(OH), 25-hydroxyvitamin.

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