![]() The exclusion of secondary causes of hyperparathyroidism may have been overlooked in some of the retrospective observational studies, thereby leading to conflicting results regarding complications of this disorder. The diagnosis of NHPT is based on persistently high serum PTH levels in the setting of persistently normal serum total and ionized calcium levels, measured at least three times consecutively over a period of 3 to 6 months, after secondary causes of increased serum PTH have been excluded. Diagnosis The Fourth International Workshop on the Management of Asymptomatic Primary Hyperparathyroidism in 2014 further defined the consensus definition of NHPT. This review will focus on the diagnosis and clinical implications of NHPT and summarize recent findings on this topic. ![]() This means that only abnormal PTH levels are required to make the diagnosis, yet serum PTH levels may be affected by many other factors that must be excluded before labeling persistent hyperparathyroidism as NHPT. While PHPT classically requires the presence of increased serum calcium with increased or inappropriately high-normal parathyroid hormone (PTH) values, NHPT requires persistently normal serum calcium and consistently high serum PTH levels. As a result, a consensus is lacking regarding whether the same criteria should be used for referral of patients with NHPT for surgery as are used for patients with mild PHPT, as well as regarding whether surgery improves outcomes compared to observation in patients with NHPT who have classical complications of PHPT, including osteoporosis and kidney stones. These studies have been highly heterogeneous in terms of patient selection. A multitude of manuscripts has been published on the prevalence and possible complications of NHPT since then, but consensus guidelines for management are still lacking because the diagnosis requires fulfillment of strict criteria, which were not followed in many of the retrospective observational studies. Normocalcemic primary hyperparathyroidism (NHPT) was first recognized in the Third International Workshop on Parathyroid Disorders in 2008. This newer variant has generated new questions regarding diagnosis and clinical management. The newly defined normocalcemic variant has become a focus of interest among endocrinologists interested in parathyroid disorders and among surgeons with expertise in parathyroid surgery. These include the moderately symptomatic phenotype that is less common in the modern era, as well as the mildly symptomatic and asymptomatic phenotypes. PHPT is well known to present with different phenotypes. Parathyroid gland autonomy needs to be established by the endocrinologist during the evaluation of patients suspected of having PHPT. These considerations apply to primary hyperparathyroidism (PHPT), given that the term “primary” implies parathyroid gland autonomy. This is because a correct diagnosis of a disease has certain implications, and the same disease might have variable treatment options for a given patient. INTRODUCTION The era of precision medicine requires that all criteria for a given diagnosis be met precisely. Keywords: Hyperparathyroidism Osteoporosis Nephrolithiasis Parathyroid surgery Calcium Parathyroid hormone.This review will focus on clinical aspects and suggest an approach to NHPT. 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. 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. Non-classical complications, especially cardiovascular complications, have been associated with NHPT, indicating that hyperparathyroidism may be a cardiovascular risk factor. Innovative approaches to define NHPT have been proposed that still need to be validated in prospective studies. 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. 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. Guidelines for the management of this condition are still lacking, and making the diagnosis requires fulfillment of strict criteria. 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.
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