Primary Hyperparathyroidism: Mechanisms and Treatment

A special issue of Metabolites (ISSN 2218-1989). This special issue belongs to the section "Endocrinology and Clinical Metabolic Research".

Deadline for manuscript submissions: 31 December 2025 | Viewed by 1123

Special Issue Editors


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Guest Editor
Division of Endocrinology, Diabetology and Metabolic Diseases, Department of Medicine, A. O. Santa Croce e Carle—S.Croce Hospital, Via Coppino, Cuneo, Italy
Interests: bone; parathyroid; primary hyperparathyroidsm; calcium; phosporus

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Guest Editor
Department of Pathology, University of Pisa, 56124 Pisa, Italy
Interests: hypoparathyroidism; hyperparathyroidism; parathyroid tumors; thyroid hormone analogs and metabolites; vitamin D metabolism; serum vitamin D levels and heart failure; endocrinology
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Special Issue Information

Dear Colleagues,

Primary hyperparathyroidism (PHPT) is one of the most common endocrine disorders, characterized by hypercalcemia and elevated or unsuppressed levels of parathyroid hormone (PTH) due to dysfunction in one or more parathyroid glands. Historically, PHPT has often been associated with severe skeletal and renal complications, but milder forms of the disease, including asymptomatic and normocalcemic PHPT, have become more prevalent in recent years.

In patients with classic symptomatic PHPT, diagnosis is straightforward, and the primary treatment is surgical parathyroidectomy, which restores calcium and PTH levels and often improves bone mineral density (BMD) while reducing the risk of nephrolithiasis. However, in milder forms of the disease, such as normocalcemic PHPT, diagnosis is more challenging and treatment decisions are more complex. Recent studies suggest a trend toward earlier intervention, even in cases with less severe biochemical abnormalities, given the long-term metabolic consequences of untreated disease.

Parathyroidectomy has been shown to lead to significant metabolic improvements, including increased BMD and a reduction in kidney stone formation. While medical therapies can also improve BMD or lower serum calcium, no single agent has been found to address both issues simultaneously.

The metabolic impact of PHPT extends beyond calcium and phosphate homeostasis, affecting bone remodeling, renal function, and potentially other metabolic pathways. Understanding the biochemical markers associated with disease progression and treatment response is critical in optimizing management. Furthermore, the localization of hyperfunctioning parathyroid tissue, particularly in cases of multiglandular disease or ectopic adenomas, presents additional challenges that can complicate both diagnosis and treatment.

This Special Issue will explore the metabolic mechanisms underlying PHPT, from calcium and bone metabolism to the clinical effects of surgical and medical interventions. By examining the metabolic pathways involved in PHPT and the metabolic outcomes of treatment strategies, we aim to provide insights into more personalized and effective management of this common endocrine disorder.

Dr. Elena Castellano
Dr. Federica Saponaro
Guest Editors

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Keywords

  • primary pyperparathyroidism
  • mechanism
  • metabolism

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Published Papers (1 paper)

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Review

17 pages, 2581 KB  
Review
Uric Acid in Primary Hyperparathyroidism: Marker, Consequence, or Bystander?
by Matteo Malagrinò and Guido Zavatta
Metabolites 2025, 15(7), 444; https://doi.org/10.3390/metabo15070444 - 2 Jul 2025
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Abstract
Background: Several recent studies have documented an increased cardiovascular risk in patients with primary hyperparathyroidism (PHPT), thereby stimulating interest in the association with uric acid (UA), a metabolite linked to cardiovascular disease and chronic kidney disease (CKD) progression, whose role in these conditions [...] Read more.
Background: Several recent studies have documented an increased cardiovascular risk in patients with primary hyperparathyroidism (PHPT), thereby stimulating interest in the association with uric acid (UA), a metabolite linked to cardiovascular disease and chronic kidney disease (CKD) progression, whose role in these conditions is still the subject of study. The aim of this review is to summarize the underlying pathophysiological mechanisms of the PHPT-UA relation and discuss their potential clinical implications. Methods: We conducted a comprehensive literature review, with a focus on the physiological and clinical aspects of the relationship between PHPT and UA. Results: The evidence in the literature supports the association between PHPT and elevated UA levels, although the underlying mechanisms still need to be elucidated. Key mechanisms seem to involve tubular and intestinal transporters, particularly the ABCG2 transporter, as well as indirect effects mediated by hypercalcemia and inflammatory processes. Conclusions: The association between PHPT and UA, though recognized for years, highlights the existence of linked pathophysiological mechanisms between mineral and purine metabolism. However, the current knowledge does not clarify whether uric acid plays an active role in the development of complications related to hyperparathyroidism or if it just represents an indirect marker of metabolic dysfunction. In the absence of specific guidelines, measuring UA levels to screen for hyperuricemia, especially in patients with additional risk factors, should be considered to prevent related complications. Future studies could clarify the role of UA in PHPT, improving our understanding of the disease and potentially leading to new therapeutic strategies to prevent cardiovascular, renal and joint manifestations. Full article
(This article belongs to the Special Issue Primary Hyperparathyroidism: Mechanisms and Treatment)
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