What does hyperparathyroidism with normocalcemia indicate?

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Last updated: February 14, 2025View editorial policy

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From the Guidelines

Hyperparathyroidism with normocalcemia indicates a variant of primary hyperparathyroidism (PHPT) where patients have an elevated parathyroid hormone (PTH) concentration despite normal calcium values, and are still at risk for developing complications associated with classic PHPT 1.

Key Characteristics

  • Elevated PTH concentration
  • Normal calcium values
  • Risk for developing complications associated with classic PHPT

Importance of Accurate PTH Measurement

Accurate measurement of PTH is crucial for establishing the diagnosis of normocalcemic primary hyperparathyroidism, as elevated PTH is a key characteristic of this condition 1.

Clinical Implications

Patients with normocalcemic PHPT are still at risk for developing complications associated with classic PHPT, emphasizing the importance of accurate diagnosis and management. Third-generation assays may be useful in distinguishing between parathyroid carcinoma and benign disease, but their use is limited by practical considerations and the presence of the posttranslationally modified form of PTH in healthy individuals and those with PHPT or CKD 1.

From the Research

Definition and Characteristics

  • Hyperparathyroidism with normocalcemia, also known as normocalcemic primary hyperparathyroidism (NPHPT), is a condition characterized by elevated parathyroid hormone (PTH) levels with normal serum calcium concentrations 2, 3, 4, 5, 6.
  • NPHPT is a formally recognized variant of primary hyperparathyroidism (PHPT), with normal total and ionized serum calcium concentrations and elevated PTH levels, in the absence of secondary causes for hyperparathyroidism 5.

Clinical Presentation and Complications

  • Patients with NPHPT may present with hypertension, nephrolithiasis, impaired glucose tolerance, osteoporosis, and fragility fractures, similar to those with classical hypercalcaemic PHPT (hPHPT) 2, 4, 5, 6.
  • NPHPT is commonly seen in younger individuals, with a high incidence of kidney stones and osteoporosis 3.
  • The prevalence of complications such as nephrolithiasis, fragility fractures, and osteoporosis in NPHPT is similar to that in hPHPT 5.

Management and Treatment

  • The management of NPHPT is controversial, and a consensus is yet to be reached on the optimal management strategy 3, 4, 6.
  • Parathyroid surgery may be considered in patients with significant end-organ involvement, with careful consideration of risks and benefits on an individualized basis 4, 6.
  • Medical management with alendronate has been shown to be effective in NPHPT patients where surgery is not possible 4.
  • Annual clinical and biochemical surveillance is recommended to identify progression to hypercalcaemia or worsening end-organ involvement in patients who do not meet the criteria for surgery 6.

Comparison with Hypercalcemic PHPT

  • NPHPT may be a heterogeneous disease entity of PHPT with high rates of multi-gland disease, which appears to be biochemically milder but symptomatic 3.
  • NPHPT patients are more likely to present with multi-glandular disease and require remedial surgery compared to hPHPT patients 4.
  • The short-term outcomes of NPHPT after surgery do not differ from that of TPHPT 3.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

An overview of normocalcemic primary hyperparathyroidism.

Current opinion in endocrinology, diabetes, and obesity, 2015

Research

Normocalcaemic primary hyperparathyroidism: what is the role of parathyroid surgery?

Therapeutic advances in endocrinology and metabolism, 2021

Research

Normocalcemic Primary Hyperparathyroidism: A Comparison with the Hypercalcemic Form in a Tertiary Referral Population.

Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme, 2018

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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