What is the workup for hyperparathyroidism (Primary Hyperparathyroidism)?

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From the Guidelines

The workup for hyperparathyroidism begins with laboratory testing to confirm the diagnosis, including serum calcium, intact parathyroid hormone (PTH), phosphorus, 25-hydroxyvitamin D, and renal function tests, as recommended by the most recent guidelines 1. The diagnosis of hyperparathyroidism is made through biochemical testing, and imaging has no role in confirming or excluding the diagnosis, but rather in localizing the abnormally functioning gland or glands with high accuracy and high confidence to facilitate targeted curative surgery 1. Once elevated calcium and PTH levels are confirmed, imaging studies are necessary to localize the abnormal parathyroid gland(s). The first-line imaging is typically a sestamibi scan combined with a neck ultrasound, which together have higher sensitivity than either modality alone, as suggested by recent studies 1. For patients with inconclusive initial imaging, 4D-CT scan or MRI may be used as second-line options. Additional laboratory tests should include 24-hour urinary calcium excretion to assess for hypercalciuria and bone mineral density testing to evaluate for osteoporosis, which is a common complication. Patients should also undergo assessment for nephrolithiasis with renal ultrasound or CT scan if they have a history of kidney stones. For patients with suspected familial hyperparathyroidism, genetic testing for MEN syndromes should be considered. The workup aims to distinguish between primary, secondary, and tertiary hyperparathyroidism, as management differs significantly between these conditions, with primary hyperparathyroidism typically caused by a parathyroid adenoma, while secondary hyperparathyroidism often results from chronic kidney disease or vitamin D deficiency, as noted in the guidelines 1. It is essential to note that parathyroidectomy is indicated in patients with severe hyperparathyroidism associated with hypercalcemia and/or hyperphosphatemia that are refractory to medical therapy, and imaging of parathyroid glands with 99 Tc-Sestamibi scan, ultrasound, CT scan, or MRI should be done prior to re-exploration parathyroid surgery, as recommended by the guidelines 1. In summary, the workup for hyperparathyroidism involves a combination of laboratory testing, imaging studies, and additional tests to confirm the diagnosis, localize the abnormal parathyroid gland(s), and distinguish between different types of hyperparathyroidism, with the goal of guiding targeted curative surgery and improving patient outcomes, as emphasized by the most recent and highest quality study 1.

From the FDA Drug Label

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From the Research

Workup for Hyperparathyroidism

The workup for hyperparathyroidism involves several steps, including:

  • Biochemical screening to detect hypercalcemia and elevated parathyroid hormone (PTH) levels 2, 3
  • Medical history and physical examination to identify symptoms and signs of hyperparathyroidism, such as skeletal fragility, nephrolithiasis, and nephrocalcinosis 2, 3
  • Imaging studies, such as ultrasound or sestamibi scan, to localize parathyroid adenomas or hyperplasia 3

Diagnostic Criteria

The diagnostic criteria for hyperparathyroidism include:

  • Elevated serum calcium levels (> 1 mg/dL above the upper limit of normal) 3
  • Elevated or inappropriately normal PTH levels 2, 3
  • Presence of symptoms, such as osteoporosis, nephrolithiasis, or nephrocalcinosis 2, 3
  • Age < 50 years 2, 3

Differential Diagnosis

The differential diagnosis of hyperparathyroidism includes:

  • Familial hypocalciuric hypercalcemia (FHH) 4
  • Secondary hyperparathyroidism (SHP) due to vitamin D deficiency, kidney disease, or other causes 4, 5
  • Tertiary hyperparathyroidism (THP) due to prolonged SHP 4

Management

The management of hyperparathyroidism depends on the severity of the disease and the presence of symptoms. Treatment options include:

  • Parathyroidectomy, which is the only curative treatment for primary hyperparathyroidism 2, 3, 6
  • Medical therapy, such as calcium and vitamin D supplementation, antiresorptive therapy, and cinacalcet, to manage symptoms and prevent complications 2, 3, 6

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Parathyroid Disorders.

American family physician, 2022

Research

Vitamin D and Secondary Hyperparathyroid States.

Frontiers of hormone research, 2018

Research

Primary hyperparathyroidism.

Nature reviews. Endocrinology, 2018

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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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