Primary hyperparathyroidism

Overview 
Theory 
Diagnosis 
Management 
Follow up 
Resources 

Last reviewed: 12 Apr 2025

Last updated: 08 Apr 2024

Primary hyperparathyroidism is confirmed biochemically with synchronous elevation of serum calcium and inappropriate elevation of parathyroid hormone (PTH).

Normal serum intact PTH in the setting of hypercalcemia does not rule out disease.

Depression, cognitive changes, change in sleep pattern, fatigue, and myalgia or muscle weakness are nonspecific subjective complaints. There may be a history of nephrolithiasis or low bone mineral density.

Physical examination is usually normal, but examination of the neck is essential to look for a hard, dense mass, suggestive of parathyroid carcinoma.

Parathyroidectomy is the only definitive cure. Monitoring is an option for patients who have mild hypercalcemia without surgical indications, such as renal stones, impaired kidney function, or osteoporosis.

Definition

Primary hyperparathyroidism (PHPT) is an endocrine disorder in which autonomous overproduction of parathyroid hormone (PTH) results in derangement of calcium metabolism. In approximately 85% of cases, over-production of PTH is due to a single parathyroid adenoma and, less commonly, multi-gland involvement may occur.[1] An elevated serum calcium level with a higher or inappropriately normal (i.e., non-suppressed) plasma PTH level confirms a diagnosis of PHPT.[1][2] Inherited forms, affecting a minority of patients, lead to hyperfunctioning parathyroid glands. Importantly, hyperparathyroidism is rarely caused by parathyroid cancer characterized by severe hypercalcemia.[3]

Normocalcemic PHPT is recognized as a variant of PHPT. It is characterized by persistently high levels of parathyroid hormone in the setting of normal serum and ionized calcium levels, after secondary causes of PTH elevation have been excluded.[1] The clinical features of normocalcemic PHPT can be similar to the classical form, including nephrolithiasis and low bone mineral density.[1][4] Some, but not all, patients will go on to develop PHPT.[1]

History and exam

Key diagnostic factors

incidental finding on biochemical testing
history of osteoporosis or osteopenia
family history of hyperparathyroidism or features suggestive of hypercalcemia
nephrolithiasis

Full details

Other diagnostic factors

poor sleep
fatigue
myalgia
anxiety
depression
memory loss
overt neuromuscular dysfunction
cardiovascular and metabolic dysfunction
gastrointestinal symptoms

Full details

Risk factors

female sex
age ≥50-60 years
multiple endocrine neoplasia (MEN) 1, 2A, or 4
current or historical lithium treatment
hyperparathyroidism-jaw tumor syndrome
family history of PHPT
history of head and neck irradiation

Full details

Diagnostic tests

1st tests to order

serum calcium
serum intact PTH with immunoradiometric or immunochemical assay

Full details

Tests to consider

25-hydroxyvitamin D level
serum alkaline phosphatase
serum phosphorus
24-hour urinary calcium
dual-energy x-ray absorptiometry (DXA) scan
trabecular bone score
neck ultrasound
technetium-99m sestamibi scanning
single photon emission CT (SPECT)
CT neck
4-Dimensional (4D) CT neck
MRI neck

Full details

Emerging tests

radiolabeled choline PET
machine learning to identify primary hyperparathyroidism

Treatment algorithm

ONGOING

asymptomatic with surgical indications or symptomatic

asymptomatic with no surgical indications

Contributors

Authors

John Ayuk, MD

Consultant Endocrinologist

University Hospitals Birmingham

Birmingham

Disclosures

JA declares that he has no competing interests.

Neil Gittoes, MD, PhD

Consultant Endocrinologist and Honorary Professor of Endocrinology

Associate Medical Director

University Hospitals Birmingham

Birmingham

Disclosures

NG is an author of several references cited in this topic and is a member of the 2021 European Society of Endocrinology Educational Program of Parathyroid Disorders (PARAT) Working Group.

Acknowledgements

Dr John Ayuk and Professor Neil Gittoes would like to gratefully acknowledge Dr Fausto Palazzo, Dr Swaroop Gantela, and Dr Nancy D. Perrier, the previous contributors to this topic. FP, SG, and NDP declare that they have no competing interests.

Peer reviewers

Brendan C. Stack Jr, MD, FACS, FACE

Chairman, Endocrine Surgery Section

American Head and Neck Society

Professor and former inaugural Chairman

Department of Otolaryngology-Head and Neck Surgery

Southern Illinois University School of Medicine

Springfield

Disclosures

BCS declares that he has no competing interests.

Petros Perros, BSc, MBBS, MD, FRCP

Department of Endocrinology

Elliott Building

Royal Victoria Infirmary

Newcastle-upon-Tyne

Disclosures

PP declares that he has no competing interests.

References

Our in-house evidence and editorial teams collaborate with international expert contributors and peer reviewers to ensure that we provide access to the most clinically relevant information possible.

Key articles

Bilezikian JP, Khan AA, Silverberg SJ, et al. Evaluation and management of primary hyperparathyroidism: summary statement and guidelines from the fifth international workshop. J Bone Miner Res. 2022 Nov;37(11):2293-314.Full text Abstract

Wilhelm SM, Wang TS, Ruan DT, et al. The American Association of Endocrine Surgeons guidelines for definitive management of primary hyperparathyroidism. JAMA Surg. 2016 Oct 1;151(10):959-68.Full text Abstract

Bollerslev J, Rejnmark L, Zahn A, et al. European expert consensus on practical management of specific aspects of parathyroid disorders in adults and in pregnancy: recommendations of the ESE educational program of parathyroid disorders. Eur J Endocrinol. 2022 Feb 1;186(2):R33-63.Full text Abstract

Walker MD, Silverberg SJ. Primary hyperparathyroidism. Nat Rev Endocrinol. 2018 Feb;14(2):115-25.Full text Abstract

Petranović Ovčariček P, Giovanella L, Carrió Gasset I, et al. The EANM practice guidelines for parathyroid imaging. Eur J Nucl Med Mol Imaging. 2021 Aug;48(9):2801-2822.Full text Abstract

Reference articles

A full list of sources referenced in this topic is available to users with access to all of BMJ Best Practice.

Differentials
- Familial hypocalciuric hypercalemia (FHH)
- Humoral hypercalcemia of malignancy
- Multiple myeloma
More Differentials
Guidelines
- Practice parameter for the performance and interpretation of diagnostic ultrasound of the thyroid and extracranial head and neck
- Evaluation and management of primary hyperparathyroidism: summary statement and guidelines from the fifth international workshop
More Guidelines
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Primary hyperparathyroidism

Summary

Definition

History and exam

Key diagnostic factors

Other diagnostic factors

Risk factors

Diagnostic tests

1st tests to order

Tests to consider

Emerging tests

Treatment algorithm

asymptomatic with surgical indications or symptomatic

asymptomatic with no surgical indications

Contributors

Authors

John Ayuk, MD

Disclosures

Neil Gittoes, MD, PhD

Disclosures

Acknowledgements

Peer reviewers

Brendan C. Stack Jr, MD, FACS, FACE

Disclosures

Petros Perros, BSc, MBBS, MD, FRCP

Disclosures

References

Key articles

Reference articles

A full list of sources referenced in this topic is available to users with access to all of BMJ Best Practice.

Differentials

Guidelines

Log in or subscribe to access all of BMJ Best Practice

Log in or subscribe to access all of BMJ Best Practice

Log in to access all of BMJ Best Practice