Hypoparathyroidism

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Theory 
Diagnosis 
Management 
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Last reviewed: 8 Apr 2025

Last updated: 15 Nov 2024

15 Nov 2024

FDA approves palopegteriparatide for hypoparathyroidism in adults

The US Food and Drug Administration (FDA) has approved palopegteriparatide for the treatment of hypoparathyroidism in adults. It is the first and only treatment approved for hypoparathyroidism.

Palopegteriparatide is a prodrug consisting of parathyroid hormone (1‐34) conjugated to a methoxypolyethylene glycol (mPEG) carrier.

In a 26-week phase 3, double-blind trial of adults with chronic hypoparathyroidism, 79% of patients randomized to palopegteriparatide, and 5% to placebo, maintained normal calcium levels without needing conventional therapy (i.e., active vitamin D and high doses of calcium).[37]

Palopegteriparatide is approved in Europe for the treatment of chronic hypoparathyroidism in adults.

See Management: emerging

Original source of update

Hypoparathyroidism has a wide variety of presentations: from the asymptomatic patient with dramatically low serum calcium to the acutely symptomatic patient with neuromuscular irritability, tetany, painful muscle cramps, stridor, and even seizures with low serum calcium in the emergency department or recovery room.

Majority of cases are post-surgery for benign and malignant thyroid disorders, hyperparathyroidism, and laryngeal or other head and neck cancers.

Nonsurgical etiologies include: rare genetic conditions and syndromes; autoimmune destruction of the glands; destruction or invasion due to tumor, radiation, or infiltration by iron or copper; hypomagnesemia and magnesium depletion; and idiopathic.

Laboratory testing should confirm low ionized or albumin-corrected total calcium and low or inappropriately normal intact plasma parathyroid hormone, while also verifying normal serum magnesium and 25-hydroxyvitamin D levels.

If symptoms are present, replacement of calcium and/or magnesium should be promptly instituted with careful monitoring along with activated vitamin D metabolites for chronic treatment.

Definition

Hypoparathyroidism is caused by relative or absolute deficiency of plasma parathyroid hormone (PTH) synthesis and secretion.[1] This leads to low albumin-corrected serum total calcium and elevated serum phosphate. Signs and symptoms can involve the neuromuscular, psychiatric, cardiac, ocular, dermatologic, gastrointestinal, and renal/urologic systems. Patients can also be asymptomatic.

Definitions of permanent postsurgical hypoparathyroidism vary. Persistently low intact PTH levels in the presence of hypocalcemia requiring treatment for at least 6 months (some guidelines state at least 12 months) post-procedure generally indicates that the condition is permanent.

History and exam

Key diagnostic factors

history of thyroid, parathyroid, or laryngeal surgery
chronic alcoholism
malnutrition, malabsorption, diarrhea
muscle twitches, spasms, cramps
paresthesias, numbness, tingling
poor memory, slowed thinking
Chvostek sign
convulsions
irregular heart beat, tachycardia
Trousseau sign

Full details

Other diagnostic factors

anxiety
dry hair, brittle nails
cataracts
history of mucocutaneous candidiasis
history of chronic transfusions in patients with thalassemia
dyspnea
laryngeal spasm

Full details

Risk factors

thyroid surgery
parathyroid surgery
hypomagnesemia
moderate and chronic maternal hypercalcemia (neonatal hypocalcemia)
autosomal dominant conditions (e.g., mutations in CASR, GATA3)
hereditary hemochromatosis
transfusional iron overload in thalassemia
Wilson disease
metastatic cancer

Full details

Diagnostic tests

1st tests to order

serum calcium
plasma intact PTH
serum albumin
serum magnesium
serum 25-hydroxyvitamin D
serum phosphorus
serum creatinine
ECG

Full details

Tests to consider

24-hour urine calcium, creatinine
24-hour magnesium, creatinine
liver function tests
arterial blood gases (ABGs)
serum free thyroxine, thyrotropin
morning cortisol and adrenocorticotropin (ACTH) stimulation testing
complete blood count
serum iron, transferrin, ferritin
serum copper
ophthalmologic exam
audiology
renal imaging
autoantibodies to type 1 interferon or 21-hydroxylase
gene sequencing

Full details

Treatment algorithm

INITIAL

severe symptomatic hypocalcemia (albumin-corrected serum total calcium <7.5 mg/dL [<1.88 mmol/L])

ACUTE

asymptomatic temporary postoperative hypocalcemia

ONGOING

chronic hypoparathyroidism

Contributors

Authors

Dolores Shoback, MD

Professor of Medicine

University of California San Francisco

Endocrine Research Unit

San Francisco VA Medical Center

San Francisco

Disclosures

DS declares that her institution receives research money from Ascendis Pharmaceuticals to conduct a clinical trial in hypoparathyroid patients on which she is the Principal Investigator. This company is testing a new treatment for hypoparathyroidism. DS has participated in an advisory board for Ascendis (Dec 2022) to review data on this new treatment.

Quan-Yang Duh, MD, FACS

Professor of Surgery

Section of Endocrine Surgery

University of California San Francisco

San Francisco

Disclosures

QYD declares that he has no competing interests.

Acknowledgements

Professors Dolores Shoback and Quan-Yang Duh would like to gratefully acknowledge Professor Ronald Merrell, a previous contributor to this topic.

Disclosures

RM declares that he has no competing interests.

Peer reviewers

Wail Malaty, MD

Adjunct Clinical Professor

Department of Family Medicine

University of North Carolina

Chapel Hill

Disclosures

WM 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

Khan AA, Bilezikian JP, Brandi ML, et al. Evaluation and management of hypoparathyroidism summary statement and guidelines from the Second International Workshop. J Bone Miner Res. 2022 Dec;37(12):2568-85.Full text Abstract

Mannstadt M, Cianferotti L, Gafni RI, et al. Hypoparathyroidism: genetics and diagnosis. J Bone Miner Res. 2022 Dec;37(12):2615-29.Full text Abstract

Orloff LA, Wiseman SM, Bernet VJ, et al. American Thyroid Association statement on postoperative hypoparathyroidism: diagnosis, prevention, and management in adults. Thyroid. 2018 Jul;28(7):830-41.Full text Abstract

Gafni RI, Collins MT. Hypoparathyroidism. N Engl J Med. 2019 May 2;380(18):1738-47. 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
- Hypomagnesemia
- Hypoalbuminemia
- Chronic kidney disease
More Differentials
Guidelines
- Evaluation and management of hypoparathyroidism: summary statement and guidelines
- Standards of care for hypoparathyroidism in adults: a Canadian and international consensus
More Guidelines
Videos
Trousseau sign
Chvostek sign
More videos
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Hypoparathyroidism

FDA approves palopegteriparatide for hypoparathyroidism in adults

Summary

Definition

History and exam

Key diagnostic factors

Other diagnostic factors

Risk factors

Diagnostic tests

1st tests to order

Tests to consider

Treatment algorithm

severe symptomatic hypocalcemia (albumin-corrected serum total calcium <7.5 mg/dL [<1.88 mmol/L])

asymptomatic temporary postoperative hypocalcemia

chronic hypoparathyroidism

Contributors

Authors

Dolores Shoback, MD

Disclosures

Quan-Yang Duh, MD, FACS

Disclosures

Acknowledgements

Disclosures

Peer reviewers

Wail Malaty, MD

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

Videos

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