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Parathyroid Carcinoma Clinical Presentation

  • Author: Lawrence Kim, MD; Chief Editor: Jules E Harris, MD, FACP, FRCPC  more...
Updated: Dec 01, 2015


The history should focus on symptoms of hypercalcemia plus the other symptoms of hyperparathyroidism. The onset is usually more abrupt, and the symptoms more severe than hyperparathyroidism due to benign disease.

  • Bone pain, pathologic fracture, or other evidence of bone disease (approximately 90% of patients)
  • Renal stones (50-80% of patients)
  • Symptoms of hypercalcemia - Fatigue, weakness, confusion, depression, constipation


See the list below:

  • Palpable mass in the neck (approximately 50% of patients)
    • A palpable mass is virtually never present with benign parathyroid adenomas or hyperplasia.
    • If a parathyroid mass is palpable, parathyroid carcinoma should be suspected.
    • A study by Schaapveld et al found that a palpable neck mass, parathyroid hormone levels of more than 3 times the upper normal limit, and profound hypercalcemia suggest carcinoma and warrant surgical exploration.[16]
  • Signs of hypercalcemia


The etiology is unknown in most cases. Parathyroid cancer may be associated with the genetic disease hyperparathyroidism jaw tumor syndrome. It also may be associated with a history of neck irradiation.

Mutations of the gene encoding CDC73 (HRPT2, 1q31.2) cause hyperparathyroidism jaw tumor syndrome, and a relatively high proportion (approximately 15%) of these patients develop parathyroid cancer. Many sporadic parathyroid carcinomas also exhibit defects in this gene.[17] HRPT2 encodes a protein called parafibromin. It is thought that most parathyroid carcinomas exhibit loss of parafibromin expression.[18] Parafibromin is thought to act as a tumor suppressor gene but may have several other effects, including histone modification and activation of signaling pathways.[19] HRPT2 mutations can also be seen in benign parathyroid adenomas, but carcinomas more frequently exhibit alterations in gene copy number and have large-scale chromosomal deletions.[19]

Cyclin D1 overexpression has been associated with parathyroid carcinoma.[20] Parafibromin can negatively regulate cyclin D1 and may be responsible at least in part for this observation.[21]

Allelic loss of the retinoblastoma protein has been shown to be associated with parathyroid carcinoma.[22]

Mutations of the MEN1 gene can occasionally be seen in parathyroid carcinomas.[23]

Contributor Information and Disclosures

Lawrence Kim, MD Professor, Department of Surgery, Division of Surgical Oncology, University of North Carolina at Chapel Hill School of Medicine

Lawrence Kim, MD is a member of the following medical societies: Association for Academic Surgery, Association of VA Surgeons, International Association of Endocrine Surgeons, Society of Surgical Oncology, Society of University Surgeons, American Association of Clinical Endocrinologists, American Association of Endocrine Surgeons, American College of Surgeons, Southwestern Surgical Congress

Disclosure: Received income in an amount equal to or greater than $250 from: Affinergy, LLC.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Chief Editor

Jules E Harris, MD, FACP, FRCPC Clinical Professor of Medicine, Section of Hematology/Oncology, University of Arizona College of Medicine, Arizona Cancer Center

Jules E Harris, MD, FACP, FRCPC is a member of the following medical societies: American Association for the Advancement of Science, American Society of Hematology, Central Society for Clinical and Translational Research, American Society of Clinical Oncology

Disclosure: Nothing to disclose.

Additional Contributors

Sanjiv S Agarwala, MD Chief of Oncology and Hematology, St Luke's Cancer Center, St Luke's Hospital and Health Network; Professor, Temple University Shool of Medicine

Sanjiv S Agarwala, MD is a member of the following medical societies: American Association for Cancer Research, American Head and Neck Society, European Society for Medical Oncology, American Society of Clinical Oncology, Eastern Cooperative Oncology Group

Disclosure: Received honoraria from BMS for speaking and teaching; Received consulting fee from Novartis for consulting; Received consulting fee from Merck for consulting.


Wendy Hu, MD Consulting Staff, Department of Hematology/Oncology and Bone Marrow Transplantation, Huntington Memorial Medical Center

Wendy Hu, MD is a member of the following medical societies: American Association for the Advancement of Science, American College of Physicians, American Society for Blood and Marrow Transplantation, American Society of Hematology, and Physicians for Social Responsibility

Disclosure: Nothing to disclose.

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Photomicrograph of parathyroid carcinoma showing typical fibrotic septae. Histologic diagnosis can be difficult.
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