Clinical Pearls & Morning Reports

Posted by Carla Rothaus

Published December 2, 2020


Is parathyroid cancer easily distinguished from atypical parathyroid adenoma?

Ectopic parathyroid tumors may not be detected on sestamibi scanning if it is limited to the neck and does not include the chest. Read the NEJM Clinical Problem-Solving Article here.

Clinical Pearls

Q: What are some of the causes of parathyroid hormone (PTH)-mediated and non-PTH-mediated hypercalcemia?

A: Measurement of the serum PTH level is indicated to differentiate PTH-mediated from non–PTH-mediated hypercalcemia. Elevated or inappropriately normal PTH levels usually indicate primary hyperparathyroidism but can also indicate familial hypocalciuric hypercalcemia or tertiary hyperparathyroidism. Low PTH levels generally suggest cancer (except in cases of parathyroid carcinoma and the ectopic secretion of PTH from a nonparathyroid tumor), granulomatous disease, or vitamin D intoxication.

Q: Is ectopic parathyroid tissue in the differential diagnosis for an anterior mediastinal mass?

A: An anterior mediastinal mass observed on computed tomography may represent a thymic mass, a lymphoma, a germ-cell tumor, or intrathoracic thyroid or parathyroid tissue. During embryogenesis, the parathyroid glands descend into the neck; the inferior glands travel with the thymus and can be pulled into locations within or adjacent to the thymus in the anterior mediastinum. An ectopic parathyroid neoplasm can explain hypercalcemia with elevated PTH levels.

Morning Report Questions

Q: Is parathyroid cancer easily distinguished from atypical parathyroid adenoma?

A: Parathyroid cancer is rare, accounting for less than 1% of primary hyperparathyroidism cases and 0.005% of all cancers in the United States. Chronic kidney disease and previous neck irradiation have been associated with an increased incidence, and parathyroid cancer may occur as part of a familial syndrome. It can be difficult to discern the histologic difference between atypical adenomas and carcinoma. In addition to routine histologic assessment, the use of an immunohistochemical panel of markers may aid in diagnosis. In some cases, a definitive diagnosis cannot be made on the basis of histologic assessment alone but becomes apparent when local recurrence or distant metastasis develops. Parathyroid cancer may metastasize to the lung, bone, and liver. 

Q: How is parathyroid cancer treated?

A: The only curative treatment for parathyroid cancer is surgery with en bloc dissection. Adjuvant radiotherapy is of limited benefit (its use has been reported only in small observational studies), and chemotherapy has not been shown to be beneficial. If surgery cannot be performed in a timely manner or the patient is not a surgical candidate, cinacalcet added to a regimen of bisphosphonate or denosumab or both may ameliorate hypercalcemia, the major driver of morbidity and mortality. Cinacalcet, which increases the sensitivity of the calcium-sensing receptor to calcium, has been associated with a reduction in PTH secretion and serum calcium levels and is indicated for the treatment of hypercalcemia in patients with parathyroid cancer. Parathyroid cancer recurrence is common and typically manifests as a gradual increase in serum calcium and PTH levels. Surgical tumor debulking is the main treatment for recurrent or metastatic disease. Lifetime tumor surveillance, conducted by monitoring PTH and calcium levels, is recommended.

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