Parathyroid Carcinoma

Parathyroid carcinoma is a rare malignancy affecting the parathyroid glands, which are four pea-sized glands located in the neck. These glands are responsible for producing parathyroid hormone (PTH), a very important regulator of serum calcium levels. The hormone promotes calcium reabsorption from bones, thereby maintaining normal serum calcium levels, while being antagonised by calcitonin, which facilitates calcium storage.

Since its discovery in 1904, fewer than a thousand cases have been documented, making it significantly less common than parathyroid adenoma. The occurrence rate of parathyroid carcinoma is between 0.5% to 5%, and it poses challenges in surgical excision due to its invasive nature.

Signs and Symptoms

Most patients with parathyroid carcinoma present with moderate to severe hypercalcaemia and elevated PTH levels. A noticeable large mass in the neck is often observed, along with common kidney and bone abnormalities. These symptoms are primarily due to the excessive production of PTH, leading to elevated calcium levels in the blood.

Risk Factors

Parathyroid carcinoma typically affects individuals in midlife, with an equal incidence rate among men and women. Certain conditions are associated with an increased risk of developing this cancer, including multiple endocrine neoplasia type 1, autosomal dominant familial isolated hyperparathyroidism, and hyperparathyroidism-jaw tumour syndrome, which is hereditary. Additionally, exposure to external radiation has been linked to parathyroid cancer, although this association is more commonly seen with parathyroid adenoma.

Diagnosis

Diagnosis of parathyroid carcinoma often involves a combination of imaging studies and laboratory tests. On a Sestamibi parathyroid scan, intense radioactivity greater than that of the submandibular gland on delayed images, no washout between early and delayed images, and high PTH concentration in individuals over 40 years of age are suggestive of parathyroid carcinoma. Some authors propose that elevated levels of human chorionic gonadotropin (HCG) can serve as a marker for parathyroid carcinoma in the appropriate clinical context. However, it is very important to differentiate it from other thyroid diseases such as multinodular goitre, Hashimoto thyroiditis, thyroid adenoma, and thyroid carcinoma, which can also retain the radiotracer due to their high metabolic activity. Therefore, a definitive diagnosis requires pathological examination of the excised tissue.

Treatment

Parathyroid carcinoma is sometimes identified during surgery for primary hyperparathyroidism. When the surgeon suspects carcinoma based on the severity or invasion of surrounding tissues by a firm parathyroid tumour, an aggressive surgical approach is undertaken. This may involve the excision of the thyroid and surrounding tissues as necessary to ensure complete removal of the carcinoma.

In addition to surgical intervention, pharmacological agents such as calcimimetics (e.g., cinacalcet) are employed to manage hypercalcaemia. These agents mimic calcium and activate the parathyroid calcium-sensing receptor, thereby tricking the gland into perceiving elevated calcium levels. This mechanism helps lower serum calcium levels, thus mitigating the hypercalcaemia associated with parathyroid carcinoma.

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Self-assessment MCQs (single best answer)

Which hormone is primarily produced by the parathyroid glands?

What is the primary function of parathyroid hormone (PTH)?

Parathyroid carcinoma results in elevated levels of which substance in the blood?

Which imaging study is typically used in the diagnosis of parathyroid carcinoma?

Which of the following conditions is NOT a risk factor for parathyroid carcinoma?

What symptom is commonly observed in patients with parathyroid carcinoma?

Which pharmacological agent is used to manage hypercalcaemia in parathyroid carcinoma?

During surgery for primary hyperparathyroidism, what might indicate the presence of parathyroid carcinoma?

Which age group is most commonly affected by parathyroid carcinoma?

What is a definitive method for diagnosing parathyroid carcinoma?