Parathyroid carcinoma (PC) is one of the rarest endocrine malignancies [1]. It is known to cause 0.5% to 5% of primary hyperparathyroidism (HPT) and usually develops in patients aged between 40 and 50 with no gender preference [2,3].

Secondary HPT is one of the common complications in patients with chronic kidney disease (CKD). In CKD patients, decreased activation of vitamin D causes hypocalcemia and hyperphosphatemia, which leads to overproduction of parathyroid hormone [4]. Most of the PC cases are associated with primary HPT, however, there are few cases of PC are combined with secondary or tertiary HPT. In this paper, we report a rare case of secondary HPT due to multiple PC in a patient with CKD.

In this paper, we presented a case of multiple PCs with secondary HPT. Secondary HPT is one of the most frequent complications in patients with chronic hemodialysis. However, we rarely encounter secondary HPT which is caused by PC, since majority of the cases are due to parathyroid adenoma or hyperplasia. Considering that clinical presentation of PC is similar to that of benign primary HPT, preoperative diagnosis of PC from other benign parathyroid diseases is rather challenging [5]. Even parathyroid gland ultrasonography and ^99mTc sestamibi scan do not provide definitive differential diagnosis between benign and malignant masses of parathyroid gland [6]. Low incidence of PC also makes it difficult to distinguish it from parathyroid adenoma or hyperplasia. In addition, for subjects who are on chronic hemodialysis, it is even more difficult to suspect PC before surgery than in patients with normal kidney disease. One of the reasons could be relatively low calcium level, due to hemodialysis and oral calcimimetics. Furthermore, continuous stimulating of four parathyroid glands owing to low serum vitamin D level can lead to high serum iPTH level, which can make the differential diagnosis of PC and benign diseases more complicated [7]. For these reasons, most PC cases are likely to be confirmed by histological examination after surgical removal of the tissue in patients with end-stage renal disease. Like benign parathyroid disease, signs and symptoms of PC can include hypercalcemia, bone and joint pain, osteoporosis, nephrolithiasis, renal and cardiac dysfunction [2]. However, PC tends to present with more severe course than benign parathyroid lesions. Referring to several literatures, severe hypercalcemia (>14 mg/dL), markedly elevated iPTH level, palpable neck mass (>3 cm) and significant renal or skeletal involvement may indicate features of PC [8,9]. In this case, initial serum calcium level was 10.56 mg/dL which was gently elevated. Possible causes could be hemodialysis, or oral cinacalcet which the patient had been taking.

Generally, postsurgical hypocalcemia occurs more in patients with secondary HPT than in primary HPT [10], postoperative hypocalcemia or hungry bone syndrome should be carefully examined. This patient is also taking calcium and vitamin D supplements, on close observation. He had autotransplantation parathyroid gland on his right arm, and generally it takes 2 to 3 months for transplanted parathyroid become viable, he might need to maintain taking oral supplements for some periods.

Multiple PC is a rare disease. Referring to the data from previous literature, multiple PC occurs infrequently, and there are just a few case reports [11,12]. In this case, the patient had three individual cancers developed from each parathyroid gland. Although we did not know those parathyroid lesions were malignant before the surgery, we readily decided to remove most of the sites of parathyroid glands because of the high iPTH level despite of maximal medical therapy. To some degree, it was an unexpected result that all of the three parathyroid lesions were cancerous. It is difficult to distinguish PC from benign diseases before surgery. Even fine-needle aspiration of the parathyroid mass is not recommended as it may cause tumor rupture and seeding [13]. Therefore, intraoperative findings are important to make the appropriate decision. The size, color (grayish-white), hardness, and soft tissue adherence could be the findings in high suspicion of carcinoma [5].

Surgical resection is the mainstay of the treatment for PC, and en bloc resection is generally recommended, to bring the optimal prognosis [14]. Complete exploration of all four parathyroid glands and watchful inspection for adjacent structures can minimize the recurrence rate. According to previous study, patients who had been diagnosed PC preoperatively and underwent en bloc resection had a recurrence rate of 33%, while those who were diagnosed PC postoperatively and underwent suboptimal resection had a recurrence rate of 50% [15]. However, recognition of malignancy before or even during the surgery is not simple; only 12% of PC patients are reported to have en bloc resection [16]. Our patient also had not been diagnosed malignancy preoperatively, and extensive manipulation was not routinely done during the surgery. Further surveillance might be crucial in this patient.

In this case, we presented an extraordinary case of secondary HPT with multiple PC in patient with chronic hemodialysis. Although it is rare, multiple PC can cause secondary HPT. Therefore, clinicians should suspect multiple PC when patient’s serum iPTH level is exceptionally high. Additionally, since PC could occur in multiple glands, autotransplantation of parathyroid gland after parathyroidectomy should be done carefully.