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January 2006, Volume 56, Issue 1

Case Reports

Minimally Symptomatic Severe Hypercalcaemia in a Patient with Parathyroid Carcinoma.

Aisha Sheikh  ( Department of Medicine, Aga Khan University Hospital, Karachi. )
Najmul Islam  ( Department of Medicine, Aga Khan University Hospital, Karachi. )


Serum Calcium level above 14mg/dl is considered as severe hypercalcaemia and the patients are usually acutely ill necessitating urgent hospitalization and treatment. 1 Clinical manifestations affect the neuromuscular, gastrointestinal, renal, skeletal, and cardiovascular systems. The most common causes of hypercalcaemia are primary hyperparathyroidism and malignancy. 1 Hypercalcaemic crisis is a life-threatening emergency. Aggressive intravenous rehydration is the mainstay of management in severe hypercalcaemia, and antiresorptive agents, such as calcitonin and bisphosphonates, frequently can alleviate the clinical manifestations of hypercalcaemic disorders. 1,2 We report a case that had serum calcium of more than 20mg/dl and he walked into the endocrine clinic

Case Report

A 38 years old man who had one year history of generalized pains more marked in shoulders and legs, fatigability, anorexia, constipation and polyuria was seen at a medical care facility and was found to have a serum calcium of 17.6mg/dl (normal range: 8.6-10.5mg/dl) with an intact Parathyroid Hormone (PTH) of 1205pg/ml (normal range: 7-53mg/dl). Suspecting Parathyroid adenoma a Sestamibi scan was done which showed a functioning left inferior parathyroid tumor. He had a pepper pot skull on radiograph. He was treated with bisphosphonates with which his symptoms improved and there was a reported fall in serum calcium to 10.4mg/dl. He was advised surgery but he was lost to follow up.

Six months later he presented to our endocrine clinic with history of pain in extremities, weakness, fatigability, anorexia, constipation and vomiting of one week duration and had a report of his serum calcium which was 20.6mg/dl. He was alert and oriented and his clinical examination was unremarkable except that there was a small nodule (<1cm) palpable on the left side of the neck. He was admitted and was treated with normal saline infusions followed by pamidronate infusion and intravenous frusemide. He had a serum creatinine of 3.3mg/dl which was thought to be due to renal impairment secondary to hypercalcemia. His intact PTH was 2240pg/ml. He was screened for multiple endocrine neoplasia which turned out to be negative. His 25-hydroxyvitamin D level was 9.4mg/dl (normal range: 9.0-37.6mg/dl). With treatment his serum calcium fell to 11.3 g/dl and then he underwent surgical removal in which left inferior parathyroidectomy and left thyroid lobectomy was done. Immediately after surgery his PTH level came down to 138pg/ml.

Figure. Parathyroid Carcinoma infiltrating the thyroid gland

The histopathology revealed cellular neoplastic lesion composed of pleomorphic cells arranged in trabeculae and clusters incompletely separated by thick fibrous bands. The cells were pleomorphic having clear cytoplasm with indistinct cell boundaries. Nuclei showed pleomorphism and hyperchromasia with inconspicuous nucleoli. Increased mitotic activity was noted. Cellular invasion was identified. Neoplastic cells were seen abutting the thyroid acini (Figure). These findings were consistent with parathyroid carcinoma.

Our patient's serum calcium levels remained in normal range in the immediate postoperative period on supplemental calcium and calcitriol. Five months after surgery his serum calcium levels are within normal range on follow ups. His serum creatinine level has also come down to 2.0mg/dl but has not normalized.


The most common cause of hypercalcaemia is primary hyperparathyroidism, followed by malignancy. Together they account for more than 90% of cases2; however, malignancy accounts for the majority of cases of severe hypercalcaemia and hypercalcaemic crises. 1 A case of hypercalcaemic crisis (serum calcium 5.9mmol or 23.6mg/dl) due to parathyroid hormone related protein (PTHrP) secreting pancreatic neuroendocrine tumor in pregnancy has been reported by Abraham et al. 3

Hypercalcaemia in the setting of raised intact parathyroid hormone is pathognomonic for primary hyperparathyroidism. Benign primary hyperparathyroidism rarely produces severe hypercalcaemia and/or hypercalcaemic crises, unless renal insufficiency and/or dehydration is superimposed on the underlying hyperparathyroidism 1 . In contrast parathyroid carcinoma is associated with severe hypercalcaemia i.e. more than 14mg/dl level. 1,4 Severe hypercalcaemia produces gastro-intestinal symptoms-anorexia, nausea, vomiting and constipation, neuro-psychiatric symptoms-fatigue, lethargy, poor concentration, depression, obtundation, coma and occasionally causes cardiovascular complications-bradyarrhythmias, heart block and cardiac arrest. 1,5 Our patient was minimally symptomatic with serum calcium of 20.6mg/dl which might be due to the chronic nature of his illness.

Parathyroid carcinoma is an uncommon cause of PTH-dependent hypercalcaemia 4,6 and it accounts for less than 1% of patients with primary hyperparathyroidism.7 Different case series have reported serum calcium in the range of 9.9-18.4mg/dl8,9 and 11.4-15.6mg/dl9 in patients with parathyroid carcinomas. Spinelli C et al reported three cases of parathyroid carcinoma, one of them had serum calcium of 20.2mg/dl.10 Our patient had serum calcium of 20.6mg/dl which is the highest reported with parathyroid carcinomas.

The initial treatment of severe hypercalcaemia is the same regardless of the etiology. Therapy is aimed at increasing renal excretion of calcium and decreasing bone resorption. Patients with hypercalcaemic crisis are volume depleted and initial therapy should be intravenous hydration with isotonic saline as was done in our patient. Following aggressive rehydration intravenous loop diuretics are used to inhibit calcium resorption in the distal tubule. Bisphosphonates, which directly inhibit osteoclast activity, are the most effective of the pharmacological agents. Pamidronate has often been used in such cases as was used in our patient. Calcitonin, glucocorticoids and rarely pliamycin and gallium nitrate have been used for hypercalcaemic crisis with variable success. In patients with renal failure, dialysis with a low or zero calcium dialysate should be initiated. 1,5

The single most effective therapy for parathyroid carcinoma is complete resection of the primary lesion at the time of initial operation when extensive local invasion and distant metastases are less likely. 5 Surgical treatment results in prompt correction of serum calcium and parathyroid hormone with gradual resolution of the metabolic consequences of severe hypercalcaemia. The prognosis of parathyroid carcinoma is quite variable. Five-year survival rates vary from 40-86%.5 Persistent hypercalcaemia following initial surgery is a poor prognostic indicator as 60% of patients die within 3 years. 11


We are grateful to Dr. Sohail Muzaffar, Associate Professor, Department of Pathology for providing the histopathology slides.


1. Carroll MF, Schade DS. A practical approach to hypercalcemia. Am Fam Physician 2003;69:1959-66.

2. Taniegra ED. Hyperparathyroidism. Am Fam Physician 2004;69:333-39.

3. Abraham P, Ralston HS, Hewison M, Fraser WD, Bevan JS. Presentation of a PTHrP-secreting pancreatic neuroendocrine tumor, with hypercalcaemic crisis, pre-eclampsia, and renal failure. Postgrad Med J 2002;78:752-53.

4. Hundahl SA, Fleming ID, Fremgen AM, Menek HR. Two hundred eighty-six cases of parathyroid carcinoma treated in the U.S. between 1985-1995: A national cancer data base report. Cancer 1999;86:538-44.

5. Snell SB, Gaar EE, Stevens SP, Flynn MB. Parathyroid cancer, a continued diagnostic and therapeutic dilemma: report of four cases and review of the literature. Am Surg 2003;69:711-16.

6. Ou HY, Hung CJ, Hsu WH, Yu EH, Wu TJ. Variability of clinical presentations in three cases of parathyroid carcinoma. J Formos Med Assoc 2003;102:266-69.

7. Shane E. Parathyroid carcinoma. J Clin Endocrinol Metab 2001;86:485-93.

8. Shortell CK, Andrus CH, Phillips CE Jr, Schwartz SI. Carcinoma of the pararthyroid gland: a 30-year experience. Surgery 1991;110:704-08.

9. Kebebew E, Arici C, Duh Q. Localization and reoperation results for persistent and recurrent parathyroid carcinoma. Arch Surg 2001;136:878-85.

10. Spinelli C, Berti P, Miccoli P. Carcinoma of parathyroids. Surgical experience in 3 cases. Minerva Chir 1994;49:1343-47.

11. Bhansali A, Kataria RN, Dutta P, Saha MM, Singh P, Dash RJ. Parathyroid Carcinoma: Difficult Management Options. Indian Journal of Cancer 2002;39:119-22.


The case of a 38 years old man with generalized pains fatigue, anorexia, constipation, polyuria serum calcium level of 20.6mg/dl in paired renal function parathyroid hormone is presented. Sestamibi scan showed a functioning left inferior parathyroid tumor, which was successfully removed. Before surgery he was managed with rehydration, diuretics and pamidronate infusion.

Five months post surgery the serum calcium levels are normal and renal function has improved.

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