Hypercalcaemia Due to Hyperparathyroidism in a Patient with Chronic Renal Failure and Renal Carcinoma
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J Clin Pathol: first published as 10.1136/jcp.32.3.234 on 1 March 1979. Downloaded from Journal of Clinical Pathology, 1979, 32, 234-239 Hypercalcaemia due to hyperparathyroidism in a patient with chronic renal failure and renal carcinoma J. J. SZWED, L. J. GOTT, R. E. LEMPKE, AND IN SOOK SEO From the Departments of Medicine, Surgery, and Pathology, Clowes Research Laboratories, Wishard Memorial Hospital, Indiana University Medical Center, Indianapolis, Indiana 46202, USA SUMMARY A 65-year-old woman with a history of a left heminephrectomy for renal carcinoma developed hypercalcaemia 11 years after the operation. The same kidney was found to contain a recurrent renal carcinoma. After the radical nephrectomy of the left kidney, hypercalcaemia remitted but reappeared 11 months later. The right kidney was small but functioned at a level of creatinine clearance of 10-15 ml/min. Metastatic work-up was negative, and secondary causes ofhypercalcaemia were excluded. A neck exploration revealed a parathyroid adenoma. With parathyroid resection the serum calcium declined to normal, and the risk of hypercalcaemic nephropathy in the remaining kidney was precluded. copyright. Hypercalcaemia is a common manifestation of Case report malignancy of numerous organs, including the kid- ney (Albright and Reifenstein, 1948; Connor et al., The patient is a woman who was found to have a 1956; Plimpton and Gellhorn, 1956; Gold and carcinoma of the left kidney during evaluation of in 1965 at age 54. The physical Shnider, 1959; Lucas, 1960; David et al., 1963; vaginal prolapse http://jcp.bmj.com/ Noenickx et al., 1962; Moses and Spencer, 1963; examination was normal except for obvious vaginal Samuelsson and Werner, 1963; Goldberg et al., prolapse. The full blood count, urine analysis, 1964). Primary hyperparathyroidism is a relatively serum electrolytes, serum calcium and phosphate, common disorder, usually benign, with a frequency and creatinine clearance were normal. She under- of 1 case per 1000 persons per year. The most went segmental resection of the left kidney (Fig. 1). common manifestation of this disorder is hyper- On microscopic examination the tumour was a renal calcaemia (Thorn et al., 1977). The association of carcinoma. There were no metastases nor was there renal carcinoma and hyperparathyroidism in the evidence of local invasion. At the time of the on September 26, 2021 by guest. Protected same patient is uncommon and has rarely been operation the patient was described as being quite diagnosed before the death of the patient (Bernstein 'irritable' by several physicians. She was discharged et al., 1965; Salama et al., 1971; Nemoto et al., from hospital and followed with yearly intravenous 1977). pyelograms. This report describes a patient with chronic renal In July 1976, 11 years after the first operation, she failure, who had had a total left nephrectomy for a was found to have progressive dilatation and club- recurrent renal carcinoma accompanied by hyper- bing of upper pole calyces, and an angiogram (Fig. calcaemia and, 11 months later, was found to 2) showed a 7 x 4 x 5 cm tumour mass involving have recurrent hypercalcaemia. The recurrent hyper- one-half to two-thirds of the upper pole of the left calcaemia was not due to recurrent renal carcinoma kidney. The right kidney appeared to be small but but rather to a parathyroid adenoma. After removal without gross tumour involvement. Investigation of a parathyroid adenoma the hypercalcaemia revealed that the haemoglobin was 12-0 g/dl, WBC remitted. 7-8 x 109/l with a normal differential. The urine was clear with pH 6-0 and SG 1 -010; there were 10-20 RBCs/hpf, 5-10 WBCs/hpf, and no casts nor Received for publication 5 September 1978 bacteria. Urine cultures were negative on three 234 J Clin Pathol: first published as 10.1136/jcp.32.3.234 on 1 March 1979. Downloaded from Hypercalcaemia due to hyperparathyroidism in a patient with chronic renalfailure 235 Ra 11 I Llo-If - E 31 8~~~~~~~~ ---_- p4 04 1000- 800 916 900 600 800 800 *E100 * -We ZW 50 \ Q-4 copyright. 11/65 7/76 8/76 8 6 9/76 9/76 5/77 8/77 8/77 9/77 10/77 Fig. 1 A graph depicting the patient's course by following serum calcium, phosphate, PTH, and creatinine clearance. separate occasions. Serum electrolytes were: sodium disease. Postoperatively the urine output from ranged http://jcp.bmj.com/ 135 mEq/l (135 mmol/l), potassium 4-1 mEq/l (4-1 50 to 100 ml/day for 48 hours and then rose to 1500 mmol/l), chloride 99 mEq/l (99 mmol/l), carbon- ml/day; creatinine clearance stabilised at 10-15 ml[ dioxide combining power 26 mEq/l (26 mmol/l). min during the next 10 days. The serum calcium Total serum proteins 6-3 g/dl (63 g/l) with albumin level was 9 0 mg/dl (2 25 mmol/l) and serum phos- 3-6 g/dl (36 g/I). Serum calcium levels of 11 -2 mg/dl phate was 3-0 mg/dl (0 97 mmol/l) at discharge in (2-8 mmol/l), 11 -0 mg/dl (2-75 mmol/l), and 11 -5 mg/ October 1976. dl (2-88 mmol/l) (normal range: 8&4-10-0 mg/dl; Before operation in 1976 the patient's parathyroid 2 1-2-5 mmol/l) were found with corresponding serum hormone level had been 916 pg/ml. Postoperatively, on September 26, 2021 by guest. Protected phosphate levels of 3 2 mg/dl (1 03 mmol/l), 3 0 mg/ the level declined to 800 pg/ml and has remained at dl (0 97 mmol/l), and 2-8 mg/dl (0 90 mmol/l). The approximately the same elevated level to the present ionised serum calcium was 2-54 mEq/l (1 27 mmol/l) time. While the patient's renal function gradually preoperatively, falling to 2-22 mEq/l (1 11 mmol/l) improved with hypertrophy of the remaining kidney, postoperatively (normal range: 1-78-2-28 mEq/l; the serum calcium began to rise again and in August 0-89-1-14 mmol/l), creatinine clearance was 100 ml/ 1977 reached values of 10-5-11l5 mg/dl (2-63-2-88 min. All other laboratory or radiological investiga- mmol/l); the ionised calcium was also elevated at tions were normal. 2-60 mEq/l (1 -3 mmol/l). Initially, the hypercalcaemia The remainder of the left kidney was resected in was thought to be due to the renal carcinoma, but September 1976 and found to contain a well- the postoperative rise in 1977 suggested that the- encapsulated neoplasm measuring 5-5 x 6-0 cm. On patient had a recurrence of tumour or had another, section it had a yellow, vascular cut surface with areas occult cause of hypercalcaemia. After another work- of haemorrhagic necrosis and microscopically was up for metastatic neoplasm was found to be negative- composed predominantly of polygonal clear cells radiologically and biochemically, secondary causes- (Fig. 3). No evidence of metastases was found at of hypercalcaemia were evaluated. Bone marrow and operation. The renal vessels and ureter were free of serum protein electrophoresis were both normal and J Clin Pathol: first published as 10.1136/jcp.32.3.234 on 1 March 1979. Downloaded from 236 J. J. Szwed, L. J. Gott, R. E. Lempke, and In Sook Seo Fig. 2 Renal angiogram demonstrating large tumour of the left kidney and the small right kidney. copyright. http://jcp.bmj.com/ 4 A ~~~A on September 26, 2021 by guest. Protected V Fig. 3 Renal cell carcinoma showing typical clear cells with highly vascular 4 7k stroma (Haematoxylin and ~ ~ ~ ~ ~~~~~~~~~~~~~~~~~~~~~~~ eosin x 100). 4~~~~~~~~~~~~~4 4 4.W~~~~~~~~~~~~~~~~44 .A 4rl -1 4 J Clin Pathol: first published as 10.1136/jcp.32.3.234 on 1 March 1979. Downloaded from Hypercalcaemia due to hyperparathyroidism in a patient with chronic renalfailure 237 Fig. 4 Functioning parathyroid adenoma containing chiefcells growing in sheets and glandular pattern (H and E x 100). copyright. excluded the largest group of multiple myelomas, the serum calcium levels returned to the 9-5-100 mg/ that is, secretary myelomas. Thyroid function studies dl (2 38-2 5 mmol/l) range with a serum phosphate were normal. Sarcoidosis was not suggested by either reading 3 0-3 4 mg/dl (0 97-1 10 mmol/l) two months history, physical findings, or radiological examina- after surgery. The patient now feels well, but her tion. The patient was taking no vitamins nor diuretics, irritability persists. Her renal function continues to nor was she ingesting any milk products or antacids improve gradually and her creatinine clearance is http://jcp.bmj.com/ in large quantities to our knowledge. It was, there- now 45 ml/min. fore, concluded that a parathyroid adenoma might be present, although this diagnosis was supported Discussion only by the patient's chronic irritability, noted by many observers, and her hypercalcaemia. The relationship between malignancy and increased Since the renal function was slowly improving parathyroid hormone (PTH) levels can be ascribed with one kidney, it was decided to explore her neck to the production of PTH by tumour tissue. The on September 26, 2021 by guest. Protected for a possible parathyroid adenoma. While the level development of hypercalcaemia and hypophos- of serum calcium was not life-threatening, the phataemia in patients with malignant neoplasms has residual kidney was at risk and its function could been reported. On the basis of histological studies, deteriorate if the hypercalcaemia persisted. At reasonably convincing evidence has been produced operation three parathyroid glands were identified. that a PTH-like substance can be formed in patients A mass removed from the right superior region of the with tumours and hypercalcaemia (Kohout, 1966).