The incidence of hypercalcemia in squamous cell carcinoma of the head and neck

Hypercalcemia is a well-recognized phenomenon in squamous cell carcinoma of the head and neck, but the incidence of hypercalcemia in this group of patients is not clear. We have reviewed the records of 166 patients with squamous cell carcinoma of the head and neck presented at the Boston VA Medical Center over a 2-year period (October 1981 to September 1983). Hypercalcemia (greater than 11 mg/dl), for which a benign etiology could not be identified, occurred in the clinical course of seven patients (4.2%). Of the hypercalcemic patients, 5/7 (71.4%) had advanced stage IV disease and serum calcium levels ranging from 11.2 to 15 mg/dl at presentation. The incidence of hypercalcemia in this stage IV group was 5/78 (6.4%). On the basis of concomitant serum alkaline phosphatase, x-ray films, and radionuclide bone scans in these patients, bone metastases or a humoral factor were felt to be the etiologic agent. Six of the seven patients died within 77 days of the onset of the hypercalcemia despite vigorous antihypercalcemic and chemotherapeutic measures, and the remaining patient is under chemotherapy at present. We conclude that hypercalcemia is a late manifestation of advanced squamous cell carcinoma of the head and neck and is an ominous prognostic sign. Hypercalcemia without bone metastases is presumably due to the production of ectopic parathormone (PTH)-like substances from the tumor. To control this hypercalcemia, the underlying tumor must be treated vigorously in conjunction with symptomatic treatment.(ABSTRACT TRUNCATED AT 250 WORDS)     

Hypercalcemia associated with extracorporeal life support in neonates

BACKGROUND/PURPOSE: Disturbances in calcium homeostasis are common at initiation of extracorporeal life support (ECLS). At the authors' institution many neonates undergoing ECLS have developed hypercalcemia. To determine the frequency of hypercalcemia in neonates during ECLS we performed retrospective chart review of neonates that required ECLS at our neonatal intensive care unit. METHODS: The authors identified 76 consecutive neonates who underwent ECLS before 10 days of age at Cincinnati Children's Hospital Medical Center from July 1, 1991 to June 30, 1996. The hospital charts and ELSO forms were reviewed. Demographic, clinical, and laboratory data for each of the patients were reviewed, both before initiation and during ECLS. Hypercalcemia was defined as total serum calcium concentration of greater than 11 mg/dL (2.74 mmol/L) on at least one occasion beyond the first 24 hours of ECLS. RESULTS: The hospital charts and ELSO forms from 70 patients were available for review. One patient was excluded because he was only on ECLS for 33 hours, and there were no calcium levels obtained after 24 hours of ECLS and until death. Twenty-five (36%) neonates undergoing ECLS had hypercalcemia (serum Ca > 11 mg/dL [2.74 mmol/L]). Hypercalcemia was associated with longer duration of ECLS (hypercalcemia group, 243 +/- 115 hours and normocalcemia group, 139 +/- 64 hours) and greater requirements for platelet transfusions (hypercalcemia group, 538 +/- 282 mL and normocalcemia group, 372 +/- 233 mL). This could not be explained by differences in primary diagnosis, amounts of calcium administered, and acid-base status. CONCLUSIONS: Hypercalcemia was found to be common in neonates that require ECLS and is associated with longer duration of ECLS support. Conservative calcium administration for neonates while on ECLS may be warranted.     

Sphenoid sinus brown tumor, hypercalcemia, and blindness: an unusual presentation of primary hyperparathyroidism

This is a first report of primary hyperparathyroidism (HPT) masquerading as a destructive fibrous sphenoid sinus "Brown tumor" associated with progressive blindness and hypercalcemia. Diagnosis of a Brown tumor was delayed despite serial computerized tomography of the head and repeated transnasal and transethmoid sphenoid biopsies demonstrating diffuse fibrosis. Only detection and medical evaluation of hypercalcemia, demonstrating elevation of both serum calcium and C-terminal parathyroid hormone with an elevated chloride/phosphate ratio, prompted neck exploration, thus confirming a solitary left superior parathyroid adenoma. Postoperative normocalcemia occurred synchronously with the return of light perception and the arrest of sphenoid sinus and parasellar erosion. Although maxillary Brown tumors of secondary HPT have been reported, this is the first report of osteitis fibrosa of the sphenoid sinus. Differential diagnosis of an erosive sphenoid lesion with cranial nerve dysfunction, exclusive of inflammatory or vascular disease, should include sarcoidosis, primary and metastatic sphenoid carcinoma, fibrous dysplasia, giant cell reparative granuloma, midline lethal granuloma, chordoma, and chondrosarcoma. Furthermore, the bony destructive lesions with concomitant hypercalcemia of sarcoidosis and HPT are distinguishable by radiographic and laboratory analyses and by the Dent corticosteroid suppression test. Hypercalcemia of primary HPT is associated with elevated serum C-terminal parathormone, osteitis fibrosa, a negative Dent test, and a chloride/phosphate ratio greater than 33 in 94% of primary HPT patients. Hypercalcemia of sarcoidosis is associated with a normal or decreased C-terminal parathormone assay and a positive Dent test, as well as elevated serum immunoglobulins and erythrocyte sedimentation rate, and a positive angiotensin-converting enzyme assay.(ABSTRACT TRUNCATED AT 250 WORDS)     

Prognostic significance of disordered calcium metabolism in hormone-refractory prostate cancer patients with metastatic bone disease

Bone metabolic disruption that occurs in bone metastatic prostate cancer could lead to disturbances of calcium metabolism. The prognostic role of either hypocalcemia or hypercalcemia was assessed in a consecutive series of hormone-refractory bone metastatic prostate cancer patients. Serum calcium was measured in 192 patients. The presence of hypocalcemia and hypercalcemia was related with baseline biochemical and clinical characteristics and the role of these two calcium disturbances in predicting prognosis and adverse skeletal-related events (SREs) was assessed. As compared to normocalcemic patients, hypocalcemic patients (n=51) had higher tumor load in bone (P=0.005), higher plasma chromogranin A (CgA, P=0.01), serum alkaline phosphatase (P=0.01), urinary N-telopeptide (NTX, P=0.002) and lower hemoglobin values (P=0.01), while hypercalcemic patients (n=16) had higher plasma CgA (P=0.001) and serum lactate dehydrogenase values (P=0.001), higher bone pain (P=0.003) and a lower frequency of pure osteoblastic lesions (P=0.001). Hypercalcemia was significantly associated with poor prognosis: hazard ratio (HR), 1.9 (95% confidence Interval (CI) 1.2-3.3) and higher risk to develop SREs HR, 2.5 (95% CI 1.2-5.2, P=0.01), while hypocalcemia was not associated with poor prognosis. The prognostic role of hypercalcemia was maintained in multivariate analysis after adjusting for validated prognostic parameters: HR, 2.72 (95% CI 1.1-6.8, P=0.03). These data suggest that serum calcium levels should be taken into account in the clinical decision-making process of bone metastatic prostate cancer patients. Patients with asymptomatic hypercalcemia could benefit of a strict follow-up and an immediate bisphosphonate treatment. Further prospective clinical trials are needed to confirm this finding.     

Surgical management of hyperparathyroidism due to primary hyperplasia.

A series of 104 consecutive patients treated at the Massachusetts General Hospital between 1933 and 1978 for primary hyperplasia was reviewed. Early in this period (1933-1958) nine patients were treated by what was the considered subtotal resection (five with clear cell and four with chief cell hyperplasia). Hypercalcemia persisted in four cases; three from inadequate resection and one (case 170) associated with a fifth gland in the mediastinum that was removed at a second stage operation. Later (1959-1978), adequate subtotal resection, leaving 30 to 50 mg of viable hyperplastic tissue, was performed in 28 patients (7 with clear cell and 21 with chief cell hyperplasia). The operation was successful in 27 patients (96%). In one patient (case 442) subtotal resection failed, and hypercalcemia recurred, requiring a second operation. Sixty-seven patients in this series had excision of one, two, or three (but not more than three) glands. Of these 21 (31%) had persistent hypercalcemia after operation and required further surgery. Transient hypocalcemia occurred in 40 patients, permanent hypocalcemia in two. This study shows that subtotal resection, leaving 30 to 50 mg of viable tissue, is the surgical treatment of choice for primary parathyroid hyperplasia. It is effective in the great majority of patients. We have not found total parathyroidectomy with autotransplantation necessary and believe that it should be reserved only for selected cases.     

Oral Paricalcitol Reduces the Prevalence of Posttransplant Hyperparathyroidism: Results of an Open Label Randomized Trial

Postkidney transplant hyperparathyroidism is a significant problem. Vitamin D receptor agonists are known to suppress parathyroid hormone (PTH) secretion. We examined the effect of oral paricalcitol on posttransplant secondary hyperparathyroidism by conducting an open label randomized trial in which 100 incident kidney transplant recipients were randomized 1:1 to receive oral paricalcitol, 2 μg per day, for the first year posttransplant or no additional therapy. Serial measurements of serum PTH, calcium and bone alkaline phosphatase, 24‐h urine calcium and bone density were performed. The primary endpoint was the frequency of hyperparathyroidism 1‐year posttransplant. Eighty‐seven patients completed the trial. One‐year posttransplant, 29% of paricalcitol‐treated subjects had hyperparathyroidism compared with 63% of untreated patients (p = 0.0005). Calcium supplementation was discontinued in two control and 15 treatment patients due to mild hypercalcemia or hypercalcuria. Paricalcitol was discontinued in four patients due to hypercalcuria/hypercalcemia and in one for preference. Two subjects required decreasing the dose of paricalcitol to 1 μg daily. Hypercalcemia was asymptomatic and reversible. Incidence of acute rejection, BK nephropathy and renal function at 1 year were similar between groups. Moderate renal allograft fibrosis was reduced in treated patients. Oral paricalcitol is effective in decreasing posttransplant hyperparathyroidism and may have beneficial effects on renal allograft histology.     

Persistent hypercalcemia is a significant risk factor for graft dysfunction in renal transplantation recipients

Hypercalcemia is a common problem in renal transplant recipients, although in most cases, spontaneous resolution occurs within 1 year after renal transplantation. This condition may persist in some patients producing effects on renal function which are not well understood. In this study, we sought to analyze the effect of persistent hypercalcemia in the posttransplantation period on the function of renal transplants. A total of 121 recipients (31 women, 90 men; mean age, 34.1 +/- 9.9 years) underwent renal transplantation between 1999 and 2002. All patients underwent prospective evaluation of their serum calcium levels at 6-month intervals. A sustained corrected mean serum calcium level higher than 10.2 mg/dL was defined as "persistent hypercalcemia." Patients who had a gradual increase in their serum creatinine levels to >2 mg/dL or a 50% rise above the baseline were considered to display chronic allograft dysfunction (CAD). Among 121 recipients, 52 patients (43%) developed CAD and 37 patients (30.6%) had persistent hypercalcemia. Among the CAD patients, 22 suffered persistent hypercalcemia, while the other 15 patients were without CAD, a difference that was statistically significant (42.3% vs 21.7%, P = .01). The mean calcium levels were lower among patients without than with CAD, a difference that did not reach statistical significance (9.9 +/- 0.4 mg/dL vs 10.1 +/- 0.6 mg/dL, P = .1). In conclusion, persistent hypercalcemia in the posttransplantation period may significantly contribute to the development of chronic allograft nephropathy.     

Hypercalcemia and elevated serum 1.25-dihydroxyvitamin D in an end-stage renal disease patient with pulmonary cryptococcosis

Hypercalcemia occurs relatively often in dialysis patients. The most common cause of hypercalcemia in dialysis patients is the conventional therapy with calcium and calcitriol. Besides, secondary hyperparathyroidism, low turnover bone diseases, and immobilization are also common causes of hypercalcemia in dialysis patients. Fungal infection associated with hypercalcemia has been infrequently reported. We describe a 71-year-old female woman with end-stage renal disease and diabetes mellitus, who developed severe hypercalcemia. Pulmonary cryptococcosis, with increased concentration of serum 1,25-dihydroxyvitamin D (1,25(OH)2D), was diagnosed. Her serum concentration of calcium and 1,25(OH)2D returned to normal after antifungal treatment. Thus, hypercalcemia was mediated by extrarenal overproduction of 1,25(OH)2D in this patient.     

Paraneoplastic hypercalcemia associated with bladder carcinoma: report of 2 cases

Hypercalcemia associated with bladder carcinoma is rare. We report on 2 patients with hypercalcemia and bladder tumor without bone metastases. In both patients serum calcium returned to normal after removal of the tumor. Serum immunoreactive parathyroid hormone levels were normal in both patients. In 1 case a high gradient of immunoreactive parathyroid hormone across the tumor was demonstrated but the secretion of nephrogenous cyclic adenosine monophosphate was normal. Urinary excretion of prostaglandins also was normal in this case. These data show that hypercalcemia was caused by the tumoral production of some humoral factor different from parathyroid hormone.     

Acute renal failure and hypercalcemia

Hypercalcemia can result from excessive bone resorption, renal calcium retention, excessive intestinal calcium absorption, or a combination of these conditions. Hypercalcemia may also provoke acute renal failure (ARF) or hypertension, or aggravate the tubular necrosis that is frequently found in cases of ARF. The association of ARF and hypercalcemia was studied retrospectively in eight patients based in the data in their charts. Data are expressed as median and percentile (25th; 75th). Our results show that ARF associated with hypercalcemia was related with comorbidity in all cases (cancer, multiple myeloma, hyperparathyroidism, sarcoidosis, vitamin D intoxication, and leprosy). Maximum median serum creatinine levels were 3.3 mg/dL (2.7, 3.8 mg/dL) before treatment and 1.1 mg/dL (0.9, 1.3 mg/dL) after treatment. Maximum total median serum calcium was 15.9 mg/dL (13.5, 19.8 mg/dL) before treatment and 9.1 mg/dL (8.4, 9.7 mg/dL) after treatment. Maximum median ionized serum calcium was 2.1 mmol/L (1.8, 2.2 mmol/L) before treatment and 1.1 mmol/L (1.0, 1.2 mmol/L) after treatment. Different kinds of treatment induced a rapid fall in serum calcium concentration. All patients were treated with hydration and diuretics, and three patients also received calcitonin. Serum creatinine concentration always fell simultaneously with the decrease in serum calcium in all cases. All patients progressed with nonoliguric renal failure. In conclusion, in ARF, patients are frequently hypocalcemic. Usually, the presence of hypercalcemia associated with ARF is indicative of the presence of comorbidity, as observed in all eight patients studied here. There was an improvement of renal function in all cases as serum calcium levels decreased.     

Acute Renal Failure and Hypercalcemia

Hypercalcemia can result from excessive bone resorption, renal calcium retention, excessive intestinal calcium absorption, or a combination of these conditions. Hypercalcemia may also provoke acute renal failure (ARF) or hypertension, or aggravate the tubular necrosis that is frequently found in cases of ARF. The association of ARF and hypercalcemia was studied retrospectively in eight patients based in the data in their charts. Data are expressed as median and percentile (25th; 75th). Our results show that ARF associated with hypercalcemia was related with comorbidity in all cases (cancer, multiple myeloma, hyperparathyroidism, sarcoidosis, vitamin D intoxication, and leprosy). Maximum median serum creatinine levels were 3.3 mg/dL (2.7, 3.8 mg/dL) before treatment and 1.1 mg/dL (0.9, 1.3 mg/dL) after treatment. Maximum total median serum calcium was 15.9 mg/dL (13.5, 19.8 mg/dL) before treatment and 9.1 mg/dL (8.4, 9.7 mg/dL) after treatment. Maximum median ionized serum calcium was 2.1 mmol/L (1.8, 2.2 mmol/L) before treatment and 1.1 mmol/L (1.0, 1.2 mmol/L) after treatment. Different kinds of treatment induced a rapid fall in serum calcium concentration. All patients were treated with hydration and diuretics, and three patients also received calcitonin. Serum creatinine concentration always fell simultaneously with the decrease in serum calcium in all cases. All patients progressed with nonoliguric renal failure. In conclusion, in ARF, patients are frequently hypocalcemic. Usually, the presence of hypercalcemia associated with ARF is indicative of the presence of comorbidity, as observed in all eight patients studied here. There was an improvement of renal function in all cases as serum calcium levels decreased.     

Hypercalcemia-induced upper gastrointestinal bleeding after renal transplantation

Hypercalcemia is common in patients after renal transplantation and may stimulate gastrin hypersecretion with associated peptic disease. We report on 2 patients with hypercalcemia and life-threatening gastrointestinal hemorrhage controlled by subtotal parathyroidectomy. Retrospective review of our last 10 patients with gastrointestinal hemorrhage revealed that all of those with normal renal function had elevated serum calcium levels. Because of the increased mortality associated with gastrointestinal hemorrhage in renal transplant patients (43%), patients prone to development of hypercalcemia may benefit from early subtotal parathyroidectomy.     

Hypercalcemia associated with parathyroid hormone-related protein at the terminal stage of uncomplicated squamous cell carcinoma in the head and neck region.

BACKGROUND: Parathyroid hormone-related protein (PTHrP) is mainly responsible for hypercalcemia in squamous cell carcinomas (SCCs). METHODS: We retrospectively checked the appearance of hypercalcemia among 33 patients who died with head and neck SCC. Serum concentrations of C-terminal region of PTHrP (C-PTHrP) were measured in 15 of them. The intracellular PTHrP expression was immunohistochemically stained in 42 SCC sections obtained from the 33 before the appearance of hypercalcemia. RESULTS: Hypercalcemia appeared in 24 of the 33, and increased serum C-PTHrP levels were confirmed in 11 of 12 hypercalcemic patients. PTHrP was identified in all SCC sections, and a stronger intensity than in normal squamous epithelia was observed in 50% of those obtained within 1 year before the onset of hypercalcemia. CONCLUSION: A high incidence of PTHrP-induced hypercalcemia was shown among patients dying with head and neck SCCs. The intracellular increase in PTHrP might be observed preceding hypercalcemia.     

Improved survival in infants and children with primary malignant liver tumors

Forty-six infants and children with primary malignant liver tumors were studied. Thirty-three had hepatoblastomas, 9 hepatocellular carcinomas, and 4 had sarcomas. Thirty-eight patients underwent liver biopsy or excision of the tumor. Nineteen patients were treated between 1952 and 1971 (mean survival 5.5 months) and the remaining 19 were treated between 1972 and 1981 (mean length of survival 30 months, 2 year survival rate 53 percent). In 21 patients with an unresectable tumor, biopsy alone was performed (mean survival 7 months). Ten patients underwent primary resection of their liver tumor (mean length of survival 23 months, 2 year survival rate 37.5 percent). Seven other patients with an unresectable tumor were treated with chemotherapy alone or in combination with radiotherapy for a mean period of 6 months before second-look celiotomy was carried out. Six of these patients (all treated after 1975) had significant reduction in the size of their tumors. Mean length of survival in this group was 4 years 2 months, and the 2 year survival rate was 100 percent; at present, 5 of these patients are living without the disease 2.5 to 7 years after diagnosis. Improved techniques in liver resection and chemotherapy before second-look celiotomy is undertaken for an unresectable lesion have improved prognosis in children with a malignant liver tumor.     

Post Transplant Erythrocytosis in Hypercalcemic Renal Transplant Recipients

In vitro data suggest that calcium plays an important role in normal and disordered erythropoiesis. The purpose of this study is to determine whether there is an association between serum calcium, various hormone levels, and the development of post transplant erythrocytosis (PTE). Data were collected on 283 patients who underwent renal transplantation between 1994 and 1998. The relationship between serum calcium and PTE development was tested using the chi-square test. Univariate and multivariable adjusted models were employed to determine predictors of maximum hematocrit. Selected patients underwent measurement of intact parathyroid hormone (PTH), 1,25-dihydroxy vitamin D, and erythropoietin (EPO). Seventy-three patients (26%) developed PTE. Post transplant erythrocytosis was more common in patients with hypercalcemia compared with patients with normal serum calcium (34% vs. 18%, p = 0.002). In multivariable analyses, serum calcium was a strong independent predictor of maximum hematocrit post transplant, even after adjustment for renal function. A serum calcium of >or=10.2 mg/dL was associated with greater than two-fold increased odds of PTE. There were no differences in hormone levels between subjects with hypercalcemia and PTE, subjects with PTE alone, and subjects with hypercalcemia alone. Hypercalcemia is associated with the development of PTE in renal transplant recipients.     

Hypercalcemia and Elevated Serum 1.25‐Dihydroxyvitamin D in an End‐stage Renal Disease Patient with Pulmonary Cryptococcosis

Hypercalcemia occurs relatively often in dialysis patients. The most common cause of hypercalcemia in dialysis patients is the conventional therapy with calcium and calcitriol. Besides, secondary hyperparathyroidism, low turnover bone diseases, and immobilization are also common causes of hypercalcemia in dialysis patients. Fungal infection associated with hypercalcemia has been infrequently reported. We describe a 71‐year‐old female woman with end‐stage renal disease and diabetes mellitus, who developed severe hypercalcemia. Pulmonary cryptococcosis, with increased concentration of serum 1,25‐dihydroxyvitamin D (1,25(OH)₂D), was diagnosed. Her serum concentration of calcium and 1,25(OH)₂D returned to normal after antifungal treatment. Thus, hypercalcemia was mediated by extrarenal overproduction of 1,25(OH)₂D in this patient.     

Milk alkali syndrome. Does it exist and can it be differentiated from primary hyperparathyroidism?

Four patients with milk-alkali syndrome (MAS) presented with many of the characteristics of primary hyperparathyroidism including hypercalcemia, low or normal serum phosphorus levels, normal or increased urinary calcium levels, and inappropriately high or elevated serum parathyroid hormone levels. These laboratory findings differ from those classically described in MAS, i.e., hypercalcemia without hypercalciuria and a normal or high plasma phosphate level. Because the serum calcium level failed to return to normal after two weeks of hydration and a low calcium diet, and because of the inability to distinguish this syndrome from primary hyperparathyroidism, two of the four patients underwent neck exploration. Four normal parathyroid glands were histologically proven in each, and at autopsy in a third patient, there was no evidence of parathyroid hyperplasia or adenoma. Hypercalcemia eventually resolved in all patients with a low-calcium diet for as long as six months. Of the several features of MAS, hypercalcemia, alkalosis in the presence of azotemia, a history of increased calcium and alkali intake, and a response to dietary calcium restriction are helpful in differentiating this syndrome from primary hyperparathyroidism. Laboratory tests in patients with MAS may be confusing and the return to normocalcemia in response to a calcium deficient diet may be delayed.     

Place of cryosurgery in the treatment of malignant liver tumors.

OBJECTIVE: The authors evaluate the results of cryosurgery in malignant liver tumors. SUMMARY BACKGROUND DATA: The outcome of primary or secondary liver tumors is poor when resection can not be achieved. Encouraging results of cryosurgery have been reported in unresectable liver tumors, but this treatment needs further evaluation of its efficacy in homogeneous groups of patients. METHODS: From 63 patients with malignant liver tumors with various histology treated by cryosurgery in a 2.5-year period, the authors evaluated the results of 34 patients with nonresectable hepatocellular carcinoma (9 patients) or nonresectable metastases from colorectal cancer (25 patients). Cryosurgery was used either as a single treatment (4 hepatocellular carcinomas, 5 metastases) or in association with liver resection (5 hepatocellular carcinomas, 20 metastases). Systemic chemotherapy was used routinely before surgery and after surgery. RESULTS: There was no intraoperative mortality. Mortality within 2 months was 3% and was unrelated to the procedure. Postoperative morbidity consisted of one sterile fluid collection and one biliary fistula (8%). At a mean follow-up of 16 months, (range, 2-27) local recurrence rate was 0% for hepatocellular carcinoma and 44% for metastases. Cumulative survival at 24 months was 63% and 52%, respectively, with 6 patients (67%) and 5 patients (20%) currently disease free. In the group of patients with metastases, survival was related to the size of the treated tumor (p = 0.06) and the absence of residual disease (p = 0.03). CONCLUSIONS: Cryosurgery is safe and increases the number of patients with unresectable liver malignancies in whom surgery can aim at eradicating the tumor. Local recurrence is observed more frequently for metastases than for hepatocellular carcinoma. The benefit in survival is related to the complete treatment of the tumoral disease.     

Disodium pamidronate in the preoperative treatment of hypercalcemia in patients with primary hyperparathyroidism.

Nine patients (median age, 81 years) with primary hyperparathyroidism were treated with intravenous infusions of disodium pamidronate (APD), which is a bisphosphonate drug. Six patients had severe hypercalcemia (serum calcium concentration, greater than 3 mmol/L) persisting after rehydration with saline and treatment with furosemide; three patients had moderate hypercalcemia with pronounced symptoms (serum calcium concentration 2.8 to 2.9 mmol/L). Three of the patients were considered to have hypercalcemic crises. In all patients, the raised serum calcium levels were lowered by the disodium pamidronate infusions. One week after a single infusion of 15 to 60 mg disodium pamidronate, six of the nine patients had serum calcium concentrations within the normal reference interval and two patients had slightly raised values. Transient asymptomatic hypocalcemia was noted in one patient. All patients tolerated the infusions well, and no side effects were noted. In the patients with verified parathyroid adenomas, a temporary increase in parathyroid hormone levels were observed concomitant with the drop in serum calcium level. The patient with parathyroid cancer displayed no such effect indicating an autonomous parathyroid hormone secretion from the parathyroid carcinoma tumor. The good effect of treatment with the osteoclast inhibitor disodium pamidronate on hypercalcemia caused by primary hyperparathyroidism suggests that this hypercalcemia is mainly due to an increased osteoclast activity. The number of patients in this series is yet too small to allow general conclusions. But the case histories in this series show that disodium pamidronate promises to be of value in different clinical situations for the treatment of severe hypercalcemia in patients with hyperparathyroidism. It can be used (1) preoperatively to investigate whether the patient's symptoms are related to the hypercalcemia, (2) in the treatment of hypercalcemic crises when "forced diuresis" has failed to normalize the serum calcium, (3) after unsuccessful parathyroid surgery when it can be used as a long-term treatment before reoperation, giving time for localization studies and healing of the scar reaction, and (4) in aged and fragile patients where it can be tried as an alternative to surgery.     

Paraneoplastic hypercalcemia in a patient with adenosquamous cancer of the colon.

Hypercalcemia is a well-known manifestation of paraneoplastic syndromes associated with a variety of malignancies. However, colon cancer has only rarely been associated with hypercalcemia of malignancy. We present the case of a patient with recurrent adenosquamous carcinoma of the ascending colon found to have hypercalcemia. The patient is a 76-year-old white woman who initially presented with colon cancer in the cecum and underwent a right hemicolectomy. All lymph nodes and surgical margins were free of tumor. Pathological examination at that time revealed adenosquamous carcinoma of the colon. Eight months later she complained of dizziness, anorexia, and constipation and was found to have a calcium level of 13.6 mg/dL. CT scan revealed a mass measuring 10.5 to 12.7 cm in the right hepatic lobe, and a bone scan was normal. Her intact parathyroid hormone (PTH) level was 6 pg/mL (normal 12-72) and her PTH-related protein (PTHrP) level was 25.7 pmol/L (normal <1.3). She then underwent a hepatic resection. The serum PTH, calcium, and PTHrP levels normalized after resection. Hypercalcemia of malignancy in colon cancer is rare and has an association with adenosquamous histology. The hypercalcemia is attributed to PTHrP, and here we demonstrate this in the serum and tumor specimens. The effects of PTHrP are shown to be short-lived postoperatively. We find only 14 other cases in the literature of hypercalcemia related to a colonic neoplasm, and this is the only patient reported to be surviving. The diagnosis of a paraneoplastic syndrome mediated via PTHrP should be considered when hypercalcemia is encountered in the setting of metastatic colon carcinoma.