Primary hyperparathyroidism and acute pancreatitis. A rare clinical association]

Hyperparathyroidism and hypercalcaemia are considered to be a rare cause of acute pancreatitis. The relationship between hyperparathyroidism and pancreatic inflammatory disease remains controversial, but it may be related to the translation from inactive to active trypsinogen by hypercalcaemia. Surgical correction of parathyroid disease and normalization of serum calcium levels may ameliorate the acute pancreatitis. Also the mechanism of pathologic zymogen activation during acute pancreatitis remain unknown; probably the pancreatic "autodigestion" is the result of anomalous intracellular transport of secretory proteins activated by lysosomal hydrolases. A case of acute pancreatitis and hyperparathyroidism due to solitary parathyroid adenoma occurred in a 66-years-old woman is reported. After the excision of parathyroid adenoma the serum calcium levels and the function of the pancreas returned to normal. This suggests a cause and effect relationship between hyperparathyroidism and acute pancreatitis.     

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??Diagnosis and treatment of the pancreatitis as an initial manifestation of primary hyperparathyroidism?? A report of 6 cases HE Liang*, ZHANG Hao, ZHANG Ping, et al. *Department of General Surgery, the First Affiliated Hospital of China Medical University, Shenyang 110001, China
Corresponding author: ZHANG Hao??E-mail: haozhang@mail.cmu.edu.cn
Abstract Objective To evaluate the clinical characteristics, diagnosis and treatment of the pancreatitis as an initial manifestation of primary hyperparathyroidism (PHPT). Methods The clinical data of 6 cases of the pancreatitis as an initial manifestation of PHPT admitted from February 2009 to March 2013 in Department of General Surgery, the First Hospital of China Medical University were reviewed retrospectively for the diagnosis and treatment strategies. Results Of 6 patients with PHPT, 4 patients complicated with acute pancreatitis and 2 patients complicated with chronic pancreatitis. Four patients with acute pancreatitis presented rapid progression. The serum calcium concentration was higher than 3.5mmol/L and the typical hypercalcemia crisis appeared in 4 patients. Resection of parathyroid adenoma was performed in 3 patients. Two patients were cured and 1 died of drug-induced liver failure. The other one without operation died of hypercalcemia crisis. Two chronic pancreatitis patients with pancreatolithiasis showed mild symptoms. Although the serum calcium concentration was higher than 3.5mmol/L, no hypercalcemia crisis appeared. They were cured after the resection of parathyroid adenoma. One of them presented recurrent pancreatitis during the follow-up period and one patient had no recurrence. Conclusion PHPT should be suspected highly when pancreatitis appeared without common causes, especially combined with normal or elevated serum calcium concentration. Surgery is considered as the most direct and effective way to treat PHPT and could alleviate the symptom of pancreatitis and improve survival rate.     

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.     

Chronic calcifying pancreatitis associated with primary hyperparathyroidism —Report of a case and review of the literature—

A 34 year old male was hospitalized because of severe abdominal pain and diarrhea. An abdominal X-ray revealed multiple calculi in the head of pancreas and blood tests showed his serum calcium level to be high. He underwent surgery of the parathyroid gland and a parathyroid tumor was removed. Two months later, resection of the head of the pancreas was also performed. Eighteen months after his operation there has been no recurrence of abdominal pain or diarrhea and his serum calcium level is within the normal range. We report this case herein and also discuss the possible cause and effect relationship between primary hyperparathyroidism and pancreatitis, and the appropriate management, in relation to a review of the literature.     

Chronic calcifying pancreatitis associated with primary hyperparathyroidism--report of a case and review of the literature

A 34 year old male was hospitalized because of severe abdominal pain and diarrhea. An abdominal X-ray revealed multiple calculi in the head of pancreas and blood tests showed his serum calcium level to be high. He underwent surgery of the parathyroid gland and a parathyroid tumor was removed. Two months later, resection of the head of the pancreas was also performed. Eighteen months after his operation there has been no recurrence of abdominal pain or diarrhea and his serum calcium level is within the normal range. We report this case herein and also discuss the possible cause and effect relationship between primary hyperparathyroidism and pancreatitis, and the appropriate management, in relation to a review of the literature.     

Parathyroid hormone: before and after parathyroidectomy

The clinical value of measuring serum immunoreactive parathyroid hormone (iPTH) for the diagnosis of primary hyperparathyroidism is sometimes debated, and the clinical significance of an elevated postoperative serum iPTH level is unknown. Therefore we studied 141 consecutive patients with primary hyperparathyroidism before and after parathyroidectomy to determine the clinical value of measuring serum iPTH by a mid-region-specific radioimmunoassay. Eighty-eight percent of the patients with primary hyperparathyroidism had an absolute increase in the level of serum iPTH (greater than 40 microliter Eq/ml) before surgery, and the remaining patients had an inappropriately increased level of serum iPTH for the simultaneous serum calcium level. Preoperative serum iPTH level correlated positively with serum calcium level and parathyroid tumor size. Postoperative elevation of serum iPTH level was common (as high as 40%) and was associated with higher preoperative levels of blood urea nitrogen, serum creatinine, and alkaline phosphatase and larger tumors. An elevated postoperative serum iPTH level without hypercalcemia did not indicate a failed parathyroidectomy, whereas negative parathyroid exploration and postoperative hypercalcemia were the best predictors of persistent hyperparathyroidism. We conclude that preoperative serum iPTH measurement is a very sensitive diagnostic test for primary hyperparathyroidism, but postoperative serum iPTH measurement is not a good predictor for persistent or recurrent hyperparathyroidism.     

Severe primary hyperparathyroidism in a neonate having a parent with hypercalcemia: treatment by total parathyroidectomy and simultaneous heterotopic autotransplantation

Neonatal primary hyperparathyroidism is a life-threatening disease because of marked hypercalcemia and severe respiratory distress caused by the hypoplastic thorax and occasional rib fractures. We report a 29-day-old girl treated by total parathyroidectomy and simultaneous autotransplantation of parathyroid tissue (one fifth of each of the two glands) in the femoral quadriceps muscle near the groin. At the time of operation, all four of the parathyroid glands were markedly enlarged, and their total weight was 900 mg. Part of the resected parathyroid tissue was cryopreserved for further autotransplantation should hypoparathyroidism develop. Two years six months after surgery, the infant was well and had normal levels of serum calcium and immunoreactive parathyroid hormone in the absence of any supplementary treatment. Asymptomatic hypercalcemia in the presence of abnormally low fractional excretion of calcium was found in the father. Based on our experience and review of the literature, we recommend total parathyroidectomy, autotransplantation, and cryopreservation for the neonate with primary hyperparathyroidism.     

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.     

Parathyroid carcinoma associated with polycythemia vera.

A link between hyperparathyroidism and the growth of hematopoietic stem cells is suggested by this report of a parathyroid carcinoma with polycythemia vera. A 56-year-old white woman presented with splenomegaly, a palpable neck mass and hypercalcemia, recurrent six years after resection of a parathyroid tumor. She had pancytosis with a subnormal serum concentration of erythropoietin. Radiographs showed subperiosteal erosions an dosteopenia. Nephrocalcinosis was absent. Bone biopsy showed a decreased cortical width with many intracortical osteoclasts. The cancellous bone area remained normal, but the osteoid area/bone area, osteoblast perimeter and osteoclast perimeter were increased. At surgery, a parathyroid carcinoma was found in the same location operated on previously. As in two other reported cases, postoperative improvement in the hypercalcemia was associated with remission of the blood dyscrasia. A novel finding in this case is that when the hypercalcemia eventually recurred, it was again accompanied by pancytosis. With bisphosphonate therapy, the serum intact parathyroid hormone level increased in response to a decrease in the ionized calcium level, indicating that the cancer was not autonomous. This case suggests that in the presence of the ionized hypercalcemia, the parathyroid tumor may have produced or induced production of a growth factor that can stimulate pancytosis. The differential diagnosis of polycythemia and hypercalcemia should be expanded to include parathyroid tumors in addition to hepatic, adrenal, renal, and ovarian neoplasms.     

Intracranial metastatic parathyroid carcinoma: case report

OBJECTIVE AND IMPORTANCE: Parathyroid carcinoma is a rare entity, and fewer than 200 cases have been described. It is a slowly progressive disease characterized by frequent recurrences and local metastases. Most patients with parathyroid carcinoma die from metabolic complications of hyperparathyroidism. Five-year survival rates range from 25 to 50%. Functional parathyroid carcinoma is a rare cause of hyperparathyroidism that affects only 0.32 to 5% of all patients who undergo surgery for hypercalcemia. A review of the literature revealed only one other reported case of metastatic intracranial parathyroid carcinoma, in a patient who experienced local recurrence and metastatic disease when she was diagnosed with an intracranial lesion. CLINICAL PRESENTATION: We report the case of a 44-year-old African-American man with recent-onset, right lower-extremity weakness and hypercalcemia 4 years after he underwent a parathyroidectomy for parathyroid carcinoma. At presentation, his parathyroid level was 467 pg/ml, and his serum calcium level was 15.2 mg/dl. Imaging studies revealed an isolated enhancing left mesial frontoparietal mass. A systemic Cardiolite study demonstrated a single focus of radiotracer uptake in this region. No abnormal uptake was demonstrated in the neck or elsewhere. INTERVENTION: The patient underwent a frameless stereotactic interventional magnetic resonance imaging-guided resection via a parasagittal interhemispheric approach. Pathological findings were consistent with parathyroid carcinoma. After resection, his right lower-extremity weakness and secondary hyperparathyroidism resolved. CONCLUSION: The typical natural history of parathyroid carcinoma concludes with death from complications of hyperparathyroidism. This case report supports aggressive surgical management to eliminate all parathyroid hormone-secreting malignant tissue and prevent metabolic complications. In this patient, intraoperative magnetic resonance imaging was helpful to ensure complete resection.     

Prolonged hypercalcemia following acute renal failure.

A case is reported of a twenty-one year old man who developed severe hypercalcemia late in the diuretic phase of acute reversible renal failure secondary to severe trauma. Hypercalcemia persisted for approximately five months. Serum immunoreactive parathyroid hormone levels were undetectable and sub-total parathyroidectomy had no appreciable effect on the serum calcium. The most likely source of this patient's hypercalcemia was resorption of calcium from metastatic deposits in soft tissue and possibly from bone. Failure to incorporate calcium into bone during the period of immobilization may explain the prolonged hypercalcemia.     

Treatment of severe hypercalcemia due to refractory hyperparathyroidism in renal transplant patients with the calcimimetic agent cinacalcet

Calcimimetic agents increase the sensitivity of calcium sensing receptors of parathyroid glands and suppress both serum calcium levels and parathyroid hormone. There are still limited data on the treatment of renal transplant patients with severe hypercalcemia and hyperparathyroidism with calcimimetics (cinacalcet). We describe two such renal transplant patients with chronic kidney disease Stage 3 who presented with persistent hypercalcemia (serum calcium 11.5-12 mg/dl) and refractory hyperparathyroidism (iPTH 194-547 pg/ml). Control of hypercalcemia with cinacalcet (serum calcium <10 mg/dl) resulted also in an improvement of hyperparathyroidism, but with a slower rate than that of the lowering of serum calcium. Addition of a vitamin D analog together with the calcimimetic agent resulted in faster control of the resistant hyperparathyroidism in both patients (iPTH <145 pg/ml) with clinical improvement and without any side effect. It seems that this new agent will improve our clinical approach of renal bone disease permitting a more integrated and successful treatment of hyperparathyroidism and its consequences on patients with chronic kidney disease.     

Hypercalcemic Disorders in Children

Hypercalcemia is defined as a serum calcium concentration that is greater than two standard deviations above the normal mean, which in children may vary with age and sex, reflecting changes in the normal physiology at each developmental stage. Hypercalcemic disorders in children may present with hypotonia, poor feeding, vomiting, constipation, abdominal pain, lethargy, polyuria, dehydration, failure to thrive, and seizures. In severe cases renal failure, pancreatitis and reduced consciousness may also occur and older children and adolescents may present with psychiatric symptoms. The causes of hypercalcemia in children can be classified as parathyroid hormone (PTH)‐dependent or PTH‐independent, and may be congenital or acquired. PTH‐independent hypercalcemia, ie, hypercalcemia associated with a suppressed PTH, is commoner in children than PTH‐dependent hypercalcemia. Acquired causes of PTH‐independent hypercalcemia in children include hypervitaminosis; granulomatous disorders, and endocrinopathies. Congenital syndromes associated with PTH‐independent hypercalcemia include idiopathic infantile hypercalcemia (IIH), William's syndrome, and inborn errors of metabolism. PTH‐dependent hypercalcemia is usually caused by parathyroid tumors, which may give rise to primary hyperparathyroidism (PHPT) or tertiary hyperparathyroidism, which usually arises in association with chronic renal failure and in the treatment of hypophosphatemic rickets. Acquired causes of PTH‐dependent hypercalcemia in neonates include maternal hypocalcemia and extracorporeal membrane oxygenation. PHPT usually occurs as an isolated nonsyndromic and nonhereditary endocrinopathy, but may also occur as a hereditary hypercalcemic disorder such as familial hypocalciuric hypercalcemia, neonatal severe primary hyperparathyroidism, and familial isolated primary hyperparathyroidism, and less commonly, as part of inherited complex syndromic disorders such as multiple endocrine neoplasia (MEN). Advances in identifying the genetic causes have resulted in increased understanding of the underlying biological pathways and improvements in diagnosis. The management of symptomatic hypercalcemia includes interventions such as fluids, antiresorptive medications, and parathyroid surgery. This article presents a clinical, biochemical, and genetic approach to investigating the causes of pediatric hypercalcemia. © 2017 The Authors. Journal of Bone and Mineral Research Published by Wiley Periodicals Inc.     

Primary hyperparathyroidism related to a parathyroid adenoma: the dramatic clinical evolution of a misdiagnosed patient and its surgical solution

Primary hyperparathyroidism is a clinical condition related to an excessive and abnormally regulated secretion of parathyroid hormone (PTH) from the parathyroid glands which is responsible for an alteration of the calcium and phosphorus metabolism. Parathyroid adenomas are the most important cause of primary hyperparathyroidism (80-85%). A case of parathyroid adenoma observed in a patient aged 47, admitted to the Emergency Medicine Department of our Hospital with a diagnosis of hypertensive crisis, cephalea, vomiting, and a clinical history of recurrent episodes of severe abdominal and renal pain, is presented. Lab data showed severe hypercalcemia and a progressive worsening of the renal function. A severe neurological involvement with stupor, derangement of mind, the arising of acute respiratory depression, lethargy compelled the colleagues to transfer him to the Intensive Care Unit; a neck ultrasonography showed a poor-echogenous area under the right thyroid inferior pole, with signs of vascularization. The suspect of a primary hyperparathyroidism related to a single adenoma of the parathyroid gland suggested a surgical treatment. A 'concise parathyroidectomy' was performed. Our surgical approach was confirmed by the comparison of the preintervention and the post-intervention iPTH values: 2080 pg/mL (normal range: 12-65 pg/mL) before excision vs 101 pg/mL after the removal. The histologycal exam reported a parathyroid adenoma with large areas with haemorrage. Three days after surgery the patient was in good general conditions. Patients affected by primary hyperparathyroidism are often misdiagnosed because their clinical conditions can create differential diagnosis problems with other diseases. However the surgical option remains the gold standard treatment.     

Parathyroid exploration for primary hyperparathyroidism

Parathyroidectomy was studied retrospectively in 107 patients with primary hyperparathyroidism. This condition was diagnosed by measuring both the total serum calcium and ultrafilterable calcium (non-protein-bound) levels. The identification of ultrafilterable calcium is an important adjunct to parathyroid surgery as it allows the diagnosis of hyperparathyroidism when the total serum calcium level is normal. The surgical technique for selective parathyroidectomy and multiple biopsies was uniform. Parathyroid adenoma was discovered in 73 patients, diffuse hyperplasia in 26 and combined disease in 8. Postoperatively, two patients suffered from permanent hypocalcemia and three had hypercalcemia.     

A case of lung cancer with hypercalcemia which was incidentally complicated with primary hyperparathyroidism due to parathyroid adenoma.

In lung cancer patients, hypercalcemia is a fairly common metabolic problem associated with malignancy. However, the occurrence of hypercalcemia in lung cancer patients means an ominous prognostic sign. As hypercalcemia often causes early death, quick diagnosis and treatment for hypercalcemia are required. A 69-year-old woman was admitted to our hospital with anorexia caused by hypercalcemia. On admission, serum level of PTH was elevated and PTHrP was normal. From the results of CT findings and transbronchial lung biopsy, the cause of the hypercalcemia was determined as lung cancer incidentally complicated with primary hyperparathyroidism. First, serum calcium level was returned to normal through hydration with saline and bisphosphonates. Next, left hemithyroidectomy for primary hyperparathyroidism was performed. Histologically, the tumor was diagnosed as parathyroid adenoma. Fifteen days later, left lower lobectomy for primary lung cancer was performed under a video-assisted thoracoscopic approach. Histologically, the tumor was diagnosed as a moderately differentiated adenocarcinoma. Four years and three months after the operation, the patient is alive and well with no sign of recurrence. When a lung cancer patient is complicated with hypercalcemia, we need to consider that primary hyperparathyroidism is a possible cause of the hypercalcemia.     

Early biochemical response to parathyroidectomy for primary hyperparathyroidism and its predictive value for recurrent hypercalcemia and recurrent primary hyperparathyroidism

BackgroundThe traditional definition of cure after parathyroidectomy (PTX) for primary hyperparathyroidism is normocalcemia. Our hypothesis was that early postoperative levels of serum calcium and parathyroid hormone after PTX would have predictive value for later recurrence.MethodsWe performed a retrospective study of 1,146 patients with primary hyperparathyroidism who underwent PTX and had long-term biochemical follow-up. The first postoperative serum level of calcium and parathyroid hormone values were used to categorize patients into the following four early biochemical response groups: (1) complete response (normal calcium and normal parathyroid hormone), (2) partial response with hyperparathormonemia (normal calcium and increased parathyroid hormone), (3) partial response with hypercalcemia (increased calcium and normal parathyroid hormone), and (4) non-response (increases in both calcium and parathyroid hormone). Incidences of recurrent hypercalcemia and recurrent primary hyperparathyroidism >6 months after operation were then analyzed.ResultsThe overall rate of any elevated serum levels of calcium and any increase in serum levels of parathyroid hormone during >6-month follow-up was 9.8% (112 of 1146), with 6.6% (57 of 861) for group 1, 27% (35 of 129) for group 2, and 16% (20 of 127) for group 3 (P < .02). Partial biochemical responses with either increased serum calcium or increased parathyroid hormone levels were the strongest predictors of any episode of increased serum levels of calcium after 6 months and was associated with 2.7× to 4.3× the risk of recurrent primary hyperparathyroidism, respectively.ConclusionThis study demonstrates the importance of measuring parathyroid hormone in the early postoperative period to better predict later recurrent primary hyperparathyroidism.     

Ectopic thymic parathyroid adenoma and vitamin D deficiency rickets: a 5-year-follow-up case report and review of literature

Sixteen patients with primary hyperparathyroidism presenting as rickets have so far been reported in the English literature. However, no report of an ectopic thymic parathyroid adenoma presenting as rickets has been published. We report a 14-year-old Caucasian American, wheelchair-ridden male who presented with signs and symptoms suggestive of vitamin D deficiency rickets subsequently confirmed by laboratory and radiological findings. Following the intramuscular administration of 125,000 U ergocalciferol (vitamin D2), he developed hypercalcemia with persistently elevated parathyroid hormone (PTH) levels suggestive of primary hyperparathyroidism. Sestamibi scan demonstrated significant uptake in the superior chest, without uptake at the normal parathyroid glands location. Surgical exploration revealed normal parathyroid glands and a thymic mass, which was removed and confirmed by pathology to be a parathyroid adenoma. With subsequent oral ergocalciferol solution and calcium carbonate therapies, the patient's symptoms resolved, blood chemistries normalized, and radiological evidence of rickets significantly improved. To our knowledge, this is the first case of an ectopic thymic parathyroid adenoma in a patient presenting with rickets. Our patient demonstrates that hyperparathyroidism-induced hypercalcemia may be masked by severe vitamin D deficiency. Prolonged treatment with ergocalciferol after removal of the parathyroid adenoma was necessary to normalize iPTH and replenish vitamin D store.     

Normocalcemic Primary Hyperparathyroidism

Primary hyperparathyroidism, a common endocrine disorder, is traditionally defined by hypercalcemia and elevated levels of parathyroid hormone (PTH). A newer presentation of primary hyperparathyroidism has been described over the past decade, in which PTH is elevated but serum calcium is consistently normal, in the absence of secondary causes of hyperparathyroidism, such as renal disease or vitamin D deficiency. Recognition of this phenotype of primary hyperparathyroidism, normocalcemic primary hyperparathyroidism, supports a biphasic chronological time course in some individuals in which PTH levels are first elevated but serum calcium is normal, followed by the development of frank hypercalcemia. This review focuses on the available literature regarding this newly described phenotype of primary hyperparathyroidism.     

Mechanisms of hypercalcemia in patients with head and neck cancer

Hypercalcemia associated with head and neck malignancy is not an uncommon occurrence; its causes are multiple. Eight hypercalcemic patients with head and neck malignancy were studied. Serum calcium, serum phosphorus, tubular phosphorus threshold, fasting calcium excretion, plasma 1,25-dihydroxyvitamin D, nephrogenous cyclic adenosine monophosphate (AMP), and immunoreactive parathyroid hormone were measured. Excessive dietary calcium administration in the form of an oral hyperalimentation preparation appeared to be the cause of hypercalcemia in 2 patients. Six patients demonstrated humorally mediated hypercalcemia. These patients resembled patients with primary hyperparathyroidism in having elevated nephrogenous cyclic AMP excretion and reduced proximal tubular phosphorus reabsorption, but they differed from patients with primary hyperparathyroidism by having normal levels of immunoreactive parathyroid hormone, MA rkedly increased fasting calcium excretion, and strikingly reduced mean plasma levels of 1,25-dihydroxyvitamin D. These data strongly suggest that the humoral factor responsible for hypercalcemia in patients with head and neck cancer is not parathyroid hormone, and that patients with hyperparathyroidism can now be distinguished with confidence from those with malignancy-associated hypercalcemia.