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January 1, 1982, Vol 247, No. 1 >
ARTICLE | January 1, 1982

The Differential Diagnosis of Hypercalcemia: Title and subTitle BreakAn Algorithm for More Effective Use of Laboratory Tests FREE

Edward T. Wong, MD; Esther F. Freier, MS
[+] Author Affiliations

Reprint requests to Room 2175, General Hospital, Los Angeles County-University of Southern California Medical Center, 1200 N State St, Los Angeles, CA 90033 (Dr Wong).


JAMA. 1982;247(1):75-80. doi:10.1001/jama.1982.03320260053034
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References

THE PROCESS of diagnosing primary hyperparathyroidism has been one of exclusion of the other causes of hypercalcemia. In the past decade, since the measurement of parathyroid hormone (PTH) by radioimmunoassay became available through commercial laboratories, its use has grown rapidly. Theoretically, PTH levels should be elevated in primary hyperparathyroidism and possibly in malignancies producing PTH ectopically (pseudohyperparathyroidism); in the other causes of hypercalcemia, the levels should be decreased.1,2 The number of PTH assays ordered at this hospital has reached 350 per year, whereas during the period of 1970 to 1978 the number of new cases of primary hyperparathyroidism was less than ten per year. This suggested that many physicians were ordering PTH measurements early, if not even first, in the evaluation of hypercalcemia, the expectation being that PTH determinations would separate primary hyperparathyroidism from the other causes of hypercalcemia. Before direct measurements of PTH became available, laboratory tests reflecting a

REFERENCES

1 +
Habener JF, Segre GV:  Parathyroid hormone radioimmunoassay . Ann Intern Med 1979;; 91:782-785.
2 +
Potts JT Jr, Krutzik SR:  Parathyroid hormone (PTH) , in Nichols AL, Fisher DA (eds): Radioimmunoassay Manual , ed. 3. San Pedro, Calif, The Nichols Institute, 1976;, pp 209-220.
3 +
Strott CA, Nugent CA:  Laboratory tests in the diagnosis of hyperparathyroidism in hypercalcemic patients . Ann Intern Med 1968;;68:188-202.
4 +
Palmer FJ, Nelson JC, Bacchus H:  The chloride-phosphate ratio in hypercalcemia . Ann Intern Med 1974;;80:200-204.
5 +
Kaminsky NI, Broadus AE, Hardman JG, et al:  Effects of parathyroid hormone on plasma and urinary adenosine 3′, 5'-monophosphate in man . J Clin Invest 1970;;49:2387-2395.
6 +
Scholz DA, Purnell DC, Goldsmith RS, et al:  Diagnostic considerations in hypercalcemic syndromes . Med Clin North Am 1972;;56:941-950.
7 +
Lafferty FW:  Pseudohyperparathyroidism . Medicine 1966;;45:247-260.
8 +
McLellan G, Baird CW, Melick R:  Hypercalcemia in an Australian hospital adult population . Med J Aust 1968;;2:354-356.
9 +
Lee DB, Zawada ET, Kleeman CR:  The pathophysiology and clinical aspects of hypercalcemic disorders . West J Med 1978;;129:278-320.
10 +
Heath H III, Hodson SF, Kennedy MA:  Primary hyperparathyroidism: Incidence, morbidity and potential economic impact on a community . N Engl J Med 1980;;302:189-193.
11 +
Marx SJ, Spiegel AM, Brown EM, et al:  Divalent cation metabolism: Familial hypocalciuric hypercalcemia versus typical primary hyperparathyroidism . Am J Med 1978;;65:235-242.
12 +
Marx SJ:  Familial hypocalciuric hypercalcemia . N Engl J Med 1980;;303:810-811.
13 +
Raisz LG, Yajnik CH, Bockman RS, et al:  Comparison of commercially available parathyroid hormone immunoassays in the differential diagnosis of hypercalcemia due to hyperparathyroidism or malignancy . Ann Intern Med 1979;; 91:739-740.
14 +
Singer FR, Bethune JE, Massry SG:  Hypercalcemia and hypocalcemia . Clin Nephrol 1977;;7:154-162.
15 +
Dixon WJ, Brown MB (eds): BMDP-79: Biomedical Computer Programs, P-series . Berkeley, Calif, University of California Press, 1979;, pp 170-184, 711-733.
16 +
Feinstein AR:  Clinical biostatistics: XXXI. On the sensitivity, specificity, and discrimination value of diagnostic tests . Clin Pharmacol Ther 1975;;17:104-116.
17 +
Galen RS, Gambino SR: Beyond Normality: The Predictive Value and Efficiency of Medical Diagnosis . New York, John Wiley & Sons Inc, 1975;.
18 +
Amenta JS, Harkins ML:  The use of discriminant functions in laboratory medicine: Evaluation of phosphate clearance studies in the diagnosis of hyperparathyroidism . Am J Clin Pathol 1971;;55:330-341.
19 +
Fraser P, Healy M, Rose N, et al:  Discriminant functions in differential diagnosis of hypercalcemia . Lancet 1971;;1:1314-1319.
20 +
Transbol I, Jorgensen FS, Hornum I, et al:  Hypercalcemia discrimination index: A multivariate analysis of parathyroid function in 107 hypercalcemic patients . Acta Endocrinol 1977;; 86:768-783.
21 +
Watson L, Moxham J, Fraser P:  Hydrocortisone suppression test and discriminant analysis in differential diagnosis of hypercalcemia . Lancet 1980;;1:1320-1325.
22 +
Gordan GS:  Hyper- and hypocalcemia: Pathogenesis and treatments . Ann NY Acad Sci 1974;;230:181-186.
23 +
Singer FR, Powell D, Minkin C, et al:  Hypercalcemia in reticulum cell sarcoma without hyperparathyroidism or skeletal metastases . Ann Intern Med 1973;;78:365-369.

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1 +
Habener JF, Segre GV:  Parathyroid hormone radioimmunoassay . Ann Intern Med 1979;; 91:782-785.
2 +
Potts JT Jr, Krutzik SR:  Parathyroid hormone (PTH) , in Nichols AL, Fisher DA (eds): Radioimmunoassay Manual , ed. 3. San Pedro, Calif, The Nichols Institute, 1976;, pp 209-220.
3 +
Strott CA, Nugent CA:  Laboratory tests in the diagnosis of hyperparathyroidism in hypercalcemic patients . Ann Intern Med 1968;;68:188-202.
4 +
Palmer FJ, Nelson JC, Bacchus H:  The chloride-phosphate ratio in hypercalcemia . Ann Intern Med 1974;;80:200-204.
5 +
Kaminsky NI, Broadus AE, Hardman JG, et al:  Effects of parathyroid hormone on plasma and urinary adenosine 3′, 5'-monophosphate in man . J Clin Invest 1970;;49:2387-2395.
6 +
Scholz DA, Purnell DC, Goldsmith RS, et al:  Diagnostic considerations in hypercalcemic syndromes . Med Clin North Am 1972;;56:941-950.
7 +
Lafferty FW:  Pseudohyperparathyroidism . Medicine 1966;;45:247-260.
8 +
McLellan G, Baird CW, Melick R:  Hypercalcemia in an Australian hospital adult population . Med J Aust 1968;;2:354-356.
9 +
Lee DB, Zawada ET, Kleeman CR:  The pathophysiology and clinical aspects of hypercalcemic disorders . West J Med 1978;;129:278-320.
10 +
Heath H III, Hodson SF, Kennedy MA:  Primary hyperparathyroidism: Incidence, morbidity and potential economic impact on a community . N Engl J Med 1980;;302:189-193.
11 +
Marx SJ, Spiegel AM, Brown EM, et al:  Divalent cation metabolism: Familial hypocalciuric hypercalcemia versus typical primary hyperparathyroidism . Am J Med 1978;;65:235-242.
12 +
Marx SJ:  Familial hypocalciuric hypercalcemia . N Engl J Med 1980;;303:810-811.
13 +
Raisz LG, Yajnik CH, Bockman RS, et al:  Comparison of commercially available parathyroid hormone immunoassays in the differential diagnosis of hypercalcemia due to hyperparathyroidism or malignancy . Ann Intern Med 1979;; 91:739-740.
14 +
Singer FR, Bethune JE, Massry SG:  Hypercalcemia and hypocalcemia . Clin Nephrol 1977;;7:154-162.
15 +
Dixon WJ, Brown MB (eds): BMDP-79: Biomedical Computer Programs, P-series . Berkeley, Calif, University of California Press, 1979;, pp 170-184, 711-733.
16 +
Feinstein AR:  Clinical biostatistics: XXXI. On the sensitivity, specificity, and discrimination value of diagnostic tests . Clin Pharmacol Ther 1975;;17:104-116.
17 +
Galen RS, Gambino SR: Beyond Normality: The Predictive Value and Efficiency of Medical Diagnosis . New York, John Wiley & Sons Inc, 1975;.
18 +
Amenta JS, Harkins ML:  The use of discriminant functions in laboratory medicine: Evaluation of phosphate clearance studies in the diagnosis of hyperparathyroidism . Am J Clin Pathol 1971;;55:330-341.
19 +
Fraser P, Healy M, Rose N, et al:  Discriminant functions in differential diagnosis of hypercalcemia . Lancet 1971;;1:1314-1319.
20 +
Transbol I, Jorgensen FS, Hornum I, et al:  Hypercalcemia discrimination index: A multivariate analysis of parathyroid function in 107 hypercalcemic patients . Acta Endocrinol 1977;; 86:768-783.
21 +
Watson L, Moxham J, Fraser P:  Hydrocortisone suppression test and discriminant analysis in differential diagnosis of hypercalcemia . Lancet 1980;;1:1320-1325.
22 +
Gordan GS:  Hyper- and hypocalcemia: Pathogenesis and treatments . Ann NY Acad Sci 1974;;230:181-186.
23 +
Singer FR, Powell D, Minkin C, et al:  Hypercalcemia in reticulum cell sarcoma without hyperparathyroidism or skeletal metastases . Ann Intern Med 1973;;78:365-369.

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