Correspondence

Treatment of Primary Hyperparathyroidism

N Engl J Med 2000; 342:976-977March 30, 2000

Article

To the Editor:

We take issue with some of the recommendations made by Utiger in his editorial on the treatment of primary hyperparathyroidism (Oct. 21 issue).1 Measurement of serum calcium was advocated, with no mention of correction for abnormal serum albumin concentrations or measurement of serum ionized calcium. We and others have found that measurements of serum ionized calcium are superior to measurements of serum total calcium or albumin-corrected calcium in the diagnosis of primary hyperparathyroidism.2,3 In our study of 60 patients with pathologically confirmed primary hyperparathyroidism, 22 percent of the patients had corrected serum total calcium concentrations within the reference range, whereas all but 1 had high serum ionized calcium concentrations.2 In addition, Thode et al. noted a diagnostic discordance between uncorrected serum total calcium and ionized calcium concentrations in patients with high serum calcium concentrations and those with low serum calcium concentrations.3 We believe that in most patients with osteoporosis, especially postmenopausal women, serum ionized calcium should be measured to rule out primary hyperparathyroidism, which is a surgically correctable condition.

We do not believe that familial benign hypercalcemia can be distinguished from primary hyperparathyroidism by “careful history taking and measurements of urinary calcium.” The biochemical diagnosis of familial benign hypercalcemia is complex; measurements of serum parathyroid hormone and fasting urinary calcium excretion (corrected for the glomerular filtration rate) in combination provide the best means of discriminating between these disorders.4

Although preoperative imaging has improved substantially in recent years, particularly with the advent of technetium-99m sestamibi imaging, we do not believe the 1991 National Institutes of Health consensus recommendations for gland localization should be changed, as Utiger suggests. Surgical localization continues to be superior to preoperative imaging in patients who require neck exploration, particularly in those with mild hypercalcemia. Preoperative imaging should chiefly be considered if previous surgical exploration has failed.5

Paul Glendenning, M.B., Ch.B.
University of Western Australia, Perth 6009, Australia

Donald H. Gutteridge, M.B., B.S.
Robert W. Retallack, Ph.D.
Sir Charles Gairdner Hospital, Perth 6009, Australia

5 References

1. 1

   Utiger RD. Treatment of primary hyperparathyroidism. N Engl J Med 1999;341:1301-1302
   Full Text | Web of Science | Medline

2. 2

   Glendenning P, Gutteridge DH, Retallack RW, Stuckey BGA, Kermode DG, Kent GN. High prevalence of normal total calcium and intact PTH in 60 patients with proven primary hyperparathyroidism: a challenge to current diagnostic criteria. Aust N Z J Med 1998;28:173-178
   Medline

3. 3

   Thode J, Juul-Jorgensen B, Bhatia HM, et al. Comparison of serum total calcium, albumin-corrected total calcium, and ionized calcium in 1213 patients with suspected calcium disorders. Scand J Clin Lab Invest 1989;49:217-223[Erratum, Scand J Clin Lab Invest 1990;50:113.]
   CrossRef | Web of Science | Medline

4. 4

   Stuckey BGA, Kent GN, Gutteridge DH, Pullan PT, Price RI, Bhagat C. Fasting calcium excretion and parathyroid hormone together distinguish familial hypocalciuric hypercalcaemia from primary hyperparathyroidism. Clin Endocrinol (Oxf) 1987;27:525-533
   CrossRef | Web of Science | Medline

5. 5

   Heath DA. Localization of parathyroid tumours. Clin Endocrinol (Oxf) 1995;43:523-524
   CrossRef | Web of Science | Medline

Author/Editor Response

Dr. Utiger replies:

To the Editor: I began my editorial by considering how hypercalcemia is discovered in different patients; in ordinary practice, this discovery always means that serum total calcium has been measured. In patients with high serum total calcium concentrations, measurements of serum ionized calcium provide little additional information, because the values will be high unless a patient has severe acute volume depletion or, in very rare cases, an abnormal serum globulin with high affinity for calcium. It may be appropriate to measure serum ionized calcium, as Glendenning et al. suggest, if hyperparathyroidism is suspected in a patient who has a normal serum total calcium concentration.

With respect to familial benign hypercalcemia, I think “careful history taking” includes a family history, but I should have specified that urinary calcium must be measured in urine collected while the patient is fasting. I disagree that the diagnosis of this disorder is complex; a family history of mild hypercalcemia or hypercalciuria in a patient with fasting hypercalciuria, mild hypercalcemia with a normal or slightly high serum parathyroid hormone concentration, and normal bone density constitutes strong evidence of this disorder.1,2

A parathyroid adenoma or hyperplasia is better identified by a surgeon than by a radiologist, and radiologic studies are not indicated when all parties agree that surgery is indicated. However, a positive radionuclide imaging study, particularly one showing a single region of high uptake, may encourage physicians to recommend surgery for patients who have few or no symptoms of hyperparathyroidism and who otherwise do not meet the criteria for surgery recommended by the National Institutes of Health consensus conference or may aid physicians in gaining the acceptance of surgery by patients who are reluctant to undergo a full neck exploration.

Robert D. Utiger, M.D.

2 References

1. 1

   Law WM Jr, Heath H III. Familial benign hypercalcemia (hypocalciuric hypocalcemia): clinical and pathogenetic studies in 21 families. Ann Intern Med 1985;102:511-519
   Web of Science | Medline

2. 2

   Segre GV, Potts JT Jr. Differential diagnosis of hypercalcemia. In: DeGroot LJ, ed. Endocrinology. 3rd ed. Vol. 2. Philadelphia: W.B. Saunders, 1995:1075-93.