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Calcitriol Production in Hypercalcemic and Normocalcemic Patients with Non-Hodgkin Lymphoma

John F. Seymour, MBBS; Robert F. Gagel, MD; Frederick B. Hagemeister, MD; Meletios A. Dimopoulos, MD; and Fernando Cabanillas, MD
[+] Article and Author Information

From the Royal Melbourne Hospital, Victoria, Australia, and the M.D. Anderson Cancer Center, Houston, Texas. Requests for Reprints: John F. Seymour, MBBS, Department of Clinical Haematology and Medical Oncology, Royal Melbourne Hospital, Grattan Street, Parkville 3050, Victoria, Australia.


Copyright ©2004 by the American College of Physicians


Ann Intern Med. 1994;121(9):633-640. doi:10.7326/0003-4819-121-9-199411010-00001
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Objective: To determine the following: a reference range for serum calcitriol during hypercalcemia in a control group of patients with myeloma in whom calcitriol production is known to be appropriately suppressed; the incidence of elevated serum calcitriol levels in hypercalcemic patients with non-Hodgkin lymphoma according to this derived reference range; and the incidence of abnormal calcium metabolism in normocalcemic patients with non-Hodgkin lymphoma.

Design: Prospective clinical study.

Setting: Referral cancer center.

Patients: 2 groups of hypercalcemic patients: 16 control patients with myeloma and 22 patients with non-Hodgkin lymphoma divided into those with elevated or normal serum calcitriol levels; 1 group of 22 normocalcemic patients with non-Hodgkin lymphoma.

Measurements: Serum chemistries and intact parathyroid hormone, calcitriol, parathyroid hormone–related protein, and urinary electrolyte levels.

Results: On the basis of the mean serum calcitriol level of the control group plus 3 standard deviations, the reference range for serum calcitriol during hypercalcemia was defined as less than 42 pg/mL. Although serum calcium and parathyroid hormone levels in the study patients were similar to those in controls, 12 of the 22 hypercalcemic patients with non-Hodgkin lymphoma (55%) had serum calcitriol levels greater than 42 pg/mL (range, 51 to 170 pg/mL). No features distinguished the patients with elevated serum calcitriol levels from those with normal levels. Seventy-one percent of normocalcemic patients with non-Hodgkin lymphoma were hypercalciuric, and 18% had serum calcitriol levels greater than the normocalcemic reference range (20 to 76 pg/mL).

Conclusions: Serum calcitriol levels are elevated in most hypercalcemic patients with non-Hodgkin lymphoma in the absence of elevated serum levels of parathyroid hormone, which implicates extrarenal calcitriol production in the pathogenesis of this syndrome. Abnormal calcium metabolism, hypercalciuria, and dysregulated calcitriol production are also common in normocalcemic patients with non-Hodgkin lymphoma.

Figures

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Figure 1.
Distribution of serum levels of parathyroid hormone–related protein (PTHrP), intact parathyroid hormone (PTH), and calcitriol and corrected serum calcium of control patients with multiple myeloma (right column) and of patients with non-Hodgkin lymphoma and either elevated (left column) or normal (center column) serum calcitriol levels.

The reference range for each variable is indicated by the shaded area, and the median values are indicated by the horizontal bars. The reference range for serum calcitriol during hypercalcemia was defined as the mean of the serum calcitriol levels in the control patients ±3 SD. To convert serum calcium values to mmol/L, multiply by 0.2495.

Grahic Jump Location
Grahic Jump Location
Figure 2.
Distribution of urinary calcium excretion and serum levels of intact parathyroid hormone (PTH), calcitriol, and corrected calcium among normocalcemic patients with non-Hodgkinlymphoma.

The normal range is indicated by the shaded area, and the median value is indicated by the horizontal bars. To convert serum calcium values to mmol/L, multiply by 0.2495. GF = glomerular filtration.

Grahic Jump Location

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