Page 159 - Fluid, Electrolyte, and Acid-Base Disorders in Small Animal Practice

Disorders of Calcium: Hypercalcemia and Hypocalcemia 149

Serum calcium concentrations in affected dogs correlate
well with circulating PTHrP concentrations, which is
consistent with the concept that PTHrP plays a primary
role in the pathogenesis of HHM in these dogs. Dogs
with apocrine adenocarcinomas and normocalcemia
may have increased plasma PTHrP concentrations (2 to
15 pmol/L), but the concentrations are lower than those
in dogs with hypercalcemia.
Some dogs with apocrine adenocarcinomas have inap-
propriate concentrations (normal or increased) of
calcitriol for the degree of hypercalcemia. 489 This finding
suggests that the humoral factors produced by the neo-
plastic cells are capable of stimulating renal 1a-hydroxy-
lase and increasing the formation of calcitriol even in
the presence of increased serum calcium concentration.
PTH concentrations were not increased in hypercalcemic
dogs and were significantly lower than those observed in
dogs with primary hyperparathyroidism. Parathyroid
glands from dogs with apocrine adenocarcinoma were
atrophic or inactive, and there was nodular hyperplasia
of C cells in the thyroid glands because of prolonged
Figure 6-18 Hypercalcemia of malignancy associated with 379
apocrine gland adenocarcinoma of the anal sac in an elderly female hypercalcemia.
dog. Transverse section of the anal sac and associated malignancy
(arrows). (From Chew DJ, Meuten DJ. Disorders of calcium and Hematologic Malignancies
phosphorus metabolism. Vet Clin North Am Small Anim Pract Some types of hematologic malignancies present in the
1982;12:411–438.) bone marrow produce hypercalcemia by inducing bone
resorption locally. 479,480 This effect occurs most com-
monly in multiple myeloma and lymphoma. Hypercalce-
Recent reports in dogs with earlier detection note the mia has been reported in 17% of dogs 360 and 20% of cats
incidence of hypercalcemia to be lower, at 33%, 496 with multiple myeloma. 435 Hypercalcemia has also been
27%, 615 and 53% of cases. 36 Early reports also noted a noted in a case of erythrophagocytic multiple myeloma
strong bias toward the occurrence of this tumor in female in a cat. 605 In one dog with multiple myeloma, an increase
dogs, but equal sex distribution has been more recently in tCa was noted, but iCa concentration was within the
noted. 615 In some instances, the finding of hypercalcemia reference range. 580 In this case the increase in tCa con-
during routine serum biochemistry testing prompts rectal centration was presumptively due to an increase in the
palpation and subsequent discovery of an apocrine gland protein-bound serum calcium concentration. A number
adenocarcinoma. Surgical removal or radiation therapy of of paracrine factors or cytokines may be responsible for
the adenocarcinoma results in rapid return to normal of the stimulation of bone resorption in this setting. The
serum calcium and phosphorus concentrations, increased cytokines most often implicated in the pathogenesis of
serum PTH concentration, and decreased calcitriol con- local bone resorption are IL-1, TNF-a, and TNF-ß
centration. 489 Postsurgical survival of dogs with apocrine (lymphotoxin). 355,397 Other cytokines or factors that
gland adenocarcinoma and hypercalcemia ranged from may play a role include IL-6, TGF-a and TGF-ß, and
2 to 21 months, with a mean of 8.8 months. Sublumbar PTHrP. 53 Production of small amounts of PTHrP by a
metastases occur in a high percentage (72%) of affected tumor in bone may stimulate local bone resorption with-
dogs and are associated with recrudescence of the bio- out inducing a systemic response. Prostaglandins (espe-
chemical alterations in serum and urine. 36 In one study, cially prostaglandin E 2 ) may also be responsible for
dogs with hypercalcemia and anal sac adenocarcinoma local stimulation of bone resorption.
had shorter survival times compared with normocalcemic Some dogs with lymphoma and hypercalcemia have
dogs with this tumor (356 vs. 584 days) 615 ; in another localized bone resorption associated with metastases to
study, survival was not influenced by the presence of medullary cavities without evidence of increased bone
hypercalcemia. 36 resorption at sites distant from the tumor metastases. 378
Most dogs with HHM have increased concentrations Hypercalcemic dogs with lymphoma and bone metastases
of circulating PTHrP (see Fig. 6-17). Plasma had decreased PTH and calcitriol concentrations,
concentrations of PTHrP are highest (10 to 100 pmol/ increased excretion of hydroxyproline, calcium, phospho-
L) in dogs with apocrine adenocarcinomas of the anal rus, and increased concentrations of the prostaglandin E 2
sac and sporadic carcinomas associated with HHM. 489 metabolite 13,14-dihydro-15-ketoprostaglandin E 2 .