Page 158 - Fluid, Electrolyte, and Acid-Base Disorders in Small Animal Practice

148 ELECTROLYTE DISORDERS

100

N-terminal PTHrP (pM) 10

Detectability = 1.8 pM

1
Control CAC CAC Lymphoma Lymphoma Misc. Misc.
normo- hyper- normo- hyper- normo- tumor tumor
calcemia calcemia calcemia calcemia calcemia hyper- normo-
calcemia calcemia
Figure 6-17 Circulating N-terminal parathyroid hormone-related protein (PTHrP) concentrations in
normal dogs (CONTROL); dogs with hypercalcemia (>12 mg/dL) and anal sac adenocarcinomas (CAC),
lymphoma, or miscellaneous tumors (MISC TUMOR); and dogs with normocalcemia (<12 mg/dL) and anal
sac adenocarcinomas, lymphoma, or miscellaneous tumors. (From Rosol TJ, Nagode LA, Couto CG, et al.
Parathyroid hormone-related protein, parathyroid hormone, and 1,25-dihydroxyvitamin D in dogs with
cancer-associated hypercalcemia. Endocrinology 1992;131:1157–1164.)

histopathology failed to detect PTHrP in the neoplastic Canine Adenocarcinoma Derived from Apocrine
cells. 44 These findings indicate that PTHrP is an impor- Glands of the Anal Sac
tant marker of HHM in dogs with lymphoma but is The adenocarcinoma derived from apocrine glands of the
not the sole humoral factor responsible for stimulation anal sac of dogs consistently fulfills the criteria for
of osteoclasts and development of hypercalcemia. It is HHM. 377,379,473 This tumor appears primarily in mid-
likely that cytokines such as IL-1 or TNF function syner- dle-aged (mean, 10 years) dogs and rarely metastasizes
gistically with PTHrP to induce HHM in dogs with lym- to bone. Clinical signs are referable to hypercalcemia
phoma (see Fig. 6-14). 479,480 (polyuria, polydipsia, anorexia, and weakness), a mass in
Some dogs and human patients with lymphoma the perineum (tenesmus, ribbon-like stools, increased
and hypercalcemia have increased serum calcitriol odor, and protruding mass), a mass in the sublumbar
concentrations, which may contribute to the induction region, or more distant metastases. Apocrine
of hypercalcemia. 489,527 Some lymphocytes contain the adenocarcinomas often require rectal and anal sac palpa-
1a-hydroxylase (similar to that found in renal tubules) tion to confirm their presence because their sizes range
that converts 25-hydroxyvitamin D to the active metab- from 7 mm to 6 8cm(Fig. 6-18). Dogs with this tumor
olite 1,25-dihydroxyvitamin D (calcitriol). Therefore, and HHM have hypercalcemia (tCa, 12 to 24 mg/dL);
lymphomas that retain this capability may synthesize hypophosphatemia; decreased immunoreactive PTH
excessive calcitriol, which could increase calcium absorp- concentration; increased urinary excretion of calcium,
tion from the intestinal tract and facilitate development of phosphorus, and cAMP; and increased osteoclastic bone
hypercalcemia. resorption. 36,379,615 This tumor should not be confused
An early report indicated that a mediastinal mass was with the common perianal adenomas or the uncommon
detected in most dogs with lymphoma and hypercalce- perianal adenocarcinomas that arise from the circumanal
mia. 378 However, a recent report indicates that the pres- glands and have entirely different biologic behavior.
ence of a cranial mediastinal mass was not required for Perianal adenomas and adenocarcinomas affect primarily
development of hypercalcemia in dogs, and mediastinal male dogs and are not associated with hypercalcemia. 591
masses were not disproportionately more common in Hypercalcemia was present at the time of diagnosis in
those dogs with hypercalcemia. 54 80% to 100% of affected dogs in early studies. 357,360