Page 160 - Fluid, Electrolyte, and Acid-Base Disorders in Small Animal Practice

150 ELECTROLYTE DISORDERS

Prostaglandin E 2 may be an important local mediator of reference range in 73% of dogs. Primary hyperparathy-
bone resorption in these dogs. Other potential mediators roidism was caused by a solitary parathyroid gland ade-
include IL-1 and TNFs. noma in approximately 90% of dogs, whereas
parathyroid gland carcinoma and parathyroid gland
Tumors Metastatic to Bone hyperplasia each accounted for 5% of cases in one large
Solid tumors that metastasize widely to bone can produce series. 178 Adenomas occurred with nearly equal fre-
hypercalcemia by the induction of local bone resorption quency in the external and internal parathyroid glands
associated with tumor growth. This is not common in in one study, 40 but external gland adenomas
animals but is an important cause of cancer-associated predominated in another report in dogs. 619 Idiopathic
hypercalcemia in humans. 479,493,494 Tumors that often parathyroid gland hyperplasia may affect one or more
metastasize to bone and induce hypercalcemia in human glands and has been reported in six older dogs. 143
patients include breast and lung carcinomas. Carcinomas Although remnant parathyroid tissue may be found in
of the mammary gland, prostate, liver, and lungs were the cranial mediastinum near the base of the heart, neo-
most frequently reported to metastasize to bone in dogs, plastic transformation has not been reported at this site in
and the humerus, femur, and vertebrae were the most dogs or cats. An ectopic parathyroid gland adenoma cra-
common sites of metastasis. 380,495 Primary bone tumors nial to the thoracic inlet has been described in one dog. 618
are not often associated with hypercalcemia in dogs or In cats, the underlying lesion is typically benign, owing to
cats. an adenoma, bilateral cystadenomas, or hyperpla-
The pathogenesis of enhanced bone resorption is not sia, 141,172,511,550 but unilateral or bilateral carcinomas
well understood, but two primary mechanisms are secre- have also been diagnosed. 178,285,353,452
tion of cytokines or factors that stimulate local bone Primary parathyroid gland hyperplasia has been
resorption and indirect stimulation of bone resorption reported in two German shepherd dog puppies. 568 Dif-
by tumor-induced cytokine secretion from local immune fuse hyperplasia was present in all four parathyroid glands.
or bone cells. 207 Cytokines or factors that may be secreted In retrospect, this family of German shepherd dogs prob-
by tumor cells and stimulate local bone resorption include ably had an inactivating mutation in the gene for the cal-
PTHrP, 457 TGF-a and TGF-ß, and prostaglandins (espe- cium-sensing receptor. Mutations in one or both of the
cially prostaglandin E 2 ). In some cases, bone-resorbing calcium-sensing receptor genes in humans result in famil-
activity can be inhibited by indomethacin, which suggests ial hypocalciuric hypercalcemia or neonatal severe hyper-
that prostaglandins are either directly or indirectly calcemia, respectively, because of an inadequate ability to
associated with stimulation of bone resorption. The sense extracellular calcium concentration and coordinate
cytokines most often implicated in indirect stimulation the appropriate cellular response. 454 The affected puppies
of bone resorption by local immune cells include IL-1 had a disease syndrome that mimicked neonatal severe
and TNFs. hypercalcemia in humans. Neonatal severe hypercalcemia
Malignant neoplasms with osseous metastases may is lethal unless total parathyroidectomy is performed early
cause moderate to severe hypercalcemia and in life to markedly reduce increased PTH concentrations.
hypercalciuria, but serum ALP activity and phosphorus Dogs with primary hyperparathyroidism are older: in
concentrations are usually normal or only moderately one review of 210 dogs with primary hyperparathyroid-
increased. It is believed these changes are caused by ism, the mean age of affected dogs was 11.2 years (range,
release of calcium and phosphorus into the blood from 6 to 17 years); 177 in another study, the mean age of
areas of bone destruction at rates greater than can be affected dogs was 10.5 years (range, 5 to 15 years). 178
cleared by the kidneys and intestine. Bone involvement The mean age in affected cats was 12.9 years (range,
can be multifocal but is usually sharply demarcated and 8 to 15 years). 285 No sex predisposition has been noted,
localized to the area of metastasis. but keeshonds constituted 36% of affected dogs, and five
380
of eight cats were Siamese. Parathyroid gland masses
Primary Hyperparathyroidism usually cannot be palpated in dogs, but 50% of cats with
Primary hyperparathyroidism is an uncommon cause of primary hyperparathyroidism had a palpable cervical
hypercalcemia in dogs 40,87 and is even less common in mass. 141,285 Clinical signs related to hypercalcemia are
cats. 141,285 In hypercalcemic cats, primary hyperparathy- either mild (e.g., lethargy, polydipsia, polyuria, and weak-
roidism was found in 4 of 71 cases. 511 Excessive and inap- ness) or absent in many affected dogs. 40,178 In one study,
propriate secretion of PTH by the parathyroid glands most owners of affected dogs were not convinced that
relative to the serum iCa concentration characterizes this their dogs had a serious illness, 40 but some owners retro-
condition. In a review of 210 dogs with primary hyper- spectively recognized subtle signs after hypercalcemia
parathyroidism, all dogs had hypercalcemia, and 65% resolved. 178 In 210 dogs with primary hyperparathyroid-
had hypophosphatemia. BUN and serum creatinine ism, the most common clinical signs were related to uri-
concentrations were within or below the reference range nary tract infections or urolithiasis. 177 No abnormalities
in 95% of cases. Serum PTH concentration was within the were noted in 71% of dogs. Urinary tract infection was