Calcium is involved in many cellular and extracellular processes that include neuromuscular transmission, muscle contraction/tone,
hormone secretion, bone homeostasis, coagulation, membrane transport systems, and other cell regulatory pathways. Calcium
is measured as ionized (active form, roughly 50%) or total (ionized + albumin bound + anion bound). The extracellular fluid
ionized calcium is tightly regulated by interactions between the parathyroid glands, bone, the intestinal tract, and kidneys.
Parathyroid hormone (PTH) is secreted by the chief cells of the parathyroid glands primarily in response to low extracellular
ionized calcium.1 Increased ionized calcium stops the secretion of PTH. Parathyroid hormone stimulates calcium and phosphorus absorption
from the bone via increased activity of osteoclasts.1 Parathyroid hormone increases calcium reabsorption in the distal convoluted
tubule and decreases phosphorus reabsorption in the proximal renal tubules so more calcium is retained and more phosphorus
lost.1 Parathyroid hormone also increases the production of 1,25-dihydroxyvitamin D by the kidneys which increases calcium absorption
from the intestinal tract. 1,25-dihidroxyvitamin D also provides negative feedback to the parathyroid glands. Vitamin D3
(cholecalciferol) is produced from 7-dehydrocholesterol which is found in high concentration in the skin. Vitamin D3 is then
converted to 25-hydroxyvitamin D in the liver and 25-hydroxyvitamin D is converted to 1,25-dihydroxyvitamin D in the kdineys.
1,25-dihydroxyvitamin D inhibits its own synthesis. Hypercalcemia also inhibits 1,25-dihydroxyvitamin D. High serum ionized
calcium, in addition to inhibiting PTH secretion, stimulates calcitonin release from the C cells of the thyroid gland. Calcitonin
decreases serum calcium and phosphorus by decreasing osteoclastic activity within the bone. Calcitonin also promotes phosphorus
excretion via inhibition of phosphorus reabsorption in the proximal renal tubules.
Differentials for Hypercalcemia
Granulomatous disease - infectious
Increased osteoclastic activity
Vitamin D toxicosis
Renal Failure (Acute & Chronic)
Nutritional Secondary Hyperparathyroidism
Apocrine gland anal sac adenocarcinoma*
Testicular interstitial cell tumors
Primary hyperparathyroidism (PHPTH) is an uncommon disease in dogs and very rare in cats. Most masses are single adenomas
with less than 10% occurring as adenocarcinomas. There is a report of a single cat with bilateral cystadenomas and primary
hyperparathyroidism. There have also been reports of hyperplasia of the parathyroid glands in dogs and cats leading to PHPTH.
This is a disease that typically affects middle aged to older dogs and cats. There is no sex predilection. In the Keeshonden,
PHPTH is inherited as an autosomal dominant trait. There is also a single report of an inherited form of PHPTH in German shepherd
Clinical signs may be absent and hypercalcemia found incidentally. In fact in one group of dogs with PHPTH, 88/210 owners
brought their dogs in to be evaluated for reasons unrelated to PHPTH.2 The most common signs are polyuria, polydipsia, decreased appetite, weight loss, lethargy, and lower urinary tract signs.
Vomiting, diarrhea, constipation, seizures, and renal osteodystrophy are less common.Signs may be present for months to years
prior to presentation. Cats most often present with anorexia, lethargy and vomiting. Parathyroid glands are normally not palpable
in dogs and cats. Masses are not palpable in dogs with PHPTH but may be in cats.
There are no significant abnormalities on the CBC. Total serum calcium is increased consistently. Ionized calcium is increased
in most animals but may be normal. Phosphorus is usually low or low normal. Kidney values may be elevated in dogs and catsIf
renal values are increased they present a diagnostic dilemma, is this an animal with renal failure and a secondary form of
hyperparathyroidism? Does this animal have concurrent renal disease and PHPTH? Or is this an animal with PHPTH and renal
disease secondary to mineralization? Typically dogs with CRF have hyperphosphatemia and a normal to low ionized calcium whereas
with PHPTH phosphorus is normal to low with an increase in ionized and total calcium. With PHPTH, urine may be minimally
concentrated, isosthenuric or hyposthenuric. Liver enzymes are elevated in some dogs and cats with PHPTH.Uroliths and urinary
tract infections are fairly common in dogs so calcium-containing crystalluria, hematuria, pyuria, proteinuria, and bacteruria
may also be present. Urinary tract infections and calculi are rare in cats.
Assays for PTH currently utilized are either a two-site immunoradiomimetric assay or sandwich ELISA available and validated
for the dog and cat. PTH is normal to increased in dogs and cats with PHPTH.2 The importance is that as calcium increases PTH should decrease, which does not occur with PHPTH.
Radiography may be used to evaluate for other causes of hypercalcemia, concurrent disease, urinary tract calculi and boney
changes (renal osteodystrophy). Local invasion and distant metastases have not been reported with malignant tumors. Parathyroid
tumors are readily identifiable utilizing ultrasoundParathyroid adenomas are round, hypoechoic and tend to be over 4 mm in
size. Hyperplastic nodules (CRF, nutritional secondary) tend to be smaller than adenomas.15,20 The majority of animals have
a single enlarged parathyroid but a few have 2 enlarged parathyroid glands.