Physiology of Calcium Metabolism
The four parathyroid glands, through secretion of parathyroid hormone (PTH), regulate serum calcium concentrations and bone
metabolism. The concentration of serum ionized calcium is normally maintained within narrow limits by action of the PTH on
bone resorption, renal calcium excretion and metabolism of Vitamin D. Calcium is present in two main forms in plasma: ionized
and protein bound (primarily to albumin). Clinically significant hypercalcemia and hypocalcemia involve changes in the ionized
component. PTH is controlled by plasma calcium concentration with hypocalcemia promoting release and hypercalcemia inhibiting
secretion. PTH is also regulated in the long term by cellular changes in parathyroid hormone messenger RNA, and by changes
in the growth of the parathyroid glands themselves. Metabolites of Vitamin D directly inhibit the mass of parathyroid cells.
Disruptions in these processes cause hyperparathyroidism or hypoparathyroidism.
Factors that alter distribution of calcium in plasma include hypoalbuminemia, acid-base status, and methodology of the machine
measuring the level, which may be affected by such factors as lipemia or hemolysis.
Primary Hyperparathyroidism in Dogs
Primary hyperparathyroidism in dogs is a condition of uncontrolled secretion of PTH by the parathyroid chief cells. Histologically
this is most often due to parathyroid adenoma (one or more glands), but may be due to parathyroid hyperplasia (involving more
than one gland), or less commonly malignant tumors. Primary hyperparathyroidism is generally seen in older dogs and males
and females are diagnosed equally often.
Physical examination may be unremarkable, and the mass is generally non-palpable in the ventral cervical neck region. Some
dogs have poor body condition, and evidence of muscle weakness or fasciculation.
Most patients with primary hyperparathyroidism have high serum PTH concentrations, serum total calcium concentrations and
serum ionized calcium concentrations. It is possible though to have PTH within the normal range with a concurrent hypercalcemia,
which is still considered consistent with the disease.
Because parathyroid masses are usually functional, we see biochemical alterations in the patients diagnosed with this disease.
PTH stimulates calcium reabsorption and inhibits phosphate reabsortion by the kidney, stimulates synthesis of Vitamin D, and
stimulates bone resorption. The net effect is to increase serum ionized and total calcium and decrease serum phosphorus concentrations.
The initial step in diagnosis of any abnormality of calcium is to repeat the calcium measurement and ensure that the finding
is persistent and repeatable. The most common differential diagnoses for hypercalcemia and hypophosphatemia are primary hyperparathyroidism
and hypercalcemia of malignancy. Diagnosis of primary hyperparathyroidism is through process of elimination of the possibility
of neoplasia elsewhere, as well as clinical signs and diagnostic test results consistent with the disease.
Common clinical signs include: polyuria/polydipsia, lower urinary tract signs (calcium containing stones or crystals), gastrointestinal
signs, neuromuscular weakness or twitching, gastrointestinal signs such as vomiting or diarrhea, and decreased appetite. It
is possible that this disease is discovered incidentally, as many signs are slowly progressive and mild initially. In general
diagnostic testing that is required includes: complete blood count, chemistry profile, urinalysis, thoracic radiographs, abdominal
and cervical ultrasound, PTHrp and PTH measured concurrently with ionized calcium.