Managing calcium disorders (Proceedings)
Clinical signs of hypercalcemia can be difficult to detect. Usually, hypercalcemic animals have no clinical signs other than those referable to the underlying disease causing the calcium derangement. There are usually no signs due to hypercalcemia itself. In some cases, however, signs of hypercalcemia are present, and include polyuria/polydipsia (this is the most common sign), constipation, vomiting, anorexia, neurological signs, muscle wasting, fatigue, and, if calcium containing uroliths are present due to longstanding hypercalciuria, lower urinary tract signs can be present.
The number one ruleout for hypercalcemia in dogs is lymphoma. In fact, this is such a common cause that lymphoma must be pursued rigorously in any dog with hypercalcemia before another diagnosis is considered.
Hypercalcemia of MalignancyParathyroid hormone-related peptide (PTHrp) is secreted by a wide variety of neoplastic cells (notably lymphoma in the dog), and has similar actions to those of PTH on bone but not on the kidney. Roughly 40% of hypercalcemic dogs with lymphoma has mediastinal masses, but hypercalcemia is common in other types of lymphoma as well. Hypercalcemia is much less common in feline lymphoma than in its canine counterpart. Other causes of hypercalcemia of malignancy include apocrine gland adenocarcinoma of the anal sac, and any tumor that has osteolytic activity. Such tumors include multiple myeloma and osteosarcoma. These tumors are thought to secrete cytokines that activate osteoclasts, thereby resorbing bone and elevating serum calcium concentrations.
Primary hyperparathyroidism is caused by an autonomously hyperfunctioning adenoma of the chief cells of the parathyroid gland. Carcinoma of the parathyroid gland is also possible, but it is uncommon and is usually not invasive. Primary hyperparathyroidism occurs usually in older dogs, and the Keeshond is over-represented, so there may be a genetic basis for the disease in this breed. While it does occur, primary hyperparathyroidism is rare in cats.
The physical examination findings in animals with primary hyperparathyroidism are usually normal. An enlarged parathyroid gland is usually not palpable in dogs, but can be palpated about half of the time in cats with the disease. The problem with cervical palpation in cats is the difficulty in distinguishing a parathyroid adenoma from a thyroid nodule. Clinical signs of primary hyperparathyroidism are usually related to the effects of prolonged hypercalcemia rather than to the PTH-secreting mass itself.
Urinalysis is critical to the work-up of the disease. Calcium-containing crystals, isosthenuria, hematuria, and/or pyuria can be present. CBC is usually normal, but is necessary to rule out other causes of hypercalcemia. The serum chemistry profile, besides hypercalcemia, shows a normal or low serum phosphorus concentration. Azotemia can be present because of the deleterious effects of hypercalcemia on the kidney (renal mineralization).
In hypercalcemia of any cause, treatment of hypercalcemia is needed if the product of calcium x phosphorus exceeds 75. Fluid therapy is used to cause calciuresis and to increase glomerular filtration rate. Furosemide can also be used to promote urinary calcium loss. Glucocorticoids can be useful to promote urinary calcium excretion and to inhibit absorption of calcium from the gut, but extreme care must be taken to ensure that a diagnosis of lymphoma has been excluded. The phosphonate drug pamidronate can also be used to decrease bone resorption, so it is a logical choice in the treatment of hypercalcemia of malignancy.
To treat the primary condition, surgical parathyroidectomy is indicated. At the time of surgery, all four parathyroid glands must be inspected, although solitary gland involvement is by far the most common finding. Recurrence of hyperparathyroidism is extremely uncommon following surgery, and surgery is, therefore, almost always curative.