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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.
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 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.
The therapeutic option of choice is surgical removal of the affected gland. There are medical methods of symptomatically reducing the calcium level, but these are generally just used in stabilization of the patient. An alternative at some institutions is heat ablation of the affected glands, which is considered to be less invasive but is not widely available. Often medical stabilization is required prior to surgery and medical management may be required for months following surgery, so owners should be aware of this prior to consenting to the procedure.
Medical approaches to reducing the serum calcium level, if it is causing life threatening side effects, include use of furosemide, glucocorticoids, and IV fluids containing 0.9% saline. In preparation for surgery, the possibility of post operative hypocalcemia must also be considered. If the total calcium is <14 mg/dl then the risk of postsurgical hypocalcemia is small, and no pretreatment is necessary. If the total calcium is >15 mg/dl or there are multiple parathyroid masses, it is recommended that Vitamin D (with or without calcium) supplementation be started the morning of surgery or immediately on recovery from anesthesia. This is an attempt to prevent a severe life threatening drop in calcium following the procedure. After surgery the dogs are treated as for hypocalcemia (see below) until they can be weaned off the calcium and vitamin D supplementation once the other glands have become functional again.
The prognosis is excellent.
Hypoparathyroidism can cause hypocalcemia with consequent paresthesia, muscle spasms, and seizures, especially when it occurs rapidly. Chronic hypoparathyroidism can cause visual impairment from cataracts. Early indicators of hypocalcemia include decreased appetite, decreased activity, facial twitching, irritability, restlessness, and anxiousness. In general, in our veterinary patients, the onset appears to be acute and severe. Primary hypoparathyroidism is the only differential diagnosis for severe hypocalcemia that occurs without other abnormalities on the physical examination or routine laboratory testing. There are two main reasons that primary hypoparathyroidism can occur; sudden correction of hypercalcemia (parathyroidectomy), and absence/destruction of the parathyroid glands (immune mediated). Suppression of secretion of PTH is also possible, but would be very rarely encountered (hypomagnesemia). All of the clinical signs can be attributed to lack of PTH, and subsequent hypocalcemia and hyperphosphatemia resulting in muscle spasms, seizures, decreased activity, facial rubbing, stiff gait, cardiac rhythm disturbances, and cataracts.
On routine laboratory testing total and ionized calcium is below the reference range and phosphorous is elevated or in the high normal range. Clinical signs do not usually occur unless the total serum calcium is <6.5 mg/dl or ionized calcium is < 0.7 mmol/l. Other hematological or biochemical abnormalities are not common. On electrocardiogram (EKG) increased duration of the S-T segment and the Q-T segments would be expected. Also deep, wide T waves and bradycardia can be seen. Magnesium deficiency may lead to functional hypoparathyroidism and should be assessed.
The goal of acute therapy in a crisis situation is to raise the calcium above the threshold that causes clinical signs. Clinical signs will usually be responsive to a small increase in calcium. Injectable 10% calcium gluconate is the drug of choice for initial therapy. It is given slowly to effect. The dose is 0.5-1.5 ml/kg body weight slowly over 10-30 minutes. Ideally the patient should be monitored by EKG and the administration slowed if arrhythmias occur or become more frequent.
Sub-acute therapy involves the use of intravenous or subcutaneous calcium. Intravenous infusions are given at 60-90 mg/kg/day of elemental calcium. Ideally total calcium should be maintained above 8 mg/dl. In the situation of post-surgical hypocalcemia, it should ideally be maintained low normal to stimulate the other parathyroid glands to regain function. Calcium gluconate may be given subcutaneously in the short term as animals are being weaned off parenteral therapy, but may lead to calcinosis cutis if given over a long period.
Maintenance therapy is centered on administration of a Vitamin D analog. Oral calcium is generally given initially but is discontinued if there is enough calcium in the diet. The vitamin D preparations that are considered the ideal choices, are calcitriol (1,25 dihydrovitamin D) and dihydrotachysterol. Compared with other formulations, both of these drugs have relatively short half lives so that the calcium level is more easily controlled. If the disease was spontaneously occurring, the therapy will be for life. If it was initiated following parathyroidectomy for hyperparathyroidism, it should be able to be discontinued after 2-4 months of tapering. Serial measurements of calcium and phosphorous, and frequent veterinary visits should be anticipated by the owner.
The most common long-term complication of therapy for hypoparathyroidism is hypercalcemia.
The prognosis is good, but the therapy can be intense during the initial stabilization, and monitoring is likely to be frequent for the life of the dog. Owners should be made fully aware of this before significant time and expense have been invested.
Hyperparathyroidism is relatively rare in the cat. It occurs in older cats of various breeds. The presenting complaints have been anorexia, lethargy, vomiting, polyuria and polydipsia. On physical examination the parathyroid masses were palpable in most cats that have been reported, which is a significant difference from dogs. The only consistent biochemical abnormality is hypercalcemia. Diagnostic work up is the same as for dogs. Surgical removal of the affected gland(s) is the treatment of choice. Cats can have an excellent prognosis.
Hypoparathyroidism is most commonly seen following bilateral thyroidectomy in cats. The incidence of this complication is reduced with the use of the modified extracapsular technique for thyroidectomy. Naturally occurring cases have been reported, but are rare. The therapy is the same as for the dog.
References available on request.