Hypocalcemia causes the major clinical manifestations of hypoparathyroidism by increasing the excitability of both the central and peripheral nervous systems. Peripheral neuromuscular signs classically include muscle tremors, twitches, and tetany. Generalized convulsions, resembling those of an idiopathic seizure disorder, are the predominant CNS manifestation of hypoparathyroidism.
Hypoparathyroidism is a metabolic disorder characterized by hypocalcemia and hyperphosphatemia and either transient or permanent PTH insufficiency. The spontaneous disorder is uncommon in dogs and rarely reported in cats. Iatrogenic injury or removal of the parathyroid glands during thyroidectomy for treatment of hyperthyroidism is the most common cause in cats. Postoperative hypoparathyroidism secondary to parathyroidectomy for parathyroid tumor may occur because of atrophy of the remaining glands in either dogs or cats.
Diagnosis is based on history, clinical signs, laboratory evidence of hypocalcemia and hyperphosphatemia, and exclusion of other causes of hypocalcemia (eg, hypoproteinemia, malabsorption, pancreatitis, renal failure). If idiopathic hypoparathyroidism is suspected, it should be confirmed by histologic examination of the parathyroid glands and documentation of parathyroid atrophy or destruction. Because the parathyroid glands are not grossly evident in animals with hypoparathyroidism, a unilateral thyroidectomy should be performed to ensure that adequate parathyroid tissue is available for examination. Determination of serum PTH concentrations might be helpful in the diagnosis of idiopathic hypoparathyroidism and may thereby eliminate the need for cervical exploratory surgery and histologic verification.
Treatment is directed at restoring the serum calcium concentration to the low end of the normal range. This should include use of calcium supplements and vitamin D for either iatrogenic or idiopathic forms of hypoparathyroidism. If hypocalcemic tetany or seizures are present, calcium should be administered IV immediately. For maintenance of normocalcemia, oral calcium should be administered together with a vitamin D preparation.
The major complication associated with treatment of hypoparathyroidism is hypercalcemia, which develops as a consequence of overtreatment with calcium and vitamin D. If this occurs, calcium and vitamin D therapy should be temporarily discontinued; saline and furosemide should be administered if hypercalcemia is severe ( see Treatment of Hypercalcemia Treatment of Hypercalcemia Hypercalcemia can be toxic to all body tissues, but major deleterious effects occur in the kidneys, nervous system, and cardiovascular system. The development of clinical signs from hypercalcemia... read more ). With idiopathic hypoparathyroidism, longterm management with vitamin D (with or without calcium supplementation) is necessary. In contrast, with iatrogenic hypoparathyroidism, spontaneous recovery of parathyroid function or accommodation of calcium-regulating mechanisms to the absence of PTH may occur weeks to months after surgery.
Other Causes of Hypocalcemia
Chronic renal failure is probably the most frequently encountered cause of hypocalcemia. Azotemia and hyperphosphatemia result from decreased glomerular filtration rates. Mechanisms of hypocalcemia include decreased renal tubular calcium resorption, hyperphosphatemia, decreased formation of 1,25-dihydroxyvitamin D, hypoalbuminemia, and chelation of calcium with oxalate. Parathyroid gland hyperplasia occurs to maintain serum calcium in normal ranges. High PTH concentrations result in increased bone resorption. The hypocalcemia associated with renal failure, however, is rarely clinically significant (ie, muscle tremors, twitches, tetany, or convulsions do not develop). In addition, most animals with chronic renal failure have normal serum calcium concentrations. Treatment should be directed at lowering the serum phosphate concentrations by dietary restriction of phosphorus and intestinal phosphate binders. (Also see Renal Dysfunction in Small Animals Renal Dysfunction in Small Animals Failure of the filtration function of the kidneys leads to the development of azotemia (an excess of nitrogenous compounds in the blood), which may be classified as prerenal, renal, postrenal... read more .)
Animals with hypoalbuminemia may be hypocalcemic because of a decrease in the protein-bound fraction of calcium, but the ionized calcium fraction may remain normal. Clinical signs of hypocalcemia do not usually develop. The magnitude of hypocalcemia is usually mild.
When hypocalcemia occurs in animals with pancreatitis ( See also Pancreatitis in Dogs and Cats Pancreatitis in Dogs and Cats Pancreatitis is an inflammatory condition that is common in dogs and cats. It can be acute or chronic and subclinical or associated with various clinical signs. Pancreatitis is diagnosed by... read more ), it is usually mild and subclinical. The exact mechanism is unknown, but a commonly accepted theory is that calcium is precipitated in the form of insoluble soaps through saponification of peripancreatic fatty acids formed subsequent to release of the pancreatic enzyme lipase. More recent work suggests that hypocalcemia may result from a shift of calcium into soft tissues, especially muscle.
Puerperal tetany (eclampsia, see Eclampsia in Small Animals Eclampsia in Small Animals Eclampsia (periparturient hypocalcemia) is characterized by progressive neurologic signs including tremors, ataxia, and disorientation; eventually followed by seizures, coma, and death. It occurs... read more ) is an acute, life-threatening disease caused by an extreme fall in circulating calcium concentrations in the lactating bitch or queen. Severe hypocalcemia associated with eclampsia develops during the nursing period (several days to several weeks postpartum). The pathophysiology remains poorly understood but appears to result from an imbalance between the rate of inflow (eg, bone resorption, GI absorption) and outflow (eg, mammary gland) from the extracellular calcium pool. Treatment consists of slow IV administration of calcium ( see Treatment of Hypocalcemia Treatment of Hypocalcemia Hypocalcemia causes the major clinical manifestations of hypoparathyroidism by increasing the excitability of both the central and peripheral nervous systems. Peripheral neuromuscular signs... read more ) and weaning of the litter, if possible.
Phosphate Enema Toxicity:
Hypertonic sodium phosphate (eg, Fleet®) enemas may result in severe biochemical abnormalities, especially when administered to dehydrated cats with colonic atony and mucosal disruption. Hypernatremia and hyperphosphatemia result from the colonic absorption of sodium and phosphate from the enema solution, as well as transfer of intravascular water to the colonic lumen (because of the hypertonic enema). Hyperphosphatemia leads to precipitation of serum calcium with resultant hypocalcemia. Clinical signs of phosphate enema toxicosis, which result from these electrolyte and fluid alterations, include shock and neuromuscular irritability. Treatment consists of IV volume expansion with an electrolyte-poor solution (eg, 5% dextrose in water), as well as treatment of hypocalcemia ( see Treatment of Hypocalcemia Treatment of Hypocalcemia Hypocalcemia causes the major clinical manifestations of hypoparathyroidism by increasing the excitability of both the central and peripheral nervous systems. Peripheral neuromuscular signs... read more ).
EDTA (ethylenediaminetetraacetic acid), citrated blood, and oxalic acid (a metabolite of the ethylene glycol in antifreeze) all complex calcium and can cause hypocalcemia. Animals with ethylene glycol intoxication ( see Ethylene Glycol Toxicosis Ethylene Glycol Toxicosis ) also have severe metabolic acidosis, azotemia, and hyperphosphatemia from the oliguric renal failure, which results from calcium oxalate crystal precipitation in the renal tubules.
Treatment of Hypocalcemia
The definitive treatment for hypocalcemia is to eliminate the underlying cause. Supportive measures, including the following, to restore normocalcemia can be administered pending the diagnosis.
Hypocalcemic tetany or convulsions are indications for the immediate IV administration of 10% calcium gluconate (1–1.5 mL/kg), which should be slowly infused throughout a 10-min period. Close monitoring is mandatory; if bradycardia or shortening of the QT interval occurs, the IV infusion should be slowed or temporarily discontinued.
Once the life-threatening signs of hypocalcemia have been controlled, calcium can be added to the IV fluids and administered as a slow continuous infusion of 10% calcium gluconate at 0.3 mL/kg per hour. The rate of calcium administration should be adjusted as necessary to maintain a normal serum calcium concentration, and the infusion should be continued for as long as necessary to prevent recurrence of hypocalcemia. Although this continuous calcium infusion will maintain normocalcemia, its effects are short-lived; hypocalcemia will recur within hours of stopping the infusion unless other treatment is given.
Oral calcium supplementation may be beneficial in some conditions (eg, hypoparathyroidism, puerperal tetany). The daily requirements are 1–4 g for dogs and 0.5–1 g for cats. The daily dose of calcium should be based on the amount of elemental calcium in the product, rather than on the weight of the calcium salt.
In some conditions, vitamin D supplementation is necessary to increase calcium absorption from the intestines. There are three main preparations of vitamin D available, including vitamin D2 (ergocalciferol), dihydrotachysterol, and 1,25-dihydroxyvitamin D (calcitriol). The dosage and duration of response of these drugs depends on the form used. For vitamin D2, the initial required dosages are generally 4,000–6,000 IU/kg/day, whereas the final dosages required to maintain normocalcemia range from 1,000–2,000 IU/kg, once daily to once weekly. For dihydrotachysterol, initial loading dosages of 0.02–0.03 mg/kg/day are usually administered, with maintenance dosages of 0.01–0.02 mg/kg given every 24–48 hr. For calcitriol, a daily dosage of 0.025–0.06 mcg/kg (25–60 ng/kg/day) is generally required.