Primary Hypoparathyroidism – Genevieve Mak, DVM

Primary Hypoparathyroidism

Dogs and cats have 4 parathyroid glands (two pairs) and their function is to produce parathyroid hormone (PTH) for the control and regulation of the body’s calcium levels.  The effects of PTH are seen on the bones, kidneys, and intestines.  Parathyroid hormone directs the bones to release its calcium and phosphorus into the blood, through stimulation of the osteoclasts and osteoblasts.  In this way, serum calcium levels increase immediately, and over the course of months.  In the kidneys, the hormone causes increased phosphorus and decreased calcium excretion into the urine.  PTH also stimulates the kidneys to produce more 1,25-dihydroxycholecalciferol (calcitriol).  Vitamin D then directly acts on the intestines to promote increased calcium and phosphorus absorption from the gut.

In primary hypoparathyroidism, there is an absolute or relative deficiency of PTH secretion, resulting in decreased serum calcium, subsequent increased serum phosphorus, and decreased levels of 1,25-dihydroxycholecalciferol.  The cause of primary hypoparathyroidism, while classified as idiopathic, is thought to be due to immune-mediated destruction of the parathyroid glands.  In animals with hypoparathyroidism, histology of the parathyroid glands reveals lymphocytic parathyroiditis.  Approximately 60 – 80% of the normal tissue is replaced by mature lymphocytes, plasma cells, and fibroblasts, with very few functioning chief cells.  In the early disease states, the chief cells undergo hypertrophy/hyperplasia to try and compensate; as the disease progresses, there are only occasional viable cells seen.

The clinical signs of primary hypoparathyroidism stem from hypocalcemia.  Calcium is needed for cell membrane stabilization, neuromuscular transmission, and muscle contraction.  With declining ionized calcium levels, the nervous system becomes more excitable, resulting in spontaneous firing of the nerves.  Hypocalcemic dogs and cats exhibit muscle tremors, seizures, muscle cramping, stiff gait, and behavioral changes.  They may be easily excited, aggressive, irritable, and seem painful.  Facial rubbing or pawing of the eyes, muzzle, or ears has been observed in a majority of dogs with hypocalcemia due to the painful sensation and cramping of the muscles in that region (figure 1).  It should be noted that hypocalcemic seizures differ from those associated with epilepsy.  Dogs with hypocalcemic seizures may be partially conscious and appear apprehensive or nervous preceding the event.  Less common clinical signs include panting, pyrexia, lethargy, anorexia, tachycardia, and prolapse of third eyelids (in cats).

Primary hypoparathyroidism is an uncommon, if not rare disease.  It has been diagnosed in dogs as young as 6 weeks of age, and as old as 13 years.  Most dogs reported with this disease are middle aged and 65% were female.  Frequently reported breeds with primary hypoparathyroidism include poodles, miniature schnauzers, retrievers, German shepherds, and terriers.

A definitive diagnosis can be made by finding an inappropriately low or within reference range PTH level, concurrently with an ionized hypocalcemia.  Since hypocalcemia can commonly occur with various other disease processes, it is important to first rule out all other causes and conditions (figure 2).  Serum biochemistry should be performed to screen for renal disease and evaluate for hypoalbuminemia.  The owner should be carefully questioned on clinical signs, access to toxins, diet history, and medications that the pet is receiving.  A complete blood count (CBC) and urinalysis are usually unremarkable in animals with primary hypoparathyroidism.  Low serum calcium levels should be confirmed by measuring an ionized calcium level.

Treatment for primary hypoparathyroidism can be divided into acute (emergency) and chronic (maintenance) treatment, dictated by the severity of and the clinical signs seen with hypocalcemia.  For animals presenting in tetany or having hypocalcemic seizures, 0.5 – 1.5 ml/kg (5 – 15 mg/kg) of 10% calcium gluconate (elemental calcium) should be given over 10 – 20 minutes (to effect).  Calcium gluconate is the recommended calcium choice, as opposed to calcium chloride or other types of calcium salts due to its non-caustic nature.  The other calcium salts can be extremely irritating to the skin and result in tissue sloughing and calcinosis cutis if extravasated.  This initial bolus of calcium gluconate can last anywhere from 1 hour to 12 hours, therefore, it is advisable to start a constant rate of infusion of elemental calcium at 60 – 90 mg/kg/day (10% calcium gluconate contains 9.3 mg/ml of elemental calcium).  In the past, subcutaneous injections of calcium gluconate have been given once signs of tetany resolve with initial bolus therapy.  This is no longer recommended due to reported cases of calcinosis cutis, pyogranulomatous dermatitis, dermoepidermal separation, skin ulceration, and severe pyogranulomatous panniculitis.  When administering IV calcium, concurrent ECG monitoring for arrhythmias and VPC’s is recommended.  Ionized calcium should also be monitored at least once daily while on IV calcium.

Oral calcium supplementation and calcitriol therapy should be started immediately.  While there are many oral calcium salts available (carbonate, chloride, citrate, lactate, gluconate), calcium carbonate is recommended as it has the highest percentage of elemental calcium (40%), and will not cause gastric irritation.  The dosage of calcium carbonate is 25 – 50 mg/kg/day, divided over the day.  With vitamin D therapy, there are also a number of different formulations available (ergocalciferol, cholecalciferol, calcidiol, calcitriol).  Calcitriol is recommended as it is the most effective, has the most rapid onset of action, and shortest half-life.  The only downside of calcitriol over the other preparations is cost.  Initial loading dose of calcitriol is 20 – 30 ng/kg/day divided twice daily for 3 – 4 days, followed by a maintenance dose of 5 – 15 ng/kg/day.  Once ionized calcium levels are back in the low normal range, oral calcium supplementation can be discontinued, as dietary calcium is sufficient in maintaining patient needs.  The calcitriol should be continued for life; however, tapering of the medication should occur over the next few months (with ionized calcium rechecks) as to provide the lowest dosage needed.  Increases or decreases of 10 – 20% of the calcitriol are recommended to avoid wide fluctuations in serum calcium levels.

In terms of follow-up, daily ionized calcium levels are assessed until the patient is stabilized, followed by weekly measurements until the levels are in the low normal range, then quarterly for maintenance.  Long term side effects of therapy for hypoparathyroidism include hypercalciuria, nephrocalcinosis, urolithiasis, and chronic renal disease secondary to hypercalcemia and hyperphosphatemia.  This is due to the fact that while calcitriol is effective in terms of treatment, it does not function in the same capacity as parathyroid hormone.  In humans with hypoparathyroidism, synthetic PTH injections are available and provide better long term control.  However, it is not available in veterinary medicine and is cost prohibitive.   Long term prognosis for dogs and cats with hypoparathyroidism is unknown, due to the small number of cases.