Interpretation of Parathyroid Abnormalities

The 4 parathyroid glands typically measure less than 2 to 3 mm on ultrasound¹ and play a pivotal role in calcium homeostasis in both dogs and cats. Parathyroid hormone (PTH) is synthesized, stored, and secreted by parathyroid chief cells in response to low serum ionized calcium (iCa) concentration. A G-protein coupled calcium-sensing receptor is responsible for detecting low iCa concentrations, which ultimately result in PTH secretion.² PTH secretion causes increased calcium reabsorption in the distal renal tubules, increased production of calcitriol, increased intestinal calcium absorption, and increased calcium resorption from bone.³ Other stimuli for PTH secretion include increased serum phosphorus and decreased calcitriol concentrations. Inhibition of PTH secretion is primarily controlled by increased serum iCa concentrations, but increased calcitriol and decreased magnesium concentrations can also contribute to the inhibition.³ 

Primary hyperparathyroidism (PHPT) is seen more commonly in dogs (than in cats), usually at 6 years of age or older, with a median age of 11 years at diagnosis.⁴ There is no gender predisposition, but there does seem to be a breed correlation, with the highest incidence of hyperparathyroidism in the Keeshond.^4,5 The most common clinical signs seen in dogs with hyperparathyroidism include polyuria and polydipsia (57%), lower urinary tract signs (eg, pollakiuria, stranguria, hematuria; 50%), weakness (46%), decreased activity (43%), reduced appetite (37%), weight loss or muscle wasting (18%), vomiting (13%), and trembling (10%), with close to 37% of dogs exhibiting no clinical signs.<sup4 sup> 

PHPT is less frequently diagnosed in cats as compared to dogs; in cats, the median age is 13 years, with no apparent gender predisposition.⁶ The most common clinical signs include anorexia, lethargy, and vomiting, with polyuria and polydipsia, weight loss, and constipation less common.⁷ A nodule in the neck is usually palpable in cats, whereas a palpable nodule is identified less frequently in dogs.⁸ 

Primary hypoparathyroidism, which is uncommon in both dogs and cats, is usually diagnosed as idiopathic (by exclusion) or occurs as a surgical complication of thyroidectomy (accidental removal or injury).⁹ Clinical signs are attributable to hypocalcemia and include seizures, muscle tremors or fasciculations, muscle cramping, stiff gait, and behavioral changes (eg, restlessness, aggression, hypersensitivity to stimuli, disorientation).¹⁰ In a majority (77%) of dogs, duration of clinical signs prior to diagnosis is often fewer than 14 days but can be as high as 173 days.¹¹

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The standard diagnostic approach for parathyroid disorders generally consists of patient history, physical examination, complete blood count, serum chemistry profile, and urinalysis. In a large proportion of both canine and feline cases, incidental detection of decreased or increased serum total calcium typically leads to initial clinical suspicion of hypo- or hyperparathyroidism.^6,12 With a 73%¹³ and 60%¹⁴ agreement between serum total calcium (tCa) and iCa concentrations in dogs and cats, respectively, tCa concentration is a poor predictor of iCa concentration. Therefore, iCa should be evaluated after initial total hypercalcemia is confirmed on a nonhemolyzed, nonlipemic sample⁶ or in situations in which parathyroid disease is suspected based on appropriate history, signalment, and/or clinical signs. 

In patients with PHPT, cervical ultrasonography performed by an experienced ultrasonographer is recommended and often helps establish a diagnosis. Cervical ultrasonography can identify a parathyroid nodule, usually occurring as a solitary nodule in 90% of patients and averaging 4 to 6 mm in diameter in up to 100% of dogs with PHPT.⁴ Inappropriately normal to elevated PTH levels and undetectable parathyroid hormone-related protein (PTHrP) levels can also aid in the diagnosis of hyperparathyroidism, especially in cases lacking an obvious detectable parathyroid nodule on ultrasound. In patients with normal calcium homeostasis, PTH release should be inhibited by high circulating levels of iCa, resulting in low circulating PTH concentrations. However, in patients with PHPT, the negative feedback inhibition is abolished because of the excess secretion of PTH, commonly caused by a functional adenoma. 

In patients with PHPT, PTH levels are inappropriately increased, either within or above the reference range, along with a finding of concurrent hypercalcemia. It is important to have both PTH and iCa measurements performed on the same blood sample. However, results are often delayed and treatment is usually based on ruling out other differentials for hypercalcemia and findings of a parathyroid nodule on cervical ultrasonography. Scintigraphy is not commonly used to diagnose PHPT because of its low sensitivity and overall accuracy of 27%.<sup15 sup> 

Definitive diagnosis of primary hypoparathyroidism involves a PTH concentration within or below the reference interval, along with concurrent hypocalcemia. Table 1 shows iCa, phosphorus, PTH, PTHrP, and vitamin D levels associated with various diseases commonly seen in dogs and cats with hypo- or hypercalcemia.

Discussion on the treatment of parathyroid disorders is beyond the scope of this summary review but includes surgical removal or percutaneous heat ablation in patients with PHPT and medical management with oral calcium and calcitriol supplementation, usually lifelong, in patients with primary hypoparathyroidism. The overall prognosis for long-term survival in dogs and cats with parathyroid disease is usually good to excellent.⁶

Table 1. Laboratory Findings for Various Diseases Commonly Seen in Patients with Hypercalcemia and Hypocalcemia 6,16-18

↓ = decrease, ↑ = increase, N = normal, PHPT = primary hyperparathyroidism

iCa =ionized calcium, PHPT = primary hyperparathyroidism, PTH = parathyroid hormone, PTHrP = parathyroid hormone-related protein, tCa = total calcium