Chapter 11: Hypercalcemia and Primary Hyperparathyroidism in Dogs

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Hypercalcemia and Primary Hyperparathyroidism in Dogs




Differential Diagnosis and Diagnostic Approach to Hypercalcemia



Differential Diagnosis


Hypercalcemia is an abnormality that is usually serendipitously identified on serum biochemical analysis. Disorders associated with hypercalcemia in dogs, in approximate order of incidence at the University of California, include lymphosarcoma, acute and chronic renal failure, primary hyperparathyroidism (PHP), hypoadrenocorticism, vitamin D toxicosis, apocrine gland carcinoma of the anal sac, multiple myeloma, uncommonly in association with a variety of carcinomas (lung, mammary, nasal, pancreas, thymus, thyroid, vaginal, and testicular), and uncommonly in association with certain granulomatous diseases (blastomycosis, histoplasmosis, schistosomiasis). History, physical examination, complete blood count (CBC), urinalysis, serum biochemistry analysis, thoracic and abdominal radiographs, abdominal ultrasound, and examination of cytology and biopsy specimens usually provide adequate information to establish a diagnosis in dogs.



History and Physical Examination


Since hypercalcemia is almost always unsuspected, it is not a mistake to obtain a second blood sample to rule out laboratory error, although in our experience laboratory error is extremely rare. Once hypercalcemia is identified, the veterinarian should review the signalment and history with the owner to identify any clues to a definitive diagnosis that may not have been noted initially. From the history, one can attempt to identify a tentative explanation for the hypercalcemia, such as possible exposure to toxins containing vitamin D (e.g., rodenticides, inappropriate supplementation of food), evidence of pain due to a lytic bone lesion (multiple myeloma or mammary tumor), difficulty eating due to oral lesions associated with renal failure, or a waxing/waning course of illness sometimes noted with hypoadrenocorticism.


The physical examination should also be repeated in an attempt to identify a tentative explanation for hypercalcemia. The spine, ribs, and long bones should be palpated to identify bone pain due to a lytic lesion, while the mammary chain should be evaluated for neoplasia, the oral cavity for “rubber jaw” or lesions consistent with renal failure, the rectal and perineal area for apocrine gland carcinoma of the anal sac or other tumor, the heart rate (slow) and pulse quality (poor) for abnormalities consistent with hypoadrenocorticism, and the peripheral lymph nodes for enlargement suggestive of lymphoma (most dogs with hypercalcemic lymphoma have a mediastinal mass and unremarkable peripheral nodes). Dogs with PHP commonly have a physical examination that does not contribute to a diagnosis (parathyroid masses are almost never palpable).



Routine “Database”


A thorough review of the CBC, serum biochemistry profile, and urinalysis should be completed. The urine specific gravity is commonly less than 1.020 in hypercalcemic dogs with renal disease, hypoadrenocorticism, and PHP. Urinary tract infection is common in these disorders. The CBC may demonstrate a normocytic, normochromic, nonregenerative anemia, which is relatively common in renal failure; hypoadrenocorticism; and various neoplasias. The serum biochemistry profile should also be reviewed to assess the blood urea nitrogen (BUN), creatinine, and serum phosphate for increases consistent with renal failure or vitamin D toxicosis; hyperkalemia and hyponatremia suggestive of hypoadrenocorticism; hyperglobulinemia consistent with myeloma; and hypophosphatemia consistent with PHP. To this point, the only “new” expense would be the repeated serum calcium concentration (if obtained), since the recommendation is to talk with the owner, repeat a physical examination, and review the laboratory results that were already obtained in order to identify the hypercalcemia in the first place.



Radiographs and Ultrasonography


Assuming the review of the history, physical examination, and database has not defined the cause for hypercalcemia, thoracic radiographs are an important next step. The primary purpose for this study is to assess the cranial mediastinum for a mass consistent with lymphoma. If present, fine-needle aspiration or tissue obtained via biopsy should be evaluated. Radiographs also provide an opportunity to evaluate the perihilar area and lungs for neoplasia or systemic mycoses, the spine and ribs for lytic lesions caused by neoplasia, and the heart for microcardia of hypoadrenocorticism. Abdominal radiographs can also be assessed, although ultrasound examination of the abdomen is preferred. The size and consistency of the liver, spleen, and mesenteric and sublumbar lymph nodes can be evaluated for abnormalities suggestive of malignancy (lymphoma) or other conditions. Diagnostic imaging to evaluate for malignancy (lymphoma) applies to a variety of tumors located in other organs, but tumors other than lymphoma are less common causes of hypercalcemia. When possible, abnormal areas should be aspirated or biopsied to determine the presence or absence of neoplasia. The size and consistency of the kidneys can be assessed, although renal failure should have been ruled in or out on the initial blood test results. The kidneys, ureters, bladder, and urethra should be evaluated for the presence of calculi, which develop in about 30% of dogs with PHP and could develop in any hypercalcemic dog. If these assessments fail to confirm or suggest a diagnosis other than PHP, suspicion for PHP increases. Until a specific cause for hypercalcemia is confirmed, however, lymphoma should never be ruled out. Cervical ultrasonography (discussed in a later section) has become an extremely valuable screening test in dogs with hypercalcemia.



Signalment, History, and Physical Examination in Dogs with Primary Hyperparathyroidism


Dogs with PHP are usually 6 years of age or older. The mean age from our series of 335 dogs with PHP was 10.7 years. Dogs of both genders are almost equally affected, about 14% of affected dogs are Keeshonds, but a huge number of breeds have been represented. The mean body weight of the 335 dogs was 24 kg.


Dogs with PHP, unlike those afflicted with most other diseases that cause hypercalcemia, are usually not ill or not as ill. Owners of 124 of 335 PHP dogs (37%) had observed no hypercalcemia-related abnormalities in their pet. Blood had been obtained from these dogs usually for a routine geriatric evaluation, as part of a preanesthesia screen prior to a dental procedure, or for an unrelated condition.


The most common owner-observed abnormalities in dogs with PHP were polyuria and polydipsia (57% of dogs), lethargy/weakness/decreased activity (43%), decreased appetite (30%), weight loss or muscle wasting (10%), shivering or trembling (7%), and vomiting (5%). However, even when clinical signs are observed, they are often relatively mild. When signs were observed, they had been present for as little as a few days to more than 2 years. Only about 5% of the PHP dogs with urolithiasis or urinary tract infection had appropriate clinical signs (i.e., straining to urinate, increased frequency of urination, and hematuria). Since more than 90% of the dogs identified as having both PHP and cystic calculi were asymptomatic for their stones, the indication for abdominal imaging in any hypercalcemic dog is emphasized.


In 254 of 335 dogs with PHP (76%), the medical record stated that no abnormalities relative to the diagnosis of PHP were noted on physical examination. When noted, abnormalities included muscle wasting, the dog being slow to rise, and obesity in some dogs and thin body condition in others. Each of these problems was seen in fewer than 10% of dogs with PHP.

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Jul 18, 2016 | Posted by in PHARMACOLOGY, TOXICOLOGY & THERAPEUTICS | Comments Off on Chapter 11: Hypercalcemia and Primary Hyperparathyroidism in Dogs

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