Gastrict carcinoma with pseudohyperparathyroidism in a horse

Pseudohyperparathyroidism was diagnosed in a mature stallion presented for anorexia, weight loss, pollakiuria and constipation. Laboratory findings included hypercalcemia, hypophosphatemia, anemia and isosthenuria. Thoracocentesis indicated an exfoliating squamous cell carcinoma. At necropsy, a squamous cell carcinoma of the stomach with metastases to the abdominal and thoracic cavities was diagnosed. No osseous metastases were found. No gross or microscopic renal lesions were noted. Bone tissue showed arrested resorption, and the parathyroid gland was atrophic.     

Pseudohyperparathyroidism in a mare associated with squamous cell carcinoma of the vulva

An 18-year-old Appaloosa mare was examined because of squamous cell carcinoma of the vulva, anorexia with pronounced weight loss, and hypercalcemia. The tumor had developed rapidly over a period of 3 months and externally extended ventrally involving the perineum and the dorsal aspect of the udder. Necropsy examination demonstrated a large primary squamous cell carcinoma of the vulva, perineum, and mammary gland with metastases to the supramammary, sublumbar, deep inguinal, and mediastinal lymph nodes. No gross renal lesions were observed and, histologically, there was only mild vacuolation of renal tubular epithelium. Based on the normal concentration of serum parathyroid hormone, the absence of evidence of hypervitaminosis D, and normal renal function, a diagnosis was made of hypercalcemia of malignancy or pseudohyperparathyroidism. The mechanism responsible for hypercalcemia was not determined, but the histologic type of the neoplasm and the clinical course suggested possible production of a humoral hypercalcemic factor by the neoplasm, similar to that demonstrated in certain types of human squamous cell carcinoma.     

Elevated parathyroid hormone-related protein and hypercalcemia in two dogs with schistosomiasis.

Two adult dogs were evaluated for hypercalcemia. Diagnostic evaluation identified elevated parathyroid hormone-related protein (PTHrP) and presumptive humoral hypercalcemia of malignancy. At necropsy, schistosomiasis was diagnosed. North American schistosomiasis is caused by Heterobilharzia americana. Clinical findings may include dermatitis, coughing, diarrhea, and anorexia. Clinicopathological findings may include hypercalcemia, hyperglobulinemia, hypoalbuminemia, anemia, and eosinophilia. Diagnosis by fecal examination is difficult. Praziquantel or fenbendazole treatment may be curative or palliative. These are the first reported cases of hypercalcemia with elevated PTHrP in animals without diagnosed malignancy. Elevation of PTHrP has not been previously reported in hypercalcemic humans or in animals with granulomatous inflammation.     

A case of hypercalcemia in a heifer presumably due to mammary carcinoma bovine hypercalcemia of malignancy

Mammary carcinoma is rare in cattle with only a handful of cases found in the literature, and none have reported an associated hypercalcemia. An 8‐year‐old Holstein‐Friesian heifer was presented to the Purdue University Veterinary Teaching Hospital's Large Animal Hospital with a 3‐month history of lethargy. Laboratory abnormalities included ionized hypercalcemia and hypophosphatemia (2.28 mmol/L and 1.8 mg/dL, respectively). Physical examination revealed a mammary mass that was cytologically described as a suspected mammary carcinoma, which was later confirmed by histologic evaluation. On surgical removal of the mass, calcium initially decreased rapidly, and within a few days was within the RI, further supporting a diagnosis of hypercalcemia of malignancy in a heifer. However, attempts to confirm this using hormone profiles (parathyroid hormone [PTH], parathyroid hormone‐related protein [PTHrp], and calcitriol) were inconclusive due to the lack of validated assays and RIs for cattle. Immunohistochemical staining for PTHrP showed scattered cytoplasmic staining among the neoplastic cells, suggesting PTHrP production by these cells.     

Ultrasonography of the parathyroid glands in dogs--a review

The purpose of the study was to give an overview over the usefulness of ultrasonographic examination of parathyroid glands in dogs. By means of a 10 MHz high-resolution linear transducer it was possible to visualize parathyroid glands in healthy dogs. There was a positive correlation between body weight and size of the parathyroid glands, additionally the likelihood to detect 4 glands increased with an increase in body weight. Dogs with chronic renal failure had significantly larger parathyroid glands than healthy dogs and dogs with acute renal failure. In dogs with hypercalcemia of malignancy either none or parathyroids which were small in relation to body weight were detected. In contrast visualisation of parathyroid masses in dogs with primary hyperparathyroidism was easy due to their increased size and anechoic appearance. In dogs with severe azotemia the ultrasonographic examination of the parathyroid glands is helpful to differentiate between acute and chronic renal failure, in dogs with hypercalcemia to differentiate between hypercalcemia of malignancy and hypercalcemia due to primary hyperparathyroidism.     

Idiopathic hypercalcemia in cats

Unexplained hypercalcemia has been increasingly recognized in cats since 1990. In some instances, hypercalcemia has been associated with calcium oxalate urolithiasis, and some affected cats have been fed acidifying diets. We studied the laboratory findings, clinical course, and treatment of 20 cats with idiopathic hypercalcemia. Eight (40%) of the cats were longhaired and all 14 cats for which adequate dietary history was available had been fed acidifying diets. Clinical signs included vomiting (6 cats), weight loss (4 cats), dysuria (4 cats), anorexia (3 cats), and inappropriate urinations (3 cats). Hypercalcemia was mild to moderate in severity. and serum parathyroid hormone concentrations were normal or low. Serum concentrations of phosphorus, parathyroid hormone-related peptide, 25-hydroxycholecalciferol, and calcitriol were within the reference range in most cats. Diseases commonly associated with hypercalcemia (eg, neoplasia, primary hyperparathyroidism) were not identified despite thorough medical evaluations and long-term clinical follow-up. Azotemia either did not develop (10 cats) or developed after the onset of hypercalcemia (3 cats), suggesting that renal failure was not the cause of hypercalcemia in affected cats. Seven of 20 cats (35%) had urolithiasis, and in 2 cats uroliths were composed of calcium oxalate. Subtotal parathyroidectomy in 2 cats and dietary modification in 11 cats did not result in resolution of hypercalcemia. Treatment with prednisone resulted in complete resolution of hypercalcemia in 4 cats.     

Primary Hyperparathyroidism Associated With Atypical Headshaking Behavior in a Warmblood Gelding

A 14-year-old Zweibrücker Warmblood gelding was presented for evaluation of lethargy and headshaking. The horse had a history of bouts of lameness in different limbs and back problems. It also had many mild colic episodes in the past. Results of repeat laboratory tests had shown persistent hypercalcemia (4.8 mmol/L; reference interval [RI]: 2.0–3.2 mmol/L) for 1.5 years and later on hypophosphatemia (0.4 mmol/L; RI: 0.5–1.3 mmol/L) and mild hypermagnesemia (1.0 mmol/L; RI: 0.5–0.9 mmol/L). Parathyroid hormone (PTH) concentration was within the RI. Other causes of hypercalcemia, such as renal failure, vitamin D toxicosis, and granulomatous disease, and nutritional secondary hyperparathyroidism were ruled out. Furthermore, there was no evidence of neoplastic disease. Parathyroid hormone–related protein was measured but inconclusive. A diagnosis of primary hyperparathyroidism was established on the basis of hypercalcemia, hypophosphatemia, low fractional excretion of calcium, and high fractional excretion of phosphorus in combination with a PTH secretion refractory to high calcium levels. Because of the bad prognosis, the owner decided to euthanize the horse. Results of postmortem examination were unremarkable. Hypercalcemia should always be considered abnormal, and further examinations need to be performed to proof hypercalcemia and subsequently find the cause. The main differential diagnoses are renal insufficiency and humoral hypercalcemia of malignancy, but also rare diseases, such as hyperparathyroidism, have to be taken into account.     

Hypercalcemia and high serum parathyroid hormone-related protein concentration in a horse with multiple myeloma

A 13-year-old gelding was examined because of weight loss, hyperglobulinemia, and hypercalcemia. Possible causes of hypercalcemia that were considered included renal failure, primary hyperparathyroidism, vitamin D toxicosis, and malignancy. There was no history of vitamin D ingestion, and serum creatinine and parathyroid hormone concentrations were normal, making renal failure and primary hyperparathyroidism unlikely. The hypercalcemia was suspected to be a result of malignancy, but thorough testing did not reveal any neoplastic disease. Eight months later, serum parathyroid hormone-related protein (PTHrP) concentration was high, supporting the suggestion that hypercalcemia was a result of malignancy. In addition, radial immunodiffusion confirmed a selective 300-fold increase in serum IgA concentration. The horse was euthanatized, and postmortem examination revealed neoplastic infiltrates in the kidneys, lymph nodes, liver, and bone marrow. Neoplastic cells had morphologic characteristics of plasma cells, and immunohistochemical staining confirmed that neoplastic cells were expressing PTHrP and IgA. The final diagnosis was multiple myeloma with expression of IgA paraprotein.     

HIGH-RESOLUTION PARATHYROID SONOGRAPHY

The purpose of this study was to assess the diagnostic utility of parathyroid ultrasonography to differentiate causes of hypercalcemia in dogs. We analyzed qualitative and quantitative ultrasound imaging findings and clinical pathology data from 33 dogs that underwent parathyroid ultrasound examination as part of the diagnostic evaluation for hypercalcemia. Diagnoses of the diseases causing hypercalcemia included parathyroid carcinoma (n = S), parathyroid adenoma (n = 15), parathyroid adenomatous hyperplasia (n = 6), chronic renal insufficiency (n = 3), and hypercalcemia of malignancy (n = 4). All parathyroid lesions were round or oval and hypoechoic compared with surrounding thyroid parenchyma. Adenomatous and adenocarcinomatous glands were 4 mm or larger in longest linear measurement on US examination and were statistically significantly larger than hyperplastic glands. (p < 0.001) Linear measurements of parathyroid glands acquired at the time of ultrasound examination correlated well with direct siz determination after surgical excision. (r²= 0.9, p < 0.0001) Parathyroid lesions <4 mm are highly suspicious for parathyroid adenoma or carcinoma, while US lesions <4 mm most likely represent primary adenomatous hyperplasia or secondary parathyroid hyperplasia. Parathyroid size estimation from ultrasound examination is an accurate predictor of true size.     

Hypercalcemia and parathyroid hormone‐related peptide expression in a dog with thyroid carcinoma and histiocytic sarcoma

A 9.5‐year‐old, male castrated Walker Hound was presented for evaluation of progressive weakness, anorexia, and weight loss. Imaging revealed multiple abdominal and thoracic masses and ascites; fine‐needle aspirates of mesenteric and splenic masses confirmed malignancy, most likely histiocytic sarcoma. Laboratory analyses revealed increased ionized calcium and parathyroid hormone‐related peptide (PTH‐rP) concentrations, and concurrent low–normal parathyroid hormone concentration, consistent with humoral hypercalcemia of malignancy. Necropsy was performed after euthanasia. The dog had disseminated histiocytic sarcoma, including sarcomatosis, as well as bilateral thyroid carcinoma. PTH‐rP immunostaining was positive in the thyroid carcinoma but negative in the histiocytic neoplasm. These results suggest that thyroid carcinoma‐associated hypercalcemia can be caused by tumor secretion of PTH‐rP.     

Primary hyperparathyroidism in a dog.

A 6-year-old male Standard Poodle had hypercalcemia, hypophosphatemia, and a urinary concentrating defect. A parathyroid adenoma involving the left caudal parathyroid gland was surgically removed. Transient hypocalcemia followed, which resolved without treatment. A renal biopsy did not demonstrate renal parenchymal mineral deposition. Urinary concentrating ability returned after surgery.     

Effects of humoral hypercalcemia of malignancy on the parathyroid gland in nude mice.

The ultrastructure of parathyroid chief cells was examined from four groups of nude mice (NIH:Swiss) with different serum calcium concentrations. The groups consisted of eight male mice with hypercalcemia induced by transplantable canine adenocarcinoma (CAC-8), eight female mice with hypercalcemia induced by infusion of parathyroid hormone-related protein, ten male control mice, and six male mice fed a low calcium (0.01%) diet. Hypercalcemia induced by malignancy or parathyroid hormone-related protein infusion was associated with low serum phosphorus concentration, a decrease in the number of secretory and prosecretory granules in the parathyroid chief cells, and an increase in the cytoplasmic area of chief cells. Prominent myelinlike membranous whorls were present in the cytoplasm of chief cells of tumor-bearing and parathyroid hormone-related protein-infused hypercalcemic mice. Mice fed a low calcium diet had decreases in the number of secretory granules and cell area but increases in the number of prosecretory granules compared with control mice. The number of mitochondria and the nuclear area of chief cells were similar in all four groups. The prominent membranous whorls and increased cytoplasmic area of chief cells from these hypercalcemic mice mark these cells as distinctly different from the parathyroid chief cells of other species with hypercalcemia.     

Probable hypercalcemia of malignancy in a cat with bronchogenic adenocarcinoma

An eight-year-old, neutered male, domestic shorthair cat was referred with a four-day history of acute vomiting. Hypercalcemia was identified on serum biochemical testing. Thoracic radiographs showed multiple pulmonary nodular densities. Postmortem and histopathological examination identified the nodules as bronchogenic adenocarcinoma with metastases to the tracheobronchial lymph nodes, diaphragm, and parietal pleura. To the authors' knowledge, this is the first reported case of hypercalcemia of malignancy associated with bronchogenic adenocarcinoma in a cat.     

Hypercalcemia in two cats with squamous cell carcinomas

Hypercalcemia was identified in 2 cats with squamous cell carcinomas. One cat was referred because of multiple cutaneous tumors; the second cat had metastatic disease from an oral squamous cell carcinoma. In both cats, serum immunoreactive midmolecule parathyroid hormone concentration was within the range determined for clinically normal cats. The high serum calcium concentration in these cats may have resulted from the neoplastic disease, as evidenced by the reduction in serum calcium concentration after decrease in tumor size in response to treatment, and by failure to identify other known causes of hypercalcemia.     

Hypercalcemia and parathyroid hormone-related protein in a dog with undifferentiated nasal carcinoma.

Hypercalcemia was discovered in a 7-year-old, castrated male basset hound with a suspected nasal tumor. The dog died the day after admission and nasal carcinoma and disseminated intravascular coagulation were diagnosed on postmortem. Detectable levels of serum PTHrP support a diagnosis of hypercalcemia of malignancy.     

Alterations in calcium, phosphorus and C-terminal parathyroid hormone levels in equine acute renal disease

The changes in serum and urinary levels of calcium and phosphorus and serum parathyroid hormone (PTH) were studied during controlled, chemically induced, acute renal disease in 4 ponies. There was an initial rise in daily urinary calcium and hydroxyproline excretion in 2 ponies which may have indicated increased bone resorption. Mild hypercalcemia, hypophosphatemia and elevated C-terminal PTH levels were associated with oliguria. Total daily urinary excretion of calcium and phosphorus decreased as oliguria developed. The levels of C-terminal PTH were increased in all four animals. This appears to have been related to their diminished renal function in that C-terminal fragments of intact PTH (which require functioning kidneys in order to be cleared) were probably being accumulated. Although there was no evidence with regard to an actual increase in PTH secretion, prolongation of intact PTH half-life due to renal tubular damage may have contributed to the development of hypercalcemia.     

Pretreatment clinical and laboratory findings in dogs with primary hyperparathyroidism: 210 cases (1987-2004)

OBJECTIVE: To evaluate pretreatment clinical and laboratory findings in dogs with naturally occurring primary hyperparathyroidism. DESIGN: Retrospective study. ANIMALS: 210 dogs with primary hyperparathyroidism and 200 randomly selected, age-matched control dogs that did not have primary hyperparathyroidism. PROCEDURE: Medical records for dogs with primary hyperparathyroidism were reviewed for signalment; clinical features; and results of clinicopathologic testing, serum parathyroid hormone assays, and diagnostic imaging. RESULTS: Mean age of the dogs with primary hyperparathyroidism was 11.2 years (range, 6 to 17 years). The most common clinical signs were attributable to urolithiasis or urinary tract infection (ie, straining to urinate, increased frequency of urination, and hematuria). Most dogs (149 [71%]) did not have any observable abnormalities on physical examination. All dogs had hypercalcemia, and most (136 [65%]) had hypophosphatemia. Overall, 200 of the 210 (95%) dogs had BUN and serum creatinine concentrations within or less than the reference range, and serum parathyroid hormone concentration was within reference limits in 135 of 185 (73%) dogs in which it was measured. Urolithiasis was identified in 65 (31 %) dogs, and urinary tract infection was diagnosed in 61 (29%). Mean serum total calcium concentration for the control dogs-was significantly lower than mean concentration for the dogs with primary hyperparathyroidism, but mean BUN and serum creatinine concentrations for the control dogs were both significantly higher than concentrations for the dogs with primary hyperparathyroidism. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that urolithiasis and urinary tract infection may be associated with hypercalcemia in dogs-with primary hyperparathyroidism, but that development of renal insufficiency is uncommon.     

Effects of hypercalcemia on serum concentrations of magnesium, potassium, and phosphate and urinary excretion of electrolytes in horses

OBJECTIVE: To determine effects of experimentally induced hypercalcemia on serum concentrations and urinary excretion of electrolytes, especially ionized magnesium (iMg), in healthy horses. ANIMALS: 21 clinically normal mares. PROCEDURES: Horses were assigned to 5 experimental protocols (1, hypercalcemia induced with calcium gluconate; 2, hypercalcemia induced with calcium chloride; 3, infusion with dextrose solution; 4, infusion with sodium gluconate; and 5, infusion with saline [0.9% NaCl] solution). Hypercalcemia was induced for 2 hours. Dextrose, sodium gluconate, and saline solution were infused for 2 hours. Blood samples were collected to measure serum concentrations of electrolytes, creatinine, parathyroid hormone, and insulin. Urine samples were collected to determine the fractional excretion of ionized calcium (iCa), iMg, sodium, phosphate, potassium, and chloride. RESULTS: Hypercalcemia induced by administration of calcium gluconate or calcium chloride decreased serum iMg, potassium, and parathyroid hormone concentrations; increased phosphate concentration; and had no effect on sodium, chloride, and insulin concentrations. Hypercalcemia increased urinary excretion of iCa, iMg, sodium, phosphate, potassium, and chloride; increased urine output; and decreased urine osmolality and specific gravity. Dextrose administration increased serum insulin; decreased iMg, potassium, and phosphate concentrations; and decreased urinary excretion of iMg. Sodium gluconate increased the excretion of iCa, sodium, and potassium. CONCLUSIONS AND CLINICAL RELEVANCE: Hypercalcemia resulted in hypomagnesemia, hypokalemia, and hyperphosphatemia; increased urinary excretion of calcium, magnesium, potassium, sodium, phosphate, and chloride; and induced diuresis. This study has clinical implications because hypercalcemia and excessive administration of calcium have the potential to increase urinary excretion of electrolytes, especially iMg, and induce volume depletion.     

Hypercalcemia associated with blastomycosis in dogs

Hypercalcemia that could not be explained by previously recognized causes was detected in 4 dogs with systemic blastomycosis. A variety of malignancies and certain endocrine, metabolic, and renal disorders may cause hypercalcemia, but to our knowledge, no infectious diseases have been associated with hypercalcemia in dogs. Increased production of calcitriol by mononuclear cells was thought to be the mechanism of hypercalcemia in granulomatous disease.     

Diagnosis and treatment of primary hyperparathyroidism in a bobcat (Lynx rufus)

An 18-yr-old male bobcat (Lynx rufus) presented with chronic moderate weight loss and acute onset of anorexia and lethargy. Hypercalcemia and azotemia were present on the serum chemistry panel. Abdominal ultrasound revealed hyperechoic renal cortices, but no evidence of neoplasia. Ionized calcium and 25-hydroxyvitamin D were mildly elevated, intact parathyroid hormone was severely elevated, and parathormone-related protein was undetected, suggesting primary hyperparathyroidism with possible renal dysfunction. Azotemia lessened in severity following diuresis, but hypercalcemia persisted; thus primary hyperparathyroidism was considered the most probable differential diagnosis. A second ultrasound including the cervical region revealed a solitary intraparenchymal left thyroid nodule. The nodule was surgically excised; histopathology confirmed a parathyroid adenoma. Although primary hyperparathyroidism was suspected, diagnosis was not achieved from serum chemistry values alone. This case emphasizes the importance of diagnostic imaging and histopathology in the investigation of persistently abnormal laboratory values.