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.     

Mutations in genes causing human familial isolated hyperparathyroidism do not account for hyperparathyroidism in Keeshond dogs

The roles of the calcium sensing receptor gene (CaSR) and the multiple endocrine neoplasia gene (MEN1) were investigated in Keeshond dogs with familial hyperparathyroidism. Mutations in these genes have been shown to cause familial isolated hyperparathyroidism (FIH) in humans. Affected dogs were identified through measurement of blood calcium and parathyroid hormone levels. Parathyroid tissue and whole blood was used to clone the cDNAs and individual exonic sequences of both candidate genes. No sequence abnormalities were identified when comparing normal and affected dogs, suggesting that a mapping strategy may be the most appropriate approach for identifying the genetic basis of this valuable comparative canine disease model.     

Ionized Hypercalcemia in Dogs: A Retrospective Study of 109 Cases (1998–2003)

Background: Serum hypercalcemia in dogs has been reported in association with a variety of diseases. Serum-ionized calcium (iCa) concentration is a more accurate measure of hypercalcemia than total serum calcium or corrected serum calcium concentrations. The severity of hypercalcemia has been utilized to suggest the most likely differential diagnosis for the hypercalcemia.
Hypothesis: Diseases causing ionized hypercalcemia may be different than those that cause increases in total or corrected serum calcium concentrations. The severity of ionized hypercalcemia in specific diseases cannot be used to determine the most likely differential diagnosis for ionized hypercalcemia.
Animals: One-hundred and nine client-owned dogs with a definitive cause for their ionized hypercalcemia evaluated between 1998 and 2003 were included in this study.
Methods: Retrospective, medical records review.
Results: Neoplasia, specifically lymphosarcoma, followed by renal failure, hyperparathyroidism, and hypoadrenocorticism were the most common causes of ionized hypercalcemia. Dogs with lymphoma and anal sac adenocarcinoma have higher serum iCa concentrations than those with renal failure, hypoadrenocorticism, and other types of neoplasia. The magnitude of serum-ionized hypercalcemia did not predict specific disease states.
Conclusions and Clinical Importance: Serum-ionized hypercalcemia was most commonly associated with neoplasia, specifically lymphosarcoma. Although dogs with lymphosarcoma and anal sac adenocarcinoma had higher serum iCa concentrations than dogs with other diseases, the magnitude of the serum iCa concentration could not be used to predict the cause of hypercalcemia. Total serum calcium and corrected calcium concentrations did not accurately reflect the calcium status of the dogs in this study.     

Phosphorus and phosphate metabolism in veterinary patients

Objective: To review phosphorus and phosphate metabolism and the importance of phosphate abnormalities in veterinary patients. Data sources: A review of recent human and veterinary medical literature. Human data synthesis: There is a significant amount of original research on human patients with phosphate abnormalities. Hypophosphatemia has been studied in patients with diabetic ketoacidosis (DKA), head trauma, refeeding syndrome, hypothermia and in ventilator patients that fail to wean. Hyperphosphatemia has been studied in patients with renal failure and malignancy. Phosphate levels have also been evaluated for prognostic value in sepsis and acute liver failure. Veterinary data synthesis: Although animal models were used in early experimental research, fewer studies have been published on the effects of phosphate abnormalities in veterinary patients. Hypophosphatemia has been studied in animals with DKA, with refeeding syndrome and with hyperparathyroidism. Hyperphosphatemia has been studied in animals with renal failure and with secondary hypoparathyroidism. Conclusion: Phosphorus and phosphate are important in many biological functions. This paper is a review of their role in normal metabolism and the clinical importance of phosphate imbalances for our emergency and critical care patients.     

Fibrous osteodystrophy in a dromedary camel

A 6-y-old female dromedary camel (Camelus dromedarius L.) was presented for assessment of firm, bilateral swellings rostral and ventral to the eyes. Serum biochemistry revealed hyperglycemia (28.5 mmol/L), hypocalcemia (1.27 mmol/L), hyperphosphatemia (3.39 mmol/L), hypoproteinemia (total protein 50 g/L), and hypoalbuminemia (20 g/L). Based on the poor prognosis associated with the presumptive diagnosis of fibrous osteodystrophy, the camel was euthanized. Gross postmortem findings revealed expanded fibrous tissue replacing the maxilla and mandible, and bilaterally prominent parathyroid glands. Histology of the maxilla revealed proliferative loose fibrous tissue with widely scattered, regularly spaced, small spicules of mineralized bone. The parathyroid glands were prominent bilaterally; the internal and external parathyroid glands were composed of plump cells with abundant pale basophilic cytoplasm and open nuclei. The pathologic findings were consistent with the antemortem diagnosis of fibrous osteodystrophy. The camel’s diet, which was not specifically balanced for a camel, included grass hay, sweet feed, and alfalfa pellets. The camel’s caregivers reported feeding her treats of cookies. A feed analysis was not available. The biochemistry abnormalities and clinical and postmortem findings, along with a diet that was not balanced for a camel, are consistent with a diagnosis of nutritional secondary hyperparathyroidism.     

Serum fibroblast growth factor 23 (FGF-23): associations with hyperphosphatemia and clinical staging of feline chronic kidney disease

Fibroblast growth factor 23 (FGF-23) is an independent monitor of the progression of chronic kidney disease (CKD) in human medicine, and FGF-23 may have value as a biomarker in feline CKD. We evaluated the relationship between serum FGF-23 and CKD stages, and the effect of age on FGF-23 in normal cats. We measured FGF-23 and intact parathyroid hormone (iPTH) concentrations by ELISA, with intra- and inter-assay CVs ≤ 15%. The percentage recovery of FGF-23 and iPTH remained stable for up to 7 d in samples stored at −20°C and −80°C. We measured FGF-23 in 304 cats, among which 196 were diagnosed with CKD. The 108 clinically healthy cats were divided into 5 subgroups based on growth stage (0–2 y, 3–6 y, 7–10 y, 11–14 y, ≥ 15 y). No statistical difference was found in FGF-23 among age groups (p = 0.15) or by sex in healthy subjects. Using the International Renal Interest Society guideline, 34 cats were defined as CKD stage 1, 74 stage 2, 51 stage 3, and 37 stage 4. FGF-23 was higher in cats in all CKD stages than in controls. Higher serum phosphorus was observed in stage 3 (p = 0.04) and 4 (p < 0.01) compared to controls. iPTH increased as CKD progressed. Pearson analysis indicated a positive linear relationship between FGF-23 and iPTH (control: r = 0.70, p < 0.01; CKD: r = 0.46, p = 0.02). FGF-23 may be a useful biomarker of feline CKD and may precede hyperphosphatemia in advanced feline CKD.     

Rabbit model of primary hyperparathyroidism induced by high-phosphate diet

The objective of this study is to establish a new rabbit model of primary hyperparathyroidism (PHPT) induced by high-phosphate diet. One hundred twenty rabbits were divided into two groups of 60 each. The treatment group was fed a high-phosphate diet (Ca:P = 1:7) and the control group was given a normal animal diet (Ca:P = 1:0.7) for 1 to 6 mo. Serologic examinations, including parathyroid hormone (PTH), calcium and phosphorus levels, blood urea nitrogen, creatinine, and uric acid, and the histologic examination, including parathyroid, kidney, and bones, were performed at the end of each month for 6 mo. Compared with the control, serum PTH levels in the treatment groups were elevated at all six time points, whereas serum calcium levels were reduced, and serum phosphorus levels remain unchanged over the course of the first 3 mo. Serum calcium levels were increased, whereas serum phosphorus levels were reduced at 4, 5, and 6 mo. Parathyroid histopathological examination showed no change during the first month, whereas 60% of the animals exhibited mild hyperplasia starting at 2 mo, and 90% of the animals in the treatment group exhibited mild-to-moderate hyperplasia with gland enlargement starting from 3 mo through the end of the study. Histopathological examination of the kidneys showed no change at 1 mo, but focal parenchymal inflammation with calcium deposition was observed in the treatment groups at 2 to 6 mo. Fibrous tissue of the bone extended toward the cortex, and fibrosis was evident at the third month. The fibrous cells were found to be concentrated mainly on the inner and outer membranes of the bone cortex, and the amount of fibrous tissue increased as the disease progressed. We conclude that a new rabbit animal model of PHPT can be successfully created by the administration of a high-phosphate diet. This animal model can be used in various future studies related to PHPT.     

Intraoperative parathyroid hormone concentration to confirm removal of hypersecretory parathyroid tissue and time to postoperative normocalcaemia in nine dogs with primary hyperparathyroidism

Objective To determine (1) whether the intraoperative parathyroid hormone concentration ([PTH]) during parathyroidectomy (PTX) can be used to indicate cure in dogs with primary hyperparathyroidism and (2) the time taken for postoperative serum calcium concentration to normalise. Design Retrospective study (2005–10) from a private referral hospital in Sydney, New South Wales, Australia. Procedure Nine client‐owned dogs underwent surgical PTX for naturally occurring primary hyperparathyroidism. [PTH] was measured from serum samples taken immediately post‐induction (pre‐PTX]) and at least 20 min after adenoma removal (post‐PTX) for all dogs, and during parathyroid gland manipulation (intra‐PTX) for six dogs. The concentration of ionised calcium (iCa) was measured at various time points postoperatively until it normalised, then stabilised or decreased below reference ranges. Statistical analysis compared the mean pre‐, intra‐ and post‐PTX [PTH] and the average rate of decline of iCa concentration postoperatively. Results All dogs demonstrated a significant decrease from mean pre‐PTX [PTH] (168.51 pg/mL) to mean post‐PTX [PTH] (29.20 pg/mL). There was a significant increase in mean intra‐PTX [PTH] (279.78 pg/mL). The average rate of decline of iCa concentration postoperatively to within the reference range (1.12–1.40 mmol/L) occurred after 24 h. Conclusion Intraoperative measurements of [PTH] can be used clinically to determine cure of primary hyperparathyroidism. Parathyroid hormone increases significantly during parathyroid gland manipulation. Plasma iCa concentration returns to within the reference range on average 24 h after successful PTX. Not all dogs require vitamin D or calcium supplementation pre‐ or postoperatively.