Suspected primary hypoparathyroidism in a domestic ferret (Mustela putorius furo)

• Autores: Ricardo de Matos
• Localización: JAVMA: Journal of the American Veterinary Medical Association, ISSN-e 0003-1488, Vol. 245, Nº. 4, 2014, págs. 419-424
• Idioma: inglés
• Texto completo no disponible (Saber más ...)
• Resumen

  • Case Description—A 4-year-old castrated male domestic ferret (Mustela putorius furo) was examined because of a 3-week history of intermittent seizures, signs of depression, hypocalcemia, and hyperphosphatemia.

    Clinical Findings—Plasma biochemical analysis confirmed hyperphosphatemia (17.7 mg/dL) and low concentrations of total (4.3 mg/dL) and ionized (0.49 mmol/L) calcium. Serum parathyroid hormone concentration (2.30 pmol/L) was low or in the low part of the reference interval.

    Treatment and Outcome—Calcium gluconate was administered (2.0 mg/kg/h [0.9 mg/lb/h], IV), followed by a transition to administration of calcium carbonate (53 mg/kg [24.1 mg/lb], PO, q 12 h) and dihydrotachysterol (0.02 mg/kg/d [0.009 mg/lb/d], PO). Attitude of the ferret improved and seizures ceased as blood calcium concentrations increased. The ferret was reexamined because of seizures approximately 1 year after oral maintenance administration of dihydrotachysterol and calcium was initiated. The ferret responded well to emergency and long-term treatment but then was lost to follow-up monitoring. The ferret died approximately 2 years after the initial evaluation and treatment. Hypertrophic cardiomyopathy was diagnosed during necropsy, but the parathyroid glands could not be identified.

    Clinical Relevance—To the authors’ knowledge, primary hypoparathyroidism has not previously been reported in a ferret. The condition should be considered for ferrets with hypocalcemia and hyperphosphatemia without azotemia. Treatment with dihydrotachysterol and oral supplementation of calcium appeared to be a viable option for long-term management.

    A 4-year-old 1.17-kg (2.6-lb) castrated male domestic ferret (Mustela putorius furo) was referred to the Exotic Pet Service at Cornell University Hospital for Animals because of intermittent seizures. The ferret had been examined by the referring veterinarian 3 weeks prior to referral because of seizures that occurred every 2 or 3 days. Main findings of a routine CBC and plasma biochemical analysis performed by the referring veterinarian included hypocalcemia (4.7 mg/dL; reference interval,1 8.6 to 10.5 mg/dL) and hyperphosphatemia (13.4 mg/dL; reference interval,1 5.6 to 8.7 mg/dL). The blood glucose concentration (105 mg/dL) was within the reference interval. The ferret was treated by administration of calcium carbonatea (53 mg/kg [24.1 mg/lb], PO, q 12 h). No further seizure activity was detected until 48 hours prior to referral, when seizure activity was again evident. Lethargy, progression of seizure activity, and abnormal behavior (biting, aggression, and fear behavior) were also observed at that time. The ferret had not been vaccinated against rabies virus or canine distemper virus. The ferret was fed a commercially available balanced chow,b and toxin exposure was not suspected.

    Initial evaluation at our veterinary teaching hospital (day 1) revealed that the ferret's mentation varied from periods of activity to periods of lethargy with minimal response to stimuli. No other remarkable abnormalities were detected during physical examination. Plasma biochemical analysis revealed that the PCV and total solids, blood glucose,c and BUNd concentrations were within reference intervals. The plasma total calcium concentration was low (4.3 mg/dL; reference interval,1 8.1 to 9.5 mg/dL), and the phosphorus concentration was high (17.7 mg/dL; reference interval,1 5.1 to 6.5 mg/dL). The ionized calcium concentratione was 0.49 mmol/L (reference interval for dogs, 1.18 to 1.37 mmol/L; reference interval for cats, 1.07 to 1.47 mmol/L). On the basis of the reference intervals for dogs and cats and an ionized calcium concentration of 1.17 mmol/L previously reported for a healthy ferret,2 ionized calcium concentration in the ferret described here was considered to be low. Findings on ECG were within anticipated limits, except for a few brief periods of bradycardia (heart rate range, 120 to 200 beats/min; reference interval,1 200 to 400 beats/min).

    Calcium gluconatef (2 mg/kg [0.9 mg/lb]) diluted in 20 mL of saline (0.9% NaCl) solution was administered IV over a period of 20 minutes, with continuous ECG monitoring. The ionized calcium concentration was assessed 4 hours after the calcium gluconate infusion and was essentially unchanged (0.48 mmol/L). Therefore, calcium gluconate diluted in saline solution was administered as a constant rate infusion at a rate of 2 mg/kg/h (0.9 mg/lb/h), with continuous ECG monitoring. A single dose of sucralfateg (22 mg/kg [10 mg/lb], PO) was administered because of the risk for abdominal discomfort and gastric ulcers following calcium administration.

    On the morning of day 2 (approx 9 hours after the initial evaluation), the ionized calcium concentration had increased to 0.87 mmol/L. The ferret remained lethargic but was increasingly responsive to stimuli. Oral administration of calcium carbonate was resumed at the previously recommended dose (53 mg/kg, PO, q 12 h). The constant rate infusion of calcium gluconate was continued, and a single dose of vitamin Dh was administered (300 U/kg [136.4 U/lb], IM).

    Attitude and appetite of the ferret continued to improve during the subsequent 5 days. On day 3, the total calcium concentration was 7.8 mg/dL, ionized calcium concentration was 1.1 mmol/L, and phosphorus concentration was 10.9 mg/dL. On day 4, IV administration of calcium gluconate was discontinued, and SC administration of calcium carbonate was initiated (25.6 mg/kg [11.6 mg/lb], q 12 h). On day 5, total and ionized calcium concentrations decreased to 5.6 mg/dL and 0.69 mmol/L, respectively, and the phosphorus concentration increased to 11.9 mg/dL. Results of a CBC and urinalysis performed on day 5 were within reference limits, and abdominal ultrasonography findings were unremarkable, except for 2 small cortical cysts in the left kidney. The PCV decreased considerably from 42% on day 4 to 30% on day 5 (reference interval,1 36% to 48%), and melena was observed on day 6. Bismuth subsalicylatei (9.1 mg/kg [4.1 mg/lb], PO, q 8 h), metronidazolej (19.7 mg/kg [9.0 mg/lb], PO, q 12 h), and amoxicillink (10.3 mg/kg [4.7 mg/lb], PO, q 12 h) were added to the treatment regimen at that time because of concerns about gastric ulcers secondary to clinical gastroenteritis attributable to Helicobacter spp infection or calcium administration.

    Serum obtained during the initial examination on day 1 was submitted to another laboratoryl for determination of ionized calcium and PTH concentrations. The ionized calcium concentration was 0.47 mmol/L (reference interval for dogs, 1.25 to 1.45 mmol/L; reference interval for cats, 1.0 to 1.4 mmol/L), and the PTH concentration was 2.30 pmol/L (reference interval for dogs, 0.5 to 5.8 pmol/L; reference interval for cats, 0.4 to 2.5 pmol/L). Although the reference interval for PTH concentrations in ferrets has not been established, a serum PTH concentration of 13 pmol/L was previously reported2 in a healthy ferret. Thus, the PTH concentration in the ferret described here was interpreted as low or in the low part of the reference interval.

    On day 8, the ionized calcium (1.21 mmol/L) and total calcium (9.4 mg/dL) concentrations had returned to within the reference interval, and the phosphorus concentration had decreased to 10.2 mg/dL. The PCV (24%) also had continued to decrease. Treatment with famotidinem (1 mg/kg [0.45 mg/lb], SC, q 24 h) and dihydrotachysteroln (0.02 mg/kg [0.009 mg/lb], PO, q 48 h) was initiated.

    On day 11, the total calcium concentration was 7 mg/dL and the phosphorus concentration was 11 mg/dL. Subcutaneous administration of calcium gluconate was discontinued, and the ferret was discharged to the owner with instructions to continue administration of metronidazole, amoxicillin, and bismuth subsalicylate for an additional 7 days. Administration of dihydrotachysterol and calcium carbonate were to be continued at the same dose and frequency of administration until further notice.

    On day 16, the ferret's total calcium concentration was 7.7 mg/dL and the phosphorus concentration was 13.7 mg/dL. Treatment with aluminum hydroxideo (34 mg/kg [15.5 mg/lb], PO, q 12 h) was initiated because of the persistent hyperphosphatemia. On day 34, the total calcium concentration was 10.1 mg/dL and the ionized calcium concentration was 1.05 mmol/L; the phosphorus concentration remained high at 10.8 mg/dL. The aluminum hydroxide dosage was increased (51.3 mg/kg [23.3 mg/lb], PO, q 12 h), and the frequency of dihydrotachysterol administration was decreased to every 7 days.

    The ferret was examined approximately 9 weeks later (day 104) by the referring veterinarian. The calcium concentration was low (6.3 mg/dL), and the phosphorus concentration was high (13.8 mg/dL). The frequency of dihydrotachysterol administration was changed to every 5 days, but oral administration of calcium carbonate and aluminum hydroxide were not altered.

    During the next year, the owner did not detect any seizure episodes. Muscle tremors were evident in the ferret when the frequency of dihydrotachysterol administration was changed from every 5 days to every 7 days; however, these resolved when administration reverted to every 5 days.

    On day 368, the ferret was evaluated by the referring veterinarian because of vomiting, inappetence, melena, decreased activity, and a seizure episode. The client reported no changes in the treatment regimen, husbandry, or diet before the seizure episode. Results of a CBC and biochemical analysis revealed leukocytosis (24 × 103 leukocytes/μL; reference interval,1 5.6 × 103 leukocytes/μL to 10.8 × 103 leukocytes/μL) with neutrophilia (17,040 × 103 neutrophils/μL; reference interval,1 616 × 103 neutrophils/μL to 7,020 × 103 neutrophils/μL) and lymphocytosis (6,960 × 103 lymphocytes/μL; reference interval,1 1,728 × 103 lymphocytes/μL to 4,704 × 103 lymphocytes/μL), high activities of alanine aminotransferase (311 U/L; reference interval,1 65 to 128 U/L) and aspartate aminotransferase (793 U/L; reference interval,1 70 to 100 U/L), hypocalcemia (6.2 mg/dL), and hyperphosphatemia (18.0 mg/dL). Radiography revealed increased pulmonary opacity but no other abnormalities.

    On day 369, the ferret had no improvement and was brought to the emergency service of our veterinary teaching hospital. Physical examination revealed that the ferret was lethargic but responsive to stimuli. Bruxism, melena, bradycardia (120 beats/min), tachypnea (80 breaths/min), and dyspnea were detected. A few muscle tremors and seizure activity were also observed. Results of cardiac auscultation were unremarkable. Auscultation of the lungs revealed an increase in respiratory rate and wheezes. The ionized calcium concentration was 0.63 mmol/L. Treatment included IV administration of calcium gluconate (2.4 mg/kg [1.1 mg/lb]) in 20 mL of isotonic solutionp over a 20-minute period, with continuous ECG monitoring. The muscle tremors ceased, and overall attitude of the ferret improved markedly following calcium administration. Treatment with an isotonic solutionp (3.7 mL/kg/h [1.7 mL/kg/h], IV), sucralfate (24 mg/kg [11 mg/lb], PO, q 8 h), and famotidine (0.47 mg/kg [0.21 mg/lb], IV, q 24 h) was initiated, and the ferret was placed in an oxygen cage.

    The following day (day 370), the ferret remained lethargic and tachypneic. No muscle tremors were observed. Plasma biochemical analysis revealed hypocalcemia (3.9 mg/dL), a low ionized calcium concentration (0.55 mmol/L), hyperphosphatemia (11.7 mg/dL), hypoalbuminemia (2.0 g/dL; reference interval,1 3.3 to 4.1 mg/dL), a high BUN concentration (58 mg/dL; reference interval,1 18 to 32 mg/dL), increased aspartate aminotransferase activity (597 U/L), increased alanine aminotransferase activity (1,081 U/L), and a high creatine kinase activity (15,300 U/L; reference interval,1 55 to 93 U/L). Magnesium concentration was 3.16 mg/dL (reference interval for European polecats [Mustela putorius], 1.5 to 2.76 mg/dL).q Treatment with calcium glubionater (168 mg/kg [76.4 mg/lb], PO, q 12 h), calcium gluconate (14 mg/kg [6.4 mg/lb], SC, q 8 h), aluminum hydroxide (45 mg/kg [20.5 mg/lb], PO, q 12 h), ampicillin and sulbactams (28 mg/kg [12.7 mg/lb], IV, q 8 h), and metronidazole (18.7 mg/kg [8.5 mg/lb], IV, q 12 h) was initiated. An increase in alertness and appetite was evident on day 371. Oxygen supplementation was discontinued, and a single dose of vitamin Dh was administered SC. Ionized calcium and PTH concentrations were reassessed; the ionized calcium concentration was 0.67 mmol/L, and the PTH concentration was 3.4 pmol/L. The PTH concentration was again interpreted as low or within the low part of the reference interval. Plasma biochemical analysis on day 372 revealed low concentrations of ionized calcium (0.64 mmol/L) and total calcium (5.0 mg/dL), hypokalemia (3.8 mEq/L; reference interval,1 4.5 to 6.1 mEq/L), an increase in BUN concentration (84 mg/dL), hyperphosphatemia (10.8 mg/dL), hypoalbuminemia (2.3 g/dL), and a creatinine concentration and alanine aminotransferase, aspartate aminotransferase, and creatine kinase activities within the respective reference intervals. On day 373, results for auscultation of the lungs were within anticipated limits. Administration of ampicillin and sulbactam was discontinued, and treatment with amoxicillin-clavulanatet (12.6 mg/kg [5.7 mg/lb], PO, q 12 h) was initiated. Blood concentrations of calcium and phosphorus were 9.4 and 10.2 mg/dL, respectively. The ferret was discharged to the owner on day 376 with instructions for administration of amoxicillin-clavulanate (PO for 7 days), sucralfate and famotidine (PO for 4 days), calcium glubionate (PO for 60 days), and calcium gluconate (15 mg, SC, q 24 h for 2 days). Calcium carbonate and aluminum hydroxide were to be administered until further notice. Treatment with dihydrotachysterol (0.024 mg, PO, q 5 d) was initiated 1 week after discharge to the owner.

    During the subsequent year, the ferret's condition remained unchanged, and no seizures were reported by the owner. Recurrence of muscle tremors coincided with changing the frequency of dihydrotachysterol administration from 5 to 7 days and, as before, muscle tremors resolved when the interval for dihydrotachysterol administration reverted to 5 days. Oral administration of calcium carbonate and aluminum hydroxide remained unchanged.

    The client reported that the ferret died suddenly after a brief seizure-like episode on day 724, which followed a 3-week period of a decrease in activity and appetite. Dyspnea was evident on the day the ferret died. There were no changes in the treatment regimen, husbandry, or diet. Postmortem examination revealed congestive heart failure attributable to hypertrophic cardiomyopathy, interstitial nephritis with proteinosis, and a unilateral chronic renal infarct. The parathyroid glands could not be identified grossly or histologically. Examination of serial sections of the thyroid gland failed to reveal clearly defined parathyroid gland tissue.