Effect of Thyroxine Supplementation on Glomerular Filtration Rate in Hypothyroid Dogs

Background: Glomerular filtration rate (GFR) is decreased in humans with hypothyroidism, but information about kidney function in dogs with hypothyroidism is lacking.
Hypothesis: Hypothyroidism influences GFR in dogs. The objective of this study was to assess GFR in hypothyroid dogs before implementation of thyroxine supplementation and after re-establishing euthyroidism.
Animals: Fourteen hypothyroid dogs without abnormalities on renal ultrasound examination or urinalysis.
Methods: Blood pressure and GFR (measured by exogenous creatinine clearance) were measured before treatment (T0, n = 14) and at 1 month (T1, n = 14) and at 6 months (T6, n = 11) after beginning levothyroxine supplementation therapy (20 μg/kg/d, PO). The response to therapy was monitored at T1 by measuring serum total thyroxine and thyroid stimulating hormone concentrations. If needed, levothyroxine dosage was adjusted and reassessed after 1 month. Statistical analysis was performed using a general linear model. Results are expressed as mean ± standard deviation.
Results: At T0, the average age of dogs in the study group was 6.3 ± 1.4 years. Their average body weight decreased from 35 ± 18 kg at T0 to 27 ± 14 kg at T6 ( P < .05). All dogs remained normotensive throughout the study. GFR increased significantly with levothyroxine supplementation; the corresponding results were 1.6 ± 0.4 mL/min/kg at T0, 2.1 ± 0.4 at T1, and 2.0 ± 0.4 at T6 ( P < .01).
Conclusion: GFR was <2 mL/min/kg in untreated hypothyroid dogs. Re-establishment of a euthyroid state increased GFR significantly.     

The Effect of Levothyroxine Treatment on Resting Energy Expenditure of Hypothyroid Dogs

Thirty adult, client-owned dogs were diagnosed with hypothyroidism based on history, physical examination findings, hematologic and biochemical abnormalities, thyrotropin (TSH) response testing, endogenous canine thyrotropin (cTSH) concentration, or both, and total serum thryoxine concentration. All dogs received levothyroxine (L-thyroxine) at an initial dose of 22 μg/kg PO sid in either a tablet (13 dogs) or chewable form (17 dogs). Energy expenditure of each dog during apparent rest was estimated with an open-flow indirect calorimetry system by determining the rates of carbon dioxide production and oxygen consumption. Energy expenditure of apparent rest (EE) was lower in untreated hypothyroid dogs compared with reference values for EE. After treatment with L-thyroxine, EE of the hypothyroid dogs was significantly ( P < .05) higher than pretreatment values.     

The effect of hypothyroidism on cardiac function in dogs

The thyroid hormones have direct and indirect effects on the heart. So it is possible that depression of left ventricular function is associated with hypothyroidism. This publication describes cardiac findings (auscultation, electrocardiography, echocardiography) in ten hypothyroid dogs. Low heart rates, reduced R-amplitudes and bradycardic arrhythmias (first and second-degree AV block) were found on the electrocardiogram before treatment. On the echocardiograms most of the dogs showed reduced contractillity and reduced left ventricular wall thickness. Seven dogs were reexamined after levothyroxine supplementation. Effects of treatment were increased heart rates and R-amplitudes as well as disappearance of the bradycardic arrhythmias in electrocardiographic examination. The echocardiographic examination showed increased contractility and increased left ventricular wall thickness.     

Plasma von Willebrand Factor Antigen Concentration and Buccal Mucosal Bleeding Time in Dogs With Experimental Hypothyroidism

This study was undertaken to investigate the effects of hypothyroidism on buccal mucosal bleeding time and von Willebrand factor antigen (vWf:Ag) concentrations. Hypothyroidism was induced in 8 adult dogs by administration of iodine 131. Four healthy dogs acted as controls. Measurement of plasma vWf:Ag and serum thyroxine and triiodothy-ronine concentrations, and buccal mucosal bleeding time were made before induction of hypothyroidism, for 23 weeks after ¹³¹I administration, and during 5 weeks of levothyroxine supplementation. No significant changes in buccal mucosal bleeding times were noted during the study. After an insignificant increase in vWfAg concentration in hypothyroid dogs, levothyroxine treatment was associated with a significant decrease in vWf:Ag concentration in hypothyroid dogs when compared with controls. Results of this study suggest that hypothyroidism does not induce acquired von Willebrand's disease or significant defects in primary hemo-stasis. J Vet Intern Med 1996;10:60–64. Copyright © 1996 by the American College of Veterinary Internal Medicine .     

1,3 Butanediol treatment of ethylene glycol toxicosis in dogs

In order to assess the therapeutic value of 1,3 butanediol in ethylene glycol toxicosis, mixed-bred dogs were given an oral dose of commercial antifreeze at 6 ml/kg of body weight (0 hour) and treated (IV) 7 times at 6-hour intervals with 5.5 ml/kg of body weight 1,3 butanediol solution (20% in physiological saline solution) beginning at 8, 12, and 21 hours. Serum glycolic acid concentration was quantitated by high-pressure liquid chromatography. Three dogs that were given ethylene glycol, but no 1,3 butanediol treatment, died with elevated serum glycolic acid concentrations. Five dogs were given ethylene glycol and 1,3 butanediol treatment. Of 2 dogs treated at 8 hours, 1 survived and 1 died at 39 hours; 1 treated at 12 hours and 1 treated at 21 hours survived; 1 dog died soon (27 hours) after treatment was initiated at 21 hours. Four of the 5 dogs had dramatically decreased serum glycolic acid concentrations after 1,3 butanediol treatment, indicating its effectiveness in inhibiting alcohol dehydrogenase-dependent glycolic acid formation in vivo.     

Thyrotropin stimulation test--new perspective on value of monitoring triiodothyronine

Thyrotropin (thyroid stimulating hormone; TSH) stimulus to thyroid cells of horses and dogs resulted in increased serum triiodothyronine (T3) concentrations that were detected earlier than those of thyroxine (T4). Doubling of the base-line T3 values in horses was detected 0.5 hours after injection of 5 IU of TSH IV, with peak response of 5 times base-line value detected 2 hours after injection. Doubling of T4 values in horses was noticed between 2 and 3 hours, with the peak response of 2.4 times base-line value at 4 hours after injection of TSH. Doubling of base-line T3 values in dogs in response to 0.2 IU TSH/kg of body weight (IV-5 IU maximum dose) was noticed at 1 hour, whereas T4 response doubled between 1.5 and 2 hours. Peak release of T3 and T4 in response to TSH in dogs had not developed by 4 hours; however, the percentage increase over base-line values was greater for T3 than T4 at early sampling time points, and this response has resulted in an increased T3/T4 ratio in hypothyroid dogs. Thus, in both dogs and horses, these studies indicated that T3 response to TSH could be used as a measure of thyroid function at earlier time intervals after TSH administration than one measures T4 response.     

Is it possible to diagnose canine hypothyroidism?

A definitive diagnosis of hypothyroidism can be difficult because of the many clinical abnormalities associated with thyroid hormone deficiency, and the lack of readily available diagnostic tests with high sensitivity and specificity. Thyroid function tests should be performed only in dogs with clinical findings consistent with hypothyroidism. Measurement of serum total thyroxine (T4) concentration is a useful initial screening test since most hypothyroid dogs have values below the reference range. Serum free T4 concentration measured by equilibrium dialysis is a more sensitive and specific test of thyroid function than total T4 and is particularly useful in dogs with non-thyroidal illness or atypical clinical signs. Measurement of serum endogenous thyroid-stimulating hormone concentration is also helpful, but many hypothyroid dogs have normal results. The gold standard for diagnosis of hypothyroidism remains the thyroid-stimulating hormone response test. It should be used to confirm hypothyroidism when other tests do not agree with the clinical impression or if atypical signs or non-thyroidal illness exist or there has been administration of drugs known to alter thyroid function tests. Ultimately, a positive response to treatment is expected in hypothyroid dogs treated appropriately with levothyroxine.     

Xylazine-pentobarbital anesthesia in dogs and its antagonism by yohimbine

Once a week for 4 weeks, 5 dogs were given IM injections of xylazine (2.2 mg/kg of body weight) followed in 10 minutes by IV injections of pentobarbital (14 mg/kg). The resultant duration of anesthesia, absence of pedal reflex, and time from return of consciousness to ambulation were consistent from week to week. The mean times were 137.3, 111.8, and 56.9 minutes, respectively. A second experiment using 5 other dogs was performed to evaluate the antagonistic effect of yohimbine on the anesthesia induced by the xylazine-pentobarbital combination. When yohimbine (0.1 mg/kg, IV) was administered 10, 60, and 120 minutes after the xylazine-pentobarbital injection (given as in the 1st experiment), it abolished or markedly reduced the duration of anesthesia, absence of pedal reflex, and the time from return of consciousness to ambulation. After being given yohimbine, the dogs had a smooth recovery without postanesthetic excitement. In experiment 3, IM xylazine injections caused bradycardia without changing mean arterial blood pressure. Subsequent IV pentobarbital administration abolished xylazine-induced bradycardia for approximately 20 minutes and decreased arterial blood pressure slightly and gradually. Respiration was markedly depressed for the first 20 minutes of xylazine-pentobarbital anesthesia and gradually decreased during the rest of the 50-minute monitoring period. Yohimbine injection at postpentobarbital dosing minute 50 reversed the resumed xylazine-induced bradycardia and relieved other signs of respiratory depression associated with xylazine-pentobarbital anesthesia. The xylazine-pentobarbital combination was safe and effective for inducing and maintaining up to 2 hours of anesthesia in dogs.(ABSTRACT TRUNCATED AT 250 WORDS)     

Evaluation of analgesic,sympathetic and motor effects of 1% and 2% lidocaine administered epidurally in dogs undergoing ovariohysterectomy

ObjectiveTo compare, versus a control, the sensory, sympathetic and motor blockade of lidocaine 1% and 2% administered epidurally in bitches undergoing ovariohysterectomy.Study designRandomized, blinded, controlled clinical trial.AnimalsA total of 24 mixed-breed intact female dogs.MethodsAll dogs were administered dexmedetomidine, tramadol and meloxicam prior to general anesthesia with midazolam–propofol and isoflurane. Animals were randomly assigned for an epidural injection of lidocaine 1% (0.4 mL kg⁻¹; group L1), lidocaine 2% (0.4 mL kg⁻¹; group L2) or no injection (group CONTROL). Heart rate (HR), respiratory rate (f_R), end-tidal partial pressure of carbon dioxide (Pe′CO₂), and invasive systolic (SAP), mean (MAP) and diastolic (DAP) arterial pressures were recorded every 5 minutes. Increases in physiological variables were treated with fentanyl (3 μg kg⁻¹) intravenously (IV). Phenylephrine (1 μg kg⁻¹) was administered IV when MAP was <60 mmHg. Postoperative pain [Glasgow Composite Pain Score – Short Form (GCPS–SF)] and return of normal ambulation were recorded at 1, 2, 3, 4 and 6 hours after extubation.ResultsThere were no differences over time or among groups for HR, f_R, Pe′CO₂ and SAP. MAP and DAP were lower in epidural groups than in CONTROL (p = 0.0146 and 0.0047, respectively). There was no difference in the use of phenylephrine boluses. More fentanyl was administered in CONTROL than in L1 and L2 (p = 0.011). GCPS–SF was lower for L2 than for CONTROL, and lower in L1 than in both other groups (p = 0.001). Time to ambulation was 2 (1–2) hours in L1 and 3 (2–4) hours in L2 (p = 0.004).Conclusions and clinical relevanceEpidural administration of lidocaine (0.4 mL kg⁻¹) reduced fentanyl requirements and lowered MAP and DAP. Time to ambulation decreased and postoperative pain scores were improved by use of 1% lidocaine compared with 2% lidocaine.     

Actinomycin D as rescue therapy in dogs with relapsed or resistant lymphoma: 49 cases (1999--2006)

OBJECTIVE: To evaluate response rate and disease-free interval in dogs with relapsed or resistant lymphoma treated with actinomycin D, determine hematologic toxicoses, and identify prognostic factors associated with response to treatment. DESIGN: Retrospective case series. ANIMALS: 49 dogs with relapsed or resistant lymphoma. PROCEDURES: Medical records were reviewed for information regarding signalment, physical examination findings, results of diagnostic testing, substage, previous chemotherapy, previous treatment with prednisone, actinomycin D dosage, number of doses administered, response, disease-free interval, and results of CBCs performed after treatment. RESULTS: Actinomycin D was administered at a median dosage of 0.68 mg/m2 (range, 0.46 to 0.72 mg/m2), IV, every 3 weeks for 5 treatments or until disease progression. Twenty-six (53%) dogs received prednisone concurrently. Twenty (41%) dogs had a complete remission, and median disease-free interval in these dogs was 129 days. Thrombocytopenia was the most common hematologic toxicosis (n = 22 [45%]). Concurrent prednisone administration, a shorter duration of first remission, and an increased number of previous chemotherapy agents were significantly associated with a lower likelihood of responding to actinomycin D treatment. Concurrent prednisone administration and an increased number of previous chemotherapy agents were significantly associated with a shorter disease-free interval. CONCLUSION AND CLINICAL RELEVANCE: Results suggested that administration of actinomycin D as a single agent was effective for rescue chemotherapy of dogs with relapsed or resistant lymphoma and that treatment was well tolerated, although mild thrombocytopenia developed commonly.     

Comparison of 2 Doses of Recombinant Human Thyrotropin for Thyroid Function Testing in Healthy and Suspected Hypothyroid Dogs

Background: Various protocols using different doses of recombinant human thyrotropin (rhTSH) in TSH stimulation testing have been described. However, the influence of TSH dosage on thyroxine (T4) concentration has not yet been evaluated in suspected hypothyroid dogs.
Objective: To evaluate the effectiveness of 2 doses of rhTSH.
Animals: Fifteen dogs with clinical signs consistent with hypothyroidism and abnormal stimulation results with 75 μg rhTSH and 18 clinically healthy dogs.
Methods: All dogs were stimulated with 75 and 150 μg rhTSH IV in a 1st and 2nd stimulation test, respectively. Blood samples were taken before and 6 hours after rhTSH administration for determination of total T4 concentration.
Results: Using the higher dose led to a normal test interpretation in 9 of the 15 dogs, in which stimulation had been abnormal using the lower dose. Based on follow-up information, hypothyroidism was excluded in 7 of these 9 dogs. In all 6 dogs with a blunted response to the higher dose, hypothyroidism could be confirmed. Healthy dogs showed significantly higher post-TSH T4 concentrations with the higher compared with the lower dose. Post-TSH T4 concentrations after TSH stimulation were not related to dogs' body weight in either healthy or diseased dogs.
Conclusions and Clinical Relevance: TSH dose significantly influenced test interpretation in suspected hypothyroid dogs. Differentiation between primary hypothyroidism and nonthyroidal disease was improved with 150 μg rhTSH. Because this effect was independent of the dogs' body weight, the higher dose is recommended in dogs that have concurrent disease or are receiving medication.     

Comparison of acute hemodynamic effects of lidocaine and procainamide for postoperative ventricular arrhythmias in dogs

Heart rate and systolic, diastolic, and mean pressures were measured in two groups of dogs during treatment of postoperative ventricular arrhythmias either with intravenous (IV) 2% lidocaine hydrochloride or procainamide hydrochloride. Hemodynamic parameters were not significantly changed after IV administration of either drug. Additionally, changes in hemodynamic parameters for dogs treated with 2% lidocaine were not significantly different from those of dogs treated with procainamide. When dosed appropriately in the clinical setting, one bolus of IV procainamide was safe for the treatment of postoperative ventricular arrhythmias.     

Evaluation of adding diltiazem therapy to standard treatment of acute renal failure caused by leptospirosis: 18 dogs (1998–2001)

Objective: To assess efficacy and safety of intravenous (IV) diltiazem as a treatment for acute renal failure (ARF) secondary to leptospirosis in dogs. Design: Retrospective study Animals: Eighteen dogs with ARF caused by Leptospira spp treated during the months of September to December (1998–2001). Procedure: All dogs treated for ARF caused by Leptospira spp were enrolled in the study and were treated with standard care consisting of IV fluids, +/? furosemide, and antibiotics. With owner consent some dogs were treated with diltiazem at 0.1–0.5 mg/kg (0.045–0.22 mg/lb) IV slowly, followed by 1–5 μg/kg/minutes (0.45–2.2 mg/lb/minutes) constant rate infusion. Outcome measures were compared between the 2 groups (diltiazem versus standard). Diltiazem was administered within 60 hours of admission until serum creatinine fell into the normal range or stabilized. The primary outcome measurement of safety was systolic blood pressure (SBP). The primary measurement of efficacy outcome was the rate and magnitude of reduction of serum creatinine Results: Eleven out of 18 dogs received diltiazem. The rate of reduction in creatinine in the diltiazem group was 1.76 times faster than the standard group (P=0.054). Recovery of renal function showed a trend towards significant association with treatment group (exact P=0.08, odds ratio=3.62). This effect may be clinically relevant. Diltiazem had no clinically relevant effect on SBP. Conclusions and clinical relevance: Renal recovery in dogs with acute renal failure secondary to leptospirosis is improved with the administration of diltiazem in addition to ‘standard’ therapy.     

Histologic and ultrastructural studies of juvenile onset renal disease in four Rottweiler dogs

Juvenile onset renal disease is described in 2 male and 2 female young Rottweiler dogs. Histologic changes in all dogs were cystic dilatation of Bowman's space, mesangial hypercellularity, and glomerulosclerosis. Three dogs also had glomerular crescents and moderate to severe interstitial fibrosis. Electron microscopy revealed glomerular basement membranes of variable thickness, with extensive splitting or lamellation of the lamina densa. These ultrastructural findings are similar to those found in people and in other breeds of dogs with inherited defects in type IV collagen.     

Congenital Hypothyroid Dwarfism in a Family of Giant Schnauzers

Congenital hypothyroid dwarfism was diagnosed in a family of Giant Schnauzers. Three female and two male puppies from different litters were evaluated for dwarfism, lethargy, somnolence, gait abnormalities, and constipation. On physical examination, disproportionate dwarfism (n = 5), macroglossia (n = 3), hypothermia (n = 3), delayed dental eruption (n = 3), ataxia (n = 2), and abdominal distension (n = 1) were identified. Results of initial laboratory tests showed anemia (n = 4), hypercholesterolemia (n = 4), hypercalcemia (n = 2), and transudative abdominal effusion (n = 1). Radiographic skeletal surveys disclosed epiphyseal dysgenesis and delayed skeletal maturation (n = 5). A diagnosis of hypothyroidism was established on the basis of low basal serum thyroxine concentrations that failed to increase following the administration of TSH (n = 5) and markedly reduced to absent thyroid image when evaluated with gamma camera imaging of the thyroid gland (n = 4). In the two dogs that were most thoroughly evaluated, the results of thyroid histology, prolonged TSH testing, and repeat thyroid imaging, after three daily injections of TSH, were all consistent with secondary or tertiary, rather than primary, hypothyroidism. When TSH was administered over a period of 3 consecutive days (5 IU/day, subcutaneously), serum thyroid hormone response became normal and resulted in a normal thyroid image in the two dogs re-evaluated with gamma camera imaging. Daily treatment with oral levothyroxine (20 micrograms/kg) resulted in complete remission in puppies (n = 4) treated prior to 4 months of age. The other puppy failed to attain normal breed standards for height.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of thyrotropin-releasing hormone on serum concentrations of thyroxine and triiodothyronine in healthy, thyroidectomized, thyroxine-treated, and propylthiouracil-treated dogs

Effects of thyrotropin-releasing hormone (TRH) on serum concentrations of thyroid hormones were studied in 36 mixed-bred dogs. Dogs were randomly assigned to 7 groups. Significant increases (P less than 0.05) of serum thyroxine (T4) values occurred as early as 2 hours and reached a peak at 6 to 8 hours after IV injection of 300 to 1,100 micrograms of TRH. Thyroxine concentrations in response to a TRH dose greater than 500 micrograms were similar to those observed with the 300-micrograms dose. Transient coughing, vomiting, salivation, and defecation after large doses (900 and 1,100 micrograms) were observed. Mean serum T4 concentration decreased from 2.1 micrograms/dl to 0.9 micrograms/dl within 1 day of thyroidectomy. Clinical signs of hypothyroidism, including lethargy, dry coats, and diffuse alopecia, were present in 2 dogs at a month after surgical operation. Thyroxine concentrations were detectable for greater than 2 months. Injection (IV) of 700 micrograms of TRH 6 weeks after surgical operation had no effect on serum concentration of T4 in thyroidectomized dogs. In 5 T4-treated dogs, TRH (700 micrograms, IV) significantly increased the serum T4 value, indicating that pituitary thyrotropes were responsive to TRH, in spite of daily medication of 0.8 mg of T4. Four dogs were treated orally with 200 mg of propylthiouracil/day for 5 weeks. Intravenous injection of 700 micrograms of TRH in propylthiouracil-treated dogs had no effect on the serum T4 concentration, indicating that TRH had no effect on serum T4 values in these dogs during the experimental period. These results indicate that TRH can replace bovine thyrotropin for the canine thyroid function test.(ABSTRACT TRUNCATED AT 250 WORDS)     

Congenital Type III von Willebrand’s disease unmasked by hypothyroidism in a Shetland sheepdog

A 7-year-old, spayed female Shetland sheepdog had sudden onset of right-sided epistaxis. Diagnostic tests revealed Type III von Willebrand’s disease and primary hypothyroidism leading to an acute hypothyroid crisis and acquired factor VIII (FVIII) deficiency. Levothyroxine therapy normalized the serum thyroxine and FVIII concentrations. The delayed onset of disease and the reversible FVIII deficiency that was corrected with levothyroxine therapy, support a role for hypothyroidism in the pathogenesis of this dog’s sudden bleeding tendency as has been seen with hypothyroidism in humans.     

Administration of levothyroxine to euthyroid dogs does not affect echocardiographic and electrocardiographic measurements.

The effects of a replacement dose of levothyroxine on electrocardiographic and echocardiographic parameters in euthyroid dogs were examined. Two-dimensional guided M-mode echocardiograms and electrocardiograms were obtained before and after administration of levothyroxine (0.5 mg m-2 twice a day) to 10 euthyroid dogs for a period of eight weeks; four untreated dogs acted as controls. The resting serum total thyroxine concentration was significantly increased in treated dogs during weeks 4 to 8. There were no significant differences in any of the echocardiographic or electrocardiographic measurements resulting from treatment.     

Endotoxin-induced hemodynamic changes in dogs: role of thromboxane and prostaglandin I2

Plasma concentrations of thromboxane and prostaglandin I2 (PGI2) before and after IV injection of endotoxin and resulting hemodynamic changes were evaluated. Effects of flunixin meglumine on plasma concentrations of these prostaglandins and the related hemodynamic changes were also determined. Shock was induced in 2 groups of anesthetized dogs. Four dogs were given endotoxin only and 4 dogs were given endotoxin and then were treated with flunixin meglumine. Arterial blood pressure (BP), cardiac output (CO), and heart rate were measured, and blood samples were collected at postendotoxin hours (PEH) 0, 0.1, 0.25, 0.5, 1, 2, 3, and 4. Plasma thromboxane and PGI2 concentrations were increased in canine endotoxic shock. Thromboxane concentration was highest early in shock, and appeared to be associated with an initial decrease in BP and CO. The increased concentration of PGI2 was associated with systemic hypotension at PEH 1 to 2. Treatment of dogs with flunixin meglumine at PEH 0.07 prevented further increase of thromboxane and blocked the release of PGI2, resulting in an increased CO, BP, and tissue aerobic metabolism.