Evaluation of serum free thyroxine and thyrotropin concentrations in the diagnosis of canine hypothyroidism

Canine thyroid-stimulating hormone (cTSH), total thyroxine (T4) and free T4 by equilibrium dialysis (fT4d) were measured in serum samples from 107 dogs with clinical signs suggestive of hypothyroidism in which the diagnosis was either confirmed (n = 30) or excluded (n = 77) by exogenous TSH response testing. Median serum total T4 and fT4d concentrations were significantly lower and cTSH significantly higher (P < 0.001) in hypothyroid compared with euthyroid dogs. Differential positive rate analysis determined optimal cut-off values of less than 14.9 nmol/litre (total T4), less than 5.42 pmol/litre (fT4d), greater than 0.68 ng/ml (cTSH), less than 17.3 (T4 to cTSH ratio), and less than 7.5 (fT4d to cTSH ratio) for hypothyroidism. These had a sensitivity and specificity of 100 and 75.3 per cent, 80 and 93.5 per cent, 86.7 and 81.8 per cent, 86.7 and 92.2 per cent, and 80 and 97.4 per cent, respectively, for diagnosing hypothyroidism. Corresponding areas under the receiver operating characteristic curves were 0.92, 0.93, 0.87, 0.93 and 0.93. Unexpectedly low cTSH values in hypothyroid dogs may have resulted from concurrent non-thyroidal illness. Unexpectedly high serum cTSH values in the euthyroid dogs might have resulted from recovery from illness or concurrent potentiated sulphonamide therapy. Measurement of endogenous cTSH concentration is a valuable diagnostic tool for canine hypothyroidism if used in association with assessment of T4. Estimation of fT4d added only limited additional information over total T4 measurement.     

Thyroid-stimulating hormone and total thyroxine concentrations in euthyroid, sick euthyroid and hypothyroid dogs

Canine thyroid-stimulating hormone (cTSH) was measured in a variety of clinical cases (n= 72). The cases were classified as euthyroid, sick euthyroid, hypothyroid or hypothyroid on non-thyroidal therapy on the basis of their history, clinical signs, laboratory results (including total thyroxine concentrations and, where indicated, thyroid-releasing hormone [TRH] stimulation tests) and response to appropriate therapy. Additional samples were taken during some of the TRH stimulation tests to measure the response of cTSH concentrations following TRH administration. A reference range (0 to 0–41 ng/ml) was calculated from the basal concentrations of cTSH in a group of 41 euthyroid dogs. Six of nine cases of confirmed hypothyroidism had basal cTSH concentrations above the reference range, whereas the remainder were within the normal range. One of these three remaining cases was a pituitary dwarf and did not show a rise in cTSH concentration following TRH stimulation. In contrast, only one of a group of six hypothyroid dogs that had been on non-thyroidal treatment within the previous four weeks had increased concentrations of basal cTSH. This study also found that five of a group of 16 dogs with sick euthyroid syndrome had increased cTSH concentrations. It was concluded that cTSH measurements are a useful additional diagnostic test in cases of suspected hypothyroidism in dogs but that dynamic testing is still required to confirm the diagnosis of hypothyroidism.     

Evaluation of recombinant human thyroid-stimulating hormone to test thyroid function in dogs suspected of having hypothyroidism

OBJECTIVE: To evaluate the use of recombinant human (rh) thyroid-stimulating hormone (TSH) in dogs with suspected hypothyroidism. ANIMALS: 64 dogs with clinical signs of hypothyroidism. PROCEDURES: Dogs received rhTSH (75 microg/dog, IV) at a dose independent of their body weight. Blood samples were taken before and 6 hours after rhTSH administration for determination of total serum thyroxine (T(4)) concentration. Dogs were placed into 1 of 3 groups as follows: those with normal (ie, poststimulation values indicative of euthyroidism), unchanged (ie, poststimulation values indicative of hypothyroidism; no thyroid gland stimulation), or intermediate (ie, poststimulation values between unchanged and normal values) post-TSH T(4) concentrations. Serum canine TSH (cTSH) concentration was determined in prestimulation serum (ie, before TSH administration). RESULTS: 14, 35, and 15 dogs had unchanged, normal, and intermediate post-TSH T(4) concentrations, respectively. Basal T(4) and post-TSH T(4) concentrations were significantly different among groups. On the basis of basal serum T(4) and cTSH concentrations alone, 1 euthyroid (normal post-TSH T(4), low basal T(4), and high cTSH concentrations) and 1 hypothyroid dog (unchanged post-TSH T(4) concentration and low to with-in reference range T(4) and cTSH concentrations) would have been misinterpreted as hypothyroid and euthyroid, respectively. Nine of the 15 dogs with intermediate post-TSHT(4) concentrations had received medication known to affect thyroid function prior to the test, and 2 of them had severe nonthyroidal disease. CONCLUSIONS AND CLINICAL RELEVANCE: The TSH-stimulation test with rhTSH is a valuable diagnostic tool to assess thyroid function in selected dogs in which a diagnosis of hypothyroidism cannot be based on basal T(4) and cTSH concentrations alone.     

Effects of sulfamethoxazole-trimethoprim on thyroid function in dogs

OBJECTIVE: To evaluate effects of trimethoprim-sulfamethoxazole (T/SMX) on thyroid function in dogs. ANIMALS: 6 healthy euthyroid dogs. PROCEDURE: Dogs were administered T/SMX (14.1 to 16 mg/kg, PO, q 12 h) for 3 weeks. Blood was collected weekly for 6 weeks for determination of total thyroxine (TT4), free thyroxine (fT4), and canine thyroid-stimulating hormone (cTSH) concentrations. Schirmer tear tests were performed weekly. Blood was collected for CBC prior to antimicrobial treatment and at 3 and 6 weeks. RESULTS: 5 dogs had serum TT4 concentrations equal to or less than the lower reference limit, and 4 dogs had serum fT4 less than the lower reference limit after 3 weeks of T/SMX administration; cTSH concentrations were greater than the upper reference limit in 4 dogs. All dogs had TT4 and fT4 concentrations greater than the lower reference limit after T/SMX administration was discontinued for 1 week, and cTSH concentrations were less than reference range after T/SMX administration was discontinued for 2 weeks. Two dogs developed decreased tear production, which returned to normal after discontinuing administration. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that administration of T/SMX at a dosage of 14.1 to 16 mg/kg, PO, every 12 hours for 3 weeks caused decreased TT4 and fT4 concentrations and increased cTSH concentration, conditions that would be compatible with a diagnosis of hypothyroidism. Therefore, dogs should not have thyroid function evaluated while receiving this dosage of T/SMX for >2 weeks. These results are in contrast to those of a previous study of trimethoprim-sulfadiazine.     

Tertiary hypothyroidism in a dog

: A nine-year-old male entire Labrador was diagnosed with pituitary dependent hyperadrenocorticism. Following seven months of successful mitotane therapy, the dog presented with marked weight gain, seborrhoea and alopecia. Routine clinicopathological analyses revealed marked hypercholesterolaemia. Serum total and free thyroxine (T4) concentrations were below their respective reference ranges. Serum thyroid stimulating hormone (cTSH) concentration was within reference range. TSH and thyrotropin releasing hormone (TRH) response tests revealed adequate stimulation of total T4 in both, and cTSH in the latter test. Magnetic resonance imaging revealed a mass arising from the pituitary fossa, with suprasellar extension. A diagnosis of tertiary hypothyroidism was made. Following four weeks of levothyroxine therapy, circulating cholesterol concentration had declined, weight loss had ensued and dermatological abnormalities had improved. Euthanasia was performed four months later due to the development of neurological signs. A highly infiltrative pituitary adenoma, with effacement of the overlying hypothalamus was identified on post mortem examination. Tertiary hypothyroidism has not been previously reported in dogs.     

Altered Serum Thyrotropin Concentrations in Dogs with Primary Hypoadrenocorticism before and during Treatment

Background

Thyrotropin (TSH) can be increased in humans with primary hypoadrenocorticism (HA) before glucocorticoid treatment. Increase in TSH is a typical finding of primary hypothyroidism and both diseases can occur concurrently (Schmidt's syndrome); therefore, care must be taken in assessing thyroid function in untreated human patients with HA.

Objective

Evaluate whether alterations in cTSH can be observed in dogs with HA in absence of primary hypothyroidism.

Animals

Thirty dogs with newly diagnosed HA, and 30 dogs in which HA was suspected but excluded based on a normal ACTH stimulation test (controls) were prospectively enrolled.

Methods

cTSH and T4 concentrations were determined in all dogs and at selected time points during treatment (prednisolone, fludrocortisone, or DOCP) in dogs with HA.

Results

cTSH concentrations ranged from 0.01 to 2.6 ng/mL (median 0.29) and were increased in 11/30 dogs with HA; values in controls were all within the reference interval (range: 0.01–0.2 ng/dL; median 0.06). There was no difference in T4 between dogs with increased cTSH (T4 range 1.0‐2.1; median 1.3 μg/dL) compared to those with normal cTSH (T4 range 0.5‐3.4, median 1.4 μg/dL; P=0.69) and controls (T4 range 0.3‐3.8, median 1.8 μg/dL; P=0.35). After starting treatment, cTSH normalized after 2–4 weeks in 9 dogs and after 3 and 4 months in 2 without thyroxine supplementation.

Conclusions and Clinical Relevance

Evaluation of thyroid function in untreated dogs with HA can lead to misdiagnosis of hypothyroidism; treatment with glucocorticoids for up to 4 months can be necessary to normalize cTSH.     

The effect of thyroid replacement in dogs with suboptimal thyroid function on owner-directed aggression: A randomized,double-blind,placebo-controlled clinical trial

The efficacy of thyroid hormone replacement therapy (THRT) as treatment for owner-directed aggression in client-owned dogs with borderline low thyroid hormone levels was evaluated by means of a 6-week-long, parallel design, double-blind placebo-controlled study. The designation of “borderline hypothyroid” was made if the dog's free normal thyroxine (T4) value was frankly low or in the bottom 20th percentile of the normal range and either total T4, total triiodothyronine (T3), or free T3 was frankly low or in the bottom 30th percentile of the normal range. The presence of thyroid autoantibodies also qualified a dog for enrollment. Owners recorded the number of aggressive episodes directed toward family members on a daily basis for 8 weeks (2-week baseline phase and 6-week study phase). Twenty-nine dogs completed the study; 14 in a treatment group and 15 in a placebo group. The median number of aggressive episodes per day decreased significantly from baseline in both treated and placebo group dogs in weeks 1-2, 3-4, 5-6, and week 6 (treatment, χ² = 24.8, P < 0.001; placebo, χ² = 20.2, P < 0.001), however the median frequency of aggression was significantly lower in the treatment group (1.21 episodes/day) than in the placebo group (1.71 episodes/day) during week 6 of the study (χ² = 4.047, P = 0.044). Three thyroxine-treated dogs had borderline-low thyroid levels on the final day of the study (day 42). When aggression frequency was compared between the treatment and placebo groups after the removal of 3 thyroxine-treated dogs, the treatment group did not have a significantly lower aggression frequency than the placebo group during week 6 (Kruskal–Wallis statistic: χ² = 3.035, n = 26, P = 0.08). The authors discuss the role of thyroid hormones in the regulation of aggression and other cognitive issues and provide rationale for using THRT in dogs exhibiting owner-directed aggression that also have low normal or baseline thyroid hormone levels.     

Endogenous TSH in the diagnosis of hypothyroidism in dogs

To determine whether measurement of canine thyrotropin (cTSH) would aid in the diagnosis of hypothyroidism, serum samples of 65 dogs with clinical signs suggestive of hypothyroidism were evaluated. Diagnosis was confirmed in 26 dogs and excluded in 39 dogs based on TSH-stimulation testing. Total thyroxine (T4) was significantly lower and cTSH significantly higher in hypothyroid dogs compared to euthyroid dogs. Canine TSH was above (> 0.6 ng/ml) in 15 (57.7%) and below the upper limit of the reference range in 11 (42.3%) of the hypothyroid dogs. All of the euthyroid dogs had a cTSH < 0.6 ng/ml. In all dogs with a cTSH above the upper limit of the reference range hypothyroidism could be confirmed. Therefore, our results show that measurement of cTSH has an excellent specificity (100%) and is a valuable tool in confirming canine hypothyroidism. However, due to the low sensitivity of cTSH assays (60%), it can not be recommended to exclude the disease.     

Dynamic adrenal function testing in eight dogs with hyperadrenocorticism associated with adrenocortical neoplasia.

The results of adrenocorticotropin (ACTH) stimulation and low-dose dexamethasone suppression tests (LDDST) were evaluated retrospectively in eight dogs with clinical signs of hyperadrenocorticism arising from functional adrenocortical tumours, and compared with the results from 12 dogs with confirmed pituitary-dependent hyperadrenocorticism (PDH). The post-ACTH cortisol concentration in the dogs with adrenocortical tumours ranged from 61 to 345-6 nmol/litre (median 251.5 nmol/litre) and they were within the reference range (150 to 450 nmol/litre) in five and unexpectedly low (< 150 nmol/litre) in three dogs. Both the basal and post-ACTH cortisol concentrations were significantly lower in the dogs with adrenocortical neoplasia than in the dogs with PDH. Eight hours after the LDDST, only two of six dogs with adrenocortical tumours had a cortisol concentration above 30 nmol/litre, and the median resting, three, and eight-hour cortisol concentrations were 31.5, 23.0, and 22.7 nmol/litre respectively. There was no significant cortisol suppression during the LDDST, although interpretation was complicated by the low cortisol concentrations, but two dogs showed a pattern of apparent suppression. Two dogs with adrenal tumours showed a diagnostically significant increase in 17-OH-progesterone concentration in response to ACTH although their cortisol concentrations did not increase greatly. These results differ from previous reports of the response of functional adrenal tumours to dynamic endocrine tests.     

Cortisol response to two different doses of intravenous synthetic ACTH (tetracosactrin) in overweight cats

Fifteen middle-aged to older, overweight cats attending a first-opinion clinic were investigated to rule out hyperadrenocorticism as a cause of their weight problem, using two different protocols for the adrenocorticotropic hormone (ACTH) stimulation test. The cats received intravenous synthetic ACTH (tetracosactrin) at an initial dose of 125 microg; a second test was performed between two and three weeks later, using a dose of 250 microg intravenously. The mean basal serum cortisol concentration was 203 nmol/litre (range 81 to 354 nmol/litre). The highest mean serum cortisol concentration occurred at 60 minutes following the 125 microg dose and at 120 minutes following the 250 microg dose. There was, however, no statistically significant difference between these peak cortisol concentrations attained using either dose of tetracosactrin. A significantly higher mean serum cortisol concentration was attained after the higher dose at the 180 minutes time point, indicating a more prolonged response when compared with the lower dose. The cats were followed up for one year after the initial investigations and none were found to develop hyperadrenocorticism during this time.     

Clinical,hematological, biochemical and endocrinological aspects of 32 dogs with hypothyroidism

During the years of 1996-2001, hypothyroidism was diagnosed at the clinic for small animal internal medicine, University of Zurich, in 32 dogs. Most of the dogs were large breeds. The most frequent clinical characteristics observed were exercise intolerance, obesity, dermatological, neurological and gastrointestinal signs. Predominant laboratory abnormalities were a low red blood cell count, increased concentration of cholesterol, triglycerides and fructosamin. 29 dogs had a T4 below the reference range (< 1.5 micrograms/dl), one dog had a T4 at the lower limit thereof (1.6 micrograms/dl). One dog had a T4 within the reference range (3.4 micrograms/dl), another had a very high T4 of 206.8 micrograms/dl; the results of the latter 2 dogs were interpreted as incorrectly increased T4 values due to in vitro interference with T4-autoantibodies. Diagnosis was confirmed in all of the dogs based on TSH-stimulation testing. Endogenous TSH (cTSH) measured parallelly, was elevated in only 60% of the dogs. In about 67% of the dogs, hypothyroidism was associated with thyroglobulin-autoantibodies. Canine hypothyroidism is a rather rare endocrine disorder in Switzerland. The TSH-stimulation test remains the gold standard in confirming the disease; a definitive diagnosis can be challenging for practitioners because bovine TSH, used for the TSH-stimulation test is not licensed for use in dogs. Since assessment of cTSH using current assays shows normal values in a high percentage of hypothyroid dogs, the diagnostic value is only limited. In most of the hypothyroid dogs T4 is decreased, with the presence of autoantibodies to T4, it can be normal or increased.     

Thyroid function testing in Greyhounds.

OBJECTIVE: To evaluate thyroid function in healthy Greyhounds, compared with healthy non-Greyhound pet dogs, and to establish appropriate reference range values for Greyhounds. ANIMALS: 98 clinically normal Greyhounds and 19 clinically normal non-Greyhounds. PROCEDURES: Greyhounds were in 2 groups as follows: those receiving testosterone for estrus suppression (T-group Greyhounds) and those not receiving estrus suppressive medication (NT-group Greyhounds). Serum thyroxine (T4) and free thyroxine (fT4) concentrations were determined before and after administration of thyroid-stimulating hormone (TSH) and thyroid-releasing hormone (TRH). Basal serum canine thyroid stimulating hormone (cTSH) concentrations were determined on available stored sera. RESULTS: Basal serum T4 and fT4 concentrations were significantly lower in Greyhounds than in non-Greyhounds. Serum T4 concentrations after TSH and TRH administration were significantly lower in Greyhounds than in non-Greyhounds. Serum fT4 concentrations after TSH and TRH administration were significantly lower in NT-group than T-group Greyhounds and non-Greyhounds. Mean cTSH concentrations were not different between Greyhounds and non-Greyhounds. CONCLUSIONS AND CLINICAL RELEVANCE: Previously established canine reference range values for basal serum T4 and fT4 may not be appropriate for use in Greyhounds. Greyhound-specific reference range values for basal serum T4 and fT4 concentrations should be applied when evaluating thyroid function in Greyhounds. Basal cTSH concentrations in Greyhounds are similar to non-Greyhound pet dogs.     

Results of thyroid function tests and concentrations of plasma proteins in dogs administered etodolac

OBJECTIVE: To determine the effects of etodolac administration on results of thyroid function tests and concentrations of plasma proteins in clinically normal dogs. Animals: 19 healthy random-source mixed-breed dogs. PROCEDURE: Blood samples for measurement of serum thyroxine (T4), 3,5,3'-triiodothyronine (T3), free T4 (fT4), and endogenous canine thyroid stimulating hormone (cTSH) were measured twice before as well as on days 14 and 28 of etodolac administration (mean dosage, 13.7 mg/kg, PO, q 24 h). Plasma total protein, albumin, and globulin concentrations and serum osmolality were measured once before as well as on days 14 and 28 of etodolac administration. RESULTS: Etodolac administration did not significantly affect serum T4, T3, fT4, or cTSH concentrations or serum osmolality. Significant decreases in plasma total protein, albumin, and globulin concentrations were detected on days 14 and 28 of administration. CONCLUSIONS AND CLINICAL RELEVANCE: Results of thyroid function tests are not altered when etodolac is administered for up to 4 weeks. Therefore, interpretation of results of these tests should accurately reflect thyroid function during etodolac treatment. Plasma total protein, albumin, or globulin concentrations that are less than the respective reference range in a dog administered etodolac for > or = 2 weeks may be an effect of treatment rather than an unrelated disease process. A decrease in plasma protein concentrations may reflect subclinical injury of the gastrointestinal tract.     

Mega-oesophagus secondary to acquired myasthenia gravis

Fifteen dogs with confirmed adult onset idiopathic megaoesophagus, in which no generalised muscle weakness was observed, were tested for the presence of acetylcholine receptor antibodies. Of these, six were found to have values greater than 0–6 nmol/litre, previously determined to be diagnostic of acquired myasthenia gravis. The mean serum titre value for these dogs was 5–59 nmol/litre (range 0–78 to 8–72 nmol/litre). It appears that a significant proportion of dogs presenting with megaoesophagus have myasthenia gravis and, if a prompt diagnosis and appropriate treatment can be instituted, clinical signs may improve.     

Radioactive iodine therapy for feline hyperthyroidism: Efficacy and administration routes

The efficacy of radioactive iodine (¹³¹I) administration was studied in a series of 50 hyperthy-roid cats. The dose administered to each cat was based on the clinical severity of the thyrotoxicosis, the serum total thyroxine (TJ concentration and the size of the goitre estimated by palpation. The activity ranged from 80 to 200 MBq (mean ± SD, 143 ± 24 MBq}. The ¹³¹I was injected intravenously in 27 cases and subcutaneously in 23 cases. Each cat was hospitalised for 30 days after the injection. Regardless of the route of injection, none of the cats exhibited any side effects after therapy and all tolerated the hospitalisation period well. There was a significant (P<0.001) decrease in the serum total T₄ concentration (reference range, 10.4 to 42.0 nmol/litre) from a mean ± SD of 181.3 ± 111.4 nmol/litre (range, 43.8 to 575.6 nmol/litre) to a mean ± SD of 19.0 ± 29.6 nmol/litre (range, 2.0 to 175.7 nmol/litre) 30 days following the injection of the radioisotope. Five cats remained hyperthyroid, although in each case the serum total T₄ concentrations had decreased from pre-treatment values. Two of the cats subsequently became euthyroid within three and five months of therapy, respectively, two were lost to adequate follow-up and the remaining cat was successfully retreated four months later. Before treatment, four of these cases had high scores based on the three criteria used for dose estimation. Serum total T₄ concentrations below the reference range developed after treatment in many cases, but were often transient. Clinical evidence of hypothyroidism was not apparent in any cat. Recurrence of hyperthyroidism has not occurred in follow-up periods of up to 32 months. There was no difference in the outcome between the cats injected intravenously or subcutaneously and the latter was considered to be safer and simpler. The administration of an approximated dose of ¹³¹I proved to be an effective treatment for hyperthyroidism in 47 (94.0 per cent) of the cats and obviated the need for sophisticated nuclear computer facilities. There may be a lag period in some cases before euthy-roidism is achieved and this should be considered before the administration of a second dose. ¹³¹I can be administered subcutaneously without untoward effects.     

Serum free and total iodothyronine concentrations in dogs with hyperadrenocorticism.

Serum concentrations of total and free thyroxine (T4 and FT4, respectively), 3,5,3'-triiodothyronine (T3), 3,3',5'-triiodothyronine (reverse T3) were measured in 42 dogs with hyperadrenocorticism, and were compared with values determined in clinically normal dogs. Mean total T4 concentration in dogs with hyperadrenocorticism (14.3 nmol/L) was significantly (P less than 0.001) lower than the normal value (25.7 nmol/L), with 38% of the dogs having low serum T4 concentration. Although 16 (38%) of the 42 dogs with hyperadrenocorticism had a high FT4 fraction, indicative of diminished serum T4 binding, normal FT4 concentration was found in only 6 of the 16 dogs (38%) with low total T4 values. Mean serum T3 concentration in dogs with hyperadrenocorticism (0.79 nmol/L) was also significantly (P less than 0.001) lower than the normal value (1.16 nmol/L), with 39% of the dogs having T3 values below the normal range. Individual T3-to-T4 and T3-to-FT4 ratios, indices of T3 production and/or clearance, were above the normal range in 29 and 24% of dogs with hyperadrenocorticism, respectively. Mean reverse T3 concentration in dogs with hyperadrenocorticism (0.17 nmol/L) was also significantly (P less than 0.001) lower than the normal mean value (0.39 nmol/L), with 48% of the dogs having reverse T3 values below the normal range. Of the 21 dogs in which all iodothyronines were measured, 6 (29%) had undetectable values for all hormones.(ABSTRACT TRUNCATED AT 250 WORDS)     

Serum thyroid hormone concentrations and thyroglobulin autoantibodies in trained and non-trained healthy whippets

Numerous factors including non-thyroidal systemic diseases and drug administration can significantly alter canine thyroid function test results. Furthermore, the importance of breed specific variations has probably been underestimated. In this study, total thyroxine (TT4), free thyroxine (FT4), canine endogenous thyroid stimulating hormone (cTSH) serum concentrations and thyroglobulin autoantibodies (TgAA) were determined in a population of healthy whippets and compared to a control group of different breeds. Mean TT4 values were significantly lower in the whippets but no significant differences were seen between whippets and control dogs for FT4 and for cTSH. The prevalence of serum TgAA in the whippets was 2%, and this was not significantly different from the controls. The results suggest a breed variation for TT4, but not for FT4, cTSH and TgAA serum concentrations in whippets. Serum thyroid hormone concentrations were also compared between trained and non-trained whippets and it was concluded that regular training did not seem to have any significant influence.     

Evaluation of the basal and post-adrenocorticotrophic hormone serum concentrations of 17-hydroxyprogesterone for the diagnosis of hyperadrenocorticism in dogs

Serum concentrations of 17-hydroxyprogesterone and cortisol were measured before and after the administration of exogenous adrenocorticotrophic hormone (ACTH) to three groups of dogs: 27 healthy dogs (group 1), 19 dogs with non-adrenal illness (group 2) and 46 dogs with hyperadrenocorticism (group 3). The median (range) post-ACTH concentrations of 17-hydroxyprogesterone were 5.0 (22.2 to 16.8), 6.9 (2.0 to 36.2) and 14.4 (1.7 to 71) nmol/litre in groups 1, 2 and 3, respectively. There were no significant differences in the basal or post-ACTH concentrations of cortisol or 17-hydroxyprogesterone between groups 1 and 2. The post-ACTH concentrations of 17-hydroxyprogesterone in group 3 were significantly (P<0.001) greater than those in groups 1 and 2 combined. The area under the receiver operating curve (ROC) for the post-ACTH concentration of cortisol (0.94) was significantly greater than that for the post-ACTH concentration of 17-hydroxyprogesterone (0.76). Using a two-graph ROC analysis, a cut-off of 8.5 nmol/litre was found to maximise both the sensitivity and specificity of the post-ACTH concentration of 17-hydroxyprogesterone for the diagnosis of hyperadrenocorticism at 71 per cent. With a cut-off of 4.5 nmol/litre the sensitivity increased to 90 per cent but the specificity decreased to 40 per cent; with a cut-off of 16.7 nmol/litre the specificity increased to 90 per cent but the sensitivity decreased to 47 per cent.     

Plasma aldosterone concentrations and plasma renin activity in healthy dogs and dogs with hyperadrenocorticism

The mean (se) basal plasma aldosterone concentrations were significantly lower in 31 dogs with pituitary-dependent hyperadrenocorticism (PDH) (75 [9] pmol/litre) than in 12 healthy dogs (118 [14] pmol/litre), whereas in five dogs with hyperadrenocorticism due to an adrenocortical tumour they were significantly higher (205 [109] pmol/litre). The mean basal renin activity was not significantly different between the dogs with PDH (303 [48] fmol/litre/second), the dogs with an adrenocortical tumour (141 [63] fmol/litre/second), and the control dogs (201 [25] fmol/litre/second). At three and four hours after the intravenous administration of 0.1 mg/kg dexamethasone, the concentrations of aldosterone decreased significantly to about 60 per cent of their initial values in the control dogs but did not change in the dogs with PDH or an adrenocortical tumour. In the dogs with PDH the renin activity increased significantly after the administration of dexamethasone.     

Ovarian function suppression with a GnRH analogue: D-ser(But[t])[6]-Arzgly[10]-LHRH (Goserelin) in hormone dependent canine mammary cancer

Hormones and hormone level modifying substances have long been used to treat hormone-dependent tumours in humans. Recently, attempts have been made to use hormone manipulation regimens for the treatment of these tumours in veterinary medicine. The aim of the present study was to evaluate the activity of the luteinizing hormone-releasing hormone (LHRH)-agonist, D-ser(But[t])[6]-Azgly[10]-LHRH (Goserelin) in hormone-dependent mammary cancer in dogs. Eighteen female dogs with hormone-dependent mammary cancer (T2-T4, N0, M0 according to TNM clinical staging classification) were selected and allocated into two groups: nine dogs not treated with Goserelin (Group 1) referred to as control; and nine dogs treated with 60 microg/kg depot Goserelin every 21 days for 12 months (Group 2). Goserelin treatment decreased circulating levels of oestradiol and progesterone and reduced the size of mammary tumours; all the animals showed objective response (OR) to treatment after 3 months, and the relapse-free survival after 2 years was 88%. Haematology and blood chemistry parameters, measured every month from the beginning of treatment, as well as physical examination, showed that the drug was without toxic effects. This suggests that, at the dose administered, Goserelin blocks the hypothalamus-pituitary-ovary axis, and consequently can be useful to treat hormone-dependent mammary tumours in female dogs.