Use of recombinant human thyroid-stimulating hormone for thyrotropin-stimulation testing of euthyroid cats

OBJECTIVE: To evaluate response of euthyroid cats to administration of recombinant human thyroid-stimulating hormone (rhTSH). ANIMALS: 7 healthy cats. PROCEDURE: Each cat received each of 5 doses of rhTSH (0, 0.025, 0.050, 0.100, and 0.200 mg), IV, at 1-week intervals. Serum concentration of total thyroxine (TT4) and free thyroxine (fT4) was measured immediately before each injection (time 0) and 2, 4, 6, and 8 hours after administration of each dose. RESULTS: Overall TT4 response did not differ significantly among cats when administered doses were > or = 0.025 mg. Serum TT4 concentrations peaked 6 to 8 hours after administration for all doses > or = 0.025 mg. For all doses > or = 0.025 mg, mean +/- SEM TT4 concentration at 0, 6, and 8 hours was 33.9 +/- 1.7, 101.8 +/- 5.9, and 101.5 +/- 5.7 nmol/L, respectively. For all doses > or = 0.025 mg, mean fT4 concentration at 0, 6, and 8 hours was 38.7 +/- 2.9, 104.5 +/- 7.6, and 100.4 +/- 8.0 pmol/L, respectively. At 8 hours, the fT4 response to 0.025 and 0.050 mg was less than the response to 0.100 and 0.200 mg. Adverse reactions after rhTSH administration were not detected. CONCLUSIONS AND CLINICAL RELEVANCE: The TSH stimulation test can be performed in cats by IV administration of 0.025 to 0.200 mg of rhTSH and measurement of serum TT4 concentrations at time of injection and 6 or 8 hours later. Clinical validation of the TSH stimulation test would facilitate development of additional tests of thyroid gland function, such as a TSH assay.     

Use of recombinant human thyroid-stimulating hormone for thyrotropin stimulation test in euthyroid dogs

The purpose of this study was to evaluate the effects of the recombinant human thyroid-stimulating hormone (rhTSH) on serum total thyroxine (TT4) concentration in euthyroid dogs. Six healthy beagle dogs were used in each of the 3 phases of this study. Phase I: thyroid-stimulating hormone response tests were performed by using a total dose of 25 micrograms, 50 micrograms, and 100 micrograms of rhTSH, administered intravenously. Phases II and III: thyroid-stimulating hormone response tests were performed by using 50 micrograms of rhTSH administered by intramuscular and subcutaneous routes, respectively. In each phase and following all the administered doses of rhTSH, an increase in the serum TT4 concentration was noted, although it was not always significant. For phase I, there was a significant increase in serum TT4 concentrations. Based on this study, 50 micrograms was judged to be the optimal intravenous dose of rhTSH. For phases II and III, there was no significant increase in serum TT4 after the administration of rhTSH. Results of this study suggest that rhTSH could be a good substitute for bovine TSH, when used by the intravenous route, for the TSH stimulation test in dogs. Further studies are required to confirm its clinical usefulness.     

Use of recombinant human thyroid-stimulating hormone for thyrotropin stimulation test in healthy, hypothyroid and euthyroid sick dogs

Recombinant human thyroid-stimulating hormone (rhTSH) was evaluated for the diagnosis of canine hypothyroidism, using TSH response tests. Phase I stimulation tests were performed in 6 healthy dogs weighing over 20 kg, using 50 and then 100 microg of freshly reconstituted rhTSH administered intravenously. In phase II, the same dogs were stimulated by using 100 microg of rhTSH frozen for 3 months at -20 degrees C. Phase III stimulation tests were performed by using 50 or 100 microg of freshly reconstituted or frozen rhTSH in healthy (n = 14), euthyroid sick (n = 11) and hypothyroid dogs (n = 9). A dose of 100 microg of rhTSH was judged more appropriate for dogs weighing more than 20 kg. Biological activity of rhTSH after freezing at -20 degrees C for up to 12 weeks was maintained. When stimulated, significant (P < 0.05) increases in total thyroxine concentration were observed only in healthy and euthyroid sick dogs. Results of this study show that the rhTSH stimulation test is able to differentiate euthyroidism from hypothyroidism in dogs.     

Comparison of the biological activity of recombinant human thyroid-stimulating hormone with bovine thyroid-stimulating hormone and evaluation of recombinant human thyroid-stimulating hormone in healthy dogs of different breeds

OBJECTIVE: To evaluate whether use of recombinant human (rh) thyroid-stimulating hormone (TSH) induces equivalent stimulation, compared with bovine TSH (bTSH), and to evaluate activity of rhTSH in dogs of various large breeds. ANIMALS: 18 healthy research Beagles and 20 healthy client-owned dogs of various breeds with body weight > 20 kg. PROCEDURES: The 18 Beagles were randomly assigned to 3 groups, and each dog received either 75 microg of rhTSH, IM or IV, or 1 unit of bTSH, IM, respectively, in a crossover design. The 20 client-owned dogs received 75 microg of rhTSH, IV. Blood samples were taken before and 6 hours after TSH administration for determination of total serum thyroxine (T(4)) concentration. Additional blood samples were taken after 2 and 4 hours in Beagles that received rhTSH, IM. RESULTS: There was a significant increase in T(4) concentration in all dogs, but there were no differences between values obtained after administration of bTSH versus rhTSH or IV versus IM administration of rhTSH. Although there was a significant difference in age and body weight between Beagles and non-Beagles, there was no difference in post-TSH simulation T(4) concentration between the 2 groups. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated an equivalent biological activity of rhTSH, compared with bTSH. Use of 75 microg of rhTSH, IV, did not induce a different magnitude of stimulation in large-breed dogs, compared with Beagles. Euthyroidism was confirmed if post-TSH simulation T(4) concentration was > or = 2.5 microg/dL and at least 1.5 times basal T(4) concentration.     

Effect of recombinant human TSH on the uptake of radioactive iodine (I) by the thyroid gland in healthy beagles

In human medicine, recombinant human thyroid-stimulating hormone (rhTSH) increases thyroid radioactive iodine uptake (RAIU), allowing radioiodine-131 (¹³¹I) dose reduction and greater efficacy in the treatment of differentiated thyroid cancer and multinodular goiter. The goal of this study was to evaluate the effect of rhTSH, administered 24 h and 48 h before radioiodine-123 (¹²³I), on the thyroid RAIU in healthy dogs. Seven healthy euthyroid beagles were randomly allocated to 3 groups (2 groups of 2 dogs and 1 group of 3 dogs) in a prospective, blinded, crossover study. At Week 1, 1 group received ¹²³I for a baseline RAIU; 1 group received 100 μg of rhTSH IV 24 h before ¹²³I, and 1 group received 100 μg of rhTSH IV 48 h before ¹²³I. All dogs received 37 MBq of radioactive ¹²³I IV, and thyroid RAIU was determined 8 h, 24 h, and 48 h thereafter. The study was designed in such a manner that each dog received the 3 treatments and a wash-out period of 3 wk was respected in between. Blood samples were taken for measurement of serum total thyroxine (TT4) and thyrotropin (TSH) concentrations at baseline and 6 h, 12 h, 24 h, and 48 h after rhTSH administration. Recombinant human TSH caused no significant change on thyroid RAIU. The overall mean thyroid RAIU significantly decreased during the study independent of the treatment. Recombinant human TSH significantly increased serum TT4 concentration, which peaked 6 h after rhTSH administration. Compared to baseline, serum TSH concentration remained higher at 6 h, 12 h, 24 h, and 48 h. However, a statistically significant difference was reached only at 6 h and 12 h after rhTSH administration. No adverse effects of rhTSH were observed during the study. Further studies are needed to determine the best timing and dosage of administration of rhTSH in healthy and thyroid carcinoma dogs.     

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.     

Effect of recombinant human thyroid stimulating hormone on serum thyroxin and thyroid scintigraphy in euthyroid cats

This study investigated the thyroidal response to administration of recombinant human thyroid stimulating hormone (rhTSH) by means of serum total thyroxine (TT(4)) concentration and pertechnetate uptake by the thyroid gland in six healthy euthyroid spayed female cats. A pertechnetate scan was performed on day 1 to calculate thyroid/salivary gland (T/S) uptake ratio. On day 3, 25 microg rhTSH was injected intravenously. Six hours later the thyroid scan was repeated as on day 1. Blood was drawn for serum TT(4) measurement prior to injection of rhTSH and performance of the pertechnetate scan. Statistically significant differences in mean serum TT(4) concentration, T/S uptake ratio before and 6h after rhTSH administration and T/S uptake ratio between left and right lobes were noted. We can conclude that 25 microg rhTSH increases pertechnetate uptake in the thyroid glands of cats, this should be taken into account when thyroid scintigraphy after rhTSH administration is interpreted.     

Effect of thyroid hormone supplementation on survival of euthyroid dogs with congestive heart failure due to systolic myocardial dysfunction: a double-blind, placebo-controlled trial

Nineteen euthyroid dogs of 12 breeds with echocardiographic signs of dilated cardiomyopathy (DCM) and radiographic and clinical signs of congestive heart failure (CHF) were evaluated in a randomised, double-blind, and placebo-controlled study. The dogs received either thyroxine or placebo as an adjunct to digoxin, furosemide and propranolol. The group assignment of individual dogs and serum concentrations of thyroid hormones remained unknown to owners and investigators during the entire study period. Dogs were evaluated clinically and with electrocardiography (ECG), thoracic radiography, echocardiography and measurement of total thyroxine (tT4) and thyroid stimulating hormone (TSH) before beginning of the trial, and then one week, 2 months, 6 months and yearly after initial examination, and, when applicable, at the time of euthanasia. End-point of the study was euthanasia (n = 17) due to severe congestive heart failure or sudden death (n = 2). Survival times ranged from 17 to 1030 days (median 187 days) in the placebo group, and from 18 to 1000 days (median 73 days) in the treatment group. There was no statistically significant difference in survival times between the treatment group and the placebo group (p = 0.46). Post mortem and histopathologic examinations revealed the attenuated wavy fiber type of DCM in 11 dogs, and myocardial infarcts, arteriosclerosis and chronic valvular disease in one dog. In conclusion, there was a wide range in survival times of dogs treated with digoxin, furosemide and propranolol. Adding thyroid hormones to the treatment did not significantly influence survival.     

Use of compounded adrenocorticotropic hormone (ACTH) for adrenal function testing in dogs

Serum cortisol concentrations were measured in five healthy dogs in response to five adrenocorticotropic hormone (ACTH) preparations. Cortisol concentrations were similar at time 0 (pre-ACTH) and at 30 and 60 minutes after injection of all forms of ACTH. However, at 90 and 120 minutes post-ACTH, serum cortisol concentrations were significantly lower following injection of two compounded forms of ACTH. The data showed that injection of four compounded forms of ACTH caused elevations in serum cortisol concentrations of a similar magnitude as cosyntropin in samples collected 60 minutes after administration; but concentrations at later times varied, depending on the type of ACTH used.     

Effect of a Limited Iodine Diet on Iodine Uptake by Thyroid Glands in Hyperthyroid Cats

Background

The effect of feeding a limited iodine diet on radioactive iodine uptake in the thyroid glands of hyperthyroid cats is unknown.

Objectives

To determine how feeding limited dietary iodine affects radioactive iodine uptake by the thyroid glands of hyperthyroid cats.

Animals

Eight geriatric cats with spontaneous hyperthyroidism.

Methods

Prospective study of eight client owned hyperthyroid cats fed a commercially available iodine limited diet for 6 months. Clinical signs were evaluated and TT4 and fT4 were measured during consumption of the diet. Uptake of ¹²³I was determined before and 8–16 weeks after exclusive consumption of the diet.

Results

Clinical signs of hyperthyroidism resolved in all cats, but there was no significant increase in body weight. TT4 and fT4 decreased into the reference range by 8–16 weeks in all cats. Mean TT4 before consumption of the diet was 9.7 μg/dL (SD 5.2) and after consumption of the diet was 3.1 μg/dL (SD 0.9). Scintigraphy revealed unilateral uptake of isotope in 5 cats and bilateral uptake in 3 cats. Mean percentage uptake of ¹²³I by the thyroid gland at 8 hours after isotope administration was 16.2 (SD 11.8) before diet consumption and 34.6 (SD 11.7) 8–16 weeks after exclusive consumption of the diet. The percentage increase was variable between cats (38–639%).

Conclusions and clinical importance

Limited iodine diets increase iodine uptake in the autonomous thyroid glands of hyperthyroid cats. Further studies are necessary to determine if consumption of a limited iodine diet changes sensitivity of the thyroid gland to ¹³¹I treatment.     

Diagnosis of hypothyroidism in a western lowland gorilla (Gorilla gorilla gorilla) using human thyroid-stimulating hormone assay.

Primary hypothyroidism was diagnosed in a 26-yr-old female western lowland gorilla (Gorilla gorilla gorilla) on the basis of serum levels of thyroxine (T4), free T4, and thyroid-stimulating hormone (TSH) measured by human immunoassays. Compared with clinically normal gorillas, the TSH level (107 mlIU/L) was markedly elevated, and T4 (<14.0 nmol/L) and free T4 (5.0 pmol/L) levels were decreased. Thyroid hypofunction could explain the weight gain, unsettled appetite, anxious behavior, lethargy, and poor intraspecies interactions shown by this gorilla. The antibodies in the commercial immunoassay used in this study apparently cross-reacted with gorilla TSH. Supplementation with levothyroxine sodium was initiated and was followed by a marked decrease in circulating TSH and a noticeable improvement in the animal's physiologic status and activity level.     

Effect of recombinant human granulocyte colony stimulating factor on lymphocyte blastogenesis in healthy dogs

Effects of recombinant human granulocyte colony-stimulating factor (rhG-CSF) on the number and blastogenesis of lymphocytes were evaluated in clinically healthy dogs treated subcutaneously with rhG-CSF at a dose of 2.5 microg/kg for 3 days. Significant increases in the number of leukocytes and segmented neutrophils were observed after the administration of rhG-CSF. The number of lymphocytes also increased on days 1 and 2 after the treatment. Activities of phytohemagglutinin, concanavalin A, and pokeweed mitogen-induced lymphocyte blastogenesis (LB) were augmented to twice the pretreatment levels by the administration of rhG-CSF. These results suggested that administration of rhG-CSF activated lymphocyte functions such as LB in healthy dogs.     

Effect of recombinant human granulocyte colony-stimulating factor (rhG-CSF) on leukocyte count and survival rate of dogs with parvoviral enteritis.

Dogs with clinical signs consistent with parvoviral enteritis and leukopenia (total leukocyte count < 5.0 x 10(9) l(-1)) were included in this randomised double-blind study (treatment group: n = 22; control group: n = 21). The dogs in the treatment group received a subcutaneous daily injection of 10 microg kg(-1) of recombinant human granulocyte colony-stimulating factor (rhG-CSF) for 5 days. Clinical and blood investigations were performed prior to the first injection, daily during the treatment period and on the day after treatment ended, and then once more, 26 days after the first injection. During the study, no significant differences were found between the two groups with respect to survival rate (treatment group: 68 per cent; control group: 71 per cent, P > 0 4, Fisher-Test) and other clinical findings. Similarly the total leukocyte count, neutrophil count and other haematologic and biochemical parameters did not differ significantly between the groups, based on differences from initial values (P > 0 05). Consequently, the use of rhG-CSF in the treatment of dogs with parvoviral enteritis cannot be recommended.     

补益中药对雏鸡内分泌激素T3和TSH的影响

本研究探讨了补益中药对促进禽类生长的内分泌激素T3和TSH的调控影响,结果表明,淫羊藿和当归能极显著的提高T3水平（P〈0．01）;刺五加能极显著的降低T3水平（P〈0．01）。淫羊藿,黄芪,刺五加,当归均能极显著的降低TSH水平（P〈0．01）。畜禽体内T3及TSH水平的提高能促进畜牧生长,反之则会抑制其生长。     

Adrenal response to adrenocorticotropic hormone in dogs before and after surgical attenuation of a single congenital portosystemic shunt

BACKGROUND: Dogs with single congenital portosystemic shunts (CPSS) often develop postoperative hypoglycemia and prolonged anesthetic recovery. These abnormalities could be attributable to inadequate adrenal response. However, adequacy of adrenal response after CPSS surgery is unexplored. HYPOTHESIS: Dogs with CPSS have inadequate postoperative adrenal response. ANIMALS: Eight nonoperated, 8 ovariohysterectomy (OHE), and 16 CPSS dogs. METHODS: Consecutive day ACTH stimulation tests were performed on nonoperated healthy dogs, healthy dogs before and after OHE, and CPSS dogs before and after surgery. Adequate response was defined as >50% or >30 ng/mL increase in cortisol after ACTH administration. Blood glucose (BG) was monitored before and after surgery. Prolonged anesthetic recovery and refractory hypoglycemia episodes were recorded. RESULTS: Results of consecutive day ACTH stimulation tests did not vary in normal dogs. Results of preoperative ACTH stimulation tests of CPSS and OHE dogs were not significantly different. Dogs with CPSS had higher postoperative baseline cortisol concentrations (median, 329 ng/mL) than OHE dogs (median, 153 ng/mL). Postoperative cortisol increase after ACTH in CPSS was < or =50% in 10/16 and < or =30 ng/mL in 6/16. After surgery, BG was < or =60 mg/dL in 7/16 CPSS dogs. Cortisol concentrations were not correlated with BG. Two CPSS dogs had refractory hypoglycemia and 4 had delayed recovery; all improved with dexamethasone administration (0.1-0.2 mg/kg/IV). CONCLUSIONS AND CLINICAL IMPORTANCE: Contrary to previous reports, baseline cortisol concentrations in CPSS and healthy dogs are similar. Many CPSS dogs have postoperative hypercortisolemia. Response to ACTH does not correlate with postoperative hypoglycemia or prolonged anesthetic recovery.     

Effect of propranolol on growth hormone response to GH releasing hormone (GHRH 1-44) in the dog.

The present study was undertaken to examine whether beta-adrenergic blockade with propranolol might influence and make less variable the growth hormone (GH) response to exogenous GH releasing hormone (GHRH) 1-44 in the dog. On four separate occasions eight healthy beagles, one to two years old, randomly received either propranolol (40 micrograms kg-1 intravenously) or an equivalent volume of saline, 30 minutes before either GHRH 1-44 (1 microgram kg-1 intravenously) or vehicle was injected. After propranolol alone, GH secretion did not differ from saline (area under the curve [AUC]: 649.5 +/- 128.3 v 633.2 +/- 87.7 ng min ml-1, respectively). GHRH alone elicited a significant increase in GH secretion (AUC: 1230.5 +/- 210.5 ng min ml-1) with a peak concentration of 16.7 +/- 4.8 ng ml-1. When GHRH was injected after propranolol the mean peak (59.1 +/- 14.7 ng ml-1) and secretory area (AUC: 2631.0 +/- 474.4 ng min ml-1) were greater than those observed after GHRH alone. However, from a clinical point of view propranolol pretreatment does not modify the great individual variability of the GH response to GHRH.     

Effects of long-term phenobarbital treatment on the thyroid and adrenal axis and adrenal function tests in dogs

Phenobarbital can interfere with the thyroid axis in human beings and rats by accelerating hepatic thyroxine metabolism because of enzyme induction. In human beings, it also can interfere with the low-dose dexamethasone suppression test (LDDST) used to assess adrenal function by accelerating dexamethasone metabolism. This effect can cause a lack of suppression of pituitary ACTH and subsequent adrenal cortisol release after dexamethasone administration. The effects of phenobarbital on the thyroid axis, the adrenal axis, and adrenal function tests were prospectively investigated in 12 normal, adult dogs. Phenobarbital was administered at 5 mg per kilogram of body weight (range, 4.8–6.6 mg/kg) PO q12h for 29 weeks, resulting in therapeutic serum concentrations (20–40 μg/mL). Serum total thyroxine (TT4), free thyroxine (FT4) by equilibrium dialysis, total triiodothyronine (TT3), thyrotropin (TSH), and cholesterol were determined before and during phenobarbital treatment. LDDST, ACTH stimulation tests, and ultra-sonographic evaluation of the adrenal glands were performed before and during treatment. TT4 and FT4 decreased significantly ( P ≤ .05), TT3 had minimal fluctuation, TSH had only a delayed compensatory increase, and cholesterol increased during phenobarbital treatment. The delayed increase in TSH, despite persistent hypothyroxinemia, suggests that accelerated hepatic thyroxine elimination may not be the only effect of phenobarbital on the thyroid axis. There was no significant effect of phenobarbital on either of the adrenal function tests. With the methods employed, we did not find any effects of the drug on the hormonal equilibrium of the adrenal axis.     

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.     

牛科物种甲状腺激素应答(THRSP)基因在乳脂合成中的功能作用研究进展

甲状腺激素应答(Thyriod hormone responsive, THRSP)基因参与动物从头脂肪酸的合成,主要在肝脏、乳腺和脂肪组织中表达,在转录水平上受到与脂代谢相关因子的诱导并作为转录激活剂调节下游脂肪合成酶基因的表达。本文对牛科物种THRSP基因的结构和功能、转录调控机制和调节脂肪酸合成的生物学路径及该基因多态性对泌乳性状的影响等方面的研究进展进行了综述。