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Background: Many non-thyroidal factors affect thyroid function tests. Anesthesia and surgery have been documented to affect thyroid function tests in humans but have not been extensively studied in dogs. Hypothesis: Anesthesia alone and anesthesia combined with surgery will affect thyroid function tests in dogs. Animals: 15 euthyroid mongrel dogs. Methods: Dogs were assigned to one of three groups: control, general anesthesia, and general anesthesia plus abdominal exploratory surgery. Blood samples were collected from each dog immediately prior to pre-medication, 20 minutes after pre-medication, 55 minutes after anesthesia induction, once daily for an additional 6 days, and 14 days post-procedures. Sampling was performed at identical times in the control group. Thyroxine (T4), free T4 (fT4) by equilibrium dialysis, triiodothyronine (T3), reverse T3 (rT3) and thyroid-stimulating hormone (TSH) concentrations were measured in all samples. Results: Results of all thyroid function tests were not significantly different between control and anesthesia groups. Serum T3 for the surgery group decreased significantly from baseline compared to the control and anesthesia groups at multiple times. Serum T4 and rT3 for the surgery group increased significantly from baseline compared to the control and anesthesia groups at multiple times. Serum fT4 for the surgery group increased significantly from baseline compared to the control and anesthesia groups at 48 hours only. Conclusions and Clinical Importance: Surgery has a significant effect on thyroid function tests, while the anesthetic protocol used in this study does not. Because serum T4 and fT4 concentrations increased rather than decreased, evaluating these hormones following surgery is unlikely to lead to a misdiagnosis of hypothyroidism in euthyroid dogs. / Master of Science

A dissertation submitted to the Faculty of Medicine, University of the Witwatersrand, Johannesburg, in part fulfilment of the requirements for the degree Master of Medicine in Internal Medicine. 1993. / Normal thyroid physiology and pathophysiOlogy with reference to non-thyroidal illness is reviwed, including infections, specific disease states and drugs and their effects on thyroid function tests. A review of the literature reveals that following almost any infection the serum T4 and T3 decrease as a result of diminished secretion of TSH and thyroxine, accelerated T4 disappearance, inhibition of hormone binding to transport proteins and decreased peripheral T4 to T3 conversion. [Abbreviated Abstract. Open document to view full version] / AC2017

Submitted by Jorge Silva (jorgelmsilva@ufrrj.br) on 2017-05-09T19:53:50Z No. of bitstreams: 1 2015 - Phelipe Fontanezi Campos Garcia Fontes.pdf: 1744858 bytes, checksum: 8509d8579b9954973f7546999edfab62 (MD5) / Made available in DSpace on 2017-05-09T19:53:50Z (GMT). No. of bitstreams: 1 2015 - Phelipe Fontanezi Campos Garcia Fontes.pdf: 1744858 bytes, checksum: 8509d8579b9954973f7546999edfab62 (MD5) Previous issue date: 2015-07-31 / Hypothyroidism is the most common disease caused by hormone deficiency, affecting more than 10 million people in the United States of America and about 6.6% of the adult population of S?o Paulo. Symptoms of depression and anxiety often occurs in hypothyroid pacients. Depression and anxiety disorders are the most common behavioral disorders. These behavioral disorders has high comorbidity and could aggravate the clinical progress when they occur in ill people. Thus, the depression is the major cause of disability and affects more than 350 million people. Anxiety disorders are highly prevalent, for example, 18.1% of the North American population suffers from this disorder. In this context, about 5-10% of hypothyroid patients shows symptoms depression and anxiety disorders even under treatment with levothyroxine (L-T4). Despite levels of TSH and T4 within the reference values L-T4 did not appear effective in reversing these symptoms and this can be linked to the fact that this pharmacological approach not restore euthyroidism in all tissues. Added to this, there are few studies that evaluate these behavioral disorders in hypothyroidism and effects of thyroxine. Therefore, this work studied the behavioral changes caused by hypothyroidism by total thyroidectomy protocol. Furthermore, this study aimed to verify in which the effects of replacement with thyroxine against these behavioral alterations. Therefore, the animals were divided into 3 groups: 1) Control group / false operated (SHAM); 2) thyroidectomized group (TX); 3) thyroidectomized Group receiving hormone replacement (TX + T4). These animals were subjected to a battery of behavioral tests to check behaviors similar to depression and anxiety. It was also observed body weight of the animals during the experiment to verify the onset of hypothyroidism, and adrenal weight. The TX group presented similar behavior to depression and anxiety increased when comparated with the SHAM group. The treatment with T4 reversed partially these behaviors. Given these results, we found that conventional therapy alone, failure to reverse all the behavioral symptoms caused by hypothyroidism. These data are in agreement with data presented in the literature and it shows in clinical the L-T4 ineffectiveness in reverse the symptoms reported for a portion of patients. / O hipotireoidismo ? a patologia relacionada a defici?ncia hormonal mais comum, afetando mais de 10 milh?es de pessoas nos Estados Unidos das Am?ricas e cerca de 6,6 % da popula??o adulta de S?o Paulo. Nesta doen?a ? comum aparecerem sintomas de depress?o e transtorno de ansiedade que s?o os dist?rbios comportamentais mais comuns. Essas doen?as comportamentais possuem alta comorbidade e podem agravar o quadro cl?nico quando ocorrem em indiv?duos doentes. Sendo assim, a depress?o aparece como a maior causa de incapacidade e acomete mais de 350 milh?es de pessoas. Os transtornos de ansiedade possuem alta preval?ncia, por exemplo, 18,1% da popula??o Norte Americana sofre deste transtorno. Neste contexto, cerca de 5-10% dos pacientes que sofrem de hipotireoidismo e s?o tratados com levotiroxina (L-T4) apresentam sintomas de depress?o ou transtornos de ansiedade. Mesmo apresentando n?veis de TSH e T4 dentro dos valores de refer?ncia a L-T4 parece n?o ser eficaz em reverter estes sintomas e isto pode estar associado ao fato desta abordagem farmacol?gica n?o reestabelecer o eutireoidismo e m todos os tecidos. Somado a isto, h? poucos estudos que avaliam estes transtornos comportamentais no hipotireoidismo e os respectivos efeitos da tiroxina. Portanto, o presente trabalho estudou as altera??es comportamentais ocasionadas pelo hipotireoidismo atrav?s do protocolo de tireoidectomia total. Al?m disso, este estudo objetivou-se em verificar quais os efeitos da reposi??o com tiroxina sobre essas altera??es. Para tanto, os animais foram divididos em 3 grupo: 1) Grupo controle/falso operado (SHAM); 2) Grupo tireoidectomizado (TX); 3) Grupo tireoidectomizado submetido a reposi??o hormonal (TX+T4). Estes animais foram submetidos a uma bateria de testes comportamentais para verificar comportamentos semelhantes ? depress?o e ansiedade. Tamb?m foi verificado o peso corporal dos animais durante o experimento, para verificar o aparecimento de hipotireoidismo, e o peso da adrenal. O grupo TX apresentou comportamentos an?logos a depress?o e ansiedade aumentados em rela??o ao SHAM. J? o tratamento com T4 reverteu tais comportamentos parcialmente. Diante destes resultados, observamos que a terapia convencional, monoterapia, falha em reverter todos os sintomas comportamentais ocasionados pelo hipotireoidismo. Estes dados est?o em concord?ncia com os apresentados na literatura que demonstram na cl?nica a inefic?cia da L-T4 em reverter os referidos sintomas para uma parcela de pacientes.

Due to the seasonal nature of E. coli O157:H7 shedding and of hormone production by the thyroid gland, two studies were initiated to determine whether chemical inhibition of the thyroid gland influences fecal shedding of Escherichia coli O157:H7. Twenty-four crossbred sheep (68.6 kg BW) were randomly assigned to pen and either 0.0 mg/kg BW PTU or 20 mg/kg BW PTU for 5, 11, or 14 days. Sheep were experimentally infected (d 0) with E. coli O157:H7 11 days prior to PTU treatment. Fecal and serum samples were collected for bacterial enumeration and for analysis of T3 and T4, respectively. Sheep were humanely euthanized and tissue and content samples were collected from the rumen, ileum, colon and rectum. Detection of E. coli O157:H7 increased toward the terminal end of the GI tract. In the treatment group, serum T3 levels decreased to an overall lower level than the control group. A correlation was seen between T3 levels and daily O157:H7 bacterial shedding (P=0.003; r=0.37). In experiment 2, 12 growing lambs (41.04 kg BW) were exposed to either 0.0 mg/kg BW PTU or 40 mg/kg BW PTU for 21 days. Fecal samples were collected for analysis of generic E. coli and body weights were recorded on days 0, 7, 14, and 21. Feed intake was recorded throughout the experiment. Animals were experimentally infected with E. coli O157:H7 on day 15. Sheep were humanely euthanized on day 21 and GI tract tissue and content was collected from the rumen, ilium, colon and rectum. A date by treatment interaction was observed for T4 (P=0.0016) and hormone levels decreased in treated animals. Thyroxine and E. coli O157:H7 display a multivariate treatment (P=0.0005) and date effect (P=0.0174) but no significant interaction. Triiodothyronine and E. coli O157:H7 shedding have a slight date trend (P=0.065) but no significant treatment or treatment by date interaction. Generally, the treatment group shed genreric E. coli at higher levels throughout the study period with slightly more than a log count difference between groups at the last collection point (control = 3.8 CFU/gram of feces (log10); treatment = 4.9 CFU/gram of feces (log10)). Results from these experiments suggest that correlations exist between both E. coli O157:H7 and generic E. coli shedding in sheep.

Ph.D.

M.Tech. / Thyroxine, a hormone produced by the thyroid gland, is known to be important for the growth and development of animals. A homoeopathic preparation of thyroxine added to the aquaria water of Rana temporaria tadpoles was shown to be capable of either slowing down or accelerating metamorphosis at different stages of development. In addition, ultra high dilutions of hormones (endogenous molecules) have been shown to have physiological effects on the immune system of mice. The aim of this study was to evaluate the effect of Thyroxine 15CH on the growth and development of laboratory rats. Forty male rats at the Central Animal Services of the University of Witwatersrand were administered either the placebo or Thyroxine 15CH (20 control and 20 treatment) at 16 days of age for 30 consecutive days. Body weight and linear measurements (head-body and tail lengths) were recorded from day 16 to 100 days of age, and rectal temperatures were recorded from day 58 to 100 days of age. Thereafter, rats were euthanased and the brain, heart and liver weighed, total thyroxine blood levels were determined, and bone mineral density and percentage body fat ascertained. Each control rat was paired with a treatment rat of the same litter by initial weight readings taken on day 16 to form 20 experimental couplets. The recorded data was analysed using the ANOVA for repeated measures and paired t-test for single measurements. Statistical analyses showed no significant differences between the control and treatment groups for all parameters measured (p > 0.05). In conclusion, Thyroxine 15CH did not have any statistically significant effect on the growth and development of laboratory rats. This research does not support the underlying philosophy of homoeopathy which is the Law of Similars, nor does it give evidentiary support to the theory of analogical communication as proposed by Lagache and Bastide. However, certain theories and explanations do exist to explain why no results were found, concluding that further research needs to be conducted in this field.

The secretion of two hormones with identical function by the thyroid gland has been questioned, What is the relationship between these two hormones? Why does the thyroid secrete two hormones when either one can provide for all the activity of the thyroid (Greer, 1972). Little work has been done on the relationship between the two hormones. There is some evidence showing that thyroxine (T4) is deiodinated to triiouothyronine (T3) at the tissue level in mammals. Chambers (1970) found that there was a negative interaction between T4 and T3 when pharmacologic doses were administered to the rat. The present study was done to determine if such interaction occurred at physiologic levels of the two hormones and to see if T3,T4 interaction was present in other species. The rat and chick were studied since the thyroid hormones are transported in the circulatory system of the two animals by different plasma proteins. It was thought that the difference in transport might give some information about interaction.

The effect of thyroid hormones on purine biosynthesis was studied in vitro. With 100,000 x g supernatant fraction of rat liver homogenate, the results suggested that thyroid hormones stimulated total purine synthesis from labeled glycine-1-¹⁴C. Further studies indicated that these hormones stimulated AMP synthesis but inhibited GMP synthesis. The stimulatory effect on AMP synthesis was found to be due to the stimulation of adenylosuccinate synthetase. Adenylosuccinate synthetase was isolated and purified from rat liver. The maximum stimulatory effect of these hormones occurred with 2.5 x 10⁻⁵ M thyroxine (T₄) and 2.5 x 10⁻⁹ M triiodo-L-thyronine (T₃). A slight increase or decrease in concentration of these hormones caused a drastic decrease in their stimulatory effect. Some analogues of T₄ were also studied and results of such experiments agreed qualitatively with their effects in vivo. Those which are physiologically active are capable of stimulating this enzyme and those which are physiologically inactive had little or no effect on this enzyme. Based on these results, a hypothesis, that thyroid hormones regulate the levels of AMP and GMP synthesis, was proposed. The significance of this preferential stimulatory effect on AMP synthesis was discussed. / Ph. D.

Tricyclic antidepressants have been shown to alter thyroid function in man and laboratory animals, but have not been evaluated in the dog. The effect of administration of clomipramine on canine thyroid function was studied in a prospective protocol in which 14 mature, healthy dogs were administered clomipramine (3 mg/kg PO q12h) for 112 days. Thyroid-stimulating hormone (TSH), total thyroxine (T4), total 3,5,3' triiodothyronine (T3), free thyroxine (fT4), and 3,3',5' triiodothyronine (reverse T3; rT3) concentrations were measured on selected days. Thyrotropin-releasing hormone (TRH) response tests were performed concurrently. Repeated measures analysis of variance was applied to test for effects of day of treatment; when significance (p < 0.05) was noted, it was further investigated using orthogonal polynomial trends. Significant decreases were found in serum T4 (26 ± 1.2 to 17 ± 0.5 nmol/L, p < 0.001), fT4, (29 ± 2.4 to 19 ± 1.3 pmol/L, p < 0.0002), and rT3 (1.2 ± 0.1 to 0.83 ± 0.08 nmol/L, p < 0.0001) concentrations. The effect of time on serum T3 concentration was also significant (p < 0.0001), but no consistent trend could be identified. No significant effect of time was noted in either pre- or post-TRH TSH concentrations. The results of this study indicate that significant and substantial decreases in T4 (35%), fT4 (38%), and rT3 can occur during clomipramine administration. Long-term administration of clomipramine may result in a misdiagnosis of hypothyroidism if a dog is tested while taking this medication and, since decreased serum fT4 occurs, hypothyroidism may result. / Master of Science