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

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.

Congenital hypothyroidism (CH) is a pediatric endocrine disorder caused by an insufficiency of thyroid hormone. Despite treatment following newborn screening, CH is associated with persisting memory weaknesses. Given animal research has shown thyroid hormone plays a crucial role in the development of the hippocampus, a brain structure required for normal declarative memory, it is possible that altered hippocampally-dependent processes underlie the memory weakness associated with CH. Previous studies of individuals with CH have found reduced memory abilities and left hippocampal volumes but no study has thoroughly assessed memory abilities or how the hippocampus functions to support memory. Thus, the present study compared individuals with CH and typically developing adolescents using clinical memory tests and two associative memory tasks shown in adults to activate the hippocampus during functional magnetic resonance imaging (fMRI). Results indicated groups did not differ in memory accuracy on clinical measures or either fMRI task. However, fMRI revealed hippocampal activation differed between the groups when performing the associative memory tasks. The first task utilized a visuospatial paired associates novelty detection paradigm to show the CH group increased activation relative to controls in left hippocampus and recruited right hippocampus when controls did not. Since previous research suggested the left hippocampus and verbal memory were more vulnerable to the effects of CH, the second task utilized a verbal paired associates paradigm to demonstrate that when making old and new judgments about associations versus items, the CH group increased activation relative to controls in left hippocampus. Further investigation revealed that when recognizing old associations versus items, the CH group had increased bilateral posterior hippocampal activation whereas controls showed increased activation in right anterior hippocampus, a distinction noted in previous research with this paradigm which suggests individuals with CH may retrieve associations in a less flexible manner than controls. In addition, worse memory performance and increased hippocampal activation, particularly on the left, was predicted by severity of hypothyroidism experienced early in life. In conclusion, these studies demonstrate that early thyroid hormone insufficiency associated with CH alters the functioning of the hippocampus and engenders use of compensatory mechanisms to support associative memory functions.

Congenital hypothyroidism (CH) is a pediatric endocrine disorder caused by an insufficiency of thyroid hormone. Despite treatment following newborn screening, CH is associated with persisting memory weaknesses. Given animal research has shown thyroid hormone plays a crucial role in the development of the hippocampus, a brain structure required for normal declarative memory, it is possible that altered hippocampally-dependent processes underlie the memory weakness associated with CH. Previous studies of individuals with CH have found reduced memory abilities and left hippocampal volumes but no study has thoroughly assessed memory abilities or how the hippocampus functions to support memory. Thus, the present study compared individuals with CH and typically developing adolescents using clinical memory tests and two associative memory tasks shown in adults to activate the hippocampus during functional magnetic resonance imaging (fMRI). Results indicated groups did not differ in memory accuracy on clinical measures or either fMRI task. However, fMRI revealed hippocampal activation differed between the groups when performing the associative memory tasks. The first task utilized a visuospatial paired associates novelty detection paradigm to show the CH group increased activation relative to controls in left hippocampus and recruited right hippocampus when controls did not. Since previous research suggested the left hippocampus and verbal memory were more vulnerable to the effects of CH, the second task utilized a verbal paired associates paradigm to demonstrate that when making old and new judgments about associations versus items, the CH group increased activation relative to controls in left hippocampus. Further investigation revealed that when recognizing old associations versus items, the CH group had increased bilateral posterior hippocampal activation whereas controls showed increased activation in right anterior hippocampus, a distinction noted in previous research with this paradigm which suggests individuals with CH may retrieve associations in a less flexible manner than controls. In addition, worse memory performance and increased hippocampal activation, particularly on the left, was predicted by severity of hypothyroidism experienced early in life. In conclusion, these studies demonstrate that early thyroid hormone insufficiency associated with CH alters the functioning of the hippocampus and engenders use of compensatory mechanisms to support associative memory functions.

Οι θυρεοειδικές ορμόνες (Τ3 και Τ4) είναι απαραίτητες στην ανάπτυξη, τη διαφοροποίηση και την ωρίμαση του νευρικού συστήματος. H δράση τους έχει συσχετιστεί με αλλαγές στη συμπεριφορά, ψυχικές και κινητικές δυσλειτουργίες.Η ντοπαμινεργική νεύρωση των βασικών γαγγλίων και κυρίως του ραβδωτού, είναι γνωστό ότι, παίζει κεντρικό ρόλο σ’ ένα ευρύ φάσμα κινητικών, γνωστικών και συναισθηματικών λειτουργιών.Ο υποθυρεοειδισμός προκαλεί μορφολογικές διαταραχές σε εγκέφαλο ενήλικα επίμυ, ακριβέστερα μείωση, αξονικής και δενδριτικής ανάπτυξης των νευρώνων του ραβδωτού, και τροποποιεί την ικανότητα δέσμευσης ανταγωνιστών της ντοπαμίνης. Όμως το κυτταρικό και μοριακό υπόβαθρο των ανωτέρω επιδράσεων παραμένει κατά ένα μεγάλο μέρος αδιευκρίνιστο. Κατά την διατριβή αυτή μελετήθηκε η επίδραση του υποθυρεοειδισμού στο ραβδωτό σώμα αρσενικών ενήλικων μυών στην κατάσταση του υποθυρεοειδισμού, προκειμένου να διευκρινισθεί περαιτέρω το υπόβαθρο των δράσεων των θυρεοειδικών ορμονών στο ντοπαμινεργικό σύστημα, στον ενήλικα εγκέφαλο.Με αυτοραδιογραφική μελέτη, δείχθηκε μειωμένη ποσοτική κατανομή των D2, όχι όμως και των D1,υποδοχέων ντοπαμίνης στα βασικά γάγγλια εγκεφάλου αρσενικών ενηλίκων υποθυρεοειδικών μυών συγκριτικά με τους ευθυρεοειδικούς. Με μελέτη κορεσμού και ανάλυση κατά Scatchard παρατηρήθηκε μη στατιστικά σημαντική διαφορά στη χημική συγγένεια του ανταγωνιστή των D2 υποδοχέων ντοπαμίνης [3H]-raclopride με τους υποδοχεις αυτούς. Παρατηρήθηκε επίσης στατιστικά σημαντική μείωση, 37%, στο ποσό δέσμευσης (Bmax) του ραδιενεργού προσδέτη στους D2 ντοπαμινεργικούς υποδοχείς των αρσενικών υποθυρεοειδικών μυών σε σχέση με τους ευθυρεοειδικούς. Διερευνώντας τα χαρακτηριστικά δέσμευσης των D2 ντοπαμινεργικών υποδοχέων, βρέθηκε στατιστικά σημαντικά αυξημένη η χημική συγγένεια της ντοπαμίνης σε σχέση με αυτή του ανταγωνιστή των D2 υποδοχέων ντοπαμίνης [3H]-raclopride για τη θέση υψηλής χημικής συγγένειας και μειωμένη η ποσοστιαία αναλογία των θέσεων δέσμευσης που αφορούν τη θέση υψηλής χημικής συγγένειας στο ραβδωτό σώμα υποθυρεοειδικών μυών συγκριτικά με τους ευθυρεοειδικούς. Αντίθετα στους υποθυρεοειδικούς μύες βρέθηκε μειωμένη η χημική συγγένεια στη θέση χαμηλής χημικής συγγένειας. Η ‘in vitro’ προσθήκη T3 σε ομογενοποίημα ραβδωτού σώματος εγκεφάλου αρσενικών ευθυρεοειδικών μυών προκάλεσε στατιστικά σημαντική μείωση της χημικής συγγένειας στη θέση υψηλής χημικής συγγένειας, συγκριτικά με το αντίστοιχο δείγμα ευθυρεοειδικών μυών. Επίσης, με ενεργοποίηση των Α2Α υποδοχέων αδενοσίνης μέσω του αγωνιστή των Α2Α υποδοχέων αδενοσίνης CGS 21680, παρατηρήθηκε πολλαπλάσια μείωση της χημικής συγγένειας στη θέση υψηλής χημικής συγγένειας των υποθυρεοειδικών δειγμάτων σε σχέση με τα αντίστοιχα των ευθυρεοειδικών, που σημαίνει ενισχυμένη αλληλεπίδραση των Α2Α /D2 υποδοχέων. Τέλος, τα αποτελέσματά μας έδειξαν ότι η επαγόμενη σύνθεση του cΑΜΡ από το SKF38393 (αγωνιστής των D1 υποδοχέων ντοπαμίνης) είναι στατιστικά σημαντικά μεγαλύτερη στο ραβδωτό των υποθυρεοειδικών μυών και ότι το σύστημα αλληλεπίδρασης D1/D2 υποδοχέων ντοπαμίνης στο ραβδωτό διαφέρει μεταξύ ευθυρεοειδικών και υποθυρεοειδικών μυών. Συγκεκριμένα η από το SKF38393 επαγόμενη σύνθεση του cΑΜΡ όταν αναστέλλεται υπό την παράλληλη δράση της κουινπιρόλης (αγωνιστής των D2 υποδοχέων ντοπαμίνης), παρουσιάζει στο ραβδωτό των ευθυρεοειδικών μυών μια δοσοεξαρτώμενη και αναλογική αναστολή της επαγόμενης σύνθεσης του cΑΜΡ και στο ραβδωτό των υποθυρεοειδικών μυών μια δοσοεξαρτώμενη αλλά όχι αναλογική αναστολή της επαγόμενης σύνθεσης του cΑΜΡ. Ενώ η επαγόμενη από το CGS21680 (αγωνιστής των Α2Α υποδοχέων δείχνει επίσης μεγαλύτερη επαγωγή σύνθεσης cAMP στα υποθυρεοειδικά ζώα αλλά και ενισχυμένη αλληλεπίδραση των Α2Α /D2 υποδοχέων στούς υποθυρεοειδικούς μύες, με στατιστικά σημαντικά μειωμένη σύνθεση του cΑΜΡ μόνο στους υποθυρεοειδικούς μύες. Τα αποτελέσματα της επαγόμενης σύνθεσης του cΑΜΡ πιθανόν παραπέμπουν σε τροποποιημένη δράση των G-πρωτεϊνών στους υποθυρεοειδικούς μύες. Τα αποτελέσματά μας δείχνουν επίδραση των θυρεοειδικών ορμονών στο ραβδωτό σώμα τόσο στον αριθμό των D2 ντοπαμινεργικών υποδοχέων όσο και στην μεταβίβαση σήματος μέσω των ντοπαμινεργικών υποδοχέων. Επίσης υποστηρίζουν την εμπλοκή των θυρεοειδικών ορμονών στην αλληλεπίδραση των ντοπαμινεργικών υποδοχέων με τους υποδοχείς αδενοσίνης σε μεμβρανικό επίπεδο καθώς και σε επίπεδο δευτερογενών μηνυμάτων, δείχνοντας ενισχυμένη αλληλεπίδραση των Α2Α /D2 υποδοχέων στους υποθυρεοειδικούς μύες. / Thyroid hormones (T3 and T4) are necessary in differentiation and development but also in the maturation of the central neural system. Their action has been connected with alterations in behavior, as well as with psychological and movement disorders. It is known that the dopaminergic (DA) innervation of the basal ganglia, and in particular of the striatum, plays a central role in most movement, cognitive and emotional functions. Hypothyroidism induces morphological alterations, and more precisely, reductions in the axonal and dendritic sprouting of striatal neurons of adult rat brain and also modifications in the ability of dopamine antagonists’ ligand-binding. However, the underling mechanisms involved at the cellular and molecular level remain unidentified. Aim: In the current dissertation, we studied the effect of hypothyroidism in the striatum of adult, male Balb-c mice, in order to get a better understanding on the underling mechanism(s) of the effect of thyroid hormones on the DAergic system in adult brain. Results: Autoradiography showed a quantitative reduction in the level of D2 receptors in the basal ganglia of adult, male, hypothyroid mice versus that in eythyroid mice. Saturation studies revealed a non- statistically significant alteration in the chemical affinity of D2 receptor antagonist [3H]-raclopride for these receptors. However, a statistically significant reduction (37 %) in Bmax of the radiolabeled ligand was observed in D2 dopaminergic receptors of the hypothyroid mice versus the euthyroid. Similar studies on the pharmacological profile of D2 DAergic receptor binding, showed a statistically significant increase in the binding affinity of dopamine versus [3H]-raclopride, at the high affinity site, and a reduction in the percentage of the binding sites in this site, in the striatum of male, adult hypothyroid mice versus eythyroid. The opposite effect was observed in the low affinity site, where we showed a reduction in the binding affinity. Furthermore, the “in vitro” addition of T3 in striatal homogenates of male, adult euthyroid brain resulted in a statistically significant reduction in the binding affinity, of the high affinity site, compared to euthyroid samples. Also, by activation of A2A adenosine receptors through application of the CGS21680 agonist, a statistically significant reduction was observed in the binding affinity, when at the high affinity site, of the hypothyroid compared to eythyroid samples. Finally the effect of hypothyroidism in the induction of cAMP synthesis was also examined. Our data showed that the SKF38393 (a D1 dopamine receptor agonist)-driven cAMP synthesis is statistically significant in the striatum of adult, male hypothyroid mice and that the D1/D2 interaction system of dopamine receptors is different between euthyroid and hypothyroid mice. This means that when SKF38393-driven cAMP synthesis is suppressed by quinpirole (a D2 dopamine receptor agonist), a dose dependent inhibition is observed in the striatum of euthyroid mice, which is similar, but not proportional to the inhibition observed in the striatum of hypothyroid mice. While the CGS21680 (a Α2Α adenosine receptror agonist)- driven cAMP synthesis is statistically significant in the striatum of adult, male hypothyroid mice versus to euthyroid and that the A2A/D2 interaction system of adenosine/dopamine receptors is different between euthyroid and hypothyroid mice. Only in hypothyroid mice the A2A-diven cAMP synthesis is statistically suppressed in a dose dependent manner, by costimulation of D2.receptors. Conclusions: Our results show the effect of thyroid hormones on the number of DAergic receptors level and on their signal transduction levels, after dopamine receptors activation in the striatum of adult, male mice. These observations mark the involvement of thyroid hormones in the interactions of the DAergic receptors with the adenosinergic receptors, both at the receptor-receptor and the signal transduction level.

Tez (Tıpta Uzmanlık) - Süleyman Demirel Üniversitesi, Tıp Fakültesi, İç Hastalıkları Anabilim Dalı, 2006. / Kaynakça var.

Thesis (Ph.D.)--University of Missouri-Columbia, 2004. / Typescript. Vita. Includes bibliographical references. Also available on the Internet.

Thesis (Ph.D.)--University of Missouri-Columbia, 2004. / Typescript. Vita. Includes bibliographical references. Also available on the Internet.

No description available.

INTRODUCTION Impaired sensitivity to thyroid hormone is described as any process that interferes with the effectiveness of thyroid hormone and includes defects in thyroid hormone action, transport, or metabolism. Here we present a case of a 60-year-old man with resistance to thyroid hormone (RTH), the most common form of impaired sensitivity. CASE A 60-year-old male presented to the endocrinology clinic with complaints of fatigue, decreased concentration, and impaired memory. He denied neck swelling, neck pain, peripheral edema, or any significant changes in weight, temperature sensitivity, bowel habits, and mood. His family history was significant for difficult to control thyroid disease in his brother and son. Thyroid exam was normal. Seven years ago, he was diagnosed with hypothyroidism of undetermined etiology with an elevated Thyroid Stimulating Hormone (TSH) and started on Levothyroxine. TSH was within normal limits in the first 3 years of therapy but TSH and free T4 remained high since then. MRI of the brain could not be done to rule out TSH secreting adenoma as he had pieces of metal in his face. In the absence of overt signs or symptoms of hyperthyroidism except atrial fibrillation, and a normal alpha subunit, IGF1, and prolactin, a TSH secreting adenoma is considered less likely. Levothyroxine was stopped and thyroid hormone levels were rechecked in 1 month that revealed elevated TSH with normal T3 and T4, representing compensated RTH. Genetic counseling was provided to the patient but he refused genetic testing. DISCUSSION The incidence of RTH is approximately 1 in 50,000 live births. In approximately 85 percent of cases it is due to mutations in the gene encoding the thyroid hormone receptor beta (TR-beta), while the other 15% are yet to be determined. It is characterized by reduced responsiveness of target tissue to thyroid hormones. The hallmark of RTH is the paucity of signs and symptoms of thyroid dysfunction despite the presence of high serum T4 and T3 concentrations. Clinical features include goiters, hyperactivity, and tachycardia. It can be diagnosed after other causes of hyperthyroxinemia are ruled out and confirmed with genetic testing.