Late gestation fetal hypothyroidism alters cell cycle regulation across multiple organ systems.

BACKGROUND: Hypothyroidism is a common endocrine disruption observed in utero that adversely affects fetal growth and maturation leading to long-term impacts on health; however, the exact molecular mechanisms by which these deleterious effects occur are unknown. We hypothesize that fetal hypothyroidism during late gestation will disrupt cell cycle regulation in a tissue-specific manner. To evaluate this, eight pregnant gilts were dosed with either methimazole or an equivalent negative control during days 85-106 out of 114 days of gestation (n = 4/group). Following treatment, the gilts were humanely euthanized, and tissue samples of fetal heart, ileum, kidney, lung, liver, muscle, spleen, and thymus taken from two male and two female fetuses (n = 32) from each gilt. RESULTS: The relative expression of three cell cycle promoters (CDK1, CDK2, and CDK4), and one cell cycle inhibitor (CDKN1A) was compared in each tissue to determine the effect of hypothyroidism on the developing fetus. All of the eight tissues examined experienced at least one significant up- or downregulation in the expression of the aforementioned genes as a result of treatment with methimazole. Substantial changes were observed in the liver and muscle, with the latter experiencing significant downregulations of CDK1, CDK2, and CDK4 as a result of treatment. In addition, all tissues were examined for changes in protein content, which further elucidated the impact of hypothyroidism on the fetal liver by the observation of a marked increase in protein content in the methimazole-treated group. Finally, the heart and liver were histologically examined for evidence of cellular hyperplasia and hypertrophy by measuring average nuclei density and size in each tissue, with the results showing a significant decrease in average nuclei size in the liver of hypothyroid fetuses. CONCLUSIONS: Collectively, these findings indicate the occurrence of organ-specific disruptions in cell cycle progression as a result of in utero hypothyroidism, which may explain the long term and widespread effects of hypothyroidism on fetal development.

Changes in thyroid hormone concentrations over time in dogs with autoimmune thyroiditis.

OBJECTIVE: The objective of this study was to follow long-term changes in the concentration of thyroid hormones in dogs with subclinical thyroiditis. SAMPLES: Samples were obtained from 125 dogs with subclinical thyroiditis. The study population included 70 female and 55 male dogs. The mean testing interval was 3.9 years from initial testing (SD, 2.3 years; range, 1 to 9 years). METHODS: Dogs with subclinical thyroiditis were identified retrospectively using results from the Orthopedic Foundation for Animals Canine Thyroid Profile performed by the Endocrinology Section of the Michigan State University Veterinary Diagnostic Lab. Owners were invited to submit follow-up serum samples with their veterinarian along with a medical history form, including subsequent treatments. RESULTS: At the time of retesting, 30% of the dogs had progressed to hypothyroidism and/or were treated with thyroxine. Fifty percent maintained positive or equivocal thyroglobulin autoantibody (TgAA) results while remaining euthyroid. Fourteen percent of the dogs became TgAA negative and remained euthyroid. In 6% of the cases tested, proper medical histories were not available, and a final classification could not be determined. CLINICAL RELEVANCE: These results indicate that most dogs with elevated thyroglobulin autoantibodies either exhibit persistent autoimmune thyroiditis with continued risk of hypothyroidism or progress to hypothyroidism when monitored for more than 1 year. Thyroid function in dogs with subclinical thyroiditis should be monitored every 12 months or if there is change in the clinical presentation.

Blood pressure in hyperthyroid cats before and after radioiodine treatment.

BACKGROUND: Hyperthyroid cats commonly have systemic hypertension, with a reported prevalence of 7% to 48%. Although hypertension might be expected to resolve once treatment restores euthyroidism, it can persist or only first develop after treatment. OBJECTIVES: To determine the proportion of hyperthyroid cats with hypertension (systolic blood pressure [SBP] ≥160 mm Hg), persistence or first development of hypertension after successful radioiodine treatment, and correlation of post-treatment hypertension with azotemia or hypothyroidism. ANIMALS: Four hundred one hyperthyroid nonazotemic cats were included in the study. METHODS: Prospective, cross-sectional and before-and-after studies. All hyperthyroid cats had SBP measured by Doppler; 255 had SBP rechecked 6 months after successful radioiodine (131I) treatment. RESULTS: Of untreated hyperthyroid cats, 108/401 (27%) were hypertensive. A higher proportion of hypertensive cats were nervous/excited compared with normotensive cats (47% vs 12%; P < .001). Of the initially hypertensive cats, 87/108 cats were reexamined after 131I treatment; 43/87 (49%) cats normalized SBP, whereas 44/87 (51%) remained hypertensive. Of the initially normotensive cats, 16/168 (9.5%) first developed hypertension after successful 131I treatment. 7/60 (12%) of the 131I-treated hypertensive cats were azotemic and 9/60 (15%) were hypothyroid. A higher proportion of cats remaining hypertensive had nervous/excited demeanor than did normotensive cats (50% vs 17%; P < .001). CONCLUSIONS/CLINICAL IMPORTANCE: Hypertension, when present, resolves in many hyperthyroid cats after successful treatment. Hyperthyroid cats uncommonly develop new hypertension after treatment. Persistent or newly detected hypertension was unrelated to azotemia or iatrogenic hypothyroidism. More frequently perceived nervousness/anxiety in radioiodine-treated hypertensive cats suggests that many of these cats might have "situational" hypertension, as hyperthyroid-induced hypertension should resolve after treatment.

Assessment of the likelihood of hypothyroidism in dogs diagnosed with and treated for hypothyroidism at primary care practices: 102 cases (2016-2021).

BACKGROUND: There is a possibility that an incorrect diagnosis of hypothyroidism could be made in euthyroid dogs, and the prevalence of hypothyroidism in the dog population remains unknown. OBJECTIVES: To retrospectively assess the percentage of dogs diagnosed with, and treated for, hypothyroidism at first opinion practice which are likely to be hypothyroid and require levothyroxine supplementation. ANIMALS: One hundred two client-owned dogs were included in this study. MATERIALS AND METHODS: The computerized databases of 7 first opinion practices were searched to identify dogs treated with levothyroxine supplementation. Three European College of Veterinary Internal Medicine-Companian Animals (ECVIM-CA) diplomates independently assigned 1 of 4 clinical assessments to each case as follows: confirmed or likely hypothyroid, hypothyroidism suspected but not confirmed, hypothyroidism considered unlikely, and no reason to suspect hypothyroidism. They commented as to whether or not they thought levothyroxine supplementation was appropriate. RESULTS: The clinical assessments of "confirmed or likely hypothyroid"; "Hypothyroidism suspected but not confirmed"; "Hypothyroidism considered unlikely"; and "No reason to suspect hypothyroidism" was assigned respectively by Clinician 1 to 38.2%, 5.9%, 3.9%, and 52% of cases, by Clinician 2 to 48%, 22.6%, 22.6%, 6.9% of cases, and by Clinician 3 to 55.9%, 11.8%, 13.7% and 18.6%. Clinician 1, Clinician 2, and Clinician 3 considered levothyroxine supplementation not indicated in 58.8%, 52.9%, and 45.1% of cases, respectively. CONCLUSION: These results support the concern that hypothyroidism might be overly and incorrectly diagnosed in first opinion practice, and that thyroid function testing should be performed only in those dogs with a high pretest probability of the disease.

Evaluation of a novel, sensitive thyroid-stimulating hormone assay as a diagnostic test for thyroid disease in cats.

OBJECTIVE: Clinicians commonly use thyroid-stimulating hormone (TSH) concentrations to diagnose thyroid disorders in humans and dogs. In cats, canine TSH chemiluminescent immunoassays (CLIA) assays are commonly used to measure TSH, but these TSH-CLIAs cannot measure low TSH concentrations (< 0.03 ng/mL) and therefore cannot distinguish between low-normal concentrations and truly low TSH concentrations (characteristic of hyperthyroidism). Our aim was to evaluate a novel TSH assay based on bulk acoustic wave (BAW) technology that has lower functional sensitivity (0.008 ng/mL) than TSH-CLIAs. ANIMALS: 169 untreated hyperthyroid cats, 53 cats treated with radioiodine (131I), 12 cats with chronic kidney disease (CKD), and 78 clinically healthy cats. METHODS: Serum concentrations of T4, TSH-CLIA, and TSH-BAW were measured in all cats. Untreated hyperthyroid cats were divided into 4 severity groups (subclinical, mild, moderate, and severe), whereas 131I-treated cats were divided into euthyroid and hypothyroid groups. RESULTS: Test sensitivity, specificity, and positive predictive value for identifying hyperthyroidism were higher for TSH-BAW (90.5%, 98.9%, and 86.9%) than TSH-CLIA (79.9%, 76.7%, and 21.7%; P < .001). Test sensitivity for identifying 131I-induced hypothyroidism was only 45.5% for T4 versus 100.0% for both TSH-CLIA and TSH-BAW (P = .03), whereas TSH-BAW had a higher positive predictive value (100%) than did either TSH-CLIA (81.2%) or T4 (71.9%). CLINICAL RELEVANCE: Serum TSH-BAW alone or together with T4 is a highly sensitive and specific diagnostic test for evaluating feline hyperthyroidism and iatrogenic hypothyroidism. Finding low serum TSH-BAW concentrations is most useful for diagnosing subclinical and mild hyperthyroidism, in which serum T4 remains within or only slightly above the reference interval.

Diagnosis and management of thyroid disorders and thyroid hormone supplementation in adult horses and foals.

Equine thyroid disorders pose a diagnostic challenge in clinical practice because of the effects of nonthyroidal factors on the hypothalamic-pituitary-thyroid axis, and the horse's ability to tolerate wide fluctuations in thyroid hormone concentrations and survive without a thyroid gland. While benign thyroid tumours are common in older horses, other disorders like primary hypothyroidism or hyperthyroidism in adult horses and congenital hypothyroidism in foals are rare. There is a common misunderstanding regarding hypothyroidism in adult horses, especially when associated with the clinical profile of obesity, lethargy, and poor performance observed in dogs and humans. Low blood thyroid hormone concentrations are often detected in horses as a secondary response to metabolic and disease states, including with the nonthyroidal illness syndrome; however, it is important to note that low thyroid hormone concentrations in these cases do not necessarily indicate hypothyroidism. Assessing equine thyroid function involves measuring thyroid hormone concentrations, including total and free fractions of thyroxine (T4) and triiodothyronine (T3); however, interpreting these results can be challenging due to the pulsatile secretion of thyroid hormones and the many factors that can affect their concentrations. Dynamic testing, such as the thyrotropin-releasing hormone stimulation test, can help assess the thyroid gland response to stimulation. Although true hypothyroidism is extremely rare, thyroid hormone supplementation is commonly used in equine practice to help manage obesity and poor performance. This review focuses on thyroid gland pathophysiology in adult horses and foals, interpretation of blood thyroid hormone concentrations, and evaluation of horses with thyroid disorders. It also discusses the use of T4 supplementation in equine practice.

Contrast-enhanced ultrasonography of the thyroid gland in healthy dogs, hypothyroid dogs and dogs with non-thyroidal illness.

Diagnosis of canine hypothyroidism remains challenging, as non-thyroidal illness (NTI)-syndrome and medical treatment can influence thyroid hormone concentrations. Conventional ultrasound may give additional hints, however high interobserver variability has been described. Contrast-enhanced ultrasound (CEUS) allows detection of changes in tissue perfusion. The purpose of the present study was to assess the possible diagnostic value of CEUS regarding diagnosis of hypothyroidism. CEUS of the thyroid gland was performed in 52 healthy dogs, 16 hypothyroid dogs, and 20 NTI patients. The following perfusion parameters were calculated: Thyroid/carotid artery (TG/CA) ratios for peak enhancement (PE) and area under the curve (AUC), time to peak (TTP) and wash-in and wash-out rates (WiR, WoR) of the thyroid gland. Impact of sedation on perfusion parameters was investigated in 8 calm healthy dogs which were examined before and after sedation using midazolam and butorphanol. Significantly higher median TG/CA ratios for PE were detected for the left and right thyroid lobe in dogs with hypothyroidism (0.97/0.96) compared to healthy dogs (0.85/0.85) and dogs with NTI (0.84/0.84). AUCs were also significantly increased in hypothyroid dogs when compared to other groups. Dogs with NTI showed significantly lower WiR and WoR compared to other groups. Values for TTP were not significantly different between groups. Sedation had only impact on results of TTP which was significantly prolonged in sedated dogs. In conclusion, CEUS of the thyroid gland can provide an additional tool for diagnosis of hypothyroidism in dogs and support its differentiation from NTI. Sedation has limited impact on CEUS results.

A study of the effect of hypothyroidism during pregnancy on human milk quality based on rheological properties.

Hypothyroidism has been found to have an effect on the nutritional composition of human milk during pregnancy. This study aims to explore the combined influence of rheological properties, macronutrient content, particle size, and the zeta potential of milk fat globules, as well as the composition of milk fat globule membrane (MFGM) proteins on the quality of human milk in gestational hypothyroidism. The study revealed that human milk from the group with hypothyroidism during pregnancy (AHM) was less viscoelastic and stable when compared with normal pregnancy group human milk (NHM). Furthermore, the particle size and macronutrient content of NHM were found to be larger than that of AHM. In contrast, the zeta potential of AHM was greater than that of NHM. The sodium dodecyl sulfate-PAGE results disclosed that the composition of MFGM proteins in these 2 groups were generally the same, but the content of AHM was lower than that of NHM. In conclusion, this study confirms that hypothyroidism during pregnancy can have a significant effect on the quality of human milk.

Alterations in serum concentrations of visfatin and betatrophin in dogs with hypothyroidism.

BACKGROUND: Hypothyroidism in dogs is associated with obesity and altered lipid and carbohydrate metabolism. The adipokines, visfatin, and betatrophin, affect glucose tolerance. Betatrophin is involved in lipid regulation. HYPOTHESIS: Visfatin and betatrophin serum concentrations are altered in hypothyroid dogs. ANIMALS: Dogs with naturally occurring hypothyroidism (n = 25) and healthy dogs (n = 25). METHODS: Insulin, visfatin, and betatrophin serum concentrations were measured in all dogs and 19 of the hypothyroid dogs after 30 days of thyroxine treatment. Body condition score (BCS) was determined (1-9 scale). RESULTS: Visfatin concentrations were lower in hypothyroid compared with healthy dogs (mean, 95% confidence interval [CI]; 2.0 ng/mL, 1.2-3.3 vs 5.1 ng/mL, 3.3-7.8; P = .004) and increased post-treatment (3.1 ng/mL, 1.9-4.9 vs 2.6 ng/mL, 1.6-4.1; P = .05). Betatrophin concentrations were lower in lean to normal (body condition score [BCS], 3-5) hypothyroid dogs compared to lean to normal healthy dogs (52 pg/mL, 9-307 vs 597 pg/mL, 216-1648; P = .03), but were not different between overweight (BCS, 6-9) hypothyroid and healthy dogs (341 pg/L, 168-695 vs 178 pg/mL, 77-415; P = .26), and decreased post-treatment in overweight dogs (206 pg/mL, 87-488 vs 268 pg/mL, 112-640; P = .004). Visfatin concentrations were higher in overweight compared with lean to normal dogs (4.7 ng/mL, 3.3-6.6 vs 2.2 ng/mL, 1.2-4.2; P = .04). Betatrophin concentrations were positively correlated with BCS (r = .47, P = .02) and insulin concentrations (r = .48, P = .03) in hypothyroid dogs and negatively correlated with BCS (r = -.47, P = .02) and thyroid stimulating hormone concentrations (r = -.56, P = .01) in healthy dogs. CONCLUSIONS AND CLINICAL IMPORTANCE: Hypothyroidism in dogs is associated with alterations in visfatin and betatrophin concentrations that partially resolve with thyroxine treatment.

Urine concentrating ability in cats with hyperthyroidism: Influence of radioiodine treatment, masked azotemia, and iatrogenic hypothyroidism.

BACKGROUND: Hyperthyroid cats often have urine specific gravity (USG) values <1.035. It remains unclear how USG changes after treatment, if USG can be used to predict azotemia after treatment, or how iatrogenic hypothyroidism influences USG values. OBJECTIVES: To determine the proportion of hyperthyroid cats with USG <1.035 vs ≥1.035; if USG changes after treatment; and whether USG <1.035 correlated with unmasking of azotemia or hypothyroidism. ANIMALS: Six hundred fifty-five hyperthyroid cats treated with radioiodine; 190 clinically normal cats. METHODS: Prospective, before-and-after study. Hyperthyroid cats had serum thyroxine, thyroid-stimulating hormone, and creatinine concentrations, and USG measured before and 6 months after successful treatment with radioiodine. RESULTS: Of untreated hyperthyroid cats, USG was ≥1.035 in 346 (52.8%) and <1.035 in 309 (47.2%). After treatment, 279/346 (80.6%) maintained USG ≥1.035, whereas 67/346 (19.4%) became <1.035; 272/309 (88%) maintained USG <1.035, whereas 37/309 (12%) became ≥1.035. Only 22/346 (6.4%) with USG ≥1.035 developed azotemia after treatment, compared with 136/309 (44%) with <1.035 (P < .001). Of cats remaining nonazotemic, 38% had USG <1.035, compared with 20% of normal cats (P < .001). The 137 cats with iatrogenic hypothyroidism had lower USG after treatment than did 508 euthyroid cats (1.024 vs 1.035), but USGs did not change after levothyroxine supplementation. USG <1.035 had high sensitivity (86.1%) but moderate specificity (65.2%) in predicting azotemia after treatment. CONCLUSIONS AND CLINICAL IMPORTANCE: Hyperthyroidism appears not to affect USG in cats. However, cats with evidence of sub-optimal concentrating ability before radioiodine treatment (USG < 1.035) are more likely to develop azotemia and unmask previously occult chronic kidney disease. Iatrogenic hypothyroidism itself did not appear to affect USG values.

Influence of medications on thyroid function in dogs: An update.

Erroneous thyroid function test results can occur because of drugs that alter thyroid hormone physiology in one or more aspects, including synthesis, secretion, distribution, and metabolism. Research since publication of the last review in the Journal of Veterinary Internal Medicine (JVIM) 20 years ago has evaluated the effects of amiodarone, zonisamide, inhalant anesthetics, clomipramine, trilostane, and toceranib on thyroid function tests in the dog. In addition, recent work on the effects of glucocorticoids, sulfonamides, phenobarbital, and nonsteroidal anti-inflammatory drugs will be reviewed. Awareness of these effects is necessary to avoid misdiagnosis of hypothyroidism and unnecessary treatment.

2023 AAHA Selected Endocrinopathies of Dogs and Cats Guidelines.

Canine and feline endocrinopathies reflect an endocrine gland disease or dysfunction with resulting hormonal abnormali ties that can variably affect the patient's wellbeing, quality of life, and life expectancy. These guidelines provide consensus recommendations for diagnosis and treatment of four canine and feline endocrinopathies commonly encountered in clini cal practice: canine hypothyroidism, canine hypercortisolism (Cushing's syndrome), canine hypoadrenocorticism (Addi son's disease), and feline hyperthyroidism. To aid the general practitioner in navigating these common diseases, a stepwise diagnosis and treatment algorithm and relevant background information is provided for managing each of these diseases. The guidelines also describe, in lesser detail, the diagnosis and treatment of three relatively less common endo crinopathies of cats: feline hyperaldosteronism, feline hypothyroidism, and feline hyperadrenocorticism. Additionally, the guidelines present tips on effective veterinary team utilization and client communication when discussing endocrine cases.

Multiple pituitary hormone deficiencies in a kitten: Hyposomatotropism, hypothyroidism, central diabetes insipidus and hypogonadism.

In humans, post-traumatic hypopituitarism (PTHP) is a common complication of traumatic brain injury, with the most frequently reported hormonal deficiencies resulting in hyposomatotropism and hypogonadism, followed by hypothyroidism, hypocortisolism, and central diabetes insipidus. To date, PTHP has rarely been reported in cats, and the reported cases often describe a single hormone deficiency. This report details an approximately 7-month-old cat with a history of suspected traumatic brain injury at 5 wk of age, that presented with growth retardation (1.53 kg) and polyuria-polydipsia. Thyroid panel, thyrotropin-releasing hormone stimulation test, thyroid scan with Technetium-99, repeat measurement of serum IGF-1, resting cortisol, endogenous ACTH concentration, and ACTH stimulation testing were performed. The cat was diagnosed with presumptive PTHP leading to hyposomatotropism, hypothyroidism, central diabetes insipidus, and hypogonadism. In this case, treatment of the hypothyroidism and central diabetes insipidus were successful. Hyposomatotropism and hypogonadism were not treated. Although reported feline PTHP cases have described a single hormone deficiency, this report details a cat with presumptive PTHP leading to hyposomatotropism, hypothyroidism, central diabetes insipidus, and hypogonadism. Attention should be paid to the potential for the development of PTHP in cats secondary to traumatic brain injury. Key clinical message: Post-traumatic hypopituitarism in cats can lead to multiple hormone deficiencies, leading to hyposomatotropism, hypothyroidism, central diabetes insipidus, and hypogonadism.

Insuffisances hormonales hypophysaires multiples chez un chaton : hyposomatotropisme, hypothyroïdie, diabète insipide central et hypogonadisme. En médecine humaine, l'hypopituitarisme post-traumatisme crânien (HPPT) est une complication fréquente après un trauma crânien. Les insuffisances hormonales les plus fréquemment rapportées sont l'hyposomatotropisme et l'hypogonadisme, suivis de l'hypothyroïdie, de l'hypocortisolisme et du diabète insipide central. À ce jour, l'HPPT a rarement été décrit chez le chat, et les cas publiés décrivent bien souvent une déficience hormonale unique. Dans le cas présent, un chat âgé d'environ 7 mois, avec un antécédent de trauma crânien suspecté à l'âge de 5 semaines, a été présenté avec un retard de croissance (1,53 kg) et un syndrome polyurie-polydipsique. Les examens d'endocrinologie complémentaires incluaient le dosage des hormones thyroïdiennes, la stimulation de l'hypophyse par la thyrolibérine, une scintigraphie thyroïdienne (Technetium-99), le dosage de l'IGF-1, du cortisol basal, de la concentration d'ACTH endogène, et un test de stimulation à l'ACTH. Le chat a été diagnostiqué de manière présomptive avec un HPPT causant de multiples insuffisances hormonales hypophysaires : hyposomatotropisme, hypothyroïdie, diabète insipide central et hypogonadisme. Chez ce chat, le traitement de l'hypothyroïdie et du diabète insipide central a été réussi. L'hyposomatotropisme et l'hypogonadisme n'ont pas été traités. Alors que les rapports de cas publiés sur l'HPPT félin décrivent souvent une seule déficience hormonale, ce chat a été diagnostiqué avec de multiples insuffisances hormonales hypophysaires. Les cliniciens doivent rester attentifs au développement potentiel d'un hypopituitarisme après un trauma crânien.Message clinique clé :L'hypopituitarisme post-traumatique chez le chat peut entraîner de multiples déficiences hormonales, entraînant un hyposomatotropisme, une hypothyroïdie, un diabète insipide central et un hypogonadisme.(Traduit par les auteurs).

Thyroid evaluation in suspicious hypothyroid adult dogs before and after treatment.

The purpose of this study was to measure circulating TSH, T4 and fT4 concentrations in dogs submitted to a clinical visit for general symptoms (weight gain, polyuria and polydipsia, changes in hair coat). Twenty-eight dogs, 14 cross-breed and 14 purebreds (Golden Retriever, Labrador, Doberman), of both sexes (14 males and 14 females), aged 8 to 14 years, were assessed. No significant differences of circulating TSH, T4 , fT4 concentrations between the baseline and after therapeutic treatment nor between intact and neutered females were observed. Compared to baseline values, intact males showed higher TSH concentrations (p⟨0.01), and castrated males lower TSH concentrations (p⟨0.01) after therapeutic treatment. Compared to intact males, castrated males showed baseline TSH concentrations higher (p⟨0.01), but lower (p⟨0.01) after therapeutic treatment. No significant differences of T4 and fT4 concentrations between baseline conditions and after therapeutic treatment, nor between intact and castrated males, were observed. The experimental sample considered in this study falls within that casuistry involving elevated TSH concentrations but low serum T4 and fT4 concentrations or close to the minimum physiological cut-off, in which the common clinical signs suggestive of hypothyroidism was, essentially, overweight and neglected appearance of the hair.

Changes in biomarkers of redox status in serum and saliva of dogs with hypothyroidism.

BACKGROUND: Hypothyroidism is the most common endocrine disorder diagnosed in dogs, leading to deleterious effects on a dog's life quality. This study aims to evaluate changes in the redox status in canine hypothyroidism. For this purpose, a comprehensive panel of antioxidants and oxidants biomarkers were measured in serum and saliva of 23 dogs with hypothyroidism, 21 dogs with non-thyroidal illness, and 16 healthy dogs. Among the antioxidants, cupric reducing antioxidant capacity (CUPRAC), ferric reducing ability of plasma (FRAP), Trolox equivalent antioxidant capacity (TEAC), thiol, paraoxonase type 1 (PON-1) and glutathione peroxidase (GPx) were determined in serum and CUPRAC, ferric reducing ability of saliva (FRAS) and TEAC in saliva. The oxidant biomarkers included were total oxidant status (TOS), peroxide-activity (POX-Act), reactive oxygen-derived compounds (d-ROMs), advanced oxidation protein products (AOPP), and thiobarbituric acid reactive substances (TBARS) in serum and AOPP and TBARS in saliva. RESULTS: Results showed a significantly higher TEAC, PON-1, GPx, TOS, POX-Act, and d-ROMs, and a significantly lower AOPP in serum of dogs with hypothyroidism. Meanwhile, significantly lower FRAS and AOPP were observed in saliva of dogs with hypothyroidism. Once salivary concentrations were corrected based on their total protein concentrations, the only analyte showing significant changes was TBARS which was significantly higher in dogs with hypothyroidism. CONCLUSIONS: Our results show that dogs with hypothyroidism present alterations in the redox status in both serum and saliva. This study should be considered a preliminary study and further research addressing these changes should be made using larger populations.

Laboratory indicators of hypothyroidism and TgAA-positivity in the Eurasian dog breed.

BACKGROUND: Hereditary hypothyroidism represents a concern for dog breeders; thus, surveillance programs have been established for several dog breeds. METHODS: Thyroid profiles (total thyroxine (TT4), thyrotropin (thyroid stimulating hormone (TSH)), and thyroglobulin autoantibodies (TgAA)) collected as part of a breed surveillance program in Eurasians (2009-2017) were retrospectively analyzed. The study included data from 1,501 Eurasians from a German breeding club. Classification was exclusively based on laboratory data. Hypothyroidism was defined as a combined decrease in TT4 and increase in TSH in serum and was classified as TgAA-positive and TgAA-negative hypothyroidism. Thyroglobulin autoantibodies (TgAA) independent of the concentrations of TT4 and TSH were determined. The overall prevalence of hypothyroidism, TgAA-positive hypothyroidism, TgAA-negative hypothyroidism and TgAA-positivity was assessed when the dogs entered the program. Follow-up laboratory data was available for 324 dogs without hypothyroidism on initial examination. RESULTS: The initial screening was performed at a median age of 18 months (interquartile range (IQR): 15-29). The overall prevalence of hypothyroidism was 3.9% (n = 58; 95% CI: 2.9-4.8%) and the prevalence of a positive TgAA status was 7.9% (n = 118; 95% CI: 6.6-9.3%). The prevalence of TgAA-positive and TgAA-negative hypothyroidism was 1.7% (n = 26; 95% CI: 1.1-2.4%) and 2.1% (n = 32; 95% CI: 1.4-2.9%), respectively. 22.0% of dogs with positive TgAA status (26/118) were already hypothyroid on initial examination. Overall, 42.5% (17/40) of TgAA-positive dogs on initial examination developed hypothyroidism on follow-up. CONCLUSION: The results of this study demonstrate that the Eurasian dog breed exhibits a relevant risk for hypothyroidism and presence of TgAA. The predictive value of TgAA for hypothyroidism or developing hypothyroidism was high in this breed. Further investigations with longitudinal studies in individual dogs are warranted.

Laboratory Diagnosis of Thyroid and Adrenal Disease.

Diagnosis of thyroid and adrenal disease can be confusing. Whereas the definitive diagnosis of hyperthyroidism and hypoadrenocorticism are relatively straightforward, hypothyroidism and naturally occurring Cushing's syndrome (NOCS) are more complicated. In a patient with compatible clinical signs, a single increased tT4 is enough to confirm hyperthyroidism, but a low tT4 alone is never enough to confirm hypothyroidism. A flatline result (post-stimulation cortisol <2 ug/dL) on an ACTH stimulation test (ACTHst) confirms hypoadrenocorticism, but not all dogs with NOCS have increased ACTHst results. This article explains which diagnostics should be pursued for these endocrinopathies, and how to interpret them.

Effect of 6-n-propyl-2-thiouracil or dexamethasone administration on the responses of antimicrobial components in goat milk to intramammary lipopolysaccharide infusion.

Heat stress impacts the immune system of dairy animals by altering the hypothalamic-pituitary-adrenal axis and thyroid function, leading to conditions such as hypothyroidism and hypercortisolism. This study aimed to elucidate the effect of hypothyroidism and hypercortisolism on the response of mammary innate immune function to inflammation caused by Escherichia coli in dairy goats. To induce hypothyroidism and hypercortisolism, we administered 6-n-propyl-2-thiouracil (PTU; for 21 days) and dexamethasone (DEX; for 5 days), respectively, to six goats each; six goats without treatment were used as the control group. After treatment, lipopolysaccharide (LPS) from E. coli O111 was infused into the mammary gland. Somatic cell counts (SCC) and levels of lactoferrin (LF), S100A7, immunoglobulin A (IgA), and interleukin-8 (IL-8) in milk until 7 days after LPS infusion were measured. An increase in SCC after LPS infusion was inhibited in both PTU and DEX groups, and an increase in LF after LPS infusion was inhibited in PTU group, compared with that in the control group. The results of the present study suggest that the recruitment of neutrophils and LF production decreased under hypothyroidism or hypercortisolism, which may be one of the causes underlying increased incidence of mastitis in dairy animals under heat stress conditions.

Changes in the salivary metabolome in canine hypothyroidism: A pilot study.

Hypothyroidism is the most commonly diagnosed endocrine disorder in dogs. It produces a deficiency of thyroid hormones which impacts negatively the dog's quality of life. The objective of this study is to evaluate the possible changes in the salivary metabolic profile in dogs with hypothyroidism. For this purpose, targeted metabolomics analysis performed by LC/MS analysis was made in saliva samples from a group of dogs with hypothyroidism and a group of healthy dogs. Twenty-three metabolites showed a significant decrease between hypothyroid and healthy dogs, most of these associated with thyroid hormone synthesis, catecholamine synthesis, and tyrosine and phenylalanine metabolism. Based on the results, it can be stated that hypothyroidism produces changes in the metabolome of saliva and some of them can reflect the metabolic changes presented in the disease and could serve as a potential biomarker of this condition.

Radioiodine treatment of hyperthyroidism in cats: results of 165 cats treated by an individualised dosing algorithm in Spain.

OBJECTIVES: Although radioiodine (131I) is the treatment of choice for feline hyperthyroidism, 131I-dosing protocols commonly induce iatrogenic hypothyroidism and expose azotaemia. A recently reported patient-specific 131I dosing algorithm minimised the risk of 131I-induced hypothyroidism and azotaemia, while maintaining high cure rates. The aim of the study was to report results of 131I treatment in a European population of hyperthyroid cats using this patient-specific dosing algorithm. METHODS: This prospective case series (before-and-after study) evaluated 165 hyperthyroid cats referred for 131I treatment. All cats had serum concentrations of thyroxine (T4), triiodothyronine (T3) and thyroid-stimulating hormone (TSH) measured (off methimazole ⩾1 week). Thyroid volume and percentage uptake of 99mTc-pertechnetate (TcTU) were determined using thyroid scintigraphy. An initial 131I dose was calculated by averaging dose scores for T4/T3 concentrations, thyroid volume and TcTU; 70% of that composite dose was then administered. Twenty-four hours later, percentage 131I uptake was measured, and additional 131I administered as needed to deliver an adequate radiation dose to the thyroid tumour(s). Serum concentrations of T4, TSH and creatinine were determined 6-12 months later. RESULTS: Median calculated 131I dose was 2.15 mCi (range 1.2-7.5), with only 51 (30.9%) receiving ⩾2.5 mCi. Of 165 cats, 124 (75.2%) became euthyroid, seven (4.2%) became overtly hypothyroid, 27 (16.4%) became subclinically hypothyroid and seven (4.2%) remained hyperthyroid. A higher proportion of overtly (85.7%) and subclinically (26.9%) hypothyroid cats developed azotaemia than euthyroid cats (13.6%; P = 0.0002). Hypothyroid cats were older (P = 0.016) and more likely to have detectable TSH concentrations (P = 0.025) and symmetrical bilateral distribution of 99mTc-pertechnetate uptake (P = 0.0002), whereas persistently hyperthyroid cats had higher severity scores (P = 0.012). CONCLUSIONS AND RELEVANCE: Our results confirm that 131I dosing with this new algorithm results in high cure rates, with a lowered prevalence of 131I-induced overt hypothyroidism and azotaemia. Age, serum TSH concentrations, bilateral, symmetrical uptake and severity score help predict outcome.