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Thyroid tumors occur in many domestic species, but are most common in the dog, in which they are classified as follicular or medullary. During 2012-2016, we received tissue specimens or whole carcasses of 4 dogs with variable enlargement of the thyroid glands. The 2 males and 2 females were of mixed (mongrel) inbreeding, 3-4.5-y-old. All tumors had lobulated architecture forming follicular structures variably containing colloid. On immunohistochemistry of the tumors from 3 of the dogs, 2 were thyroglobulin positive, and all 3 were negative for calcitonin, confirming follicular thyroid carcinoma in 2 of the dogs. Thyroid carcinomas have not been reported previously in related mongrel dogs, to our knowledge., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objective: To describe cytologic findings from mandibular and superficial cervical lymph nodes in dogs with thyroid carcinoma and to determine prognostic factors associated with lymph node metastasis., Animals: A total of 71 client-owned dogs with confirmed thyroid carcinoma that had cytologic results from at least 1 mandibular or superficial cervical lymph node between 2010 and 2020., Procedure: Medical records from 2 referral veterinary hospitals were retrospectively reviewed. Cytology of lymph nodes was reviewed for presence of metastasis by diplomates of the American College of Veterinary Pathologists. Thyroid tumor diameter and volume, tumor fixation, bilateral location, vascular invasion, and stage were recorded to determine effects on nodal metastasis., Results: A total of 154 lymph nodes (104 mandibular and 50 superficial cervical lymph nodes) from 71 dogs were cytologically evaluated, and 1/154 (0.6%) and 2/154 (1.3%) lymph nodes were noted to be definitively metastatic or probably metastatic, respectively. Given the infrequent rate of nodal metastasis (1.9% or less), statistical analysis of potential prognostic variables was not completed., Conclusion and Clinical Relevance: Routine lymph node cytology of mandibular and superficial cervical lymph nodes appeared to be of low yield when assessing for metastasis of canine thyroid carcinomas. The medial retropharyngeal and deep cervical lymph nodes should continue to be evaluated as they appeared to have higher metastatic rates, based on historic reports. Additional studies are needed to determine prognostic factors associated with lymph node metastasis and effects on patient survival., (Copyright and/or publishing rights held by the Canadian Veterinary Medical Association.)

Tumors located at the heart base are rare in dogs and cats and aortic body tumors (chemodectoma/paraganglioma), hemangiosarcoma, ectopic thyroid carcinoma, lymphoma, and other uncommon neoplasia can be found at that location. The objective of this retrospective case series was to describe the CT characteristics of canine and feline heart base tumors. CT studies of 21 dogs and four cats with histologically or cytologically confirmed heart base tumors were reviewed for size, location, shape, margination, contrast enhancement, adjacent neovascularization, invasion, mass effect, cavitary effusions, and metastasis. Neuroendocrine tumors (15 aortic body tumors, three ectopic thyroid carcinoma, and three nonspecific neuroendocrine) were more commonly observed than hemangiosarcoma (4) and were frequently located between the cranial vena cava and aortic arch (12/21; 57%) and or dorsal to the pulmonary trunk bifurcation/pulmonary arteries (10/21; 48%). Hemangiosarcoma was more commonly found cranioventral to the aortic arch and cranial to the right auricular appendage (3/4; 75%). Mediastinal and peritumoral neovascularization was associated with 16/21 (76%) neuroendocrine tumors but none of the hemangiosarcoma. Median postcontrast attenuation in Hounsfield units (HU) was higher in neuroendocrine (110 HU) than in hemangiosarcoma (51 HU). Pericardial effusion was frequently observed with hemangiosarcoma (3/4; 75%) and infrequently in neuroendocrine (3/21; 14%). In four cases (all neuroendocrine), concurrent cranial mediastinal masses were present. CT provides useful information regarding the characteristics of heart base tumors, indicating differences between the appearance of neuroendocrine tumors and hemangiosarcoma. However, no differences were found between aortic body tumors and ectopic thyroid carcinoma., (© 2024 The Authors. Veterinary Radiology & Ultrasound published by Wiley Periodicals LLC on behalf of American College of Veterinary Radiology.)

Thyroid tissue in teleosts is located mainly in the pharyngeal region, usually reaching other adjacent anatomical locations. Herein, a nodular lesion located in the left operculum of a Senegal seabream (Diplodus bellottii) was surgically excised and sent for microscopical evaluation. Microscopically, the lesion presented irregular borders and consisted in columnar epithelial cells arranged in a tubulopapillary pattern, surrounding a central lumen filled with acellular, acidophilic and homogeneous, material ('colloid'). To determine the lesion's histogenesis, immunohistochemistry was performed employing antibodies for AE1/AE3, CK7, thyroglobulin and vimentin. The neoplastic cells presented low mitotic index and positive immunolabelling for CK7 and thyroglobulin. Therefore, a diagnosis of ectopic thyroid adenoma was made. Herein, the successful employment of antibodies classically used in mammals for accurate diagnosis of thyroid disorders is described. Proliferation of thyroid tissue in fish may reflect environmental and physiological imbalances, making the study and correct diagnosis of these tumours in this species important., (© 2024 John Wiley & Sons Ltd.)

In this report, we describe the gross, histopathology, and immunohistochemical findings of a thyroblastoma that arose in the right lobe of the thyroid gland in a 2-month-old rhesus macaque (Macaca mulatta)., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Research on modulation of iodine uptake by thyroid cells could help improve radioiodine treatment of dogs with thyroid tumors. The aim of this study was to characterize the immunohistochemical expression of thyroid transcription factor-1 (TTF-1), thyroglobulin, thyrotropin receptor (TSHR), sodium iodide symporter (NIS), pendrin, thyroid peroxidase (TPO), vimentin, and Ki-67 in follicular cell thyroid carcinomas (FTCs) and medullary thyroid carcinomas (MTCs), and to compare protein expression between FTC causing hyperthyroidism and FTC of euthyroid dogs. Immunohistochemistry was performed in 25 FTCs (9 follicular, 8 follicular-compact, and 8 compact) and 8 MTCs. FTCs and MTCs were positive for TTF-1, and expression was higher in FTCs of euthyroid dogs compared with FTCs of hyperthyroid dogs ( P = .041). Immunolabeling for thyroglobulin was higher in follicular and follicular-compact FTCs compared with compact FTCs ( P = .001), while vimentin expression was higher in follicular-compact FTCs compared with follicular FTCs ( P = .011). The expression of TSHR, NIS, pendrin, and TPO was not significantly different among the different subtypes of FTCs or between FTCs causing hyperthyroidism and FTCs in euthyroid dogs. TSHR, NIS, pendrin, and TPO were also expressed in MTCs. Ki-67 labeling index was comparable between FTCs and MTCs, and between FTCs causing hyperthyroidism and FTCs in euthyroid dogs. Proteins of iodine transport were also expressed in canine MTCs, which could have implications for diagnosis and treatment. The different expression of thyroglobulin and vimentin between FTC histological subtypes could reflect variations in tumor differentiation., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: The high doses of radioiodine-131 ( 131 I) and, subsequently, the high radioactive burden for dog and environment warrants optimization of 131 I therapy in dogs with thyroid carcinoma (TC)., Hypothesis/objectives: To evaluate the effect of a revised protocol with recombinant human thyroid stimulating hormone (rhTSH) on tumor radioactive iodine uptake (RAIU) in dogs with TC., Animals: Nine client-owned dogs diagnosed with TC., Methods: A prospective cross-over study in which tumor RAIU was calculated and compared at 8 hours (8h-RAIU) and 24 hours (24h-RAIU) after injection of radioactive iodine-123 ( 123 I), once with and once without rhTSH (ie, 250 μg, IM, 24 and 12 hours before 123 I) in each dog. Simultaneously, serum total thyroxine (TT4) and TSH were measured at baseline (T 0 ), and 6 (T 6 ), 12 (T 12 ), 24 (T 24 ), and 48 hours (T 48 ) after the first rhTSH administration., Results: Tumor RAIU was significantly higher at 24 hours with rhTSH compared to no rhTSH (mean difference = 8.85%, 95% CI of [1.56; 16.14]; P = .03), while this was non-significant at 8 hours (mean difference = 4.54%, 95% CI of [0.35; 8.73]; P = .05). A significant change of serum TT4 (median difference T 24  - T 0  = 35.86 nmol/L, interquartile range [IQR] = 15.74 nmol/L) and TSH (median difference T 24  - T 0  = 1.20 ng/mL, IQR = 1.55 ng/mL) concentrations occurred after administration of rhTSH (P < .001)., Conclusions and Clinical Importance: Recombinant human TSH could optimize 131 I treatment in dogs with TC by increasing tumor RAIU and thus 131 I treatment efficacy., (© 2024 The Author(s). Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC on behalf of American College of Veterinary Internal Medicine.)

Objective: To determine the rate of nodal metastasis in dogs with thyroid cancer and evaluate whether immunohistochemistry (IHC) identifies additional metastases beyond evaluation with H&E., Animals: 70 prospectively enrolled client-owned dogs with thyroid cancer managed with thyroidectomy., Methods: Dogs underwent thyroidectomy with concurrent elective bilateral medial retropharyngeal (MRP) ± deep cervical lymphadenectomy. Thyroid tumors and associated lymph nodes were reviewed by a single board-certified pathologist. Immunohistochemistry was used for all primary tumors (thyroid transcription factor-1 and calcitonin) to support a diagnosis of follicular or medullary carcinoma. Lymph nodes without evidence of metastasis after H&E review were labeled with the antibody associated with the wider uptake in the primary tumor., Results: 77 thyroid cancers were resected from the 70 dogs enrolled, including 61 (79.2%) follicular, 8 (10.7%) medullary, and 7 (9.3%) mixed follicular/medullary carcinomas, with 1 (1.3%) carcinosarcoma. Twelve dogs had evidence of nodal metastasis following H&E review. Occult micrometastasis was identified in 1 dog following nodal IHC, resulting in documented metastasis in 13 of 70 (18.6%) dogs. Metastasis was more common with medullary (5/8) and follicular/medullary carcinoma (3/7) than follicular carcinoma (5/61). All MRP metastases were ipsilateral (7/77 [9.1%]), without contralateral MRP metastases (0/62). Fourteen of 41 (34.1%) deep cervical lymph nodes were metastatic., Clinical Relevance: Nodal metastasis was uncommon for follicular carcinoma but was seen in > 50% of dogs with thyroid cancer involving a medullary component. Routine nodal IHC appears to be low yield for thyroid carcinoma. Extirpation of ipsilateral MRP and identifiable deep cervical lymph nodes is recommended with thyroidectomy until detailed preoperative risk stratification becomes available.

Thyroid follicular tumours may take up iodide via the sodium-iodide symporter. Knowledge of iodide uptake could then allow treatment with I-131 in dogs with high-risk tumours. The objective of this study was to determine the relationship between clinically detectable iodide uptake (as determined by scintigraphy and/or thyroxine concentrations) and sodium iodide symporter immunohistochemical labelling on histologically fixed thyroid tumours. Nineteen dogs were identified who were diagnosed with thyroid carcinoma and underwent surgery from November 2017 to July 2021. All had recorded thyroid hormone concentrations and were hyperthyroid and/or underwent preoperative nuclear imaging using planar scintigraphy (technetium-99m or I-123), or I-124 PET-CT. All dogs subsequently underwent surgery to remove the thyroid mass. Twenty-two tumours were submitted for histopathologic analysis immediately following surgery, which confirmed a diagnosis of thyroid carcinoma for each tumour. Images and/or thyroid hormone concentrations were reviewed for the included cases, and tumours were sorted into an avid/functional group (group 1) and a non-avid/functional group (group 2). The tumour tissues were re-examined histologically using sodium iodide symporter (NIS) immunohistochemistry (IHC). Group 1 contained 15 avid/functional tumours. Twelve of these tumours had membranous NIS IHC labelling. Group 2 contained 7 non-avid tumours. One of these tumours had membranous NIS IHC labelling. This resulted in an overall sensitivity and specificity for identification of avid/functional tumours with membranous NIS of 80.0% and 85.7%, respectively. NIS IHC may predict ion trapping in canine follicular thyroid tumours. Further studies using iodide-based imaging are warranted to better determine the clinical utility of this diagnostic modality., (© 2024 John Wiley & Sons Ltd.)

Non-neoplastic thyroid hyperplasia is common in terrestrial animals, secondary to nutritional imbalances or other goitrogenic compounds. Thyroid hyperplasia is relatively common in teleost fish; however, malignant thyroid neoplasia is rarely reported. We diagnosed cases of thyroid neoplasia in a population of jade perch ( Scortum barcoo ). The 3,000 affected fish had grossly apparent, bilateral pharyngeal swellings. Histologic examination confirmed proliferative thyroid lesions ranging from hyperplasia to well-differentiated follicular cell carcinoma. In addition, the younger population of animals on the farm also had bacterial septicemia and mild Dactylogyrus sp. gill infections. Feed analysis revealed a severe deficiency of iodine and vitamin C in the homemade fish diet used on the farm. The concentrations of other minerals, such as zinc, were also on the lower end of the recommended requirements for freshwater fish. The farm was using surface water in its recirculating aquaculture system. We recommended a switch to a commercial aquaculture diet, as well as to use well water rather than surface water to avoid any contaminants, and to treat the younger fish with an antibiotic for bacterial septicemia. Our case provides evidence of progression from nutritional-associated thyroid hyperplasia to neoplasia in farmed teleost fish., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Canine thyroid carcinomas are relatively common malignant endocrine neoplasms in dogs derived from either thyroid follicular cells (forming follicular thyroid carcinomas) or medullary cells (parafollicular, C-cells; forming medullary thyroid carcinomas). Older and recent clinical studies often fail to discriminate between compact cellular (solid) follicular thyroid carcinomas and medullary thyroid carcinomas, which may skew conclusions. The compact subtype of follicular thyroid carcinomas appears to be the least differentiated subtype of follicular thyroid carcinomas and needs to be differentiated from medullary thyroid carcinomas. This review includes information on the signalment, presentation, etiopathogenesis, classification, histologic and immunohistochemical diagnosis, clinical management, and biochemical and genetic derangements of canine follicular and medullary carcinomas, and their correlates with human medicine., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Currently, a histological diagnosis of highly vascularized canine (c) thyroid carcinoma (TC) is primarily obtained following excisional biopsy (EB) through thyroidectomy. Non-EBs are contraindicated in unresectable invasive cTCs due to their highly vascularized nature, which subsequently, lack histological diagnosis. We hypothesised ultrasound-guided core needle biopsy (UGCNB) to be a safe biopsy technique to obtain an accurate histological diagnosis in unresectable TCs. Nine client-owned dogs with suspected naturally occurring TC, presented for surgical excision, were included. First, a UGCNB was taken from the cervical tumour, followed by EB. Haemorrhage following UGCNB was evaluated preoperatively and once the tumour was surgically exposed by visual inspection and ultrasonography. Histological analysis, including cell organisation, tumour capsular and vascular invasion, and immunohistochemistry were performed and compared between both biopsy specimens (i.e., UGCNB and EB) of the same dog. Pre- and peroperative visual inspection revealed minor, localised haemorrhage, subsequent to the UGCNB, in 7/9 dogs. Histology of the EBs confirmed TC in 8/9 dogs and was inconclusive in 1/9 dogs. Histology of the UGCNBs revealed neoplastic thyroid tissue in 7/9 UGCNBs and was inconclusive in 1/9 UGCNBs. The remaining UGCNB contained no mass related tissue and was, therefore, excluded. Histological parameters (i.e., cell organisation, tumour capsular and vascular invasion) were not concordant between 6/8 included UGCNBs and their respective EB. Immunolabelling for thyroglobulin and calcitonin was concordant between all eight included UGCNBs and their respective EB. The remaining evaluated immunohistochemical markers (i.e., cyclooxygenase-2 [COX-2], P-glycoprotein and vascular endothelial growth factor [VEGF]) were concordant between the included UGCNBs and the EBs in 6/8 dogs. To conclude, UGCNBs can be safely obtained in suspected cTCs and enable a reliable diagnosis of the thyroid origin, thyroid cell origin and potential therapeutic markers such as COX-2, P-glycoprotein and VEGF. Subsequently, UGCNB enables clinicians to establish an individually tailored treatment plan in dogs with unresectable TC., (© 2023 John Wiley & Sons Ltd.)

Background: Few studies have assessed predictors of outcome in dogs with thyroid tumors undergoing thyroidectomy., Objective: To estimate the survival and identify prognostic factors in dogs with thyroid tumors treated by thyroidectomy., Animals: A total of 144 client-owned dogs with thyroid neoplasia that underwent thyroidectomy., Methods: Retrospective study. Data for analysis included hospital attended and year of surgery, signalment, thyroxine concentration, thyroid tumor features (lobe involvement, size, invasiveness, histopathological type), thrombosis, metastasis, additional surgery and therapy, administration of adjuvant chemotherapy. The association of predictors with survival (time from surgery to death) were assessed by calculating cause-specific hazard ratios (HR cs ) and 95% confidence intervals (CI). Causes of death were classified as thyroid-related or because of other cause., Results: Overall median survival time was 802 days (CI95% = 723-1015 days); 89 dogs (77.4%) survived >500 days. Metastases were identified at admission in 12 (8.3%) dogs and were associated with higher thyroid cancer-related fatality (HR = 5.83, CI95% = 1.56-21.78; P = .009). Thrombosis occurred in 40 dogs and was associated with increased risk of death because of other cause (HR = 2.73, CI95% = 1.18-6.35; P = .019). Nonfollicular carcinoma (HR = 4.17, CI95% = 1.27-13.69; P = .018) and administration of chemotherapy (HR = 3.45, CI95% = 1.35-8.82; P = .01) were associated with higher risk of thyroid cancer-related death., Conclusions and Clinical Importance: Dogs with thyroid tumors undergoing thyroidectomy have a long life expectancy. Despite the rare presence of nonfollicular carcinoma and metastases, thyroidectomy should still be considered in some of these dogs., (© 2023 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC on behalf of American College of Veterinary Internal Medicine.)

Organoid cultures could constitute a valuable in vitro model to explore new treatments for canine (c) medullary thyroid carcinoma (MTC). The study's objectives were to establish and characterize 3D organoid cultures of cMTC using histology and immunohistochemistry (IHC) and to evaluate the effect of antitumor drugs on organoids' viability. Five cMTC tissue samples were used to develop organoid cultures of which one organoid line, named cMTC N°2, could be passaged for an extended period. This cMTC N°2 organoid line was further compared to the primary tumour regarding morphology and IHC expression of thyroid transcription factor-1 (TTF-1), thyroglobulin, calcitonin, synaptophysin, vimentin, Ki-67, cyclooxygenase-2 (COX-2), P-glycoprotein and vascular endothelial growth factor (VEGF). Quality control of the cMTC N°2 organoid line was achieved by a single nucleotide polymorphism (SNP) array of the organoids, primary tumour and healthy blood cells of the same dog. The effect of carboplatin, meloxicam and toceranib phosphate (TOC) on cMTC N°2 organoids' viability was evaluated. The cMTC N°2 organoid line was cultured for 94 days and showed similar histological features with the primary tumour. Immunolabelling for TTF-1, thyroglobulin, calcitonin and VEGF was similar between the primary tumour and cMTC N°2 organoids. Compared to the primary tumour, organoids showed higher immunolabelling for vimentin and Ki-67, and lower immunolabelling for synaptophysin, COX-2 and P-glycoprotein. The SNP genotype was similar for each chromosome between healthy blood cells, primary tumour and cMTC N°2 organoids. Carboplatin, meloxicam and TOC had no effect on cMTC N°2 organoid cell viability within achievable in vivo concentration range. In conclusion, the cMTC N°2 organoid line is a promising first milestone towards an established in vitro organoid model to explore pathophysiology and new treatment modalities in cMTC., (© 2022 John Wiley & Sons Ltd.)

A 10 yr old female spayed domestic shorthair was referred for an 11mo history of persistent total hypercalcemia and elevated ionized calcium with intermittent episodes of lethargy, vomiting, and diarrhea with a history of recurrent urinary tract infections and intermittently elevated kidney values. An abdominal ultrasound, thoracic radiographs, cervical ultrasound, and ionized calcium level, parathyroid hormone (PTH), and PTH-related peptide (PTHrp) levels were assessed. Results were consistent with chronic kidney disease, splenomegaly, diffuse thickening of small intestines, nodular lesions noted in the left thyroid and right parathyroid, and elevated ionized calcium, PTH, and elevated PTHrp levels. A left thyroidectomy and right cranial parathyroidectomy were performed. Hypocalcemia and anemia developed postoperatively, which were managed with calcium carbonate, calcitriol, and calcium gluconate and benign neglect of anemia. Histopathology was consistent with a left thyroid carcinoma and right cranial parathyroid adenoma. Thyroid carcinoma and parathyroid adenomas have not previously been reported to occur concurrently in domestic felines and should be considered when ionized calcium is elevated with both PTH and PTHrp levels increased in addition to ultrasonographic lesions., (© 2023 by American Animal Hospital Association.)

A 10-year-old female mixed breed dog was presented for thyroid scintigraphy due to a cervical mass. Apart from 99m-Technetium-pertechnetate (Tc-pertechnetate) scintigraphy, a second scintigraphy using 99m-Technetium sestamibi (Tc-MIBI) was performed because of additional hypothyroidism suspective for a "cold" nodule and as screening for metastases.Twenty minutes following intravenous injection of 38 MBq Tc-pertechnetate, a "hot" cervical as well as a "hot" intrathoracal nodule were seen with an uptake of 8.40 and 0.25 %, respectively. The second scintigraphy was performed 20 minutes after intravenous injection of 364 MBq Tc-MIBI and 70 minutes following the first. After subtraction of pertechnetate activity and decay correction, both nodules showed an uptake of 0.99 and 0.03 %. Additionally, both thyroid lobes were visible in the thyroid loge with a weak MIBI-uptake. For both lesions, the ratio Tc-uptake/Tc-MIBI-uptake was 8.48 and 8.33, respectively.Following the extirpation of the cervical mass, histopathology revealed atrophied healthy thyroid tissue almost completely displaced by a well-differentiated follicular thyroid carcinoma.This case report describes performance, utility and calculative correction of consecutive pertechnetate- and MIBI-scan, that enable a visualization of hypofunctional thyroid tissue.Therefore and because of their similar MIBI metabolic activity, both nodules were considered to be dystopic tissue/metastases so that this dog had to be classified as prognostically less favorable WHO stabe IV. Different from human patients, both scintigraphies should be performed shortly after another in dogs in order to avoid the necessity of a second anesthetic procedure. A reliable qualitative/visual evaluation of the MIBI-scan is therefore not possible, so that a quantitative assessment using the uptake after calculative correction of the pertechnetate activity is recommended., Competing Interests: Die Autoren bestätigen, dass kein Interessenkonflikt besteht., (Thieme. All rights reserved.)

A 12-y-old, castrated male Weimaraner dog was presented for a wellness examination. A 7-cm, firm mass was palpated on the left, ventral, mid-lateral neck. The neck mass was removed surgically and submitted for histopathology. A thyroid carcinoma was diagnosed based on microscopic examination. Immunohistochemistry for chromogranin-A, calcitonin, and thyroglobulin identified dual immunoreactivity of the latter two, and a final diagnosis was of a well-differentiated, compact, mixed medullary and follicular cell thyroid carcinoma. These neoplasms are rare in humans and have not been reported in dogs, to our knowledge.

Objectives: Radioactive iodine ( 131 I) is the preferred treatment for feline hyperthyroidism but neither the optimal 131 I dose nor consistent predictors of post-treatment azotaemia have been determined. The aims of the study were to evaluate the relationships between: (1) 131 I dose and survival; and (2) pretreatment and post-treatment serum creatinine concentration., Methods: Medical records of hyperthyroid cats treated with 131 I at a single referral hospital were reviewed. Information regarding signalment, body weight, pretreatment and post-treatment serum total thyroxine concentration (TT4), serum creatinine concentration, 131 I dose and survival were determined. Multivariable Cox proportional hazards analysis was used to identify variables associated with survival. Multivariable linear regression analysis was used to identify variables associated with post-treatment serum creatinine concentration., Results: One hundred and ninety-eight (79 male, 119 female) cats were treated for hyperthyroidism with 131 I (median dose 138 MBq; interquartile range 92-168). Median survival time was 1153 days (range 16-1871). Post-treatment serum creatinine ( P <0.001) and age ( P  = 0.049) were significantly associated with survival. Every 10 µmol/l increase in post-treatment serum creatinine concentration and every year increase in age was associated with a 1.07-fold (confidence interval [CI] 1.04-1.11) and 1.17-fold (CI 1.00-1.37) increase in the daily hazard of death, respectively. Pretreatment serum creatinine concentration was directly, and post-treatment serum TT4 concentration was inversely, associated with post-treatment serum creatinine concentration. Every 1 μmol/l increase in pretreatment serum creatinine concentration was associated with an increase in post-treatment serum creatinine concentration of 0.7 μmol/l (SE 0.17; P <0.001). Conversely, every 1 nmol/l decrease in post-treatment serum TT4 concentration was associated with a 1.2 μmol/l (SE 0.61; P <0.001) increase in post-treatment serum creatinine concentration., Conclusions and Relevance: Post-treatment serum TT4 concentration was associated with post-treatment azotaemia, which was associated with survival. Although 131 I dose was not directly associated with survival, dosing strategies that minimise post-treatment hypothyroidism and azotaemia could improve patient survival.

Background: We previously reported a familial thyroid follicular cell carcinoma (FCC) in a large number of Dutch German longhaired pointers and identified two deleterious germline mutations in the TPO gene associated with disease predisposition. However, the somatic mutation profile of the FCC in dogs has not been investigated at a genome-wide scale., Results: Herein, we comprehensively investigated the somatic mutations that potentially contribute to the inherited tumor formation and progression using high depth whole-genome sequencing. A GNAS p.A204D missense mutation was identified in 4 out of 7 FCC tumors by whole-genome sequencing and in 20 out of 32 dogs' tumors by targeted sequencing. In contrast to this, in the human TC, mutations in GNAS gene have lower prevalence. Meanwhile, the homologous somatic mutation in humans has not been reported. These findings suggest a difference in the somatic mutation landscape between TC in these dogs and human TC. Moreover, tumors with the GNAS p.A204D mutation had a significantly lower somatic mutation burden in these dogs. Somatic structural variant and copy number alterations were also investigated, but no potential driver event was identified., Conclusion: This study provides novel insight in the molecular mechanism of thyroid carcinoma development in dogs. German longhaired pointers carrying GNAS mutations in the tumor may be used as a disease model for the development and testing of novel therapies to kill the tumor with somatic mutations in the GNAS gene., (© 2022. The Author(s).)

Radioactive iodine is frequently used for staging of human thyroid carcinomas. Iodine-124 scans performed using position emission tomography (PET) allow for more precise dosimetry of therapeutic radioiodine. The distribution of I-124 has not previously been described in veterinary medicine. The purpose of this prospective, exporatory, descriptive study is to evaluate the whole-body distribution of I-124 in dogs with suspected thyroid carcinoma. Ten dogs with either a cytologic diagnosis of a neuroendocrine neoplasm or biochemical hyperthyroidism were enrolled in a prospective clinical study. Whole-body I-124 PET/CT scans were performed and were evaluated for physiologic and pathologic uptake of I-124. The maximum and mean standardized uptake values (SUVmean) were recorded for several normal and abnormal tissues. Varying degrees of uptake were found in thyroid tumors (SUVmean = 66.37), ectopic thyroid masses (21.44), presumed metastatic lesions in lymph nodes (32.14), and the pulmonary parenchyma (4.50). In most dogs, physiologic uptake above background, measured in maximum SUV, was identified in parotid and mandibular salivary glands (14.00 and 1.57) the urinary tract (1.83), the gastrointestinal tract (19.90 stomach, 6.15 colon), the liver (1.41), and the heart (1.88). Occasionally, uptake was identified in the nasolacrimal duct (3.42), salivary duct (2.73), gallbladder (2.68), and anal gland (2.22). Physiologic uptake was also identified in normal thyroid glands and ectopic thyroid tissue. This study provides a baseline of pathologic and physiologic uptake of I-124 in dogs with thyroid carcinoma, to guide interpretation of future studies., (© 2021 American College of Veterinary Radiology.)

Thyroid carcinomas (TCs) originating from follicular cells of the thyroid gland occur in both humans and dogs, and they have highly similar histomorphologic patterns. In dogs, TCs have not been extensively investigated, especially concerning the familial origin of TCs. Here, we report familial thyroid follicular cell carcinomas (FCCs) confirmed by histology in 54 Dutch origin German longhaired pointers. From the pedigree, 45 of 54 histopathologically confirmed cases are closely related to a pair of first-half cousins in the past, indicating a familial disease. In addition, genetics contributed more to the thyroid FCC than other factors by an estimated heritability of 0.62 based on pedigree. The age of diagnosis ranged between 4.5 and 13.5 years, and 76% of cases were diagnosed before 10 years of age, implying an early onset of disease. We observed a significant higher pedigree-based inbreeding coefficient in the affected dogs (mean F, 0.23) compared to unaffected dogs (mean F, 0.14), suggesting the contribution of inbreeding to tumour development. The unique occurrence of familial thyroid FCC in this dog population and the large number of affected dogs make this population an important model to identify the genetic basis of familial thyroid FCC in this breed and may contribute to the research into pathogenesis, prevention and treatment in humans., (© 2021 The Authors. Veterinary and Comparative Oncology published by John Wiley & Sons Ltd.)

Background: While rare, multiple individual case reports have described mixed thyroid tumours in dogs containing both epithelial and mesenchymal neoplastic components., Objectives: In this retrospective case series, we describe the clinical presentation, treatment and outcome of 14 dogs of canine thyroid tumours with concurrent mesenchymal and epithelial neoplastic populations., Methods: Fourteen cases were retrospectively abstracted from nine institutions. Histopathologic samples and reports were collected from 10/14 dogs and reviewed by a single board-certified anatomic pathologist., Results: All 14 dogs had curative-intent surgery to remove the thyroid neoplasm. The most common surgery performed was a unilateral thyroidectomy (10/14 dogs). Postoperatively, systemic therapy was administered in eight dogs. Six dogs developed local recurrence with a median time to loco-regional recurrence of 53 days. Ten dogs developed metastatic disease with the most common metastatic site being the lungs (6/10 dogs), with a median time to metastasis of 93 days. Ten dogs were euthanised due to locoregional or distant progression of their mixed thyroid neoplasm. The overall median survival time was 156 days (95%CI: 49-244). The median survival time for dogs treated with adjuvant therapy was 189 days (95%CI: 24-244), whereas dogs without adjuvant therapy had a median survival time of 156 days (95%CI: 35-upper limit could not be calculated; p = 0.62)., Conclusion: The thyroid tumours with both mesenchymal and epithelial components in this small sample set were associated with a poor prognosis after surgical excision with or without adjunctive therapy., (© 2022 The Authors. Veterinary Medicine and Science published by John Wiley & Sons Ltd.)

Radioactive iodine ( 131 I) has previously been reported to prolong survival in dogs with thyroid carcinoma. This study aimed to describe tumour response and progression-free interval (PFI) in dogs with thyroid carcinomas treated with 131 I. Secondary aims were to describe overall survival time (OST) and prognostic factors. A bi-institutional retrospective review of records identified 66 dogs with thyroid carcinoma treated with 131 I from January 2010 to April 2020. Response was described using RECIST or a subjective response assessment where specific tumour measurements were not available. Forty-eight dogs (72.7%) were treatment naïve and 18 dogs (27.3%) had received prior therapy at the time of 131 I treatment. Objective responses were available for 34 dogs and subjective responses for 58 dogs. The overall response rate was 35.3% (four complete and eight partial responses). Improvement of clinical signs was seen in 76.2% of dogs (32/42). Kaplan-Meier-estimated median PFI (95% confidence interval [CI]) was 301 (217-578) days and OST (95% CI) was 564 (421-865) days. Prior therapy was associated with a lower hazard for progression (hazard ratio [HR] 0.260 95% CI 0.123-0.548, p = .0004). Treatment of thyroid carcinoma using 131 I can effectively alleviate clinical signs and reduce disease burden in a proportion of dogs., (© 2021 John Wiley & Sons Ltd.)

Excellent outcomes have been reported following thyroidectomy for thyroid carcinoma in dogs, but outcomes for thyroid carcinomas with gross vascular invasion are poorly described. This study describes the clinical outcomes and complications in dogs with thyroid carcinomas with gross vascular invasion undergoing thyroidectomy. Medical records of dogs that underwent thyroidectomy between January 1st 2010 and December 31st 2019 were reviewed at 10 hospitals. Signalment, diagnostic data, primary and adjuvant treatments performed, and outcome were abstracted. Survival was calculated using Kaplan-Meier analysis. Multiple logistic regression was used to identify variables associated with disease-specific survival. Seventy-three dogs were included, of which 58 underwent unilateral thyroidectomy and 15 underwent bilateral thyroidectomy. Complications were reported in five dogs (three major, two minor; 6.8%) intraoperatively and 12 dogs (two major leading to death, 10 minor; 16.4%) postoperatively. Seven (9.6%) dogs developed locoregional recurrence at a median of 238 days postoperatively (range: 15-730 days). Distant metastasis was suspected or confirmed in nine dogs (12.3%) at a median of 375 days postoperatively (range: 50-890 days). Twenty-seven dogs (37%) received adjuvant therapy (chemotherapy: n = 21; radiotherapy: n = 6). Thirty-nine dogs were euthanized or died, with 20 deaths related to disease (n = 10) or of unknown cause (n = 10), 19 due to unrelated causes, and nine lost to follow-up. Median overall and disease-specific survival were 621 days and not reached respectively. One-year disease-specific survival rate was 82.5%. No variables were associated with disease-specific survival in our dataset. Surgery may be considered for loco-regional therapy in dogs with thyroid carcinoma with gross vascular invasion., (© 2021 John Wiley & Sons Ltd.)

Background: Historical and recent literature disagree on whether a higher PO 131 I dosage, compared to IV or SC routes, is required for successful resolution of spontaneous hyperthyroidism in cats, necessitating investigation into the effect of PO and injectable radioactive iodine administration on % thyroidal radioactive iodine uptake (RAIU)., Hypothesis/objectives: To investigate the effect of PO and SC routes of 123 I administration on paired % thyroidal RAIU in euthyroid cats. Specifically, a 1.5-fold difference (50% relative change) was hypothesized, which in absolute terms can be expressed as a 3.25% increase in the mean %RAIU of 7.04% after PO 123 I administration to 10.56% after SC dosing., Animals: Seven healthy euthyroid teaching-research colony cats., Methods: A randomized, radiologist-blinded crossover study comparing %RAIU after PO and SC 123 I administration., Results: Percentage thyroidal RAIU values (mean ± SD; 95% confidence interval) after PO (4.81% ± 1.63%; 3.30%-6.23%) and SC (5.26% ± 2.43%; 3.01%-7.51%) 123 I administration were associated with a median within-pair absolute difference of 0.2% (range: min, 0.1%-max, 4.9%). Statistical significance was not achieved (P  =  .45). Six of 7 cats had a within-pair absolute difference of 0.1% to 0.9% (relative change of 4%-20%), but a single outlier cat had a within-pair absolute difference of 4.9% (relative change of 108%)., Conclusions and Clinical Importance: This study did not detect an effect of 123 I administration route on paired % thyroidal RAIU in euthyroid cats. However, a type 2 statistical error due to small sample size is possible., (© 2021 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC on behalf of American College of Veterinary Internal Medicine.)

Thyrotropin receptor (TSHR), sodium iodide symporter (NIS), pendrin, and thyroid peroxidase (TPO) are essential for the uptake of iodine by follicular thyroid cells. The aim of this study was to establish immunohistochemistry (IHC) protocols for TSHR, NIS, pendrin, and TPO in canine tissues and characterize their expression in organoids derived from canine follicular cell thyroid carcinoma (FTC) and in the respective primary tumors. This constitutes a fundamental step to establish organoids as a model to study the uptake of iodine in canine FTC. Commercially available antibodies directed against human proteins were selected. Antibody specificity was confirmed by western blot using lysates of the HTori-3 human thyroid cell line and healthy canine thyroid gland. IHC was validated using HTori-3 cells and a set of canine normal tissues including healthy thyroid gland. The expression of TSHR, NIS, pendrin, and TPO was evaluated in 3 organoid lines derived from FTC and respective primary tumors. All 4 antibodies produced specific bands by western blot and cytoplasmic labeling in follicular cells by IHC in both human HTori-3 cells and canine thyroid gland. NIS also showed basolateral membrane immunolabeling in follicular cells. All 4 proteins were highly expressed in organoids derived from FTC. The expression was similar or higher compared to the primary tumors. The results of this study characterize organoids derived from canine FTC as a suitable in vitro model to investigate iodine uptake, opening new research possibilities in the field of canine thyroid cancer therapy.

Background: Hyperthyroid cats might have a predisposition to arterial thrombus formation. The mechanism for thrombogenesis currently is unknown but could be associated with systemic hypercoagulability as seen in hyperthyroid humans., Objective: Our purpose was to evaluate markers of hemostasis in hyperthyroid cats compared to healthy cats, and in hyperthyroid cats before and after radioactive iodine treatment (RIT)., Animals: Twenty-five cats with hyperthyroidism and 13 healthy euthyroid cats >8 years of age., Methods: Prothrombin time (PT), activated partial thromboplastin time (aPTT), fibrinogen concentration, antithrombin (AT), D-dimers, thrombin-antithrombin complexes (TAT), von Willebrand Factor antigen (vWF : Ag), and activity of factors VIII and IX were measured. An echocardiogram was performed in all cats. Hemostatic markers and echocardiogram were evaluated again 6 to 9 months after successful RIT in 7 cats., Results: Hyperthyroid cats had higher fibrinogen concentration (P < .0001), AT activity (P < .0001), and vWF : Ag concentration (P = .01) than healthy control cats with all results decreasing significantly post-RIT. Hyperthyroid cats were not more likely to be in a hypercoaguable state than euthyroid cats (P = .08). Serum T4 concentration was not a predictor of a hypercoagulable state (P = .53)., Conclusions and Clinical Importance: Hyperthyroid cats have evidence of altered hemostasis that does not appear to be solely attributable to cardiac abnormalities, but no evidence of a hypercoagulable state. Findings suggest altered hemostasis resolves after RIT. Hyperthyroid cats could have endothelial dysfunction as indicated by increased vWF : Ag which could potentiate thrombogenesis., (© 2021 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC on behalf of American College of Veterinary Internal Medicine.)

Background: Radioactive iodine (RAI) is considered the gold standard treatment for feline hyperthyroidism. Currently exposure limits to radiation are regulated by national legislation, therefore the length of the isolation period in hospital for cats receiving radioactive treatment varies according to the place where the radioactive facility is located. The aim of this study was to establish when retained radioactivity decreases in cats receiving subcutaneous I-131 to a level that would allow discharge of cats from the hospital while being compliant with current United Kingdom legislation., Methods: Clinical records of cats treated with subcutaneous I-131 were retrospectively reviewed. Radioactive emission rates were measured using an external probe. Retained radioactivity below 11 MBq at the point of discharge was required by the initial risk assessment to ensure that a 0.3 mSv dose constraint was maintained for owners following standard cat-owner contact restrictions. Average retained activity for each treatment regimen at the time of discharge was calculated. The biological half-life for iodine retention was also calculated., Results: Overall, an end activity below 11 MBq was reached at day 11 in 49% of cats, and at day 13 in 91% of cats. These cats were allowed to be discharged according to UK legislation, as long as contact restrictions were applied at home for 2 weeks., Conclusion: Based on our study, an isolation period of 13 days before allowing discharge of cats treated with subcutaneous RAI (I-131) is compliant with current UK legislation., (© 2021 British Veterinary Association.)

Background: There is limited published information on the outcome for cats where total thyroxine concentration (TT4) remains elevated after treatment with radioactive iodine (RAI)., Objective: To determine the frequency of, and predictors for, subsequent treatment failure in cats for which TT4 remains elevated at hospital discharge, and to report clinical outcomes for cats requiring repeat treatment., Animals: One hundred twenty-one cats with TT4 ≥40 nmol/L after treatment with RAI (out of an original, treated study sample of 959 cats)., Methods: Retrospective study. Data regarding signalment, weight, TT4 concentration (before RAI treatment, at discharge, and percentage change), day of sampling, and I-131 dose were acquired. Logistic regression was performed to evaluate predictors of treatment failure., Results: In the 87 cats for which classification was possible, 35 (40%) became euthyroid without further treatment. All TT4 variables and weight normalized RAI dose were independently predictive of subsequent treatment failure. In multivariate analysis, TT4 concentration at discharge (P < .001) and weight normalized RAI dose (P = .04) remained in the final model. All 28 cats with TT4 concentration ≥150 nmol/L at discharge ultimately failed treatment, compared with 13/40 (32.5%) and 11/19 (57.9%) cats with TT4 concentrations of 40-100 nmol/L and 100-150 nmol/L, respectively. Of the 52 cats that failed treatment, 14 were subsequently managed medically, 12 underwent thyroidectomy (4 with carcinoma), 14 had repeat RAI treatment which was successful in 12/14 (86%) cats, and 13 had no further treatment., Conclusions and Clinical Importance: Cats with TT4 >150 nmol/L at discharge after RAI might be candidates for immediate repeat treatment., (© 2021 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC on behalf of American College of Veterinary Internal Medicine.)

Background: Metastatic disease is frequently present at the time of diagnosis of canine thyroid carcinoma; however, utilisation of computed tomography (CT) alone for staging pre-treatment has been rarely reported in the veterinary literature., Methods: The aims of this retrospective study were to stage affected dogs using CT findings of the cervical and thoracic regions, combined with histopathology/cytology results, in order to assess whether metastatic disease/WHO staging was of prognostic significance., Results: Fifty-eight dogs were included in the study. Classification of cases into WHO stages I, II, III and IV were 10%, 50%, 9% and 31%, respectively. No statistically significant effect of WHO stage classification on overall survival/follow-up time was found (P = .576). Surgery resulted in a statistically significant increase in overall survival/follow-up time (P < .01). There was no statistically significant effect on overall survival/follow-up time in dogs that received medical therapy, either as sole therapy or as an adjunctive post-surgery (P = .198)., Conclusion: In summary, this study documents the metastatic rate of canine thyroid carcinoma using CT for staging pre-treatment. Staging utilising CT revealed a higher distant metastatic rate in dogs with thyroid carcinoma when compared to historical studies using different imaging techniques. As long-term outcomes are possible for cases with advanced disease, surgical intervention could still be considered., (© 2021 British Veterinary Association.)

Background: Injectable radioactive iodine (I-131) frequently is used to treat hyperthyroidism in cats. In human medicine, residual activity after injection of radionuclides has been reported, and the actual quantity administered is recorded after administration., Objective: Our aim was to evaluate actual administered dose variability after administration of preprepared I-131 single unit doses for the treatment of hyperthyroidism in cats., Animals: Twenty-seven cats with hyperthyroidism treated with I-131 between April 2017 and March 2019., Methods: Retrospective observational study of cats treated with preprepared single unit I-131 doses. For each dose, the measured activity before administration and residual activity were recorded. The measured dose and the actual dose administered were compared to the prescribed dose., Results: Measured activity before administration ranged from 88.4% to 103.3% of the prescribed dose. Mean residual activity was 5.2 ± 3.0 MBq (ranging from 1.5% to 15% of the prescribed dose). The actual dose administered (measured activity - residual activity) ranged from 79.1% to 100.2% of the prescribed dose. Seventeen of 28 (60.7%) of the actual administered doses differed between 10% and 20% of the prescribed dose. One administered dose had a >20% difference compared to the prescribed dose (79.10% of the prescribed dose)., Conclusion and Clinical Importance: Our study identified variability in the residual and actual administered activity of I-131 as compared to the prescribed dose, which should be taken into consideration when treating cats with (predrawn) I-131., (© 2021 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC on behalf of American College of Veterinary Internal Medicine.)

Objective: To describe the clinical presentation, clinical course, and management of a dog with thyroid storm (TS) secondary to a functional thyroid carcinoma., Case Summary: A 12-year-old neutered female Golden Retriever was evaluated for severe weight loss, hyperthermia, and tachycardia. The dog had a ventral neck mass and markedly increased thyroxine concentration. Cervical ultrasound showed a suspected left thyroid mass with invasion into the jugular vein. Despite aggressive therapy, the patient progressed to a clinical TS. Postmortem examination was supportive of the clinical diagnosis., New or Unique Information Provided: To the authors' knowledge, this is the first report of TS in a dog., (© Veterinary Emergency and Critical Care Society 2021.)

There are few pathological and immunohistochemical descriptions of thyroid neoplasms in cats. We investigated neoplasms of the thyroid in 31 cats (average age 15.6 years) in Southern Brazil. Most (96.8%) of these cases were classified as follicular adenomas and were predominantly unilateral and multinodular. Histologically, macrofollicular adenomas were the most common type observed. Carcinomas represented 3.2% of the investigated tumours. By immunohistochemical labelling, thyroglobulin was expressed more commonly than paired box gene 8 or thyroid transcription factor 1 in the follicular adenomas. One carcinoma was immunopositive for thyroglobulin, pancytokeratin, chromogranin A and synaptophysin, suggestive of a calcitonin-negative neuroendocrine carcinoma., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Objectives: This study aimed to describe the clinical and diagnostic characteristics, as well as outcomes of radioiodine treatment in dogs with hyperthyroidism caused by a non-resectable ectopic thyroid tumour., Materials and Methods: This retrospective study reviewed the medical records between 2008 and 2018 of dogs diagnosed with hyperthyroidism secondary to a non-resectable ectopic thyroid tumour and treated with radioiodine., Results: Five dogs were included in the study. Three dogs had sublingual ectopic tumours, of which one also had a unilateral cervical thyroid tumour. The remaining two dogs were diagnosed with an ectopic thyroid tumour at the level of the caudal pharynx and the heart base, respectively. All cases were treated with radioiodine. The size of the ectopic masses decreased after radioiodine treatment. Total thyroxine concentrations returned to reference ranges in all dogs. Further, clinical signs of hyperthyroidism disappeared after treatment in all patients. One dog developed myelosuppression secondary to radioiodine treatment. The dog with metastasis had a very short survival compared to the four dogs without metastasis (3 months compared to 7, 36, 50 and 24 months, respectively) and succumbed most likely to thyroid-related problems. In the remaining four dogs, their quality of life improved. They died due to diseases unrelated to the ectopic thyroid tumour., Clinical Significance: Radioiodine therapy should be considered as a treatment option in dogs diagnosed with hyperthyroidism due to a non-resectable ectopic thyroid tumour., (© 2020 British Small Animal Veterinary Association.)

Objective: To determine the rate of nodal metastasis to the medial retropharyngeal (MRP) and deep cervical lymph nodes in dogs surgically treated for thyroid carcinoma., Study Design: Retrospective study., Animals: Twenty-two client-owned dogs., Methods: Medical records between July 2015 and October 2019 at the Universities of Missouri and Florida were reviewed. Dogs that underwent thyroidectomy with concurrent elective MRP lymphadenectomy ± deep cervical lymphadenectomy were included. Tumor site, preoperative staging, and histopathological findings were recorded., Results: Twenty-two dogs with 26 total thyroid carcinomas were included. Primary tumors were lateralized in 19 dogs, bilateral in two dogs, and bilateral and midline ectopic in one dog. All dogs underwent ipsilateral MRP resection, including bilateral resection in dogs with bilateral tumors. Three contralateral MRP lymph nodes were excised from dogs with unilateral carcinomas. Four deep cervical lymph nodes and one superficial cervical lymph node were excised. Metastases were identified in 14 lymph nodes in 10 of 22 (45%) dogs. All four excised deep cervical lymph nodes and one contralateral MRP lymph node were identified as metastatic. Size of deposit could be classified in 13 of 14 metastatic lymph nodes. Macrometastasis was detected in seven lymph nodes, micrometastasis was detected in one node, and isolated tumor cells were detected in five lymph nodes., Conclusion: Regional metastasis was common within the lymph nodes sampled in this population of dogs with thyroid carcinoma., Clinical Significance: These results provide evidence to justify further exploration of a larger population to verify the rate of regional metastasis and determine the prognostic impact of nodal metastasis., (© 2020 The American College of Veterinary Surgeons.)

Thyroid carcinoma develops spontaneously in dogs, with only 25% to 50% of cases amenable to surgery at diagnosis. Local control for unresectable tumours can be provided with external beam radiotherapy. The aim of this retrospective study is to describe the safety and efficacy of stereotactic body radiation therapy (SBRT) for treatment of canine thyroid carcinoma. Twenty-three dogs met inclusion criteria; median tumour volume before SBRT was 129.9 cm 3 (range, 2.7-452.8 cm 3 ). Sixteen patients (70%) had unresectable tumours. Pulmonary metastasis was present or suspected in 10 patients (44%) before SBRT. Patients were prescribed 15 to 40 Gy to targeted tumour volume in one to five fractions. Twenty patients evaluated had overall response rate of 70% (complete response, n = 4; partial response, n = 10). Thirteen out of sixteen (81%) symptomatic patients had clinical improvement within a median time of 16 days (range, 2-79 days). Median progression free survival (MPFS) was 315 days. Median survival time (MST) was 362 days. Nine patients (39%) had grade 1 acute radiation toxicity. Three patients had grade 1 late radiation toxicity (two leukotrichia and one [4%] with intermittent cough). Responders had significantly longer MPFS (362 vs 90 days; HR 4.3; 95% CI 1.4-13.5; P = .013) and MST (455 vs 90 days; HR 2.9; 95% CI 1-8.4; P = .053). Presenting with metastasis was not a significant negative prognostic factor (MST 347 vs 348 days without metastasis; P = .352). SBRT is a safe and effective treatment modality for non-resectable canine thyroid carcinoma., (© 2020 John Wiley & Sons Ltd.)

Thyroid carcinoma is the most common endocrine malignancy in dogs. Thyroidectomy and radiation therapy control local disease, yet are not always feasible, and efficacious medical therapies need to be identified. Toceranib phosphate has been reported to provide clinical benefit (CB) in dogs with thyroid carcinoma, while its role in treatment-naïve thyroid tumours has not been well-described. The objective of this study was to describe the use of toceranib in the management of thyroid carcinomas in dogs in both the naïve-disease and prior therapy- settings. A medical record search identified 42 dogs diagnosed with thyroid carcinoma and treated with toceranib, of which 26 and 16 dogs were in settings of naïve-disease and after prior therapy, respectively. Twenty-three (88.4%) and twelve (75%) dogs experienced CB in the naïve and prior therapy settings, respectively. The median [95% confidence interval] progression free interval (PFI) for dogs in the naïve and prior therapy settings were 206 [106,740] and 1015 [92,1015] days, respectively. The median overall survival time (OST) for dogs in the naïve and prior therapy settings were 563 [246,916] and 1082 [289,1894] days, respectively. Overall, the data provided no evidence for differences in overall PFI (P > .20) or OST (P = .15) between settings. However, when asymptomatic at the time of diagnosis, dogs in the naïve setting showed poorer survival prognosis (estimated hazard ratio 17.2 [1.8, 163]) relative to dogs in the prior therapy setting. This study characterizes PFI, OST and CB with minimal AE in dogs with thyroid carcinoma treated with toceranib in both the naïve and prior therapy settings., (© 2020 John Wiley & Sons Ltd.)

Background: Information on scintigraphy findings in dogs with thyroid neoplasia is scarce. The use of single-photon emission computed tomography (SPECT) could improve detection of metastatic disease., Hypothesis/objectives: To describe planar and SPECT imaging findings in dogs with thyroid tumors, and to compare SPECT and thoracic radiography for metastasis detection., Animals: Sixty-eight dogs with thyroid neoplasia., Methods: Retrospective study, search of medical records for dogs with thyroid neoplasia (2008-2018)., Results: Thyroid scintigraphy was available from 68 dogs, of which 6 presented after surgical resection. Radionuclide uptake was increased in 56% of dogs, decreased in 24%, and comparable to that of the salivary glands in 13%. The remainder had multiple masses with variable uptake. A homogeneous uptake pattern was present in 16% and a heterogeneous uptake pattern in 73%. In 11% (all dogs with multiple masses), various uptake patterns were present. Thyroid tumors were well delineated in 55%. There was a significant association between hormone status and uptake pattern (P = .009), with a heterogeneous uptake pattern in the majority of euthyroid dogs, and hormone status and tumor circumscription (P = .003), with well-circumscribed margins in the majority of hypothyroid and hyperthyroid dogs. Thoracic SPECT imaging was available in 39 dogs and identified metastatic lesions in 15 dogs. Thoracic radiographs were performed in 14 of these dogs, and detected metastases in 3 dogs., Conclusions and Clinical Importance: SPECT imaging is a viable imaging technique to screen for thoracic metastasis and wider use of SPECT imaging is recommended in dogs with thyroid neoplasia., (© 2020 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC on behalf of American College of Veterinary Internal Medicine.)

Objective: To describe the clinical features and outcome of functional thyroid tumours in dogs., Materials and Methods: Retrospective multi-institutional study of 70 dogs diagnosed with thyroid mass and concurrent hyperthyroidism. Clinical data regarding presentation, treatment, outcome and functional thyroid status were retrieved., Results: Overall median survival of dogs with functional thyroid tumours was 35.1 months and 1- and 3-year survival rates were 83 and 49%, respectively. Median survival time was 72.6 months for dogs treated with surgical excision and 15.7 months for dogs that did not receive surgery. Of the 50 dogs treated by surgery and for which thyroid status was known following treatment, 64% developed hypothyroidism after surgery. Histopathologically confirmed metastasis was identified in 3% of dogs., Clinical Significance: Dogs with functional thyroid tumours may survive a long time after surgical excision, although post-operative hypothyroidism is common., (© 2020 British Small Animal Veterinary Association.)

Thyroid carcinomas are a common form of endocrine neoplasia in dogs. In the present study, we combined histopathology with immunohistochemistry (IHC) to search for the presence of oestrogen receptor alpha (ORα), Cox-2 and Ki67 in canine thyroid carcinomas. Forty-eight thyroid carcinomas were diagnosed throughout the study period. Thyroglobulin and calcitonin IHC distinguished between thyroid tumours with a follicular and medullary (C-cell) origin, respectively. IHC-based diagnosis showed that 42 (87.50%) of the cases were follicular cell carcinoma. In these cases, the follicular-compact pattern was the most frequent (n = 20/42; 47.62%) and six cases (12.5%) were medullary cell (C-cell) carcinomas. Both medullary (C-cell) and follicular carcinomas expressed Ki67 and Cox-2. No differences were observed between medullary and follicular carcinomas with respect to expression of Ki67 (P = 0.34) and Cox-2 (P = 0.9523) markers. A total of 4.17% (n = 2/48) of thyroid carcinomas showed positive nuclear labelling for ORα, suggesting that oestrogen does not directly participate in the pathogenesis of canine thyroid neoplasia., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

A 20-year-old male brown bear (Ursus arctos) with a 20 × 25 cm necrotic mass adjacent to the trachea was diagnosed as having an anaplastic thyroid carcinoma. Metastases were observed in the lungs and one adrenal gland and, histologically, these had anaplastic and follicular carcinoma patterns, respectively. E-cadherin labelling was observed in the adrenal mass only, while N-cadherin immunolabelling was detected in the thyroid gland and lung masses. Thyroid-specific markers (thyroid transcription factor-1, thyroglobulin) were expressed in the adrenal gland metastasis. This case illustrates an example of a primary epithelial-mesenchymal transition (EMT) enabling metastasis to distant organ sites, followed by a mesenchymal-epithelial transition within the adrenal gland microenvironment, allowing invasion and reacquisition of thyroid epithelial cell features. EMTs help to understand the phenomenon of carcinoma cell plasticity in enabling colonization and growth of metastases., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Thyroid cancer is the most common endocrine malignancy in dogs. Dogs and humans are similar in the spontaneous development of thyroid cancer and metastasis to lungs; however, thyroid cancer has a higher incidence of metastasis in dogs. This study developed a preclinical nude mouse model of canine thyroid cancer using a canine thyroid adenocarcinoma cell line (CTAC) and measured the expression of important invasion and metastasis genes in spontaneous canine thyroid carcinomas and CTAC cells. CTAC cells were examined by electron microscopy. Short tandem repeat analysis was performed for both the original neoplasm and CTAC cells. CTAC cells were transduced with luciferase and injected subcutaneously and into the tail vein. Tumors and metastases were monitored using bioluminescent imaging and confirmed with gross necropsy and histopathology. Invasion and metastasis genes were characterized in 8 follicular thyroid carcinomas (FTCs), 4 C-cell thyroid carcinomas, 3 normal thyroids, and CTAC cells. CTAC cells grew well as xenografts in the subcutis, and they resembled the primary neoplasm. Metastasis to the kidney and lung occurred infrequently following subcutaneous and tail vein injection of CTAC cells. STR analysis confirmed that CTAC cells were derived from the original neoplasm and were of canine origin. Finally, 24 genes were differentially expressed in spontaneous canine thyroid carcinomas, CTAC, and normal thyroids. This study demonstrated the usefulness of a nude mouse model of experimental canine thyroid carcinoma and identified potential molecular targets of canine follicular and C-cell thyroid carcinoma.