Histologic and ultrastructural evaluation of thyroid lesions associated with hypothyroidism in dogs

Thyroid lesions in 16 pet dogs with hypothyroidism were evaluated by light and electron microscopy. Lymphocytic thyroiditis, found in seven dogs, was characterized by diffuse infiltration of the thyroid gland by lymphocytes, plasma cells and macrophages with formation of some lymphoid nodules and destruction of follicles, progressing to replacement of most of the thyroid by fibrous connective tissue. The basement membrane around follicles was thick and had electron-dense deposits. The morphology of the thyroid lesions and the presence of circulating thyroglobulin autoantibodies suggested that lymphocytic thyroiditis was immune-mediated. Idiopathic follicular atrophy, found in nine dogs, was characterized by loss of thyroid parenchyma and replacement by adipose connective tissue. Degeneration of individual follicular cells was present in the early stage, with exfoliation into the colloid and interfollicular area. Most of the thyroid gland consisted of adipose connective tissue with either interspersed small follicles or individual follicular cells that had dilated rough endoplasmic reticulum, large Golgi apparatus, and intracytoplasmic microfollicles in the advanced stage. Follicular atrophy was a degenerative lesion of follicular cells of unknown cause, not associated with inflammatory destruction in the thyroid gland.     

猪不同生长阶段甲状腺结构的形态计量学研究

为观察猪不同生长发育阶段甲状腺的形态学变化,本研究选用大约克夏猪,分别于初生、体质量为20、40、80和100kg时屠宰,测定甲状腺质量、长度、宽度、增殖细胞数量以及血清中甲状腺素的表达,并对猪的甲状腺石蜡切片进行组织学观察,应用Nikon NIS-Elements Documentation图像分析系统对甲状腺滤泡腔以及滤泡上皮细胞进行形态计量学指标的测量,并在不同生长阶段进行比较分析。结果表明,随着猪的生长发育,甲状腺增殖细胞的数量、甲状腺素的表达以及滤泡腔数密度、上皮细胞高度均逐渐降低;滤泡腔截面积及其等效直径、滤泡腔截面积密度逐步升高;而上皮细胞核截面积及其等效直径、上皮细胞核数密度变化规律不明显。相关分析表明,血清中FT3的表达与甲状腺宽度存在显著的负相关、与上皮细胞高度呈显著正相关;FT4、TT4的表达与体质量、甲状腺质量、甲状腺长度、甲状腺宽度、滤泡腔截面积、滤泡腔截面积等效直径存在显著负相关,与上皮细胞高度以及上皮细胞核数密度存在显著正相关。上述形态学测量结果为深入研究猪甲状腺在不同生长发育阶段所发生的形态学变化提供了准确的定量资料。     

Perineuronal Nets in the Central Nervous System

The remnant of ultimobranchial (UB) body in the thyroid gland of adult buffalo was studied. This remnant appeared in the form of irregular and elongated follicles of various size and shape with folded lumen. These structures occupied a peripheral location beneath the capsule, as well as being embedded mostly in the vascular connective tissue of the thyroid. Calcitonin cells were predominantly localized in the UB follicles. Scanning electron microscopy revealed that surface of most UB follicular cells was almost flat and polyhedral or hexagonal in shape. Other follicles possessed cells with dome shaped apical surface demarcated by a shallow intercellular depression. The luminal surface of the follicular cell lining was studded with microvilli that appeared with various density and length and were numerous at the cellular borders. Interestingly, most of UB follicular cells were provided with single cilium, projecting over the cell surface. Notably some UB follicles presented various stages of apocrine activities.     

Surface Ultrastructure of Ultimobranchial Remnants in the Thyroid Gland of Buffalo (Bos bubalis)

The remnant of ultimobranchial (UB) body in the thyroid gland of adult buffalo was studied. This remnant appeared in the form of irregular and elongated follicles of various size and shape with folded lumen. These structures occupied a peripheral location beneath the capsule, as well as being embedded mostly in the vascular connective tissue of the thyroid. Calcitonin cells were predominantly localized in the UB follicles. Scanning electron microscopy revealed that surface of most UB follicular cells was almost flat and polyhedral or hexagonal in shape. Other follicles possessed cells with dome shaped apical surface demarcated by a shallow intercellular depression. The luminal surface of the follicular cell lining was studded with microvilli that appeared with various density and length and were numerous at the cellular borders. Interestingly, most of UB follicular cells were provided with single cilium, projecting over the cell surface. Notably some UB follicles presented various stages of apocrine activities.     

Overexpression of c-Ras in hyperplasia and adenomas of the feline thyroid gland: an immunohistochemical analysis of 34 cases

Formalin-fixed, paraffin-embedded thyroid glands from 18 cats diagnosed with hyperthyroidism were evaluated immunohistochemically for overexpression of the products of oncogenes c-ras and bcl2 and the tumor suppressor gene p53. Fourteen thyroid glands from euthyroid cats without histologically detectable thyroid lesions were examined similarly as controls. Results from these investigations showed that all cases of nodular follicular hyperplasia/adenomas stained positively for overexpression of c-Ras protein using a mouse monoclonal anti-human pan-Ras antibody. The most intensely positively staining regions were in luminal cells surrounding abortive follicles. Subjacent thyroid and parathyroid glands from euthyroid cats did not stain immunohistochemically for pan-Ras. There was no detectable staining for either Bc12 or p53 in any of the cats. These results indicated that overexpression of c-ras was highly associated with areas of nodular follicular hyperplasia/adenomas of feline thyroid glands, and mutations in this oncogene may play a role in the etiopathogenesis of hyperthyroidism in cats.     

Hyperplastic and neoplastic changes in ultimobranchial remnants and in parafollicular (C) cells in bulls: a histologic and immunohistochemical study

Thyroid glands from 64 bulls with hyperplastic and/or neoplastic changes in ultimobranchial remnants and in the parafollicular (C) cell system were studied structurally and with immunohistochemical methods. Antibodies against thyroglobulin, calcitonin, somatostatin, and neurotensin were used to detect these substances. Two different types of changes were observed. One change was hyperplasia and neoplasia of the ultimobranchial remnants that affected all their epithelial constituents. These included ultimobranchial follicles, cysts and tubules, as well as solid nests formed by basophilic immature cells which were functionally undifferentiated and unreactive with all the antisera used. Differentiated follicular cells that formed thyroid follicles and cribriform structures with immunohistochemical evidence of thyroglobulin production were also found. In addition, differentiated light and cytoplasm-rich cells were scattered in the walls of the thyroid follicles, ultimobranchial follicles, cysts and tubules as well as in the solid component. They were argyrophilic and reacted with antibodies against calcitonin and somatostatin. The other change was a diffuse or multifocal hyperplasia of the parafollicular (C) cells that was present in other parts of the thyroid parenchyma--sometimes with gradual development of sclerotic tumors that had been exclusively formed by these cells. They corresponded to light cytoplasm-rich cells seen in the ultimobranchial lesions that were argyrophilic and harbored material reactive with antibodies against calcitonin and/or somatostatin. The changes observed in the parafollicular cell system resembled lesions seen in human thyroid glands with the familial variant of medullary carcinoma as well as those reported in thyroid glands of patients with longstanding hypercalcemia.(ABSTRACT TRUNCATED AT 250 WORDS)     

Light and electron microscopic study of the thyroid gland of the camel (Camelus dromedarius)

The thyroid gland of sexually immature dromedary camels was studied using both light and electron microscopy. The thyroid gland contained follicles of different sizes in both summer and winter. However, most of the follicles were large in summer and small in winter. The large follicles were lined by very low cuboidal or semi-squamous follicular cells whereas the small ones were lined by high cuboidal or low columnar follicular cells. Electron microscopy showed that the very low cuboidal follicular cells were poor in organelles and were considered hypoactive. High cuboidal follicular cells on the other hand, were rich in organelles that included mitochondria, cisternae of rough endoplasmic reticulum, secretory vesicles, colloid droplets, heterosomes and autophagic vacuoles; they were considered to be very active. The possible role played by these organelles is synthesis of thyroglobulin and liberation of tri- and tetraiodothyronine is discussed. A few degenerate follicular cells were infrequently encountered in the camel thyroid. Parafollicular (C) cells were not seen in this study either with light or electron microscopy.     

Induction and reversibility of thyroid proliferative changes in rats given an antithyroid compound

Sixty Fischer 344 rats were fed a diet containing 90 ppm methimazole, a known antithyroid compound. Following exposure to the test compound, groups of ten animals were terminated at 1, 3, and 6 months. Similar groups of ten treated animals were given control diet for a reversibility period of 2, 3, and 6 months, respectively. Groups of ten control rats were terminated after 1, 3, 6, and 12 months. Except for the expected effect on body weight, the treated animals had no physical signs of toxicity. The weight of thyroids increased with the duration of exposure, becoming in males after 6 months about ten times the weight of thyroids from control rats. Thyroids of treated rats after 1 and 3 months had a diffuse homogeneous hypertrophy and hyperplasia of follicular cells, decreased colloid, and increased vascularity. After 6 months' exposure to the antithyroid compound, there was diffuse hyperplasia but also a heterogeneity in the size and morphology of follicles, protrusion of follicular tissue through the gland capsule and into vascular spaces, and the development of follicular nodules. Treated rats placed on control diet, allowing for reversibility, had thyroids which were decreased in size with large follicles and flattened epithelium, and a complete remodeling of most nodules with no evidence of progression. Although the nodules produced after prolonged administration of the antithyroid compound had many of the characteristics of neoplasia, the biologic behavior supports the diagnosis of nodular hyperplasia.     

Intracardiac ectopic thyroid carcinosarcoma in a dog

A 13-year-old spayed female Labrador Retriever with a 1-year history of progressive exercise intolerance was diagnosed with an interventricular mass in the heart via echocardiogram. The animal's general condition progressively declined over the next 8 months, and it was euthanatized. The intracardiac mass, which protruded into the lumen of the right ventricle, was removed at necropsy and fixed in 10% buffered formalin. Histopathologic diagnosis was an ectopic thyroid carcinosarcoma based on the presence of 3 distinct neoplastic tissue types. Intermixed within the tumor were neoplastic thyroid follicles containing colloid and solid nests of thyroid follicular epithelial cells, vascular channels and clefts filled with blood and lined by neoplastic endothelium, and osteoid surrounded by spindle cells and often rimmed by large multinucleated cells. Immunohistochemical reaction for thyroglobulin was positive in the tumor cells forming the colloid-filled follicles and solid nests of epithelial cells. Neoplastic endothelium was positive for factor VIII-related antigen. The thyroid gland was located in its normal anatomic position and was histologically normal, ruling out the possibility that the intracardiac tumor was a metastatic lesion. To the authors' knowledge this is the first reported case of an intracardiac ectopic thyroid carcinosarcoma, and possibly the first ectopic thyroid carcinosarcoma in any location in any species.     

Congenital diffuse hyperplastic goiter associated with perinatal mortality in 11 captive-born bottlenose dolphins (Tursiops truncatus).

Diffuse hyperplastic goiter was diagnosed by histopathology in 11 perinatal bottlenose dolphins (Tursiops truncatus) that died at four separate zoos and aquaria. Thyroid morphology of these animals was compared with the histologically normal thyroids of two stranded wild bottlenose dolphin calves, a neonate and a 2-mo-old calf. Histologic changes included reduced follicular luminal diameter, markedly reduced or absent luminal colloid, hypertrophy of follicular epithelium, and follicular dysplasia. The etiology of the thyroid gland lesion was not identified. Cause of death was not determined for most of these animals, but they were presumed to have died from metabolic derangements associated with the thyroid lesion, drowning, or dystocia.     

Untersuchungen zur Form der Schilddrüse (Glandula thyreoidea) beim Geflügel mit besonderer Berücksichtigung der jahreszeitlichen Schwankungen

The thyroid glands of 31 chickens at the age of 17 to 24 months were investigated. Different methods of anatomical preparation, casts of vessels and scanning electron microscopy were used. The thyroid gland of birds is a paired organ. It is located on the ventral surface of the base of the neck within the thoracic inlet. The left thyroid gland is placed more cranially than the right one. Each thyroid gland is closely connected to the common carotid artery on the medial side, from which it is supplied and to the jugular vein on the lateral side. It is a reddish-brown organ and of lenticular profile. The gland measures on average 10 mm in length, 6 mm in width and 2 mm in thickness, and is covered by a thin connective tissue capsule which holds adipose cells. It seems that each thyroid follicle is surrounded by a net of capillaries. The investigation by scanning electron microscopy proved that the follicles are oval with a pyramidal top on each end. The cuboidal epithelium cells leave impressions in the colloid. Epithelium cells carry microvilli on the follicle side surface. Described seasonal changes of the thyroid gland in size and activity were able to be confirmed by the examination of the organ in July and December. In winter the follicular cells were higher and the follicles had a greater volume.     

Induction of Thyroid Proliferative Changes in Rats Treated with Antithyroid Compound

This study was designed to investigate the histologic changes in goitrogen-induced thyroid growth of the rat. The animals were orally treated by 1% potassium perchlorate except the controls and were sacrificed in intervals ranging from 1 to 12 months. The thyroid weight increased progressively along the treatment and after 2 months showed a diffuse homogenous hypertrophy and hyperplasia of follicular cells, decreased amount of colloid and increased vascularity. After sixth month of treatment true nodules appeared with complex morphology.     

Hyperplastic goitre and mortality in captive-reared black stilts ( Himantopus novaezelandiae )

AIM: To study the gross, histopathological and clinico-pathological findings in cases of hyperplastic goitre in sub-adult captive- reared black stilts following their release on riverbeds in the south Canterbury region of New Zealand. METHODS: Necropsies were undertaken on the recovered carcasses of 48 black stilts over a 3-year period (1997-1999). The cause of death was determined, and thyroid glands were examined histopathologically and compared with those of free-living pied stilts. Concentrations of triiodothyronine (T3) and thyroxine (T4) in the serum of sub-adult and adult stilts were measured before and after iodine supplementation. RESULTS: The main causes of death of captive-reared black stilts following release were trauma, predation and starvation. An increase in size of the thyroid gland due to follicular hyperplasia and dilation was seen in all birds with intact thyroid glands (n=27). Dysplastic follicular changes such as epithelial desquamation, lipid deposition and haemorrhage were common in a large proportion of individuals with goitre. Dietary supplementation with iodine greatly improved survival rates in sub-adults following release, and significantly increased concentrations of T3 and T4 in serum. CONCLUSIONS: Subclinical goitre due to thyroid hyperplasia and dysplasia was the cause of hypothyroidism and this contributed to the poor survival of released sub-adult black stilts raised in captivity. Iodine supplementation of the diet of captive adults and sub-adults resulted in increased concentrations of T3 and T4 in serum and improved survivability.     

Surface Ultrastructure of Ultimobranchial Epithelium in the Thyroid Gland of Donkey (Equus asinus)

Surface ultrastructural observation of the thyroid gland in donkey revealed the coexistence of certain unusual follicles or cysts, the ultimobranchial (UB) follicles, which exhibited large diameters and less regular outlines. In addition, several small follicles, cell nests or solid cellular masses were also demonstrated in association with these structures. Surface of most UB follicular cells was almost hexagonal in shape, studded with sparse or dense pleomorphic microvilli, which were much denser at the cellular borders. Each follicular cell bore single cilium that projecting over the cell surface. Interestingly, bleb-like apocrine protrusion of the apical cytoplasm of some follicular cells was frequently demonstrated. These apocrine blebs (or aposomes) were varied in shape, size and showed smooth or irregular surface. In addition to such aposomes, deep to shallow circumscribed or eroded areas of the apical cell surface was frequently demonstrated. These findings indicate that the UB follicular cells in donkeys, similar to those of camels, exhibit an apocrine activity alongside with the usual merocrine mode of secretion.     

A morphological study of the thyroid gland in Risso's Dolphin,Grampus griseus

To accumulate histological information of cetaceans and basic information about metabolic systems of marine mammals, the thyroid gland of Risso's dolphins was examined by gross anatomical and light and electron microscopic observations. Gross anatomically, right and left lobes of the thyroid were not clearly discriminated, and no isthmus was observed. By light microscopy, irregular or oval follicular lumens were seen, and surrounded by follicular epithelial cells. By electron microscopy, the rough endoplasmic reticulum (rER) was seen adjacently to mitochondria at the basal and lateral regions of the follicular epithelial cells. RERs at the basal side of the cells sometimes contained flocculent material with the same electron density as the follicular lumen component. Microvilli were poorly developed at the apical surface of the cells. In the apical regions of the cells, there were typical Golgi complexes, multivesicular bodies, and granules with various size and electron density. The parafollicular cells were recognized among the follicular epithelial cells and in the interstitial regions but never protruded into the follicular lumen. These cells were present singly and/or formed clusters among the follicular epithelial cells, and often located adjacent to capillaries. They were obviously discriminated from follicular epithelial cells by higher electron density of their granules. In their cytoplasm, well-developed rERs, primary lysosomes, secondary lysosomes, multivesicular bodies, and phagosomes were recognized.     

Immunohistochemistry of ultimobranchial thyroid carcinomas in seven slaughtered cows and one bull.

Eight thyroid gland epithelial tumors were found in 7 cows and 1 bull in a retrospective study of thyroid gland lesions in slaughtered cattle. All tumors were classified as ultimobranchial thyroid carcinomas based on morphology and immunohistochemistry. All tumors consisted of solid sheets and nests of polygonal to oval epithelial cells, with more sparsely dispersed colloid-filled follicles. Connective tissue separating nests of epithelial cells varied from delicate fibrovascular stroma to dense collagenous stroma. Fusiform epithelial cells with rare neural fibers and ganglion cells were present in 1 tumor. Cells within solid areas of these tumors were immunoreactive for calcitonin, calcitonin gene-related peptide, neuron-specific enolase, and synaptophysin. Colloid and follicle cells were immunoreactive for thyroglobulin. Few follicle cells also were reactive for calcitonin gene-related peptide. Neoplastic cells invaded the fibrous capsules in all 8 cattle. These tumors represented proliferation of a mixed population of undifferentiated cells, C cells, and thyroid follicular epithelial cells, presumably derived from the thyroid ultimobranchial bodies. These ultimobranchial carcinomas in slaughtered cattle are comparable to ultimobranchial tumors described in dairy bulls and the intermediate type of thyroid gland carcinomas (mixed thyroid medullary carcinomas) described in human beings.     

ULTRASONOGRAPHIC EVALUATION OF THE PARATHYROID GLANDS IN HYPERCALCEMIC DOGS

Two hyperplastic parathyroid glands and three solitary parathyroid adenomas were identified using high-resolution ultrasonography in five adult dogs with persistent hypercalcemia. Ultrasonographic features of parathyroid adenomas included visualization of a round or oval, 5 mm or larger, hypoechoic mass in the cranial pole of one thyroid lobe. Each mass had well-defined margins between the thyroid gland and parathyroid adenoma, reduced echogenicity of the adenoma compared to surrounding thyroid parenchyma, and distal enhancement. Ultrasonographic features of the hyperplastic parathyroid glands included hypoechogenicity, compared to surrounding thyroid parenchyma, and a size of approximately 2 mm. Hyperplastic parathyroids were well marginated in one dog and poorly marginated in another dog.     

Histomorphometry and quantification of nucleolar organizer regions in bovine thyroid containing methylthiouracil residues

In order to study the morphology and morphometry and to characterize and quantify the nucleolar organizer regions (NORs) of bovine thyroids containing methylthiouracil (MTU) residues, five animals were orally treated with a suspension of MTU (5 g/animal/day) for 20 days (group A). This treatment protocol was interrupted 5 days before the the animals were slaughtered. Six animals receiving placebos composed group B. A third group (group C) was composed of normal thyroids obtained from a slaughterhouse. All glands were previously assessed for detection of antithyroid residues by chromatography, and only those glands from MTU-treated animals were positive. Follicles of glands from group A showed wide variation in size and shape. There was a predominance of small follicles covered by multiple layers of columnar cells, sometimes forming papillary projections into the lumen, characterizing severe interfollicular and intrafollicular adenomatosis. Many follicles had vacuolated cells with nuclei showing karyolysis or pyknosis and reduced amounts of a low-density and very excavated colloid. They also showed higher follicular epithelia and larger proportions of their structural components when compared with glands of groups B and C. In the thyroids from group A, the argyrophilic nucleolar organizer region-associated proteins (AgNORs) were greater in number, with small ones scattered all over the nucleus. Although the size of AgNORs in thyroids from groups B and C was variable, these AgNORs were fewer and larger than were those in glands from group A. In conclusion, the MTU induces proliferation and regressive changes in follicular cells, and the AgNOR technique is efficient to distinguish different degrees of thyroid hyperplasia.     

Thyroid follicular adenocarcinoma in a ferret

A 5-year-old male castrated ferret was presented to the Washington State University College of Veterinary Medicine for evaluation of progressive hair loss and a large, rapidly growing ventral neck mass. The patient had been diagnosed previously with an insulinoma, which was managed medically. Fine-needle aspirates of the neck mass were performed. The cytologic results were most consistent with epithelial neoplasia, likely a carcinoma; thyroid origin was considered likely based on tumor location and cell morphology. The tumor grew rapidly, and the owners elected euthanasia 1 week after examination. At necropsy, a circumscribed, ovoid mass disrupted the right cervical musculature next to the right lobe of the thyroid gland. Histopathologic evaluation revealed an infiltrative mass consisting of cuboidal cells arranged in solid sheets and irregular follicles enclosing colloid. The cells were large, with prominent nucleoli, and had a high mitotic rate. The histopathologic diagnosis was consistent with thyroid follicular adenocarcinoma. Immunochemical findings confirmed thyroglobulin production by neoplastic cells, but to a lesser extent than in normal ferret thyroid tissue. To our knowledge, this is the first case of thyroid follicular adenocarcinoma to be reported in a ferret, with only 1 other case of thyroid carcinoma, a C-cell carcinoma, described previously.