The mammalian thyroid gland is composed of 2 distinct endocrine cell populations concerned with the synthesis of 2 different classes of hormones. Follicular cells secrete the metabolically active iodothyronines whereas the C-(parafollicular) cells are concerned with the production ofcalcitonin, a hormone that influences blood levels of calcium and phosphorus, and bone cell metabolism. The synthesis of metabolic thyroid hormones is different than in other endocrine glands because the final assembly of hormone occurs within the follicular lumen. This extracellular synthesis of thyroid hormones is made possible by thyroglobulin, a glycoprotein synthesized by follicular cells. The secretion of thyroid hormones under the influence of pituitary thyrotrophin (TSH) from stores in the luminal colloid is initiated by elongation of microvilli and formation of pseudopods. FD&C Red No. 3 is a tetraiodinated derivative of fluorescein which in lifetime studies increases the incidence of thyroid follicular cell adenomas in male Sprague-Dawley rats. The striking changes in circulating levels of thyroid hormones and morphologic evidence of follicular cell stimulation are the result of alterations in the peripheral metabolism of thyroxine. An inhibition by FD&C Red No. 3 of 5'-deiodinase in the liver and kidney would explain the lower serum triiodothyronine (T,) levels. The pituitary, sensing the lowered circulating levels of T,, increased the secretion of thyroid stimulating hormone which resulted in the morphologic evidence of follicular cell stimulation in the long-term studies. Other xenobiotics increase the incidence of thyroid tumors in rodents by a direct effect on the thyroid gland to disrupt 1 of 3 or more possible steps in the biosynthesis of thyroid hormones. Physiologic perturbations alone, such as iodine deficiency or partial thyroidectomy, can disrupt thyroid hormone economy in rodents and, if sustained, increase the development of thyroid tumors. The wide variety of drugs, chemicals, and physiologic perturbations which increase thyroid tumor development appear to act through a secondary (indirect) mechanism to promote tumor development by causing a long-standing hypersecretion of thyroid stimulating hormone. Nodular and/or diffuse hyperplasia of C-cells occurs with advancing age in many strains of laboratory rats and in response to long-term hypercalcemia in certain animal species and human beings. Focal or diffuse hyperplasia often precedes the development of C-cell neoplasms. Radiation and the feeding of diets high in vitamin D resulting in hypercalcemia have been reported to increase the incidence of C-cell tumors in rats.
Abstract. 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.Hypothyroidism in pet dogs is a metabolic disorder that can result from primary diseases of the thyroid gland or be secondary to long-standing pituitary or hypothalamic lesions that interfere with the release of thyrotropin or thyrotropin-releasing hormone. Hypothyroid dogs have a gradual decline in vigor and physical activity, and often are "heat seekers" [ 12). Varied degrees of alopecia and epidermal atrophy were reported in 48% of hypothyroid dogs [17]. Hypothyroidism in pet dogs was associated with a low level of serum triiodothyronine (38.7 k 4.1 ng/dl) and thyroxine (0.8 k 0.07 pg/dl); circulating thyroid hormone concentrations did not increase significantly after thyrotropin stimulation [7]. These changes in thyroid function were specific for hypothyroid dogs compared to dogs with other endocrinopathies or normal pet dogs. Thyroglobulin autoantibodies were found in 48% (12 of 25) pet dogs with hypothyroidism, and may be related to the cause of thyroiditis [7]. Laboratory beagles with naturally occurring lymphocytic thyroiditis also have circulating thyroid autoantibodies [ 141, but the focal thyroiditis was not associated with 299
Twenty-six neoplasms of the adenohypophysis were classified either as chromophobe adenomas (20 dogs) or adenomas of the pars intermedia (6 dogs). In 62% of the dogs the neoplasms were functionally active (14 chromophobe adenomas, 2 adenomas of the pars intermedia) and associated with a syndrome of hyperadrenocorticism (Cushing's-like disease). The adrenal cortical hypertrophy and hyperplasia, muscular weakness and wasting, leukocytosis with a neutrophilia, eosinopenia and lymphopenia, deposition of fat in the liver, increased serum corticosteroid, and increased urinary 17-hydroxycorticosteroids all suggested the neoplasms were producing ACTH. Mineralization of the lungs and other tissues was consistently present in dogs with functional neoplasms. Adenomas of the pars intermedia appeared to arise from the lining epithelium of the residual hypophysial lumen covering the infundibular process. They were sharply demarcated from the compressed pars distalis.
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