ANIMAL MODELS OF DISEASE: Feline hyperthyroidism: an animal model for toxic nodular goiter
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Figure 1
Histologic section across a nodular goiter of a hyperthyroid cat stained with periodic acid-Schiff (PAS). This stain was used to highlight glycoprotein content (thyroglobulin) within the colloid as well as follicular structure. Four nodules (1, 2, 3 and 4) consisting of follicles lined by cuboidal epithelial cells with large nuclei (see inset) and filled with pale, barely stained colloid are shown. Some areas within the nodules are almost solid structures with only tiny follicular lumina. Other nodules may contain some large follicles separated by densely cellular parenchyma (3). Occasionally, even a giant follicle may form within the nodules (4). Adapted, with permission, from Peter HJ, Gerber H, Studer H, Becker DV & Peterson ME 1987 Autonomy of growth and of iodine metabolism in hyperthyroid feline goiters transplanted onto nude mice. Journal of Clinical Investigation 80 491–498 (Copyright American Society for Clinical Investigation).
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Figure 2
Histologic section of a hyperthyroid cat goiter obtained at surgery stained with periodic acid-Schiff (PAS). Note areas of hyperplastic nodular tissue with follicles lined by cuboidal or columnar epithelial cells (1) and areas of paranodular tissue with follicles filled with strongly PAS-positive colloid and lined by flat or cuboidal epithelial cells (2). Reproduced, with permission, from Peter HJ, Gerber H, Studer H, Peterson ME, Becker DV & Groscurth P 1991 Autonomous growth and function of cultured thyroid follicles from cats with spontaneous hyperthyroidism. Thyroid 1 331–338 (Copyright Mary Ann Liebert Inc).
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Figure 3
Autoradiograph of hyperthyroid cat goiter labeled with 20 μCi of 125I for 4 h before surgery, with nodular tissue then counter-stained with nuclear fast red stain. Note intense iodine organification within a hyperplastic nodule (1) and very little iodine uptake within the adjacent paranodular tissue (2). In some hyperplastic nodules, there was considerable heterogeneity of radioiodine organification among individual follicles, even within the same nodule (3). Exposure time 65 days. Reproduced, with permission, from Peter HJ, Gerber H, Studer H, Becker DV & Peterson ME 1987 Autonomy of growth and of iodine metabolism in hyperthyroid feline goiters transplanted onto nude mice. Journal of Clinical Investigation 80 491–498 (Copyright American Society for Clinical Investigation).
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Figure 4
Radioiodine uptake into xenotransplanted normal (A) and toxic goiter tissue (B) growing in T4-treated host mice labeled with 20 μCi of 131I for 3 h before being killed. 131I uptake of mean (±s.e.m.) counts per minute (c.p.m.) into normal tissues (saline control, NaCl, n=5) is low in the absence of TSH and is not enhanced by administration of hyperthyroid cat serum (serum, n=3), but 131I uptake is readily stimulated by TSH (TSH, n=5) (A). Toxic goiter tissue shows unabated high autonomous iodine uptake (NaCl, n=8) that is not significantly altered by administration of serum from the hyperthyroid donor cat (serum, n=7) (B). Reproduced, with permission, from Peter HJ, Gerber H, Studer H, Becker DV & Peterson ME 1987 Autonomy of growth and of iodine metabolism in hyperthyroid feline goiters transplanted onto nude mice. Journal of Clinical Investigation 80 491–498 (Copyright American Society for Clinical Investigation).
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Figure 5
Histological sections of a xenograft of a toxic goiter of a geriatric cat grown in a T4-treated host mice labeled with [3H]thymidine 3 months before being killed, then counter-stained with nuclear fast red. Autoradiograph A, taken from a hyperplastic area and exposed 3 months after radioiodine labeling, shows that despite the absence of TSH, a considerable fraction of the follicular cells has incorporated the thymidine label into their nuclei (arrow). The grains within the follicular lumina result from residual 131I activity. No incorporation of [3H]thymidine into follicular cell nuclei is found in autoradiograph B showing a paranodular area, exposed under identical conditions (72 days). Reproduced, with permission, from Peter HJ, Gerber H, Studer H, Becker DV & Peterson ME 1987 Autonomy of growth and of iodine metabolism in hyperthyroid feline goiters transplanted onto nude mice. Journal of Clinical Investigation 80 491–498 (Copyright American Society for Clinical Investigation).
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Figure 6
Autoradiograph showing radioiodine organification in follicles embedded in collagen gel, counter-stained with nuclear fast red. In normal follicles cultured without TSH, the density of silver grains within the lumina is low (A), whereas intense 131I organification occurs in the presence of TSH (B). In contrast, follicles from hyperthyroid goiter tissue intensely accumulate the iodine label despite the absence of TSH (C). All cultures were labeled under identical conditions, and slides were exposed for 5 days. Reproduced, with permission, from Peter HJ, Gerber H, Studer H, Peterson ME, Becker DV & Groscurth P 1991 Autonomous growth and function of cultured thyroid follicles from cats with spontaneous hyperthyroidism. Thyroid 1 331–338 (Copyright Mary Ann Liebert Inc).
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Figure 7
Autoradiograph of a histological section counter-stained with nuclear fast red showing follicular cell proliferation in follicles from normal and hyperfunctioning thyroid tissue cultured in the absence of TSH. In normal follicles (A), only an occasional cell has incorporated the thymidine label. In contrast, some clusters of follicles contain up to 12% 3H-thymidine-labeled cells in cultures from hyperthyroid goiters (B). Reproduced, with permission, from Peter HJ, Gerber H, Studer H, Peterson ME, Becker DV & Groscurth P 1991 Autonomous growth and function of cultured thyroid follicles from cats with spontaneous hyperthyroidism. Thyroid 1 331–338 (Copyright Mary Ann Liebert Inc).
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Figure 8A female, domestic shorthaired cat at 9 years of age before hyperthyroidism (A) and again at 13 years of age after diagnosis of hyperthyroidism (B). At time of diagnosis, the owner reported gradual but progressive weight loss despite an increasing appetite for at least a year. Notice the marked weight loss and muscle wasting due to the untreated, long-standing toxic nodular goiter.
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Figure 9
Serum concentrations of (A) T4 (μg/dl), (B) T3 (ng/dl), (C) free T4 (pmol/l), and (D) TSH (ng/ml) in 500 cats with toxic nodular goiter, before and after treatment with radioiodine. In each graph, the box represents the interquartile range (i.e. 25th–75th percentile range or the middle half of the data). The horizontal bar in the box represents the median value. For each box plot, the T-bars represent 5th–95th percentile. The shaded areas indicate the reference interval for each hormone. (A and B) Before treatment, notice that hyperthyroid cats have clearly high levels of both total T4 and T3, but some cats with mild hyperthyroidism may have values that remain within the reference interval. Also note that the reference intervals for total T4 and T3 in cats are ∼50% lower than the reference intervals in man (Kaptein et al. 1994, Davey 1997); the reason for this difference is that cats lack thyroxine-binding globulin (TBG), a major binding protein for both T4 and T3 in man (Larsson et al. 1985, Kaptein et al. 1994). Three months after treatment with radioiodine (post 131I), the high values have fallen into the reference interval. (C) Like total T4, serum free T4 concentration is high in almost all hyperthyroid cats and normalizes after treatment. As free T4 methods measure the fraction of T4 not bound by TBG or other serum proteins, this is considered a more accurate way to assess thyroid function in both cats and man (Davey 1997, Peterson et al. 2001, Thienpont et al. 2013). (D) Before treatment, serum TSH concentrations in the hyperthyroidism cat are low, at or below the level of quantification. After treatment the suppressed TSH values increase. Some of the 131I-treated cats develop mild to subclinical iatrogenic hypothyroidism, as evidenced by the high post-treatment TSH concentrations.
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Figure 10
Thyroid scintigraphy in a normal cat (A) and three cats with toxic nodular goiter (B, C and D), performed 1 h after intravenous administration of 110 MBq of sodium pertechnetate (99mTcO4−). (A) Image of the neck region of a cat with normal thyroid function. In normal cats, the thyroid gland appears on thyroid scans as two well-defined, focal (ovoid) areas of radionuclide accumulation in the cranial to middle cervical region. The two thyroid lobes are symmetric in size and shape and are located side-by-side; no isthmus is seen. Radioactivity in the normal thyroid closely approximates activity in the salivary glands, with an expected uptake ratio of 1:1. (B, C and D) Image of the neck region of three cats with toxic nodular goiter. In cats B and C, both thyroid lobes contain adenomatous nodules with a heterogeneous pattern of 99mTcO4− uptake. In cat D, the left thyroid lobe contains two large nodules, whereas the radionuclide uptake by the normal right thyroid lobe is decreased and cannot easily be visualized. For all three hyperthyroid cats, the uptake of the radionuclide by the hyperactive nodular goiter is higher than that by the salivary tissue. Both the calculated percent uptake of 99mTcO4− and the thyroid:salivary ratio were high, diagnostic for hyperthyroidism in all three cats.
- © 2014 Society for Endocrinology
