Thyroid adenoma

One rat also had an adenocortical adenoma, and the other had a gastric adenoma and a thyroid adenoma. 

Mutations that shift the equilibrium toward the constitutively active form will often cause disease. For example, activating mutations in the TSH or LH receptors are responsible for the development of thyroid adenomas and the development of puberty in small children, respectively. In the case of the thyroid adenomas, a normal TSH receptor is expressed in the surrounding normal thyroid tissue. 

Toxic adenomas may result in hyperthyroidism with larger nodules. Because there may be isolated elevation of serum T3 with autonomously functioning nodules, a T3 level must be measured to rule out T3 toxicosis if the T4 level is normal. After a radioiodine scan demonstrates that the toxic thyroid adenoma collects more radioiodine than the surrounding tissue, independent function is documented by failure of the autonomous nodule to decrease its iodine uptake during exogenous T3 administration. 

Osborne-Mendel rats were fed technical-grade heptachlor (73%) males received TWA doses of 1.94 and 3.9 mg/kg/day and females received TWA doses of 1.28 and 2.56 mg/kg/day for 80 weeks (NCI 1977). The results of this study showed a statistically significant increase in follicular cell neoplasms in the thyroid (adenomas and carcinomas) in females fed the high dose compared to controls. This finding was discounted by the investigators, however, because the incidence rates were low and are known to be variable in the control rat population. Rates of tumor incidences in males were not increased. 

Hyperthyroidism, for example, can result from activating germline mutations that are located in the TSHR TM domains. By contrast, thyroid adenomas and multin-odal goiter (25-31) result from a variety of somatic mutations in other regions of the TSHR. For example, a rare constitutively active TSHR mutation in the first TM domain results from a Gly substitution at the conserved Ser position (28). 

Mutations with similar outcomes have been identified in nonautoimmune autosomal dominant hyperthyroidism (toxic thyroid hyperplasia) (25,26,28,32,33). These variants are located in the third TM (Val509Ala), the seventh TM (Cys672Tyr), and the carboxyl tail (Asp727Glu) regions (34). These variants result in a form of congenital hyperthyroidism that is the germline counterpart of a hyperfunctioning thyroid adenoma, with similar functional characteristics (25,33). 

In rats, high doses of indinavir are associated with development of thyroid adenomas. 

Hydrazine was tested for carcmogenicity by oral administration to mice in several experiments, producing mammary and lung tumours. When tested by oral administration or inhalation exposure in rats, it produced lung, liver and nasal tumours and a few colon tumours. In hamsters, it produced liver tumours and thyroid adenomas following oral or inhalation exposure. 

Primary hyperthyroidism Graves disease Thyroid adenoma/carcinoma Secondary hyperthyroidism... 

The most common adverse effects are indirect hyperbilirubinemia and nephrolithiasis due to crystallization of the drug. Nephrolithiasis can occur within days after initiating therapy, with an estimated incidence of 3-15%, and may be associated with renal failure. Consumption of at least 48 oz of water daily is important to maintain adequate hydration and prevent nephrolithiasis. Thrombocytopenia, elevations of serum aminotransferase levels, nausea, diarrhea, and irritability have also been reported. There have also been rare cases of acute hemolytic anemia. In rats, high doses of indinavir are associated with development of thyroid adenomas. 

Tg is primarily used as a tumor marker in patients carrying a diagnosis of differentiated thyroid carcinoma (DTC). Although serum Tg is elevated in patients with thyroid cancer, including thyroid follicular and papillary carcinoma, elevations are also are seen in nonneoplastic conditions such as thyroid adenoma, subacute thyroiditis, Hashimoto s thyroiditis, and Graves disease. Serum Tg concentrations are not increased in patients with medullary thyroid carcinoma. 

These germ-line variants, resulting in a form of congenital hyperthyroidism, share similar functional characteristics somatic mutations present in hyperfunctioning thyroid adenoma [24, 32],... 

MNNG Larvae, 0.5-1 mg/1 Branchioblastoma, thyroid adenoma, adenocarcinoma, fibrosarcoma 37... 

Schelfhout LJDM, van Muijen GN, Fleuren GJ. Expression of keratin 19 distinguishes papillary thyroid carcinoma from follicular carcinomas and follicular thyroid adenoma. Am J Clin Pathol. 1989 92 654-658. 

LiVolsi VA. Hyalinizing trabecular tumor of the thyroid Adenoma, carcinoma, or neoplasm of uncertain malignant potential Am J Surg Pathol. 2000 24 1683-1684. 

Parma, J., Duprez, L., Van sande, J., Cochaux, P., Gervy, C., Mockel, J., Dumont, J., Vassart, G., 1993. Somatic mutations in the thyrotropin receptor gene cause hyperfunctioning thyroid adenomas. Nature 365, 649-651,... 

Mutations of the TSH receptor result in clinical thyroid dysfunction. Germline mutations can present as autosomal dominant toxic thyroid hyperplasia (gain-of-frmction mutations) or as gestational hyperthyroidism due to receptor hypersensitivity to hCG. Somatic mutations that result in constitutive activation of the receptor are associated with hyperfrmctioning thyroid adenomas. 

Figure 47.3 Nosological types of hyperthyroidism with different iodine intake levels. Relative frequency of the four most common nosological types of hyperthyroidism in Iceland, with relatively high iodine intake from consumption of fish and high iodine content of dairy products, and from East Jutland, Denmark, with mild-to-moderate iodine deficiency. MNTG, multinodular toxic goiter GD, Graves disease STA, solitary toxic thyroid adenoma SAT, subacute thyroiditis. Data from Laurberg et al., (1991).

Mixed medullary and follicular cell carcinoma Spindle cell tumor with thymus-like differentiation Carcinoma showing thymus-like differentiation Thyroid adenoma and related tumors Follicular adenoma Hyalinizing trabecular tumor... 

Notes-. 184 cases of hyperfunctioning thyroid adenoma, adenomatous nodules, or carcinomas listed in the TSHR Mutation Database II (http //www.uni-leipzig.de/ innereAsh/) were studied for their base exchanges. 

The Cooperative Thyrotoxicosis Therapy Follow-up Study showed that long-term thyroid problems occur in children treated with lower, rather than higher, doses of Thyroid adenomas developed in 30% of 30 children treated in one center with low doses of estimated to result in thyroid exposure of 25 Gy [33,50]. Yet, when children were treated with higher doses of (100-200 Gy), the incidence of thyroid neoplasms did not increase (Dobyns etal, 1974). 

---