Ultimobranchial thyroid neoplasms in bulls. A syndrome resembling medullary thyroid carcinoma in man

A syndrome of ultimobranchial thyroid neoplasms which shares many similarities with medullary thyroid carcinoma in man occurs frequently in populations of adult bulls. The results of this investigation demonstrated that ultimobranchial neoplasms were composed of poorly differentiated parafollicular (C—) cells with extensive aggregations of microfilaments, clusters of ribosomes, and prominent Golgi apparatuses. Secretion granules often were interspersed between microfilaments. Other more columnar neoplastic cells assumed a ductal pattern. The prominent stroma contained amyloid fibrils and collagen fibers. By comparison, cells comprising medullary thyroid carcinoma were more differentiated parafollicular cells with well developed cytoplasmic organelles and numerous membrane‐limited secretion granules. Calcitonin activity was demonstrated by biologic assay in both ultimobranchial adenomas (466 ± 84 MRC mU/g) and carcinomas (409 ± 93 MRC mU/g) but serum calcium and phosphorus levels were within normal limits. Plasma calcitonin‐like activity was increased significantly 1 hour after calcium infusion but rapidly returned to baseline values. Parathyroid glands from bulls with ultimobranchial neoplasms had ultrastructural evidence of atrophy and secretory inactivity. Numerous lipofuscin, granules and cytosegresomes but few secretory granules were present in chief cells. Aggregations of amyloid fibrils surrounded chief cells and capillaries. Multiple endocrine tumors (pheochromocytomas and pituitary acidophil adenomas) and vertebral osteosclerosis with ankylosing spondylosis frequently were detected in bulls coincidentally with ultimobranchial thyroid neoplasms. Copyright © 1973 American Cancer Societ

Multiple Endocrine Neoplasia Type 2B: Eighteen-Year Follow-up of a Four-Generation Family

Seven members with multiple endocrine neoplasia type 2B from a 15-member family have been followed for 18 years. All affected had the neuroma phenotype in a distribution compatible with autosomal dominant inheritance. The phenotype features have allowed 100% initial and continuing prediction of affected versus nonaffected status in as early as 1.5 years. Among the affected: immunoreactive plasma calcitonin (iCT) concentration was high in 100%; thyroid palpation was false-negative in 71%; and thyroid scintiscan was false-negative in 83%. All had total thyroidectomy, plus lymphadenectomy in three, for bilateral medullary thyroid carcinoma (MTC) or C-cell hyperplasia (in the youngest). None has died directly from MTC. The index case died at age 68 and his son at age 32 years from complications of the syndrome. All but the youngest have continuing high iCT concentrations. No patient has had parathyroid disease. During preoperative calcium infusion, immunoreactive serum parathyroid hormone concentration declined by 35% to 84% of basal. At operation, macroscopically and microscopically normal parathyroid glands were found in all. No patient has had chemical suggestion of pheochromocytomas: at postmortem the index case had no adrenal medullary disease; his son had bilateral nodular adrenal hyperplasia; his daughter has had adrenal medullary hyperplasia and a renin-secreting juxtaglomerular tumor. Initially nonaffected members remain so

PI3K activation is associated with intracellular sodium/iodide symporter protein expression in breast cancer

Background: The sodium/iodide symporter (NIS) is a membrane glycoprotein mediating active iodide uptake in the thyroid gland and is the molecular basis for radioiodide imaging and therapeutic ablation of thyroid carcinomas. NIS is expressed in the lactating mammary gland and in many human breast tumors, raising interest in similar use for diagnosis and treatment. However, few human breast tumors have clinically evident iodide uptake ability. We previously identified PI3K signaling as important in NIS upregulation in transgenic mouse models of breast cancer, and the PI3K pathway is commonly activated in human breast cancer. Methods: NIS expression, subcellular localization, and function were analyzed in MCF-7 human breast cancer cells and MCF-7 cells stably or transiently expressing PI3K p110alpha subunit using Western blot of whole cell lysate, cell surface biotinylation Western blot and immunofluorescence, and radioiodide uptake assay, respectively. NIS localization was determined in a human breast cancer tissue microarray using immunohistochemical staining (IHC) and was correlated with preexisting pAkt IHC data. Statistical analysis consisted of Student's t-test (in vitro studies) or Fisher's Exact Test (in vivo correlational studies). Results: In this study, we demonstrate that PI3K activation in MCF-7 human mammary carcinoma cells leads to expression of underglycosylated NIS lacking cell surface trafficking necessary for iodide uptake ability. PI3K activation also appears to interfere with cell surface trafficking of exogenous NIS as well as all-trans retinoic acid-induced endogenous NIS. A correlation between NIS expression and upregulation of PI3K signaling was found in a human breast cancer tissue microarray. Conclusion: Thus, the PI3K pathway likely plays a major role in the discordance between NIS expression and iodide uptake in breast cancer patients. Further study is warranted to realize the application of NIS-mediated radioiodide ablation in breast cancer

Secretion of parathyroid hormone-related protein by bovine mammary cells in vitro

Mammary cells were isolated from lactating cows at 1 to 6 weeks after calving and evaluated for their ability to secrete PTHrP in vitro. The tissue was enzymatically digested to release glandular acini. The digested acini were cultured on thin (1.0 mm) or thick (2.5 mm) layers of collagen. The cultures containing thick collagen were detached and allowed to contract on day 6. The culture medium consisted of M199 with prolation (8 µg/ml), insulin (5 µg/ml), cortisol (5 µg/ml), and fetal bovine serum (15%). PTHrP production was measured by N-terminal RIA and bioassay (stimulation of adenylate cyclase in the ROS 17/2.8 cell line). Medium was collected at 2-day intervals for 14 days. The cells reached confluence at 4–6 days. PTHrP production was low at day 2 (<0.5 ng/ml), but increased to peak production (2–4 ng/ml) at approximately day 6–8 of culture and remained constant until day 14. Immunoreactive and bioactive PTHrP levels in the culture medium correlated well. The cultures produced high levels of lactoferrin (500 to 3000 ng/ml) and low levels of α s1 -casein (14 to 77 ng/ml).Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/41592/1/774_2006_Article_BF02375695.pd

Thyrocalcitonin: Evidence for release in a spontaneous hypocalcemic disorder

Thyrocalcitonin content of thyroid gland extracts from normal postparturient cows was 3.9 times greater than in cows with postparturient paresis. The parafollicular cells in diseased cows were less numerous and appeared to have discharged their secretory products. An abrupt release of thyrocalcitonin near parturition may be related to the development of the hypocalcemia and hypophosphatemia in this disorder