Cellular actions of thyroid hormone may be initiated within the cell nucleus, at the plasma membrane, in cytoplasm, and at the mitochondrion. Thyroid hormone nuclear receptors (TRs) mediate the biological activities of T3 via transcriptional regulation. Two TR genes, α and β, encode four T3-binding receptor isoforms (α1, β1, β2, and β3). The transcriptional activity of TRs is regulated at multiple levels. Besides being regulated by T3, transcriptional activity is regulated by the type of thyroid hormone response elements located on the promoters of T3 target genes, by the developmental- and tissue-dependent expression of TR isoforms, and by a host of nuclear coregulatory proteins. These nuclear coregulatory proteins modulate the transcription activity of TRs in a T3-dependent manner. In the absence of T3, corepressors act to repress the basal transcriptional activity, whereas in the presence of T3, coactivators function to activate transcription. The critical role of TRs is evident in that mutations of th...

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Molecular aspects of thyroid hormone actions.

https://acsjournals.onlinelibrary.wiley.com/doi/epdf/10.1002/1097-0142%28196509%2918%3A9%3C1145%3A%3AAID-CNCR2820180915%3E3.0.CO%3B2-%23

Acinic cell adenocarcinoma of the major salivary glands. A clinicopathologic study of 77 cases

Publisher Summary This chapter discusses the adverse effects associated with the use of thyroid and antithyroid drugs. These include use of thyroid hormone, antithyroid drugs, and iodine preparations. Hyperthyroidism developing during therapy with normal amounts of thyroid hormones and persisting after stopping levothyroxine therapy can occasionally be observed. This is because of the activation of a previously silent autoimmune disorder (Graves' disease or TSI hyperthyroidism). The optimal intake of iodine remains a controversial topic. A nutritional intake below 50 μg/day is associated with an increased incidence of goiter and hypothyroidism. The Food and Nutritional Board of the National Academy of Sciences, USA, therefore, proposed 100 μg/day as the desirable lower limit of intake. The upper tolerance limit is defined as 1000 μg/day with 300 μg as the upper desirable limit. A high-normal intake (>300 μg/day) may be associated with an increased incidence of goiter and Hashimoto thyroiditis and a decreased remission rate after medical treatment for Graves' disease. The problem of iodine-induced or iodine related hyperthyroidism is very frequent.

Thyroid and antithyroid drugs

https://dspace.library.uu.nl/bitstream/handle/1874/24709/waard_84_the%20dom%20project%20for%20the%20early%20detection.pdf;sequence=1

The DOM project for the early detection of breast cancer, Utrecht, The Netherlands.

Fifty-one cases of acinic cell carcinoma (ACC) arising in major and minor salivary glands are reported (primary sites: parotid 37, submandibular, six, and oral cavity, eight.) These lesions usually produced painless slowly growing masses. Of 49 patients with follow-up information, 17 (35%) developed local recurrences following original surgical resection, and two (4%) had locally persistent disease. At last follow-up, 27 patients (55%) never had a recurrence, seven (14%) had experienced local recurrences but the tumors were apparently controlled by further surgical excisions, five (10%) were living with persistent disease, and 10 (20%) had died (one due to local tumor and nine due to metastases, usually to bones and lungs). The determinate 5-, 10- and 15-year survival rates were 78%, 63%, and 44%, respectively. Prognostic factors included: demonstrable tumor on lines of surgical excision, involvement of deep lobe of parotid, size of primary lesion, degree of mitotic activity and nuclear atypia, infiltrative rather than circumscribed borders, and lymph node involvement. Local recurrence was associated with an increased incidence of locally uncontrollable and metastatic disease. Type of initial therapy correlated with prognosis. Locally recurrent or persistent tumor was found in 14 of 15 patients treated with limited local excisions (including one biopsy only). Recurrences were seen in only three of 28 patients treated by wide local excisions and in two of six following radical en bloc resections. Seven of 17 patients with local recurrence were apparently cured by further more extensive resection. Radiotherapy did not appear effective in controlling these neoplasms.

Acinic cell carcinomas arising in salivary glands: a clinicopathologic study.

The occurrence of acinic cell adenocarcinoma of the parotid gland in two young women is reported. Despite the history of slow growth of the tumor with only minor symptoms, and the presence of an apparent capsule at operation, microscopic sections show clear evidence of malignancy. Histologic diagnosis is not difficult as the “water-clear” cell makes the appearance of the tumor distinctive. Other aspects of the pathologic and clinical characteristics of the tumor have been reviewed. Surgical treatment should be based upon the knowledge of common local recurrence and occasional distant metastases.

Acinic cell adenocarcinoma of the parotid gland

IT HAS recently been reported 1 that, among patients undergoing mammography at a hospital in Detroit, the prevalence of breast cancer was higher in women receiving thyroid hormone therapy than in those who were not. Prevalence of breast cancer was said to increase with increasing duration of thyroid hormone treatment, particularly in nulliparous women. Since the time that this report appeared and was widely publicized by the news media, many patients have expressed concern that the thyroid hormone they are taking may be dangerous, and they have inquired as to whether such treatment should be stopped. The American Thyroid Association, whose membership comprises physicians and basic scientists interested in the thyroid and its diseases, views the aforementioned article with concern, both because of its implication of a possible basic relationship between thyroid therapy and breast cancer and because of its potential impact on the treatment of patients who require thyroid

Breast cancer and thyroid therapy. Statement by the American Thyroid Association.

Excerpt Among patients undergoing mammography at a hospital in Detroit, Michigan, the prevalence of breast cancer was higher in women receiving thyroid hormone therapy than in those who were not (1...

American thyroid association statement: breast cancer and thyroid hormone therapy.

It has recently been reported [I] that among patients undergoing mammography at a hospital in Detroit, Michigan, the prevalence of breast cancer was higher in women receiving thyroid hormone therapy than in those who were not. Prevalence of breast cancer was said to increase with increasing duration of thyroid hormone treatment, particularly in nulliparous women. Since the time that this report appeared and was widely publicized by the news media, many patients have expressed concern that the thyroid hormone they are taking may be dangerous, and they have inquired as to whether such treatment should be stopped. The American Thyroid Association, whose membership comprises physicians and basic scientists interested in the thyroid and its diseases, views the aforementioned article with concern, because of both its implication of a possible basic relationship between thyroid therapy and breast cancer and its potential impact on the treatment of patients who require thyroid hormone therapy. Several aspects of the study reported from Detroit require clarification before the findings can be properly evaluated. The authors of the report did not provide information about any of the following important questions: the nature of the patient’s underlying thyroid disease, if any; the dosage of thyroid hormone being taken; the duration of therapy and whether it was intermittent or continuous; whether thyroid hormones were being taken at the time of the study or only in the past; and whether any patient had received radioiodine, antithyroid agents, or other medications, including other hormones. Referral patterns to the hospital, the racial and ethnic mixture of the patients in the groups treated with thyroid hormone and in the control groups, and the frequency and type of coexistent diseases were not stated. We were also not told how the diagnosis of breast cancer was confirmed. Most important, even granted that a valid relationship between thyroid hormone therapy and breast cancer had been established, the central question would remain whether breast carcinoma is associated with thyroid hormone therapy per se, as the authors of the article strongly imply, or with the disease for which thyroid hormone treatment was being employed.

Richard S. Rivlin

Papers

Acinic cell adenocarcinoma of the parotid gland

Breast cancer and thyroid therapy. Statement by the American Thyroid Association.

American thyroid association statement: breast cancer and thyroid hormone therapy.

American Thyroid Association statement on breast cancer and thyroid hormone therapy