Significance of Iodide-Perchlorate Discharge Test for Detection of Iodine Organification Defect of the Thyroid

Takeuchi, Keisuke; Suzuki, Hoji; Horiuchi, Yoshihiko; Mashimo, Keimei

doi:10.1210/jcem-31-2-144

Cited by 53 publications

(12 citation statements)

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“…However, the existence of a mild defect in iodine organification in BB-DP rats has also been disputed (Rajatanivan et al 1983), and clearly more investigations are needed in the very young BB-DP rat (less than 9 weeks old) to establish or refute such metabolic abnormality and its compensations. In patients with Hashimoto's thyroiditis, however, organification defects have been well described (Takeuchi et al 1970).…”

Section: Discussionmentioning

confidence: 99%

Pre-autoimmune thyroid abnormalities in the biobreeding diabetes-prone (BB-DP) rat: a possible relation with the intrathyroid accumulation of dendritic cells and the initiation of the thyroid autoimmune response

Simons

Delemarre²,

Jeucken³

et al. 1998

Journal of Endocrinology

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Thyroid autoimmune reactions start with an accumulation of mainly dendritic cells in the thyroid. There is increasing evidence that, apart from being antigen-presenting cells, they are also able to control the growth and hormone synthesis of neighbouring endocrine cells. The questions thus arise: are dendritic cells accumulating in the pre-autoimmune thyroid in response to an altered proliferative or metabolic activity of thyrocytes, and do cytokines, monocyte chemoattractants, or both, have a role in their accumulation? We have investigated these questions in thyrocytes of the biobreeding diabetes-prone (BB-DP) rat in relation to the start of the intrathyroid accumulation of dendritic cells -that is, at about 9 weeks of age.BB-DP rats and Wistar rats (controls) were studied from 3 to 20 weeks of age. Hyperplastic goitre development was studied by assessing the thyroid weight and by measuring the number of thyrocyte nuclei per 0·01 mm 2 thyroid section. In addition, the in situ expression of interleukin-6 (IL-6), tumour necrosis factor-(TNF-), monocyte-chemotactic protein-1 (MCP-1), and intercellular adhesion molecule-1 (ICAM-1) were studied by immunohistochemistry. The in vitro proliferative capacity of BB-DP and Wistar thyrocytes was measured by tritiated-thymidine ([ 3 H]TdR) and bromodeoxyuridine (BrdU) incorporation into reconstituted, TSHand non-TSH-stimulated, cultured thyroid follicles. Further in vitro studies consisted of measurement of the production of thyroxine (T 4 ), triiodothyronine (T 3 ), thyroglobulin, IL-6, TNF-and MCP-1 by the thyroid follicles.BB-DP rats developed a small hyperplastic goitre between the ages of 9 and 12 weeks. The in vitro proliferative rate of thyrocytes isolated from hyperplastic BB-DP thyroids was significantly lower than that of Wistar thyrocytes. This phenomenon also occurred in follicles isolated from BB-DP rats before hyperplastic goitre development, which produced significantly less T 4 , but more T 3 , than did Wistar follicles of the same age. At the time of and after hyperplastic goitre development, BB-DP follicles exhibited altered metabolic behaviour and produced significantly more T 4 , but equal amounts of T 3 compared with both Wistar follicles of the same age and follicles of younger BB-DP rats (both under basal conditions and TSH-stimulated).In vitro IL-6 production by these BB-DP thyroid follicles was also increased. There was no noteworthy difference in production of thyroglobulin and MCP-1 between BB-DP and Wistar follicles at any age. TNF-was not produced by BB-DP or Wistar thyroid follicles.Immunohistochemistry revealed the expression of IL-6 by both BB-DP and Wistar thyroid follicle cells at all times of sampling. MCP-1 and TNF-were expressed only when infiltrates were present in BB-DP thyroids (restricted to leucocytes, ages >18 weeks). Modest ICAM-1 expression was restricted to large blood vessels in both BB-DP and Wistar thyroids; in the case of infiltrates (BB-DP rat) alone, high ICAM-1 expression was found on blood vessels and leucocytes...

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Section: Discussionmentioning

confidence: 99%

Pre-autoimmune thyroid abnormalities in the biobreeding diabetes-prone (BB-DP) rat: a possible relation with the intrathyroid accumulation of dendritic cells and the initiation of the thyroid autoimmune response

Simons

Delemarre²,

Jeucken³

et al. 1998

Journal of Endocrinology

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“…A test is considered positive if <10% of activity is discharged after ClO 4 − administration. Partial organification defects show a 10-90% discharge, while discharge <90% is consistent with total organification defect [19,21,133-135]. …”

Section: Introductionmentioning

confidence: 90%

Iodide transport: implications for health and disease

Pesce

Kopp

2014

Int J Pediatr Endocrinol

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Disorders of the thyroid gland are among the most common conditions diagnosed and managed by pediatric endocrinologists. Thyroid hormone synthesis depends on normal iodide transport and knowledge of its regulation is fundamental to understand the etiology and management of congenital and acquired thyroid conditions such as hypothyroidism and hyperthyroidism. The ability of the thyroid to concentrate iodine is also widely used as a tool for the diagnosis of thyroid diseases and in the management and follow up of the most common type of endocrine cancers: papillary and follicular thyroid cancer. More recently, the regulation of iodide transport has also been the center of attention to improve the management of poorly differentiated thyroid cancer. Iodine deficiency disorders (goiter, impaired mental development) due to insufficient nutritional intake remain a universal public health problem. Thyroid function can also be influenced by medications that contain iodide or interfere with iodide metabolism such as iodinated contrast agents, povidone, lithium and amiodarone. In addition, some environmental pollutants such as perchlorate, thiocyanate and nitrates may affect iodide transport. Furthermore, nuclear accidents increase the risk of developing thyroid cancer and the therapy used to prevent exposure to these isotopes relies on the ability of the thyroid to concentrate iodine. The array of disorders involving iodide transport affect individuals during the whole life span and, if undiagnosed or improperly managed, they can have a profound impact on growth, metabolism, cognitive development and quality of life.

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“…ClO 4 − , a competitive inhibitor of NIS that is translocated electroneutrally (15), causes a rapid reduction of free I − in the thyroid (as I − can efflux from but not enter the thyrocyte in its presence). When organification is normal, ClO 4 − elicits only moderate thyroid I − discharge (∼15%) because most I − is rapidly covalently bound to Tg, whereas an organification defect can result in a ClO 4 − ‐induced I − discharge of 50% or more (16).…”

Section: Resultsmentioning

confidence: 99%

The KCNQ1‐KCNE2 K⁺channel is required for adequate thyroid I⁻uptake

et al. 2012

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The KCNQ1 α subunit and the KCNE2 β subunit form a potassium channel in thyroid epithelial cells. Genetic disruption of KCNQ1-KCNE2 causes hypothyroidism in mice, resulting in cardiac hypertrophy, dwarfism, alopecia, and prenatal mortality. Here, we investigated the mechanistic requirement for KCNQ1-KCNE2 in thyroid hormone biosynthesis, utilizing whole-animal dynamic positron emission tomography. The KCNQ1-specific antagonist (-)-[3R,4S]-chromanol 293B (C293B) significantly impaired thyroid cell I(-) uptake, which is mediated by the Na(+)/I(-) symporter (NIS), in vivo (dSUV/dt: vehicle, 0.028 ± 0.004 min(-1); 10 mg/kg C293B, 0.009 ± 0.006 min(-1)) and in vitro (EC(50): 99 ± 10 μM C293B). Na(+)-dependent nicotinate uptake by SMCT, however, was unaffected. Kcne2 deletion did not alter the balance of free vs. thyroglobulin-bound I(-) in the thyroid (distinguished using ClO(4)(-), a competitive inhibitor of NIS), indicating that KCNQ1-KCNE2 is not required for Duox/TPO-mediated I(-) organification. However, Kcne2 deletion doubled the rate of free I(-) efflux from the thyroid following ClO(4)(-) injection, a NIS-independent process. Thus, KCNQ1-KCNE2 is necessary for adequate thyroid cell I(-) uptake, the most likely explanation being that it is prerequisite for adequate NIS activity.

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Significance of Iodide-Perchlorate Discharge Test for Detection of Iodine Organification Defect of the Thyroid

Cited by 53 publications

References 0 publications

Pre-autoimmune thyroid abnormalities in the biobreeding diabetes-prone (BB-DP) rat: a possible relation with the intrathyroid accumulation of dendritic cells and the initiation of the thyroid autoimmune response

Pre-autoimmune thyroid abnormalities in the biobreeding diabetes-prone (BB-DP) rat: a possible relation with the intrathyroid accumulation of dendritic cells and the initiation of the thyroid autoimmune response

Iodide transport: implications for health and disease

The KCNQ1‐KCNE2 K⁺channel is required for adequate thyroid I⁻uptake

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Significance of Iodide-Perchlorate Discharge Test for Detection of Iodine Organification Defect of the Thyroid

Cited by 53 publications

References 0 publications

Pre-autoimmune thyroid abnormalities in the biobreeding diabetes-prone (BB-DP) rat: a possible relation with the intrathyroid accumulation of dendritic cells and the initiation of the thyroid autoimmune response

Pre-autoimmune thyroid abnormalities in the biobreeding diabetes-prone (BB-DP) rat: a possible relation with the intrathyroid accumulation of dendritic cells and the initiation of the thyroid autoimmune response

Iodide transport: implications for health and disease

The KCNQ1‐KCNE2 K+channel is required for adequate thyroid I−uptake

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The KCNQ1‐KCNE2 K⁺channel is required for adequate thyroid I⁻uptake