Differentiated thyroid cancer

TSH suppression in well-differentiated thyroid cancer and thyroid nodules -The target level for TSH suppression in these conditions has not been established in controlled studies. In addition, the efficacy of TSH suppression for benign nodular disease is controversial. Therefore, individualize the dose of levothyroxine used for TSH suppression based on the specific disease and the patient being treated. 

Cooper DS et al Management guidelines for patients with thyroid nodules and differentiated thyroid cancer. Thyroid 2006 16 109. [PMID 16420177]... 

Thyrotropin stimulates iodine uptake, and this facilitates the diagnosis and treatment of recurrent disease or metastases in the follow-up of differentiated thyroid cancer. It is used as an alternative to thyroid hormone withdrawal, to avoid symptomatic hypothyroidism (1). Headache and nausea occur in 6-40% of patients after intramuscular administration, but are usually mild and transient (2,3). 

Durski JM, Weigel RJ, McDougall IR. Recombinant human thyrotropin (rhTSH) in the management of differentiated thyroid cancer. Nucl Med Commun 2000 21(6) 521-8. 

Thyrotropin alpha has the biologic properties of pituitary TSH. It binds to TSH receptors on both normal thyroid and differentiated thyroid cancer cells. The TSH-activated receptor stimulates intracellular adenylyl cyclase activity. Increased cAMP production causes increased iodine uptake and increased production of thyroid hormones and thyroglobulin. 

Treatment of metastatic differentiated thyroid cancer requires the administration of large doses of 131I (30-200 mCi) in the presence of persistently high serum levels of TSH (see Chapter 38 Thyroid Antithyroid Drugs). Patients must withdraw from thyroid hormone replacement in order to achieve this. For treatment purposes, thyrotropin alpha administration cannot substitute for thyroid hormone withdrawal. 

The main use of Tg measurement is as a tumor marker for patients with a diagnosis of differentiated thyroid cancer. Approximately two thirds of these patients have an elevated preoperative Tg level. An elevated preoperative level of Tg confirms the tumor s ability to secrete Tg and validates the use of postoperative measurement of Tg to monitor for tumor recurrence. Postoperatively, the most sensitive method to detect residual tumor or metastasis is after TSH stimulation. In weU-differentiated tumors, a tenfold increase in Tg levels is seen after TSH stimulation. Poorly differentiated tumors, that do not concentrate iodide, may display a blunted response to TSH stimulation. 

Berge-Lefranc JL, Cartouzou G, DeMicco C, et al. Quantification of thyroglobulin messenger RNA by in-sim hybridization in differentiated thyroid cancers Difference between well-differentiated and moderately differentiated histologic types. Cancer. 1985 56 345-350. 

Wiseman SM, Melck A, Masoudi H, et al. Molecular phenotype of thyroid tumors identifiers A marker panel for differentiated thyroid cancer diagnosis. Am Surg Oncol. 2008 15 2811-2826. 

A considerable advance in the management of thyroid cancer has resulted from the introduction of recombinant human TSH (thyrogen). A dose of 0.9 mg is administered intramuscularly, followed by an identical dose 24 hours later. The serum thyroglobuLin is then measured 48-72 hours after the second TSH injection this has become the preferred diagnostic test for following patients with differentiated thyroid cancer who have had thyroidectomy and ablation of any remnant tissue with radioactive iodine. This regimen can also be used to stimulate iodine uptake by malignant cells in a total body scan (see below). 

Most thyroid cancers retain many junctional aspects of normal thyroid cells. Although the treatment of choice for these tumors—as for all thyroid cancers—is surgical removal, the fact that these differentiated thyroid cancers retain some features of normal thyroid cells has important implications for both diagnosis and therapy (see below). 

Pax-8, one of the main regulators of the NUE, is down-regulated in some thyroid cancer cells (Kogai et al., 2006). Endogenous Pax-8 expression is markedly reduced in 70% of differentiated thyroid cancers, especially in aggressive disease (Fabbro et al., 1994). Colocalization of Ref-1 and... 

The PKA-dependent pathway is also down-regulated in some thyroid cancer cells. Reduced localization of PKA to the nucleus has been observed in PCC13 rat thyroid cells constitutively expressing RET/PTCl (Venkateswaran et al., 2004). A study of specimens from 20 patients with thyroid cancer indicates that CREB mRNA and protein expression is significantly reduced in differentiated thyroid cancer tissue compared to normal tissue (Luciani et al., 2003). The level of CREB expression, however, is not correlated with the NIS expression (Luciani et al., 2003). 

More than 70% of differentiated thyroid cancer concentrates radioiodine after TSH stimulation (Robbins et al., 1991 Jarzab et al., 2003). Some differentiated thyroid cancer (approximately 10-20%), as well as anaplastic thyroid cancer, however, do not concentrate radioiodide, even after TSH stimulation (Robbins et al., 1991). Since almost all differentiated thyroid cancer expresses TSHR (Brabant et al, 1991), the absence of NIS induction in response to TSH is most likely due to defects in postreceptor signaling pathways. Recent studies have demonstrated the potential for NIS induction in poorly differentiated thyroid cancer by redifferentiation agents, such as nuclear receptor ligands, RA and peroxisome proliferator-activated receptor- (PPAR ) ligands, and inhibitors of epigenetic modifications. 

RA induces NIS mRNA expression in two foUicular thyroid cancer cell lines, FTC-133 and FTC-238, but not in rat thyroid cells (Schmutzler et al., 1997). Based on the findings, clinical trials have been conducted to evaluate the efficacy of RA for improving radioiodide uptake in recurrent/ metastatic thyroid cancer. Twenty to 42% of aggressive differentiated thyroid cancer responds to RA treatment by an increase in radioiodide uptake (Kogai et al., 2006). The studies, however, have not been randomized prospective studies of matched groups that would be necessary to confirm an effect of RA treatment. 

Differentiated thyroid cancer before and after salt iodization... 

Notes-. In an ISA anaplastic thyroid cancer is rare and the main type of differentiated thyroid cancer is papillary thyroid cancer. The ratio between papillary and follicular thyroid cancer changed due to the introduction of salf iodization. Abbreviations-. IDA, iodine deficient area rIDA, relative iodine-deficient area ISA, iodine-sufficient area DTC, differentiated thyroid cancer pap, papillary foil, follicular. 

A Low-Iodine Diet Prior to Radioiodine Administration in the Management of Differentiated Thyroid Cancer... 

Thyroid cancer is the commonest endocrine malignancy, with approximately 1000 new cases per year in the UK. Papillary and follicular thyroid cancer are referred to as differentiated thyroid cancer, and carry a favorable prognosis, with overall 10 year survival in the order of 90%. For most patients treatment for differentiated thyroid cancer consists... 

Note The table gives a summary of the reasons underlying the benefit of radioiodine in the treatment of differentiated thyroid cancer. 

Note-. The use of a low-iodine diet in combination with radioiodine as part of the treatment of differentiated thyroid cancer is supported by studies investigating a variety of surrogates for clinical outcomes. 

Morris et al. (2001) retrospectively reviewed the ablation rates following initial radioiodine treatment postthyroidectomy for differentiated thyroid cancer patients in a single institution in the US. In this center a written comprehensive low-iodine diet was introduced in 1996 to replace a policy of limited simple verbal advice to avoid iodized foods, enabling a retrospective comparison between two different cohorts. Successful ablation was deemed to have occurred if there was no radioiodine uptake in the area of the thyroid bed on a diagnostic uptake scan performed between 4 and 42 months post-ablation. The was no statistically significant difference in ablation rates between 50 patients treated prior to 1996 who received minimal dietary advice with a 62% successful ablation rate, and with 44 patients post-1996 who received the... 

A low-iodine diet is used to enhance the uptake of radioiodine by the thyroid gland in the treatment and investigation of differentiated thyroid cancer. There is a body of largely retrospective evidence supporting the benefit of a low-iodine diet. A low-iodine diet can be difficult to follow and anxiety-inducing. Advice regarding a low-iodine diet needs to be tailored to individual countries and simplified as much as possible. 

When administered as a major amount concentrates in the thyroid gland, although to a lesser extent in differentiated thyroid cancer compared with normal thyroid tissue. The short range of the emitted beta particles leads to cell damage and cell death. The emitted radiation, however, can be harmful to other organs of the patient and has the potential to induce cancer, especially with repeated treatments and high cumulative activities. Other people in the vicinity of the patient may be exposed to external radiation and contamination. For children, thyroid cancer after radiation exposure appears to be a significant risk, as has been documented after the accident in Chernobyl. 

The treatment of differentiated thyroid cancer with radioiodine relies on the ability of the malignant cells to accumulate iodine in the same way as normal thyroid epithelial cells. 

Iodide uptake after stimulation with TSH is sufficient in most differentiated thyroid cancers to utilize (3-emit-ting radioactive iodine for the treatment of residual and metastatic disease. Elevated serum TSH (which can be achieved by thyroid hormone withdrawal after thyroidectomy or administration of recombinant human TSH)... 

Radioiodine is widely-used in the treatment of metastatic differentiated thyroid cancer. 

The first published studies on the effect of Hthium in thyroid cancer patients were a small case series by Briere et al (1974) and a case study by Gershengom et al (1976). In both of these studies, Hthium increased the dose of radiation delivered to well-differentiated thyroid cancer. Movius et al (1986) showed, in a smaU series of patients with well-differentiated thyroid cancer, that the biological half life of I in individual lesions was increased... 

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