Increased sensitivity of the thyroid in iodine-depleted rats to the goitrogenic effects of thyrotropin

Bray, George A.

doi:10.1172/jci105855

Cited by 143 publications

(46 citation statements)

References 24 publications

(26 reference statements)

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“…In the latter, a recent study focusing on solitary adenomas, instead of multinodular goiters, found an incidence rate (70%) similar to that found in European patients (30). Iodine deficiency increases serum TSH levels as well as the sensitivity of the thyroid gland to the stimulatory effects of TSH (31). This in turn stimulates mitotic activity in the thyroid, thus increasing the probability of a mutation occurring in a replicating cell (24).…”

Section: Discussionmentioning

confidence: 63%

Autonomously functioning thyroid nodules in a former iodine-deficient area commonly harbor gain-of-function mutations in the thyrotropin signaling pathway

Georgopoulos

Sykiotis

Sgourou

et al. 2003

European Journal of Endocrinology

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Background: Somatic activating mutations of the thyrotropin (thyroid-stimulating hormone (TSH)) receptor (TSHR) and G as protein have been detected in solitary toxic adenomas and toxic multinodular goiters, but their role in the pathogenesis of autonomous nodules is debated. The frequency of mutations is highly variable among populations and is inversely proportional to iodine intake. Design and patients: We screened 28 clinically and histologically heterogeneous autonomous nodules from 24 Greek patients for the presence of TSHR and G as mutations. Results: By direct sequencing of genomic DNA, we detected 11 somatic heterozygous gain-of-function mutations in TSHR and one in G as . Forty-three percent (12 of 28) of all nodules and 57% (four of seven) of solitary toxic adenomas harbored an activating mutation. Typical adenomas and hyperplastic nodules did not differ in mutation frequency. Substitutions I568T and T632I were detected in both histological types of nodules. Conclusions: Our findings indicate that activating somatic mutations in the TSH signaling pathway are frequent in autonomous nodules in Greece. This may be due to earlier exposure of the population to iodine deficiency, which was corrected in Greece only over the past two decades. Gain-of-function mutations are shared by nodules with varying histological and clinical presentations. Thus, they may represent a common molecular mechanism underlying the pathogenesis of non-autoimmune thyroid autonomy.

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Section: Discussionmentioning

confidence: 63%

Autonomously functioning thyroid nodules in a former iodine-deficient area commonly harbor gain-of-function mutations in the thyrotropin signaling pathway

Georgopoulos

Sykiotis

Sgourou

et al. 2003

European Journal of Endocrinology

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“…This is a wellknown consequence of iodine deficiency (Fenzi et al 1985;Pickardt et al 1972 Studies in the rat have shown that iodine depleted thyroids are much more sensitive to TSH than those with normal iodine content (Bray 1968). Possibly, the reduced TSH level is a physiological response to protect the thyroid from additional growth.…”

Section: Discussionmentioning

confidence: 99%

Goitre epidemiology: thyroid volume, iodine excretion, thyroglobulin and thyrotropin in Germany and Sweden

Gutekunst¹,

Smolarek²,

Hasenpusch

et al. 1986

Acta Endocrinologica

180

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Abstract. Thyroid volume of 1397 German and 303 Swedish adults were estimated by sonography. Thyroid size of 6–16 year old Germans (n = 619) was determined and compared with findings on palpation. Thyroid volume was more than twice as great in German (21.4 ± 15.6 ml, mean ± sd) than in Swedish adults (10.1 ± 4.9 ml). The echopattern was abnormal in 16% of the Germans and in 3.6% of the Swedes. German children have a thyroid volume ranging from 1.8 ± 0.4 ml at 6 years to 10.8 ± 6.0 ml at 16 years of age. Palpation is by comparison an unreliable method for determining thyroid size. In Germany, the iodine excretion was less in children (n = 619, 39.5 ± 30.5, 34.1 μg I/g creatinine, mean ± sd, median) than in adults (n = 1193, 83.7 ± 94.4, 62.6), (P <0.001) and much lower than that observed in Sweden (adults n = 98, 170.2 ± 93.3, 141.4; 13 year olds n = 113, 172.9 ± 224.1, 124), (P < 0.0001). Serum thyrotropin concentration was significantly higher (P <0.001) in Sweden (n = 62, 1.49 ± 0.82 mU/ml), than in Germany (n = 91, 0.97 ± 0.52 mU/ml), while serum thyroglobulin was increased in Germany (n = 91, 72.6 ± 50.6 μg/l) as compared to Sweden (n = 62, 23.5 ± 17.4), (P <0.0001). These results indicate the goitrogenic effect of iodine deficiency and the continuing need for an effective iodine prophylaxis in the FRG.

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“…Experimentally, iodine deficiency increases the growth response of normal thyroid tissue to thyroid stimulating hormone (TSH) [12].…”

Section: Discussionmentioning

confidence: 99%

Changing patterns of thyroid cancer in Sri Lanka. Has the iodination programme helped?

Ratnatunga¹,

Amarasinghe

Ratnatunga

2011

Ceylon Med. J.

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Objectives To ascertain if there has been a change in the pattern of thyroid cancer in Sri Lanka. If so, whether there is a correlation to the implementation of the programme of iodination.Design Retrospective (1974Retrospective ( -1986Retrospective ( ) and prospective (1987Retrospective ( -2001 Setting Kandy Hospital (1974-1982), Peradeniya Hospital (1982-2001 and private hospitals in Kandy (1979Kandy ( -2001.Method Three hundred consecutive patients with cancer of the thyroid seen over 28 years period were reviewed for demography, histopathology and extent of spread at presentation. Seventy one patients of this group had a pre-existing goitre of greater than 10 years' duration and were similarly reviewed.Results A highly significant reduction of anaplastic thyroid cancer and a highly significant reduction in the extent of extra-thyroidal spread at presentation of differentiated thyroid cancer were observed after 1995. In malignancy supervening on pre-existing goitre, a significant reduction in anaplastic carcinoma and a highly significant increase in papillary carcinoma were noted in the post-1996 period. A significant reduction of extra-thyroidal spread was also observed.Conclusion A trend towards more differentiated thyroid cancer with lesser degree of spread was observed in recent years. The iodination programme implemented in 1995 is likely to be responsible for this change.

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Increased sensitivity of the thyroid in iodine-depleted rats to the goitrogenic effects of thyrotropin

Cited by 143 publications

References 24 publications

Autonomously functioning thyroid nodules in a former iodine-deficient area commonly harbor gain-of-function mutations in the thyrotropin signaling pathway

Autonomously functioning thyroid nodules in a former iodine-deficient area commonly harbor gain-of-function mutations in the thyrotropin signaling pathway

Goitre epidemiology: thyroid volume, iodine excretion, thyroglobulin and thyrotropin in Germany and Sweden

Changing patterns of thyroid cancer in Sri Lanka. Has the iodination programme helped?

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