Thyroid Autonomy

Thyroid autonomy appears as a solitary toxic nodule or toxic multinodular goitre. In toxic thyroid, the nodule s synthesis and secretion of thyroid hormones is autonomous from the thyroid-stimulating hormone (TSH), which is produced in the pituitary gland. Accordingly TSH is suppressed and the extranodular thyroid tissue is functionally downregulated. Thyroid autonomy occurs frequently in iodine-deficient countries, whereas it is much less common in iodine-sufficient areas. Constitu-tively activating mutations in the TSH receptor and in the Gs a protein are the major molecular aetiology of toxic thyroid nodules. 

Patients with multinodular goiter and thyroid autonomy, especially if they are elderly and/or live in areas of dietary iodine deficiency... 

Thyroid autonomy Exogenous sources of thyroid hormone... 

Joseph K, Mahlstedt J, Gonneemann R, Herbert K and Welcke U (1980) Early recognition and evaluation of the risk of hyperthyroidism in thyroid autonomy in an endemic goitre area. J Mol Med 4 21-37. 

Over the years, people living with iodine deficiency tend to develop multifocal thyroid autonomy, and multinodular toxic goiter is a common cause of hyperthyroidism. The difference in relative distribution of the four most common causes of hyperthyroidism in Iceland, with high iodine intake, and Judand, Denmark, with mild-to-moderate iodine deficiency, is shown in Figure 47.3. In Iceland, Graves ... 

C. Hyperthyroidism caused by thyroid autonomy C. Hyperthyroidism caused by Graves disease ... 

Functionally, the state may be compensated up to a certain degree of iodine deficiency and for a considerable period of time, described in clinical terms as euthyroid diffuse or nodular goiter. Functional failure follows only in the presence of severe iodine deficiency, and hypothyroidism may then develop. Much more frequently and somewhat paradoxically, hyperthyroidism ensues after many years of iodine depletion. Rarely, hyperthyroidism may be found in cases of diffuse goiter, which are then termed as diffuse thyroid autonomy. Fiowever, hyperthyroidism frequendy occurs in conjunction with uninodular (toxic adenoma) and multinodular goiters (toxic multinodular goiter). 

There are differences in the etiology of hyper- and hypothyroidism according to the iodine supply to a population. The main causes for hyper- and hypothyroidism in IDA are thyroid autonomy and iodine deficiency, respectively. 

This huge multicenter trial demonstrated that there was an increase of hyperthyroidism after the elevation of salt iodization with the highest RR in 1992. For oHTA the incidence increased from 30.5/100000/year in 1987 to 41.7/100000/ in 1992 and decreased to baseline incidence in 1995. In contrast, the incidence of oHGD doubled from 1987 (incidence 10.4/100,000/year) to 1993 (20.9/100,000/ year) and was still high in 1995 (18.0/100000/year). From this study, it can be concluded that increase in iodine supply (change from IDA to ISA) leads to a transient increase, followed by a decrease, in thyroid autonomy, but to a permanent increase in Graves disease. 

Abbreviations-. oHTA, overt hyperthyroidism in thyroid autonomy scHTA, subclinical hyperthyroidism in thyroid autonomy oHGD, overt hyperthyroidism in Graves disease scGD, subclinical hyperthyroidism in Graves disease MRR, maximum relative risk Inc, incidence RR, relative risk. 

In the multicenter trial performed from 1987 to 1995 in more than 400000 inhabitants of Austria it could be demonstrated that due to the increase of salt iodization hyperthyroidism increases (Mostbeck et al., 1998). However, there are differences in the cause of increase if we separate thyroid autonomy from Graves disease as a cause of hyperthyroidism. Hyperthyroidism due to thyroid autonomy increases transiently with a MRR 2 years after the increase of salt iodization and decreases thereafter. In contrast, hyperthyroidism due to Graves disease increases with a MRR 3 years after the increase of salt iodization and remains high thereafter. This means that today in Austria thyroid autonomy as cause of hyperthyroidism decreases, whereas Graves disease increases and it can be expected that for the future in Austria Graves disease will become the main cause of hyperthyroidism. 

The improvement of iodine intake in Austria led to a transient increase in hyperthyroidism caused by thyroid autonomy, but decreased thereafter. 

In 1928 Plummer proposed two origins of thyrotoxicosis a diffuse hyperplasia responding to iodine intake, or alternatively arising in nodular goiter. In 1973, it was first suggested by Vidor et al. (1973) that pre-existing thyroid autonomy plays a crucial role in the pathogenesis of iodine-induced hyperthyroidism (IIH). 

It was demonstrated that thyroid autonomy due to toxic multinodular goiter accounts for up to 60% of all cases of thyrotoxicosis in iodine deficiency. In contrast, thyroid autonomy is rare in iodine-sufficient areas (3—10% of all cases of thyrotoxicosis) (Krohn et al., 2005 Laurberg etal., 1991, 1998). 

Thyroid Autonomy Activating mutations of the TSH receptor are the most common known molecular etiology of thyroid autonomy. They were found in up to 70% of toxic thyroid nodules (Krohn et al, 2005). 

Figure 92.3 The evolution of hyperthyroidism due to thyroid autonomy. The steady growth of the small autonomous areas will lead to progressive scintigraphic visibility, progressive TSH suppression, and finally hyperthyroidism with increased fT3 and fT4.

In Austria patients with hyperthyroidism, classified as autoimmune thyroid disorders or thyroid autonomy, were studied before and after increased iodine supply. Toxic multinodular goiter showed an increased incidence in females (30 0%) compared to males (20—30%), whereas... 

Amiodarone is mostly given in a daily dose of 200 mg. This dose contains about 7 mg iodine which amounts to 35-times the daily recommended dietary iodine supply. A healthy thyroid gland compensates this overdose of iodine (Wolff—Chaikoff effect). However, patients with (subclinical) thyroid autonomy (in a euthyroid goiter in an iodine-deficient region) or subclinical thyroid autoimmune disease are very susceptible to IIH because this autoregula-tory mechanism is disturbed. 

In patients with subclinical hyperthyroidism, longstanding goiter, subchnical thyroid autonomy and, in elderly patients, a prophylactic treatment with perchlorate is recommended. 

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