Multinodular goiter

Graves disease Hot nodule and toxic multinodular goiter Etiology ... 

Fuhrer D, Krohn K, Paschke R (2005) Toxic Adenoma and toxic Multinodular Goiter. In Braverman, LE Utiger (Hrsg.) RD (eds) Lippincott Williams Wilkins, ISBN 0-7817-5047-4, The Thyroid, 508-518... 

Hyperthyroidism (thyrotoxicosis), defined as excessive thyroid activity, causes a state of thyroid hormone excess (thyrotoxicosis) characterized by an increased metabolic rate, increase in body temperature, sweating, tachycardia, tremor, nervousness, increased appetite and loss of weight. Common causes of hyperthyroidism are toxic multinodular goiter, toxic adenoma or diffuse toxic goitre ( Graves disease). Antithyroid diugs (methimazol, carbimazole, propylthiouracil) block thyroid hormone production and are hence suitable for the treatment of hyperthyroidism. 

The common causes of thyrotoxicosis are shown in Table 41-6.29,30 Thyrotoxicosis can be related to the presence or absence of excess hormone production (hyperthyroidism). Graves disease is the most common cause of hyperthyroidism. Thyrotoxicosis in the elderly is more likely due to toxic thyroid nodules or multinodular goiter than to Graves disease. Excessive intake of thyroid hormone may be due to overtreatment with prescribed therapy. Surreptitious use of thyroid hormones also may occur, especially in health professionals or as a self-remedy for obesity. Thyroid hormones can be obtained easily without a prescription from health food stores or Internet sources. 

Primary hyperthyroidism Graves disease Toxic multinodular goiter... 

In multinodular goiters (Plummer s disease), follicles with a high degree of autonomous function coexist with normal or even nonfunctioning follicles. Thyrotoxicosis occurs when the autonomous follicles generate more thyroid hormone than is required. 

In multinodular goiters, a thyroid scan shows patchy areas of autonomously functioning thyroid tissue. 

RAI is the agent of choice for Graves disease, toxic autonomous nodules, and toxic multinodular goiters. Pregnancy is an absolute contraindication to the use of RAI. 

Gabriel, E. M., Bergert, E. R., Grant, C. S., van Heerden, J. A., Thompson, G. B., and Morris, J. C. (1999) GermUne polymorphism of codon 727 of human thyroid-stimulating hormone receptor is associated with toxic multinodular goiter. J. Clin. Endocrinol. Metab. 84, 3328-3335. 

Tonacchera, M., Agretti, P., Chiovato, L., et al. (2000) Activating thyrotropin receptor mutations are present in nonadenomatous hyperfunctioning nodules of toxic or autonomous multinodular goiter. J. Clin. Endocrinol. Metab. 85, 2270-2274. 

Pituitary TSH suppressants In the treatment or prevention of various types of euthyroid goiters, including thyroid nodules, subacute, or chronic lymphocytic thyroiditis (Hashimoto), multinodular goiter, and in the management of thyroid cancer (except liothyronine). 

In the treatment of benign nodules and nontoxic multinodular goiter, TSH generally is suppressed to a higher target (eg, 0.1 to 0.5 or 1 milliunits/L). 

III.b.1.6. Radioactive iodine. Radioactive iodine (Iodine-131) is a radioactive isotope of iodine, usually taken in an oral solution formulation as sodium 1. Given orally as sodium I, radioactive iodine is rapidly absorbed, concentrated and stored in the thyroid follicles. The therapeutic effect depends on beta-ray emission and destruction of thyroid parenchyma manifests some weeks after treatment. It is relatively safe, cheap, painless and avoids side effects associated with surgery. It is widely regarded as the treatment of choice in adults with toxic multinodular goiter, toxic nodule and people who relapse after a course of antithyroid medication. 

The manifestations of hyperthyroidism depend on the severity of the disease, the age of the patient, the presence or absence of extrathyroidal manifestations, and the specific disorder producing the thyrotoxicosis. Of the various types of hyperthyroidism, only two are common Graves disease and toxic multinodular goiter. Less common causes include toxic adenoma and postpartum thyroiditis, among others. 

In older patients toxic multinodular goiter typically presents as longstanding asymptomatic multinodular goiters. Functional autonomy of the nodules develops over time by an unknown mechanism and causes the disease to move from the nontoxic to the toxic phase. The onset of hyperthyroidism is gradual, and the symptoms are usually milder than those of Graves disease. 

Thyrotoxic crisis, thyroid storm, or accelerated hyperthyroidism is an extreme accentuation of thyrotoxicosis. Although uncommon, this serious complication of hyperthyroidism usually occurs in association with Grave s disease and occasionally with toxic multinodular goiter. 

The thyroid gland also regulates its uptake of iodide and thyroid hormone synthesis by intrathyroidal mechanisms that are independent of TSH. These mechanisms are primarily related to the level of iodine in the blood. Large doses of iodine inhibit iodide organification (Wolff-Chaikoff block, see Figure 38-1). In certain disease states (eg, Hashimoto s thyroiditis), this can inhibit thyroid hormone synthesis and result in hypothyroidism. Hyperthyroidism can result from the loss of the Wolff-Chaikoff block in susceptible individuals (eg, multinodular goiter). 

TOXIC UNINODULAR GOITER TOXIC MULTINODULAR GOITER... 

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

Toxic Uninodular Goiter Toxic Multinodular Goiter... 

Toxic multinodular goiter Constitutive activation of adenylyl cyclase [31]... 

In humans, hyperthyroidism, for example, can result from mutations located in the TSHR TM domains that activate the receptor. By contrast, thyroid adenomas and multinodular goiter [24-30] result from many somatic mutations affecting other regions of the TSHR. Such an example is a constitutively active TSHR mutation in the first TM domain that results from a Gly substitution at the conserved 431Ser position [27]. 

Germline polymorphism of codon 727 of human thyroid-stimulating hormone receptor is associated with toxic multinodular goiter. J Clin Endocrinol Metab 84 3328-3335... 

Thyroid disorders. Disturbances in thyroid metabolism can occur at any level of the hypothalams-pituitary-thyroid-peripheral tissue axis. Several of these disorders have been discussed previously. Hyperthyroidism is more prevalent in women than men. The three most common causes of hyperthyroidism are Graves hyperthyroidism, toxic multinodular goiter, and toxic adenoma. The clinical features of hyperthyroidism include hyperkinesis, weight loss, cardiac anomalies (e.g., atrial fibrillation), fatigue, weakness, sweating, palpitations, and nervousness. The typical biochemical laboratory parameters are increased serum free T4 and decreased serum TSH. 

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