Toxic Multinodular Goiter

How to Cite This Chapter: Brito JP, Jarząb B, Płaczkiewicz-Jankowska E. Toxic Multinodular Goiter. McMaster Textbook of Internal Medicine. Kraków: Medycyna Praktyczna. Accessed November 27, 2020.
Last Updated: June 21, 2019
Last Reviewed: June 21, 2019
Chapter Information

Definition, Etiology, Pathogenesis Top

A toxic multinodular goiter (MNG) (MNG with functional autonomy) is the end stage of the development of MNG, often caused by iodine deficiency (Figure 5.6-9), in which nodules show autonomous secretion of thyroid hormones independent from thyroid-stimulating hormone (TSH) due to somatic mutations in the TSH receptor.

Clinical Features and Natural History Top

Hyperthyroidism usually develops very slowly (presentation of overt disease is preceded by a subtoxic MNG with subclinical hyperthyroidism [see Thyrotoxicosis]), but it may also occur suddenly after exposure to large doses of iodine, for instance, in the contrast media or drugs (amiodarone or certain disinfectants). Enlargement of the goiter or appearance of a nodule is frequently unnoticed by the patient. If the goiter is large, a sensation of neck compression may occur with dyspnea or much less commonly with dysphagia and cough.

Diagnosis Top

Diagnostic Tests

1. Hormone tests: Significantly decreased TSH secretion and significant elevation of serum concentrations of free thyroxine (FT4) and free triiodothyronine (FT3) (or FT3 only).

2. Imaging studies: Thyroid ultrasonography is used to measure goiter size and accurately assess the nodules. Thyroid radionuclide imaging is helpful in an accurate evaluation of the uptake of radioactive markers and identification of autonomously functioning nodules, which are the basis for the decision to start radioiodine therapy.

3. Cytology: For autonomously hyperfunctioning nodules observed on thyroid radionuclide imaging, fine-needle biopsy is not suggested due to the low risk of malignancy and increased risk of indeterminate results (see Thyrotoxicosis). For nonfunctioning nodules the indications for fine-needle biopsy are the same as in nontoxic MNG (see Nontoxic Multinodular Goiter). 

Diagnostic Criteria

A visible or palpable multinodular goiter of varying size (the key feature is the presence of ≥2 nodules >1 cm in diameter found on clinical examination or on ultrasonography) with concomitant hyperthyroidism.

Differential Diagnosis

Other causes of thyrotoxicosis (see Figure 5.6-2). Also see Graves Disease; see Toxic Thyroid Nodule.

Treatment Top

1. Pharmacologic treatment: Thionamides (see Thyrotoxicosis) reduce symptoms of hyperthyroidism (they should not be combined with levothyroxine), but their discontinuation invariably results in the recurrence of hyperthyroidism (after a period from several days to several months). Beta-blockers are used as in other cases of hyperthyroidism, but in toxic MNG higher doses than in Graves disease are often required because of the more severe cardiac symptoms.

2. Radical treatment is necessary, with either surgery (usually subtotal thyroidectomy) or radioiodine treatment. Treatment modality is individually selected in every patient (see Table 5.6-6).

1) Radioiodine treatment: Radiation sensitivity of autonomously functioning nodules is lower than in Graves disease (this must be considered when planning radioiodine treatment). Nonfunctioning nodules do not respond to treatment and most functioning nodules are only reduced in size and do not disappear; nevertheless, remission of hyperthyroidism is achieved (in approximately one-fourth of patients repeated radioiodine treatment is necessary after 6 months). Radioiodine treatment is usually selected for patients with small goiters and no features suggestive of malignancy and in patients with contraindications to surgery.

2) Surgical treatment is required in patients with nodules revealing cytologic or clinical features suggestive of malignancy. It should also be considered in patients with large goiters causing compression symptoms, particularly if nonfunctioning nodules are present.

Prognosis Top

Untreated toxic MNG increases the risk of arrhythmias, other cardiovascular complications, and thyrotoxic crisis (see Thyrotoxicosis and Hyperthyroidism). The risk of malignancy is the same as in other forms of nodular goiter.


Figure 5.6-9. Development of an autonomously functioning thyroid nodule.

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