toxic multinodular goitre

Symptoms of toxic multinodular goitre are similar to that of hyperthyroidism, including:

• heat intolerance
• muscle weakness/wasting
• hyperactivity
• fatigue
• tremor
• irritability
• weight loss
• osteoporosis
• increased appetite
• non-painful goitre (swelling of the thyroid gland)
• tachycardia (high heart rate - above 100 beats per minute at rest in adults)
• tracheal compression
• exophthalmos

Sequence of events:{{EMedicine|article|120497|Toxic Nodular Goiter}}

1. Iodine deficiency leading to decreased T4 production.
2. Induction of thyroid cell hyperplasia due to low levels of T4. This accounts for the multinodular goitre appearance.
3. Increased replication predisposes to a risk of mutation in the TSH receptor.
4. If the mutated TSH receptor is constitutively active, it would then become 'toxic' and produces excess T3/T4 leading to hyperthyroidism.

Hyperthyroidism is diagnosed by evaluating symptoms and physical exam findings, and by conducting laboratory tests to confirm the presence of excess thyroid hormones. It is characterized by high levels of thyroid hormone in the blood along with a low level of thyroid-stimulating hormone (TSH). After diagnosing hyperthyroidism, a thyroid scan can be performed to determine the functionality of the thyroid gland using radioactive iodine. This scan can identify toxic nodules, which appear as a single area of overactivity, as well as toxic multinodular goiter, which presents with multiple areas of overactivity. In addition, a thyroid ultrasound can be conducted to better evaluate the presence of thyroid nodules.{{Cite web |title=Toxic Nodule and Toxic Multinodular Goiter |url=https://www.thyroid.org/toxic-nodule-multinodular-goiter/ |access-date=2023-02-15 |website=American Thyroid Association |language=en-US}}

Fine-needle aspiration for cytology is generally not indicated in an autonomously functioning thyroid nodule, as the risk of malignancy is low, and it is generally difficult to distinguishing between a benign lesion and a malignant lesion in such specimens.{{cite web| last=Orlander | first=Philip R|url=https://emedicine.medscape.com/article/120497-workup?form=fpf#c6|title=Toxic Nodular Goiter Workup |website=Medscape}} Updated: Oct 25, 2021 If thyroidectomy is performed, histopathology can corroborate the diagnosis. Toxic multinodular goiter more or less corresponds to diffuse or multinodular hyperplasia of the thyroid (Grave's disease also shows hyperplasia, but typically more prominent thickening of follicular linings):

File:Histopathology of diffuse thyroid hyperplasia with variably sized follicles.jpg|Diffuse thyroid hyperplasia typically shows variably sized follicles

File:Histopathology of thyroid hyperplasia with a nodule.jpg|Thyroid hyperplasia with a hyperplastic nodule. It characteristically has no capsule (distinguishing it from thyroid adenoma or carcinoma).

File:Diffuse Thyroid Hyperplasia (3334012426).jpg|The follicular linings may be thickened, with papillary projections (but lack nuclear features of papillary thyroid carcinoma)

File:Histopathology of thyroid hyperplasia with flattened epithelium.jpg|The epithelium may also be flattened by enlarged follicles.

File:Histopathology of diffuse hypercellular hyperplastic focus of thyroid, low magnification.jpg|It can show hypercellular or microfollicular areas. There is no surrounding capsule (in contrast, a thyroid follicular adenoma or carcinoma is generally encapsulated).

File:Histopathology of diffuse hypercellular hyperplastic focus of thyroid, high magnification.jpg|As shown in these microfollicles, it can have mildly enlarged nuclei with mildly clumped chromatin, and clear cytoplasms, but cellular characteristics of papillary thyroid carcinoma are absent.

File:Histopathology of thyroid hyperplasia with a Sanderson polster.jpg|Thyroid hyperplasia with a Sanderson polster, which is a group of small follicles that protrude into the lumen of a larger follicle. It should not be confused for papillary projections.

File:Histopathology of degenerative changes in thyroid hyperplasia.png|Various forms of degeneration are typically seen, with various forms pictured.

Toxic multinodular goiter can be treated with antithyroid medications such as propylthiouracil or methimazole, radioactive iodine, or with surgery. Another treatment option is injection of ethanol into the nodules.{{cite book|editor1= J. Larry Jameson |editor2=Leslie J. De Groot |editor3= David de Kretser |display-editors=etal|title=Endocrinology: adult and pediatric|date=2010|publisher=Saunders/Elsevier|location=Philadelphia|isbn=9781416055839|page=Chapter 82|edition=6th|url=https://www.inkling.com/read/endocrinology-jameson-de-groot-6th/chapter-82/chapter082-reader-1}}

A Cochrane review compared treatments using recombinant human thyrotropin-aided radioactive iodine to radioactive iodine alone.{{Cite journal |last=Huo |first=Yanlei |last2=Xie |first2=Jiawei |last3=Chen |first3=Suyun |last4=Wang |first4=Hui |last5=Ma |first5=Chao |date=2021-12-28 |editor-last=Cochrane Metabolic and Endocrine Disorders Group |title=Recombinant human thyrotropin (rhTSH)-aided radioiodine treatment for non-toxic multinodular goitre |url=http://doi.wiley.com/10.1002/14651858.CD010622.pub2 |journal=Cochrane Database of Systematic Reviews |language=en |volume=2021 |issue=12 |doi=10.1002/14651858.CD010622.pub2 |pmc=8712889 |pmid=34961921}} In this review it was found that the recombinant human thyrotropin-aided radioactive iodine appeared to lead to a greater of thyroid volume at the increased risk of hypothyroidism. No conclusive data on changes in quality of life with either treatments were found.

The usage of terminology for types of goiter has varied over the past century. Physicians and surgeons tend to differentiate among solitary-nodule goiter, multinodular goiter, and non-nodular goiter more thoroughly in recent decades than they formerly did. Thus some sources have described, or still describe, thyroid adenoma (toxic adenoma) as synonymous with toxic multinodular goiter,{{Citation |author=Elsevier |author-link=Elsevier |title=Dorland's Illustrated Medical Dictionary |publisher=Elsevier |url=http://dorlands.com/ |postscript=.}} but other sources differentiate those two as single-nodule disease versus multinodular disease (respectively) with pathogenesis that is likely differing in most cases (e.g., single neoplastic cell clone versus multifocal or diffuse molecular metabolic change). The medical eponyms "Plummer disease" (named after American physician Henry Stanley Plummer{{WhoNamedIt2|synd|1094|Plummer's disease}} eponymously named after {{WhoNamedIt|doctor|1074|Henry Stanley Plummer}}) and "Parry disease" (named after English physician Caleb Hillier Parry) have been used to refer to toxic multinodular goiter, toxic adenoma, and toxic diffuse goiter (Graves' disease); the specific entity in each patient/case is not always clear retrospectively, especially in older literature. This is logical given that advanced medical imaging that can show what is happening at various places within a thyroid gland inside a living person (such as nuclear medicine imaging of radioiodine tracer uptake) was not available until after the 1940s.{{citation needed|date=August 2020}}

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{{Medical resources

| DiseasesDB = 13184

| ICD10 = {{ICD10|E|05|2|e|00}}

| ICD9 = {{ICD9|242.3}}

| ICDO =

| OMIM =

| MedlinePlus = 000317

| eMedicineSubj = med

| eMedicineTopic = 920

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{{Thyroid disease}}

Category:Thyroid disease