Toxic multinodular goiter

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief:

In 1913, Henry Plummer, an American physician was the first to describe toxic multinodular goiter or Plummer’s disease. In 1947, Cope, Rawson, and McArthur were the first who described the usage of radioactive iodine to demonstrate a “hot” thyroid nodule.Toxic multinodular goiter is classified into three types- Primary, secondary, tertiary hyperthyroidism.The progression to Toxic multinodular goiter usually involves the somatic gain-of-function mutations in the TSH receptor in autonomousl, toxic adenoma.The incidence of toxic multinodular goiter is estimated to be 4.8 cases per 100,000 population per year. The prevalence of toxic multinodular goiter is 100 cases per 100,000 population and accounts for 5% of all patients with hyperthyroidism. Toxic multinodular goiter commonly affects individuals older than 60 years of age. The frequency of toxic multinodular goiter increases with age. Females are more commonly affected by toxic multinodular goiter than men. Common risk factors in the development of multinodular goiter include female sex,age over 50 years,areas with decreased iodine intake, iodine supplementation, natural goitrogens, vitamin A and iron deficiency,selenium deficiency.Toxic multinodular goiter is diagnosed with a physical examination which shows nodules in the throat and rapid heart rate, among other signs such as diaphoresis and tremors. Blood screening includes tests for elevated T3 and T4 hormone levels that indicate hyperthyroidism. TSH assays are the best initial screening tool for hyperthyroidism.If left untreated, toxic multinodular goiter may progress to develop hyperthyroidism. However, the progression of toxic multinodular goiter is quite slow. Untreated patients initially have a history of thyroid enlargement followed by a long period of subclinical hyperthyroidism. Overt hyperthyroidism occurs late in the course of toxic multinodular goiter. Common complications of toxic multinodular goiter include tachycardia, arrhythmia, atrial fibrillation, heart failure (dilated cardiomyopathy), pulmonary hypertension, facial plethora, inspiratory stridor, hoarseness, dysphagia, bone mineral loss and thyroid storm. Prognosis of toxic multinodular goiter is generally good with treatment. Both surgery and radioactive iodine therapy can confer a moderate long-term risk of hypothyroidism and such patients require lifelong hormone replacement therapy. Toxic multinodular goiter is commonly seen in elderly. The majority of patients with toxic multinodular goiter are asymptomatic. However, they can present with symptoms such as swelling or pain in front of the neck, cough, shortness of breath, hoarseness, Diaphoresis, skin flushing, increased appetite, restlessness, nervousness, [[[heat intolerance]], tremors, palpitations, insomnia, anxiety, menstrual irregularities. Diagnosis of multinodular goiter is made by measurement of serum thyroid-stimulating hormone (TSH) , serum Free T4 test , total thyroxine (T4) and free triiodothyronine (T3).An ECG may be helpful in the diagnosis of hyperthyroidism due to toxic multinodular goiter. Findings on an ECG suggestive of hyperthyroidism due to include sinus tachycardia, higher voltage of P and T waves, elevated amplitude of QRS complex, prolonged P-Q and shortened Q-T intervals. Findings on an x-ray suggestive of multinodular goiter include anterior/superior mediastinal mass, that may be associated with deviation of the trachea and/or cervicothoracic sign.CT scan may be helpful in the diagnosis and fully characterizing the extent of substernal goitre. Findings on CT scan suggestive of multinodular goiter include enlarged and heterogeneous thyroid gland. CT scan is useful in defining the extent of tracheal deviation and compression.CT scan–guided fine needle aspiration biopsy(FNAB) may be helpful. MRI may be helpful in the assessment of extent of substernal goiters. Findings on MRI suggestive of multinodular goiter include enlarged and heterogeneous thyroid gland. Thyroid ultrasonography is the imaging method of choice in the diagnosis of multinodular goiter. Findings on an ultrasonography suggestive of multinodular goiter include more than one nodule including the non-palpable nodules cysts with varying echogenicity. Thyroid ultrasonography helps in assessment of size and number of nodules. Assessment of vascular characteristics of a thyroid nodule with Doppler helps in screening thyroid nodules for malignancy. Radioidodine uptake may be helpful in the diagnosis of multinodular goiter. The mainstay of treatment for Toxic multinodular goiter is Surgery. Patients with symptomatic hyperthyroidism, sub-clinical hyperthyroid patients with expected compilations and patients refusing surgical therapy are treated with beta blockers and anti-thyroid pharmacological groups. Surgery is the mainstay of treatment for Toxic multinodular goiter. Usually, subtotal thyroidectomy is performed but unilateral thyroid lobectomy can also be performed in selected cases. Effective measures for the primary prevention of toxic multinodular goiter include mainly the adequate iodine intake, smoking cessation and also by maintaining normal intake of iron and vitamin A.

In the year 40 BC, Pliny, Vitruvius, and Juvenal were the first who documented the prevalence of goiter in the Alps. In 1500, Leonardo da Vinci was the first who recognized and drew the thyroid gland. In 1913, Henry Plummer, an American physician was the first to describe toxic multinodular goiter also known as Plummer’s disease. In 1947, Cope, Rawson, and McArthur were the first who described the usage of radioactive iodine to demonstrate a “hot” thyroid nodule.

Toxic multinodular goiter is classified into three types namely primary, secondary and tertiary hyperthyroidism. Primary hyperthyroidism is further divided into grave’s disease, toxic thyroid nodule, thyroid adenoma, multinodular goiter. Secondary hyperthyroidism is divided into pituitary adenoma, intracranial tumors pressing pituitary gland. Tertiary hyperthyroidism is divided into intracranial tumors or masses involving hypothalamus.

The progression to toxic multinodular goiter usually involves the somatic gain-of-function mutations in the TSH receptor in autonomously functioning thyroid nodules.

The progression to Toxic multinodular goiter usually involves the somatic gain-of-function mutations in the TSH receptor gene.

Toxic multinodular goiter may be differentiated from other thyroid disorders. The most common differentials include grave’s disease, thyrotoxic phase of subacute thyroiditis and toxic adenoma.

The incidence of toxic multinodular goiter is estimated to be 4.8 cases per 100,000 population per year. The prevalence of toxic multinodular goiter is 100 cases per 100,000 population and accounts for 5% of all patients with hyperthyroidism. Toxic multinodular goiter commonly affects individuals older than 60 years of age. The frequency of toxic multinodular goiter increases with age. Females are more commonly affected by toxic multinodular goiter than men.

Common risk factors in the development of multinodular goiter include female sex,age over 50 years,areas with decreased iodine intake,iodine supplementation, natural goitrogens, vitamin A deficiency, iron deficiency and selenium deficiency.

Toxic multinodular goiter is diagnosed by a physical examination which reveals nodules in the throat, rapid heart rate, diaphoresis, and tremors. Screening includes testing for elevated T3 and T4 hormone levels that indicate hyperthyroidism. TSH assays are the best initial screening tool for hyperthyroidism.

If left untreated, toxic multinodular goiter may progress to develop hyperthyroidism. However, the progression of toxic multinodular goiter is quite slow. Untreated patients initially have a history of thyroid enlargement followed by a long period of subclinical hyperthyroidism. Overt hyperthyroidism occurs late in the course of toxic multinodular goiter. Common complications of toxic multinodular goiter include tachycardia, arrhythmia, atrial fibrillation, heart failure (dilated cardiomyopathy), pulmonary hypertension, facial plethora, inspiratory stridor, hoarseness, dysphagia, bone mineral loss and thyroid storm. Prognosis of toxic multinodular goiter is generally good with treatment. Both surgery and radioactive iodine therapy can confer a moderate long-term risk of hypothyroidism and such patients require lifelong hormone replacement therapy. Toxic multinodular goiter is commonly seen in elderly. Therefore, in elderly, presence of other conditions may influence the outcome of toxic multinodular goiter.

The majority of patients with toxic multinodular goiter are asymptomatic. However, they can present with symptoms such as swelling or pain in front of the neck, cough, shortness of breath, hoarseness, diaphoresis, skin flushing, increased appetite, restlessness, nervousness, heat intolerance, tremors, palpitations, insomnia, anxiety, menstrual irregularities.

The clinical features of toxic multinodular hyperthyroidism includes flushing,diaphoresis, smooth skin, onycholysis, hyperpigmentation, thinning of the hair, thyromegaly,lymphadenopathy, lid lag, shortness of breath on exertion, hypoxemia, hypercapnia, tachycardia, atrial fibrillation, weight loss, increased appetite anorexia, dysphagia, increased urinary frequency, enuresis, gynecomastia, reduced libido, erectile dysfunction, psychosis, agitation, and depression,anxiety, restlessness, irritability, and emotional lability, insomnia, confusion, poor orientation and immediate recall, amnesia, and constructional difficulties, peripheral neuropathy, carpal tunnel syndrome, tremors, myopathy, muscle weakness, proximal and distal weakness, deep tendon reflexes are usually normal or increased, osteoporosis and an increased fracture probability.

Diagnosis of multinodular goiter is made by measurement of serum thyroid-stimulating hormone (TSH) , serum Free T4 test , total thyroxine (T4) and free triiodothyronine (T3).

An ECG may be helpful in the diagnosis of hyperthyroidism due to toxic multinodular goiter. Findings on an ECG suggestive of hyperthyroidism due to toxic multinodular goiter include sinus tachycardia, higher voltage of P and T waves, elevated amplitude of QRS complex, prolonged P-Q and shortened Q-T intervals.

An x-ray may be helpful in the diagnosis of multinodular goiter. Findings on an x-ray suggestive of multinodular goiter include anterior/superior mediastinal mass, that may be associated with deviation of the trachea and/or cervicothoracic sign.

CT scan may be helpful in the diagnosis and fully characterizing the extent of substernal goitre. Findings on CT scan suggestive of multinodular goiter include enlarged and heterogeneous thyroid gland.CT scan is useful in defining the extent of tracheal deviation and compression.CT scan–guided fine needle aspiration biopsy(FNAB) may be helpful.

MRI is not routinely performed for the diagnosis of multinodular goiter. MRI can help in the assessment of extent of substernal goiters.Findings on MRI suggestive of multinodular goiter include enlarged and heterogeneous thyroid gland.

Thyroid ultrasonography is the imaging method of choice in the diagnosis of multinodular goiter. Findings on an ultrasonography suggestive of multinodular goiter include more than one nodule including the non-palpable nodules cysts with varying echogenicity. Thyroid ultrasonography helps in assessment of size and number of nodules.Assessment of vascular characteristics of a thyroid nodule with Doppler helps in screening thyroid nodules for malignancy.

Radioidodine uptake may be helpful in the diagnosis of multinodular goiter. Patchy pattern of increased radionuclide uptake in more than one nodule associated with decreased uptake in the surrounding extranodular thyroid tissue is characteristic of toxic multinodular goiter.

The most important diagnostic test to differentiate thyroid nodules from each other is fine needle aspiration (FNA).

The mainstay of treatment for Toxic multinodular goiter is Surgery. Patients with symptomatic hyperthyroidism, sub-clinical hyperthyroid patients with expected compilations and patients refusing surgical therapy are treated with beta blockers and anti-thyroid pharmacological groups.

Surgery is the mainstay of treatment for Toxic multinodular goiter. Almost all multinodular goiters can be surgically removed through a collar incision. Usually, subtotal thyroidectomy is performed but unilateral thyroid lobectomy can also be performed in selected cases.

Effective measures for the primary prevention of toxic multinodular goiter include mainly the adequate iodine intake, smoking cessation and also by maintaining normal intake of iron and vitamin A.

Surgery is recommended for the secondary prevention of toxic multinodular goiter.

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Akshun Kalia M.B.B.S.[2]

In the year 40 BC, Pliny, Vitruvius, and Juvenal were the first who documented the prevalence of goiter in the Alps. In 1500, Leonardo da Vinci was the first who recognized and drew the thyroid gland. In 1913, Henry Plummer, an American physician was the first to describe toxic multinodular goiter or Plummer’s disease. In 1947, Cope, Rawson, and McArthur were the first who described the usage of radioactive iodine to demonstrate a “hot” thyroid nodule.

The historical perspective of toxic multinodular goiter is as below:^[1][2][3]

• In 40 BC, Pliny, Vitruvius, and Juvenal were the first who documented the prevalence of goiter in the Alps.
• In 138, Soranus, a Greek physician, reported a case of neck swelling following pregnancy.
• In 1500, Leonardo da Vinci was the first who recognized and drew the thyroid gland.
• In 1543, Andreas Vesalius, Belgian physician was the first to provide anatomic description and illustration of the thyroid gland in his article ‘De humani corporis Fabrica libri septem’.
• In 1563, Eustachius was the first who introduced the term “isthmus” to describe tissue connecting the two lobes of the thyroid gland.
• In 1834, Robert Graves was the first who described a syndrome of palpitation, goiter, and exophthalmos.
• In 1913, Henry Plummer, an American physician was the first to describe toxic multinodular goiter or Plummer’s disease.
• In 1936, Dr. Saul Hertz was the first who described the usage of radioactive iodine for the study of the thyroid gland.
• In 1947, Cope, Rawson, and McArthur were the first who described the usage of radioactive iodine to demonstrate a “hot” thyroid nodule.
• In 1948, T. Templa, J. Aleksandrowicz, and M. Till were the first who described the usage of fine needle thyroid biopsy as a diagnostic method for thyroid nodules.

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief:

There is no established system for the classification of toxic multinodular goiter.

There is no established system for the classification of toxic multinodular goiter.

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Sunny Kumar MD [2]

The progression to Toxic multinodular goiter usually involves the somatic gain-of-function mutations in the TSH receptor gene.

The causes of toxic multinodular goiter are as follows:^[1][2][3][4]

• The development of multi-nodular goiter is the result of multiple genetic base substitution mutations on exon 10 of chromosome 14q31.

Frequency of mutation	TSHr gene codon	base substitution	amino acid change
Common	486	ATC/ATG	Ile/Met
Common	632	ACC/ATC	Thr/Ile
Less common	619	GAT/GGT	Asp/Gly
Less common	623	GCC/GTC	Ala/Val
Less common	629	TTG/TTT	Leu/Phe
Less common	630	ATC/CTC	Ile/Leu
Less common	633	GAC/GAG	Asp/Glu
Less common	639	CCA/TCA	Pro/Ser

Cardiovascular	No underlying causes
Chemical/Poisoning	No underlying causes
Dental	No underlying causes
Dermatologic	No underlying causes
Drug Side Effect	No underlying causes
Ear Nose Throat	No underlying causes
Endocrine	No underlying causes
Environmental	No underlying causes
Gastroenterologic	No underlying causes
Genetic	The development of multi-nodular goiter is the result of multiple genetic base substitution mutations on exon 10 of chromosome 14q31.
Hematologic	No underlying causes
Iatrogenic	No underlying causes
Infectious Disease	No underlying causes
Musculoskeletal/Orthopedic	No underlying causes
Neurologic	No underlying causes
Nutritional/Metabolic	No underlying causes
Obstetric/Gynecologic	No underlying causes
Oncologic	No underlying causes
Ophthalmologic	No underlying causes
Overdose/Toxicity	No underlying causes
Psychiatric	No underlying causes
Pulmonary	No underlying causes
Renal/Electrolyte	No underlying causes
Rheumatology/Immunology/Allergy	No underlying causes
Sexual	No underlying causes
Trauma	No underlying causes
Urologic	No underlying causes
Miscellaneous	No underlying causes

List the causes of the disease in alphabetical order.

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Aravind Reddy Kothagadi M.B.B.S[2]

Toxic multinodular goiter must be differentiated from other thyroid disorders. The most common differentials include Grave’s disease, thyrotoxic phase of subacute thyroiditis and toxic adenoma.

Toxic multinodular goiter may be differentiated from other thyroid disorders as follows:

Functional (Nuclear) Imaging for Thyrotoxicosis
Diagnosis	Degree of Thyrotoxicosis	Radioactive iodine Uptake	Scintigraphy Image
Toxic multinodular goiter	+/++	Normal or +/++	Enlarged gland with multiple “hot” or “cold” nodules
Grave’s disease	++++	++++	Enlarged gland with homogenous uptake
Thyrotoxic phase of subacute thyroiditis	++++	<1% at 4 or 24 hr.	Absent isotope uptake
Toxic adenoma	+/++	Normal or +/++	Dominant “hot” nodule with low or absent uptake in the surrounding normal gland.

Cause of thyrotoxicosis	TSH receptor antibodies	Thyroid US	Color flow Doppler	Radioactive iodine uptake/Scan	Other features
Toxic nodular goiter	–	Multiple nodules	–	Hot nodules at thyroid scan	–
Graves’ disease	+	Hypoechoic pattern	↑	↑	Ophthalmopathy, dermopathy, acropachy
Toxic adenoma	–	Single nodule	–	Hot nodule	–
Subacute thyroiditis	–	Heterogeneous hypoechoic areas	Reduced/absent flow	↓	Neck pain, fever, and elevated inflammatory index
Painless thyroiditis	–	Hypoechoic pattern	Reduced/absent flow	↓	–
Amiodarone induced thyroiditis-Type 1	–	Diffuse or nodular goiter	↓/Normal/↑	↓ but higher than in Type 2	High urinary iodine
Amiodarone induced thyroiditis-Type 2	–	Normal	Absent	↓/absent	High urinary iodine
Central hyperthyroidism	–	Diffuse or nodular goiter	Normal/↑	↑	Inappropriately normal or high TSH
Trophoblastic disease	–	Diffuse or nodular goiter	Normal/↑	↑	–
Factitious thyrotoxicosis	–	Variable	Reduced/absent flow	↓	↓ Serum thyroglobulin
Struma ovarii	–	Variable	Reduced/absent flow	↓	Abdominal RAIU

Disease		Findings
Toxic adenoma and toxic multinodular goiter		Toxic adenoma and toxic multinodular goiter are results of focal/diffuse hyperplasia of thyroid follicular cells independent of TSH regulation. Findings of single or multiple nodules are seen on physical examination or thyroid scan.[1]
Thyroiditis	Direct chemical toxicity with inflammation	Amiodarone, sunitinib, pazopanib, axitinib, and other tyrosine kinase inhibitors may also be associated with a destructive thyroiditis.[2][3]
	Radiation thyroiditis	Patients treated with radioiodine may develop thyroid pain and tenderness 5 to 10 days later, due to radiation-induced injury and necrosis of thyroid follicular cells and associated inflammation.
	Drugs that interfere with the immune system	Interferon-alfa is a well-known cause of thyroid abnormality. It mostly leads to the development of de novo antithyroid antibodies.[4]
	Lithium	Patients treated with lithium are at a high risk of developing painless thyroiditis and Graves’ disease.
	Palpation thyroiditis	Manipulation of the thyroid gland during thyroid biopsy or neck surgery and vigorous palpation during the physical examination may cause transient hyperthyroidism.
Exogenous and ectopic hyperthyroidism	Factitious ingestion of thyroid hormone	The diagnosis is based on the clinical features, laboratory findings, and 24-hour radioiodine uptake.[5]
	Acute hyperthyroidism from a levothyroxine overdose	The diagnosis is based on the clinical features, laboratory findings, and 24-hour radioiodine uptake.[6]
	Struma ovarii	Functioning thyroid tissue is present in an ovarian neoplasm.
	Functional thyroid cancer metastases	Large bony metastases from widely metastatic follicular thyroid cancer cause symptomatic hyperthyroidism.
Hashitoxicosis		It is an autoimmune thyroid disease that initially presents with hyperthyroidism and a high radioiodine uptake caused by TSH-receptor antibodies similar to Graves’ disease. It is then followed by the development of hypothyroidism due to the infiltration of the thyroid gland with lymphocytes and the resultant autoimmune-mediated destruction of thyroid tissue, similar to chronic lymphocytic thyroiditis.[7]
Iodine-induced hyperthyroidism		It is uncommon but can develop after an iodine load, such as administration of contrast agents used for angiography or computed tomography (CT), or iodine-rich drugs such as amiodarone.
Trophoblastic disease and germ cell tumors		Thyroid-stimulating hormone and HCG have a common alpha-subunit and a beta-subunit with considerable homology. As a result, HCG has weak thyroid-stimulating activity and high titer HCG may mimic hyperthyroidism.[8]

Disease	Findings
Multinodular goiter	Multinodular goiter is the multinodular enlargement of the thyroid gland. They are large nodules of more than 1 cm that produces symptoms of hyperthyroidism.
Grave’s disease	Grave’s disease is an autoimmune disease that affects the thyroid. It frequently results in hyperthyroidism and an enlarged thyroid. Pretibial myxedema and ophthalmopathy are some of the findings of grave’s disease.
Hashimoto’s disease	Hashimoto’s disease is an autoimmune disease in which the thyroid gland is attacked by a variety of cell-mediated and antibody-mediated immune processes, causing primary hypothyroidism.
Medullary thyroid carcinoma	Medullary thyroid carcinoma is a form of thyroid carcinoma which originates from the parafollicular cells (C cells), which produce the hormone calcitonin.
Thyroid lymphoma	Thyroid lymphoma is a rare malignant tumor which manifests as rapidly enlarging neck mass causing respiratory difficulty.
De Quervain’s thyroiditis	De Quervain’s thyroiditis is a subacute granulomatous thyroiditis preceded by an upper respiratory tract infection.
Acute suppurative thyroiditis	Acute suppurative thyroiditis is an uncommon thyroid disorder usually caused by bacterial infection.

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief:

The incidence of toxic multinodular goiter is estimated to be 4.8 cases per 100,000 population per year. The prevalence of toxic multinodular goiter is 100 cases per 100,000 population and accounts for 5% of all patients with hyperthyroidism. Toxic multinodular goiter commonly affects individuals older than 60 years of age. The frequency of toxic multinodular goiter increases with age. Females are more commonly affected by toxic multinodular goiter than men.

The epidemiology and demographics of toxic multinodular goiter is as below:^{[1][2][3][4][5][6]}

• The incidence of toxic multinodular goiter is estimated to be 4.8 cases per 100,000 population per year.

• The prevalence of toxic multinodular goiter is 100 cases per 100,000 population and accounts for 5% of all patients with hyperthyroidism.
• The prevalence of toxic adenomas in United States was estimated to be 1.6% of 2,846 thyrotoxic patients in a research done in Cleveland. In other words, the prevalence of toxic adenomas in United States is 1,580 cases per 100,000 population.

• Toxic multinodular goiter commonly affects individuals older than 60 years of age.
• Hyperthyroidism associated with an autonomous nodule occurred in 57% of patients aged more than 60 years, whereas 13% of those younger than 60 years were hyperthyroid.
• Toxic multinodular goiter frequency increases with age.

• Females are more commonly affected by toxic multinodular goiter than men.
• The female to male ratio is 4:1 for toxic multinodular goiter.

• Toxic multinodular goiter is a common disease that tends to affect African nations.
• In developed nations, European countries tend to have a higher prevalence of toxic multinodular goiter as compared to the United States.
  • Toxic multinodular goiter is less common in United States. This can be attributed to iodination of table salt.
  • Moreover in United States the intake of iodised salt (200 to 600 μg/day) is almost double in quantity as compared to European nations (25 to 100 μg/day).

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Mazia Fatima, MBBS [2]

Common risk factors in the development of multinodular goiter include female sex, age over 50 years, areas with decreased iodine intake, iodine supplementation, natural goitrogens, vitamin A deficiency, iron deficiency and selenium deficiency.

• Common risk factors in the development of multinodular goiter include:
  • Female sex
  • Age over 50 years
  • Smoking^[1]
  • Areas with decreased iodine intake^[2]
• Natural goitrogens associated with the development of multinodular goiter include:^[3]
  • Millet, soy beans, coconut, babassu contain flavonoids that impair thyroperoxidase enzyme.
  • Cassava, sweet potato, sorghum contain cyanogenic glucosides metabolized to thiocyanates that inhibits thyroid iodine uptake.
  • Cabbage, cauliflower, broccoli, turnips contain glucosinolates that impair thyroid iodine uptake.
  • Seaweed (kelp) contains excess iodine that inhibits release of thyroid hormones.
• Vitamin A and iron deficiency increases TSH stimulation and reduces heme-dependent thyroperoxidase activity.
• Selenium deficiency accumulates peroxidase and causes deiodinase deficiency resulting in impaired thyroid hormone synthesis.
• Head or neck irradiation in an adult is associated with increased frequency of toxic nodular goiter.
• Iodine supplementation or iodinated contrast agents or iodinated drugs, such as amiodarone, may also induce hyperthyroidism in patients with underlying nontoxic multinodular goiter (Jod-Basedow effect).^[4]

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Aravind Reddy Kothagadi M.B.B.S[2]

Toxic multinodular goiter is diagnosed by a physical examination which reveals nodules in the throat, rapid heart rate, diaphoresis, and tremors. Screening includes testing for elevated T3 and T4 hormone levels that indicate hyperthyroidism. TSH assays are the best initial screening tool for hyperthyroidism.

The screening for toxic multinodular goiter are as follows:^[1][2][3][4]

• Toxic multinodular goiter is diagnosed by a physical examination which reveals nodules in the throat, rapid heart rate, diaphoresis, and tremors.
• Screening includes testing for elevated T3 and T4 hormone levels that indicate hyperthyroidism.
• TSH assays are the best initial screening tool for hyperthyroidism. Patients with TNG will have suppressed TSH levels.
• Low levels of thyroid-stimulating hormone (TSH) are suggestive of hyperthyroidism
• An isolated increase in T4 is observed in iodine-induced hyperthyroidism or patients taking propranolol, corticosteroids, radiocontrast agents, amiodarone.
• 5-46% of patients with toxic nodules have normal free T4 levels with an elevated T3, this is called T3 toxicosis.
• Overactive nodules are found on ultrasound scans of the thyroid to create images of the thyroid, which can reveal the conjunction with a special radioactive iodine test that involves swallowing a pill prior to special scans.
• The normal range for total T3 and T4 levels may vary for each and every individual; especially in case of people with nonthyroidal illness with decreased T3 levels.

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Akshun Kalia M.B.B.S.[2]

If left untreated, toxic multinodular goiter may progress to develop hyperthyroidism. However, the progression of toxic multinodular goiter is quite slow. Untreated patients initially have a history of thyroid enlargement followed by a long period of subclinical hyperthyroidism. Overt hyperthyroidism occurs late in the course of toxic multinodular goiter. Common complications of toxic multinodular goiter include tachycardia, arrhythmia, atrial fibrillation, heart failure (dilated cardiomyopathy), pulmonary hypertension, facial plethora, inspiratory stridor, hoarseness, dysphagia, bone mineral loss and thyroid storm. Prognosis of toxic multinodular goiter is generally good with treatment. Both surgery and radioactive iodine therapy can confer a moderate long-term risk of hypothyroidism and such patients require lifelong hormone replacement therapy. Toxic multinodular goiter is commonly seen in elderly. Therefore, in elderly, presence of other conditions may influence the outcome of toxic multinodular goiter.

• If left untreated, toxic multinodular goiter may progress to develop hyperthyroidism.^[1][2][3][4]
• Untreated toxic multinodular goiter progresses slowly and initially presents with history of thyroid enlargement.
• Thyroid enlargement is followed by a long period of subclinical hyperthyroidism.
• Overt hyperthyroidism occurs late in the course of toxic multinodular goiter.
  • When hyperthyroidism is present, cardiac symptoms are the most common presentation such as palpitations, tachycardia, heart failure and atrial fibrillation.
  • Over the course of time, toxic multinodular goiter may increase in size and can lead to compression of surrounding structures such as trachea, esophagus or external jugular vein.

Common complications of toxic multinodular goiter include:^[5][6]

• Tachycardia
• Arrhythmia
• Atrial fibrillation
• Heart failure (dilated cardiomyopathy)
• Pulmonary hypertension
• Facial plethora
• Inspiratory stridor
• Hoarseness
• Dysphagia
• Bone mineral loss
• Thyroid storm
• I-131-related hypothyroidism
• Surgery-related
  • Hypothyroidism
  • Recurrent laryngeal nerve damage
  • Hypoparathyroidism

• Prognosis of toxic multinodular goiter is generally good with treatment.
• About 45% to 75% of patients stay euthyroid following I-131 therapy.
• Both surgery and radioactive iodine therapy can confer a moderate long-term risk of hypothyroidism.
• Patients with I-131 therapy who develop hypothyroidism require lifelong thyroid hormone replacement therapy
• Toxic multinodular goiter is commonly seen in elderly. Therefore, in elderly, presence of other conditions may influence the outcome of toxic multinodular goiter.

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