Thyroid nodule(s)

Question 1

What are all the pathological causes of thyroid nodules?

Answer 1

• Colloid nodule
• Non-toxic multinodular goitre
• Toxic multinodular goitre
• Toxic thyroid adenoma

Question 2

What is a colloid nodule?

Answer 2

Colloid nodules, also known as adenomatous nodules, are benign, noncancerous enlargement of thyroid tissue

• Although they may grow large,
• and there may be more than one,
• they are not malignant and they will not spread beyond the thyroid gland.

Question 3

What is the aetiology of colloid nodules?

Answer 3

• A colloid nodular goiter occurs when the thyroid gland is unable to meet the metabolic demands of the body with sufficient hormone production.
• The thyroid gland compensates by enlarging, which usually overcomes mild deficiencies of thyroid hormone.
• If the thyroid gland is then re-exposed to iodine, the nodules may produce thyroid hormone independently.
• Occasionally, the nodules may produce too much thyroid hormone, causing thyrotoxicosis. This is called a toxic nodular goiter.
• Colloid nodular goiters are also known as endemic goiters and are usually caused by inadequate iodine in diet.
  
  • They tend to occur in certain geographical areas with iodine-depleted soil, usually areas away from the sea coast. An area is defined as endemic for goiter if more than 10 % of children aged 6 to 12 years have goiters.

Question 4

What are the risk factors for colloid nodules?

Answer 4

• female
• age > 40
• inadequate dietary intake of iodine
• living in an endemic area
• FHx of goiters

Question 5

What is the definition of endemic goitre?

Answer 5

Endemic goiter is defined as thyroid enlargement that occurs in more than 10% of a population

vs sporadic goiter is a result of environmental or genetic factors that do not affect the general population

Question 6

Summarise the epidemiology of colloid nodules

Answer 6

Colloid nodules are the most common kind of thyroid nodule

Question 7

What are the SYMPTOMS & SIGNS of colloid nodules?

Answer 7

SYMPTOMS

usually asymptomatic,

so patients are unlikely to notice them until their size makes them easier to detect.

SIGNS

may have palpable mass

(Like other thyroid nodules, they are usually first noticed in a routine physical examination)

Question 8

What are the investigations for ?colloid nodules

Answer 8

see flowchart

Primary

• thyroid US
  
  • = complex appearance with both cystic and solid features; internal echo reflectors with ‘ring-down’ or ‘comet tail’ artifac

Secondary

• FNA
  
  • = predominance of abundant, thick colloid material with cracking or bubble pattern and benign-appearing follicular epithelial cells in honeycomb arrangemen

Question 9

What is non-toxic multinodular goitre?

Answer 9

nodular enlargement of the thyroid gland that:

• does not result from an inflammatory or neoplastic process
• • is not associated with abnormal thyroid function (non-toxic)

non-toxic goitres can be diffuse or nodular

Question 10

What is the aetiology of non-toxic multinodular goitre?

Answer 10

unknown

Question 11

What are the risk factors for non-toxic multinodular goitre?

Answer 11

• female
• usually present at puberty, pregnancy

Question 12

Summarise the epidemiology of non-toxic multinodular goitre

Answer 12

• female > male
• Thyroid nodules increase in incidence with age.

Question 13

What are the SYMPTOMS & SIGNS of non-toxic multinodular goitre?

Answer 13

• no specific history that is suggestive
• unless the nodules are large –> cause mass effect

Question 14

What are the investigations for ?non-toxic multinodular goitre?

Answer 14

see flowchart

• serum TSH
• US
• +/- FNA

Question 15

What is a toxic multinodular goitre?

Answer 15

A toxic multinodular goitre (also known as Plummer’s disease) contains

• multiple autonomously functioning nodules,
• –>resulting in hyperthyroidism.
• These nodules function independently of TSH
• and are almost always benign.
• However, non-functioning thyroid nodules in the same goitre may be malignant.

Question 16

What is the aetiology of non toxic multinodular goitre?

Answer 16

A toxic multinodular goitre (MNG) contains multiple autonomously functioning nodules, resulting in hyperthyroidism.

• Hyperfunctioning nodules in MNGs develop in a similar way to single toxic nodules.
• Most hyperfunctioning nodules have thyroid cell germline mutations that affect the thyroid-stimulating hormone (TSH) receptor.
• In addition, activating mutations of the TSH receptor have been found in non-adenomatous hyperfunctioning nodules in patients with toxic or autonomous MNGs.
• Non-functioning nodules in the same goitre lack these mutations.

Question 17

What are the risk factors for toxic multinodular goitre?

Answer 17

• iodine deficiency
• age >40 years
• head and neck irradiation.

weak:

• family history of thyroid nodules
• female sex

Question 18

Summarise the epidemiology of toxic multinodular goitre?

Answer 18

• Toxic multinodular goitre (MNG) accounts for about 5% to 15% of patients with endogenous hyperthyroidism,
• but the proportion is higher in iodine-deficient regions
• In Sweden, the incidence of toxic nodular goitre (including toxic MNG and solitary toxic adenoma) has been estimated at 6.5 per 100,000, with the majority of patients aged between 50 and 89 years
  
  • increasing age = RF
• Worldwide, iodine deficiency is the most common cause of (toxic) nodular goitre.
  
  • In iodine-deficient areas, toxic adenomas and toxic MNGs are more common causes of hyperthyroidism than Graves’ disease.

Question 19

What are the SYMPTOMS & SIGNS of toxic multinodular goitre?

Answer 19

• goitre
  
  • Usually irregular rather than smooth in texture
  • Absence of palpable goitre does not rule out toxic MNG

hyperthyroidism

• heat intolerance, hyperphagia, or weight loss
• depression
• nervousness or palpitations
  
  • Palpitations may suggest a dysrhythmia such as atrial fibrillation.
• oligomenorrhoea
• hyperdefecation
  
  • Less common in older than younger people.
• stare or lid lag
  
  • ​note: Stigmata of Graves’ disease (exophthalmos and pretibial myxoedema) are absent.
• warm, moist skin
• tachycardia
• irregular pulse
  
  • ​may indicate AF
• tremor
  
  • ​fine resting tremor

Question 20

What are the investigations for ?toxic multinodular goitre?

Answer 20

see flowchart

• bloods: serum TSH
• ~ US
• radioactive iodine uptake scan (scintigraphy)
  
  • = shows hot and cold nodules
  • patchy uptake vs grave’s diffuse uptake
• cold nodules (suspicion of cancer) –> may be US for suspicious signs if not done previously
  
  • suspicious signs on US =
• Can be used to define dimensions of cold nodules* + detect suspicious features
  * ​more-tall-than-wide shape
  * marked hypoechogenicity.

Question 21

What is a hot vs cold nodule?

Answer 21

On nuclear scintigraphy:

• hot nodules = high isotope uptake (autonomous) - more likely to be benign
• cold nodules = low isotope uptake - more likely to be malignant

The development of nodules correlates with the development of functional autonomy and reduction in thyroid-stimulating hormone (TSH) levels

In this test, the patient is given a small amount of radioactive iodine, usually in pill form, and then the thyroid is scanned using a scintillation counter to see how much of that iodine is taken up by the thyroid.

A normal thyroid gland will show diffuse, even uptake of the radioactive iodine

Areas of the thyroid that are very active show more uptake; areas that are less active show less uptake.

You can use both the location and intensity of the uptake to help you figure out what is going on in the thyroid.

• If there is diffuse increased uptake, it means the entire gland is overactive, and the patient probably has a disease like Graves disease.
• If there is diffuse decreased uptake, it means the entire gland is underactive, and the patient probably has a disease like Hashimoto thyroiditis.
• If there are focal areas of increased uptake and focal areas of decreased uptake, it means different parts of the gland are acting differently, and the patient probably has a multinodular goiter.
• Sometimes, you’ll just see a single area on the scan – a nodule – that is different than the surrounding thyroid. Some nodules show increased uptake compared to the rest of the thyroid; these are called “hot” nodules.
• Other nodules take up less iodine than the rest of the thyroid; these are called “cold” nodules.
  
  • Hot nodules are busy making a lot of thyroid hormone; cold nodules are just sitting there doing nothing.

Question 22

What other test can be used to distinguish between Grave’s disease and toxic multinodular goitre, other than appearance on the radioactive iodine uptake scan?

Answer 22

TSH receptor antibody test/assays

• positive = Grave’s
  
  • specific for Grave’s
• negative = toxic multinodular goitre

Question 23

What is a toxic thyroid adenoma?

Answer 23

A toxic adenoma is an autonomously functioning thyroid nodule that causes hyperthyroidism.

These nodules are almost always benign.

Some autonomous nodules cause only subclinical hyperthyroidism i.e.

• suppressed thyroid-stimulating hormone (TSH) level
• • normal free thyroid hormones levels

Question 24

What is the aetiology of toxic thyroid adenoma?

Answer 24

Single toxic adenomas are believed to be benign monoclonal tumours that grow and produce thyroid hormones independently of TSH.

• These arise after activating (gain of function) germline mutations in thyroid cells.
• The mutations most commonly affect the TSH receptor and less commonly the alpha subunit of stimulating G-protein.
• Genetic and environmental factors (e.g., iodine deficiency) and thyrocyte heterogeneity may influence which clones eventually become autonomous nodules.
• Worldwide, iodine deficiency is the best-studied epidemiological risk factor for goitre.
• In individuals with autonomous nodules, an iodine load (e.g., from iodinated radiographic contrast, amiodarone, or a change in diet) may also cause iodine-induced hyperthyroidism (the Jod-Basedow phenomenon)

Question 25

What are the risk factors for toxic thyroid adenoma?

Answer 25

• iodine deficiency
  
  • Worldwide, iodine deficiency is the most common cause of nodular goitre

weak:

• young adult age i.e. 20-40yrs
• head & neck irradiation
• FHx of thyroid nodules
• female sex

Question 26

Summarise the epidemiology of toxic thyroid adenoma

Answer 26

• The prevalence of thyroid disorders in the UK is thought to be between 0.5% and 2%
  
  • predominantly occurring in women.
• In adult women in the Netherlands the prevalence of thyrotoxicosis has been estimated at 0.8 cases per 1000 population
• Stockholm area of Sweden, the incidence of solitary toxic adenoma has been estimated at 3.3 cases per 100,000 people per year

Question 27

What are the SYMPTOMS & SIGNS of toxic thyroid adenoma?

Answer 27

• palpable thyroid nodule (>3cm if pt is hyperthyroid)

hyperthyroidism

• hyperphagia
• weight loss
• sweating/heat intolerance
• nervousness
• palpitations
• oligomenorrhoea
• hyperdefecation
• dyspnoea
• stare or lid lag
• tachycardia
• tremor
• warm moist skin

Question 28

What are the investigations for ?toxic thyroid adenoma?

Answer 28

see flowchart

• bloods: serum TSH = low
• bloods: serum T4 = high
• US = single hot nodule
  
  • Cold (i.e., non-functioning) or warm (i.e., isofunctioning) nodules
    
    • >1 cm in diameter OR
    • suspicious ultrasonographic characteristics (such as more-tall-than-wide shape, irregular margins, microcalcifications, increased vascularity, or marked hypoechogenicity)
    • –>should be considered for further evaluation such as FNA
• radioactive iodine uptake scan = single hot nodule