09-11-23 - Pathology of the thyroid and parathyroid glands Flashcards
Learning outcomes
- Describe the causes and effects of hyperthyroidism
- Describe the causes and effects of hypothyroidism
- Understand goitre
- What to do with a solitary thyroid nodule
- Overview of disease affecting the thyroid - including Graves, Hashimoto
- Neoplasms of thyroid
- Parathyroid basics: hypercalcaemia
- Appreciate the emergent role of molecular genetic testing
What is a goitre?
What group do they occur more in?
What causes goitres to form?
How can a toxic goitre present differently from a non-toxic goitre?
- A goitre is a (often multi-nodular) swelling of the thyroid gland that causes a lump in the front of your neck.
- Goitres tend to occur more in women and those in early adulthood
- Goitres are often due to an increase in cellular content, with follicles potentially being larger with increased secretions (colloid has increased)
- This can be due to something such as an iodine deficiency
- A toxic goitre can present with signs of thyroid toxicosis (hyperthyroidism)
What are 2 different types of thyroid goitre in terms of function?
How do euthyroid goitres present differently in young and old people?
What can cause hypothyroid goitres?
What are goitrogens?
What are examples of goitrogens?
What are 3 parts of the pathogenesis of goitres?
- 2 different types of thyroid goitre in terms of function:
1) Euthyroid goitre
* Goitre, but a normal functioning thyroid
* Diffuse even enlargement in younger people
* Can be multinodular in older people
2) Hypothyroid goitre
* Thyroid tissue is lost, but we can palpate scarring
* Leads to hypothyroidism
* Often has an exogenous cause e.g iodine deficiency
* There are also goitrogens that can cause hypothyroid goitres, which are compounds that interfere with the normal function of the thyroid gland.
* Goitrogens include:
1) Drugs - lithium, amiodarone
2) Diet – cabbage, turnips
- 3 parts of the pathogenesis of goitres:
1) Reactive
2) Iodine block
3) Genetic
How can goitres present differently?
Who tends to get solitary thyroid nodules?
How can we determine if a nodule is solitary?
What will often be the primary presentation of hyperthyroidism?
How does thyrotoxicosis differ from hyperthyroidism?
- A goiter can be smooth and uniformly enlarged, called diffuse goiter, or it can be caused by one or more nodules within the gland, called nodular goiter
- Females more commonly get solitary thyroid nodules
- We can determine if a nodule is solitary through physical exam or ultrasound
- Goitres will often not be the primary sign of hyperthyroidism, as these won’t be found till the exam
- There will initially be signs of thyrotoxicosis, which is a clinical state of inappropriately high levels of circulating thyroid hormones (T3 and/or T4) in the body from any cause
- Hyperthyroidism is a form of thyrotoxicosis caused by excessive endogenous thyroid hormone production.
How do benign and malignant thyroid masses present differently?
How do most patients with solitary thyroid nodules present?
What are signs of hyper and hypothyroidism?
What 3 signs and symptoms trigger rapid investigation?
Why is this?
- Benign thyroid masses are usually movable, soft, and non-tender.
- Malignancy is associated with a hard nodule, fixation to surrounding tissue, and regional lymphadenopathy.
- Most patients with solitary thyroid nodules are asymptomatic but some exhibit signs and symptoms of altered levels of thyroid hormone:
1) Hyperthyroidism
* Nervousness, heat intolerance, diarrhoea, muscle weakness, and loss of weight and appetite
2) Hypothyroidism
* Cold intolerance, constipation, fatigue, and weight gain, which, in children, is primarily caused by the accumulation of myxedematous fluid.
- 3 signs and symptoms trigger rapid investigation:
1) Local nerve involvement (recurrent laryngeal nerve)
2) Dysphagia (difficulty swallowing)
3) Hoarseness (can be due to recurrent laryngeal nerve being affected) - This is because it may indicate a carcinoma with local invasion.
What are 3 methods of diagnosis for thyroid masses?
- 3 methods of diagnosis for thyroid masses:
1) Thyroid function tests
* Elevated thyroid-stimulating hormone (TSH) level may indicate thyroiditis – this may indicated a problem with inadequate amounts of thyroxine being developed, triggering the feedback mechanism or it can indicated a problem with the hypothalamus producing thyroid stimulating hormone (TSH)
* A very low TSH level indicates an autonomous or hyperfunctioning nodule
2) Antithyroid antibodies
* Helpful in diagnosing chronic lymphocytic thyroiditis (Hashimoto thyroiditis)
3) Full blood count
* Identify an abscess
What are 4 imaging studies that can be conducted for thyroid masses?
- 4 imaging studies that can be conducted for thyroid masses:
1) Ultrasonography
* To determine whether the nodule is cystic, solid, or mixed
2) Radioiodine scintigraphy
* To determine whether the nodule is cold, warm, or hot
* This can be used to determine if the mass is functional
* Can see if nodules take up iodine
3) Chest radiography
* If malignancy is suspected, given the high incidence of early metastases to the lungs
1) Computed tomography (CT) scanning and magnetic resonance imaging (MRI)
What are 5 different ways diseases of the thyroid are classified?
- 5 different ways diseases of the thyroid are classified:
1) Trauma and toxicity
2) Goitre, solitary nodule, neoplasms
3) Chronic inflammation – immune or not
4) Acute thyroiditis, abscess
5) Metabolic, genetic
What are the 3 main causes of hyperthyroidism?
- 3 main causes of hyperthyroidism:
1) Graves’ disease (most common)
* May present as diffuse toxic goitre
* Often, the thyroid is enlarged, as it is hyper stimulated by antibodies mimicking TSH
* This results in the thyroid being over worked without a shutting off mechanism
2) Functional goitre (non-toxic)
3) Toxic adenoma
* A solitary nodule can form called an adenoma
* This can cause thyroxine to be produced, resulting in thyrotoxicosis
What are 9 symptoms/signs of hyperthyroidism?
- 9 Symptoms/signs of hyperthyroidism:
1) Muscle wasting
2) Fine hair
3) Exophthalmos
4) Goitre
5) Sweating
6) Tachycardia and high output failure
7) Weight loss
8) Oligomenorrhoea (infrequent periods)
9) Tremor
What type of condition is Graves’ disease?
What is it caused by?
What groups does it affect more?
What gene is Grave’s disease associated with?
- Graves’ disease is an autoimmune condition caused by an IgG antibody being produced that stimulate TSH receptor on thyrocytes
- More common in females under the age of 40 (Female:male 10:1)
- Graves’ disease is associated with the HLA DR3 gene and a strong family history
What are 2 potential causes of hypothyroidism?
What are 3 effects of hypothyroidism on the thyroid?
What is it important to do in the treatment of hypothyroidism?
- 2 potential causes of hypothyroidism:
1) Congenital
2) Autoimmune - 3 effects of hypothyroidism on the thyroid:
1) Defective TH production
2) Loss of parenchyma
* Loss of thyroid follicles
3) Deficient TSH
* Could be from pituitary case rather than a thyroid cause
* In the treatment of hypothyroidism, it is important to give them thyroxine slowly
- If we give them it too fast, they may get cardiac arrhythmias as the system goes from suppressed back to normal too quickly
What are 13 signs/symptoms of hypothyroidism?
- 13 signs/symptoms of hypothyroidism:
1) Muscle weakness
2) Coarse, brittle hair
3) Loss of lateral eye brows
4) Myxoedema - swelling of the skin and underlying tissues giving a waxy consistency
5) Periorbital oedema and puffy face
6) Pallor
7) Large tongue
8) Hoarseness
9) Cardiomegaly
10) Gastric atrophy
11) Constipation
12) Menorrhagia (heavy periods)
What type of condition is Hashimoto thyroiditis?
What groups is it more common in?
How can it present?
What are 2 parts of the pathogenesis of Hashimoto thyroiditis?
What is Hashimoto’s thyroiditis genetically linked to?
What are 2 other possible causal factors for Hashimoto’s thyroiditis?
How is the thyroid different on examination with this condition?
- Hashimoto’s thyroiditis is a chronic autoimmune disorder
- It is more common in Females 30-50y
- It can present as hyper- or hypo- thyroidism
- 2 parts of the pathogenesis of Hashimoto thyroiditis:
1) Autoreactive CD8 T lymphocytes
2) Autoreactive antibodies: thyroid microsomal in almost all, 95% thyroglobulin in two thirds, minority have blocking TSH receptor antibodies
- There is a strong family history associated with Hashimoto’s thyroiditis, as well as other autoimmune diseases
- 2 other possible causal factors for Hashimoto’s thyroiditis:
1) Increased iodine intake
2) Viral infection (e.g covid-19) - With this condition, the thyroid gland may be larger, but this is due to scar tissue
What is a neoplasm?
What is an example of a benign thyroid neoplasm?
What are the 5 types of malignant primary thyroid neoplasms?
How common are they?
What is an example of a type of malignant metastatic thyroid neoplasm?
- A neoplasm is an abnormal growth of tissue that can be benign (noncancerous) or malignant (cancerous).
- A type of benign thyroid neoplasm is follicular adenoma
- 5 types of malignant primary thyroid neoplasms (about 1% of cancers):
1) Papillary
2) Follicular
3) Anaplastic
4) Medullary
5) Lymphoma - Lymphoma is a malignant metastatic thyroid neoplasm
What groups are follicular adenomas more common in?
How do they present?
What are some different subtypes of follicular adenomas?
How can molecular pathology be useful for follicular adenomas?
- Follicular adenomas are more common in 30–50-year-old females
- They are 1-3 cm in size at presentation
- Different histological subtypes, with some being functional
- Molecular pathology may be useful, as there may be a Ras mutation, or absence of other mutations
What % of thyroid cancers are papillary carcinomas?
What groups are they most common in?
What are 3 causes of thyroid papillary carcinomas?
What 2 genes are implicated in thyroid papillary carcinomas?
How commonly does this metastasise to lymph nodes?
What is the treatment for this condition?
- Around 80% of thyroid cancers are papillary carcinomas
- Papillary carcinomas are more common in 20-50y females (Females: males 3:1)
- 3 causes of thyroid papillary carcinomas:
1) Radiation
2) Family history
3) Unknown - 2 genes are implicated in thyroid papillary carcinomas:
1) Rearrangement of RET oncogene in most
2) B-RAF mutation in half – associated with increased risk of LN mets - In about ¼ to 1/3, papillary carcinomas of the thyroid have already spread to the lymph nodes
- To treat this condition, we can surgically remove the lymph nodes and hope the condition hasn’t spread anywhere else, as this condition does not kill quickly
What % of thyroid cancers are follicular carcinomas?
What groups does it affect more commonly?
What 2 genes are implicated in follicular carcinomas?
What are the 2 forms of follicular carcinoma?
How is it spread?
What are the treatment options for follicular carcinomas?
- Around 20% of thyroid cancers are follicular carcinomas
- Follicular carcinomas are more common women older than 40 (Female:male 3:1)
- 2 genes implicated in follicular carcinomas:
1) RAS oncogene mutation
2) PAX8/PPARG rearrangements - There are minimally invasive and invasive follicular carcinomas
- Follicular carcinomas spready by the blood, meaning the lymph nodes may be ok, but there can still be metastases
- Treatment options for follicular carcinomas:
1) Surgery
* Surgery, ideally
2) Radioactive iodine
* If we have metastases, these are often functional, so we can give radioactive iodine
* The follicles will take this up and hopefully be killed
Development of thyroid neoplasms flow chart (in picture)
How many parathyroids are there in the body?
What is the role of parathyroids?
What can too much parathyroid hormone lead to?
What are 3 causes of primary hyperparathyroidism?
What is secondary hyperthyroidism caused by?
What is the cause of tertiary hyperparathyroidism?
What is another source of increased PTH?
- There are normally four individual parathyroids
- Parathyroids are involved in calcium regulation
- Too much parathyroid hormone (PTH) increases calcium and leads to hypercalcaemia
- 3 causes of primary hyperparathyroidism:
1) Adenoma - four fifths
* Functional adenomas can produce PTH
2) Hyperplasia (some familial)
* increased cell production in a normal tissue or organ
3) Papillary carcinoma (less than 1%)
* Secondary hyperparathyroidism is caused by chronic low calcium (eg chronic renal failure and vitamin D deficiency or increased PTH in lung cancer)
* This leads to an increase in PTH
- Tertiary hyperparathyroidism is caused by raised calcium in secondary hyperparathyroidism
- Paraneuroplastic syndromes are also a source of increased PTH
What are 8 signs/symptoms of hypercalcaemia?
- 8 Signs/symptoms of hypercalcaemia:
1) Emotional disorders
2) Muscle atrophy
3) Parathyroid adenoma or hyperplasia
4) Osteitis fibrosa cystica
5) Peptic ulcer
6) Pancreatitis
7) Kidney stones
8) Nephrocalcinosis
What is multiple endocrine neoplasia?
What does the neuroendocrine system consist of?
What is its role?
- Multiple endocrine neoplasia is a set of genetic of sporadically arising conditions that involved neuroendocrine cells, but wont affect the thyroid epithelium
- The neuroendocrine system consists of nerve and gland cells.
- It produces hormones and releases them into the bloodstream.
