4. Pathology of the thyroid and parathyroid glands Flashcards
Clinical presentation of an abnormal thyroid?
Goitre (due to swollen gland, does not diagnose)
Lump (could be part of goitre, neoplasma etc i.e. doesn’t diagnose)
Hypothyr
Hyperthyr
What decides if a goitre is toxic or non-toxic?
Production of thyroxine, is it excessive?
Non-toxic goiter:
-A simple enlargement of the thyroid gland without any increased secretion of thyroid hormone
-TSH levels rise in an attempt to enhance the production of thyroid hormones (T3 & T4)
-Symptom-less usually
Toxic goiter:
- Mainly occurs as a result of a hypersensitivity reaction to an IgG auto-antibody that acts on surface receptors for TSH on thyroid epithelium.
- In these patients, a remarkable rise occurs in both T3 and T4 concentrations. The increase in thyroid hormone levels results in reduced TSH release
Type of goitre?
Causes?
Pathogenesis?
1. Euthyroid: • Diffuse – younger people • Multinodular – older 2. Hypothyroid • Iodine deficiency - endemic or seaweed↑
Goitre, causes?
– Drugs–lithium,amiodarone
– Diet–cabbage,turnips
Pathogenesis
• Reactive
• Iodine block
• Genetic
Solitary thyroid nodule
• Who gets it? Middle adulthood, female
Confirm it’s not goitre
If it’s not goitre, then assume cancer until proven otherwise
S/S of benign vs malignant masses in solitary thyroid nodule
Benign masses are usually movable, soft, and non tender.
Malignancy is associated with a hard nodule, fixation to surrounding tissue, and regional lymphadenopathy.
Hard: They illicit fibrous stromal response
Hypothyroidism, S/S?
Muscle weakness Coarse, brittle hair Loss of lateral eyebrows Pallor Periorbital oedema and puffy face Large tongue Voice hoarseness Constipation Menorrhagia Peripheral oedema
Why is it important to rapidly investigate local nerve involvement?
May be indicative of local invasiveness from malignancy. The most important of these signs are dysphagia and hoarseness.
What 4 tests are used in solitary thyroid diagnosis?
- Thyroid function tests - An elevated thyroid-stimulating hormone (TSH) level may indicate thyroiditis; a very low TSH level indicates an autonomous or hyperfunctioning nodule
- Antithyroid antibodies - Helpful in diagnosing chronic lymphocytic thyroiditis (Hashimoto thyroiditis)
- Complete blood count (CBC) –Abscess
- Fine needle aspirate: Doesn’t show you whole picture
What imaging studies are used in solitary thyroid diagnosis?
- Ultrasonography - To determine whether the nodule is cystic, solid, or mixed
- Radioiodine scintigraphy - To determine whether the nodule is cold, warm, or hot.
- Chest radiography - If malignancy is suspected, given the high incidence of early metastases to the lungs
- Computed tomography (CT) scanning and magnetic resonance imaging (MRI) - To analyze the extent of disease by scanning the neck and chest
Hyperthyroidism:
Causes?
Commonest is Graves – may present as diffuse toxic goitre. Presents as hypersensitivity
- Functional goitre
- Toxic adenoma
Hypothyroidism causes?
Congenital or Autoimmune – Defective TH production – Loss of parenchyma – Deficient TSH
Hyperthyroidism S/S
muscle wasting Fine hair Exophthalmos Goiter Sweating Tachycardia Weight loss Oligomenorrhea Tremor
Hypothyroidism causes?
Congenital or Autoimmune – Defective TH production – Loss of parenchyma – Deficient TSH
Cause and epidemiology of Grave’s?
Cause:
Autoimmune, antibodies pressing ON switch for proliferation and hyperfunction.
Immune – IgG against TSH receptor on thyrocytes
Less than 40yrs
Females
Family history:
HLA DR3 and CTLA-4
Chronic autoimmune – Hashimoto thyroiditis Gender? Presentation? Cause? FH?
Females 30-50y
Present as hyper- or hypo- thyroidism
Causes:
•Autoreactive CD8 T lymphocytes
•Autoreactive antibodies: thyroid microsomal in almost all 95% thyroglobulin in two thirds, minority have blocking TSH receptor antibodies
•Other causal risks? Increased iodine intake, viral infection
FH:
•Family history strong and other autoimmune diseases
Risk: Lymphoma development
Benign and malignant neoplasma of the thyroid?
Benign: follicular adenoma
Malignant:
– Primary: papillary, follicular, anaplastic, medullary, lymphoma
– Metastatic: Lymphoma
Epidemiology of follicular adenoma?
Functional?
What?
30-50yrs
Females
1-3cm in size
Can sometimes be functional
This is a benign thyroid neoplasm
Papillary thyroid carcinoma: Is it important to know? Who? Causes? Molecular clues in oncogene rearrangement? Treatment?
COMMON/MAIN THYROID NEOPLASM
Is it important to know?
Around 80% of thyroid cancers
Who?
20-50yrs
Females: males 3:1
Causes?
– Radiation – eg Chernobyl
– Family history
– Unknown
Molecular clues in oncogene rearrangement?
• Rearrangement of RET oncogene in most
• B-RAF mutation in half. Associated with increased risk of Lymph Node mets
Treatment: Surgical removal
COMMON/MAIN THYROID NEOPLASM
Follicular thyroid carcinoma: -Proportion of thyroid cancers? -Age? -Gender? -Genetic changes -Invasion features? Treated by...
MORE COMMON THYROID NEOPLASM
- Around 20% of thyroid cancers
- Older than 40
- Female:male 3:1
Genetic changes:
• RAS oncogene
• PAX8/PPARG rearrangements
Invasion via:
• Minimally invasive
• Bloodspread
Radiation treatment
MORE COMMON THYROID NEOPLASM
Anaplastic thyroid carcinoma: Gender? Previous pathologies in thyroid? Mutations... Common thyroid neoplasm?
Gender: Female:male 4:1
Previous thyroid pathologies:
- Half have had chronic goitre
- May have had previous thyroid neoplasia
Mutations?
• p53 mutation common
LESS common < Follicular and papillary
Medullary thyroid carcinoma (MTC): Cause? Where does neoplasm originate from? Function of cdk5? Expression of cdk5 in mTC? Common thyroid neoplasm?
Cause:
- 20% familial in younger patients
- RET proto-oncogene activation
Medullary thyroid carcinoma (MTC) is a neuroendocrine cancer that originates from calcitonin-secreting parafollicular cells, or C cells.
We found that Cdk5 and its cofactors p35 and p25 are highly expressed in human MTC and that Cdk5 activity promotes MTC proliferation.
Cell division protein kinase 5 is an enzyme that in humans is encoded by the CDK5 gene. This enzyme allows progression of cell division to the
Less common < Follicular and papillary
Thyroid neoplasm progression..
Follicular cell
–> Toxic adenoma
or
–> Follicular adenoma –> Follicular carcinoma –> Anaplastic carcinoma
or
–> Papillary carcinoma –> Anaplastic carcinoma
neoplasms of the parathyroids?
Primary hyperparathyroidism:
- Adenoma
- Hyperplasia
- Parathyroid carcinoma
Secondary hyperparathyroidism
-Caused by low Ca (e.g. chronic renal failure and Vit D deficiency)
Tertiary hyperparathroidism
-Raised Ca in secondary
Hypercalcaemia effects?
Emotional disorders Parathyroid adenoma or hyperplasia Osteitis fibrosa cystica Peptic ulcer Pancreatitis Kidney stones Nephrocalcinosis Muscle atrophy Emotional disorders
Multiple endocrine neoplasia (MEN)
Types and structures impacted?
MEN1
- Pit
- Parathryoid
- Bronchial carcinoid
- Enteropancreatic
MEN2
- Nerve (MEN2B)
- Thyroid C cell
- Adrenal chromaffin
Susceptible to malignancy so neuroendocrine cells at a young age
Hypersensitivity type I:
Alternative name?
Mediated by?
Hypersensitivity type I:
Alternative name?
Allergy
Mediated by?
IgE
Hypersensitivity Type II:
Alternative name?
Mediated by?
Hypersensitivity Type II:
Alternative name?
Cytotoxic antibody-dependent
Mediated by?
IgM or IgG (complement)
MAC
Hypersensitivity Type III:
Alternative name?
Mediated by?
Hypersensitivity Type III:
Alternative name?
Immune complex
Mediated by?
IgG (complement)
Neutrophils
Hypersensitivity Type IIV:
Alternative name?
Mediated by?
Hypersensitivity Type IIV: Alternative name? Delayed type hypersensitivity Cell mediated immune memory response Antibody-independent
Mediated by?
T-cells
What are the S/S of a solitary thyroid nodule?
Most patients are asymptomatic but some exhibit signs and symptoms of altered levels of thyroid hormone:
•Hyperthyroidism - Nervousness, heat intolerance, diarrohea, muscle weakness, and loss of weight and appetite
•Hypothyroidism - Cold intolerance, constipation, fatigue, and weight gain, which, in children, is primarily caused by the accumulation of myxedematous fluid.
