Pathology - Thyroid and PTH Flashcards
Treatments for hyperthyroidism include?
Beta blockade for control of symptoms.
Propylthiouracil to block hormone synthesis and peripheral T4 to T3 conversion.
Iodine to block thyroglobulin proteolysis.
Radioiodine for ablation over 6-18 weeks.
What is the most common cause of hyperthyroidism?
List the other causes:
Graves’ disease accounts for 85% of cases.
Other causes include hyper functional MNG, hyper functional thyroid adenoma, pituitary TSH adenomas, thyroid inflammatory disease, and excess exogenous thyroxine.
What is the most common cause of hypothyroidism?
List the other causes:
Primary hypothyroidism is most commonly caused by autoimmune thyroiditis (in iodine-sufficient countries).
Other causes include endemic goitre, inborn errors of metabolism, and goitrogens. Genetic causes include Pendred syndrome and mutations of the TSH receptor.
What antibodies are typical in autoimmune thyroiditis?
Anti-microsomal, anti-TPO, and anti-thyroglobulin antibodies.
Features of Hashimoto thyroiditis?
What cancer is it associated with?
Hashimoto thyroiditis is the most common cause of hypothyroidism in iodine-sufficient countries.
It is most prevalent between the ages of 45-65 with a 10-20:1 female preponderance. It has a strong (40% MZT) genetic basis.
There is a small risk of subsequent B-cell NHL.
What is de Quervain thyroiditis?
Sub-acute thyroiditis attributed to a recent viral infection resulting in T-cell mediated thyroid epithelial damage.
Normal thyroid function returns in 6-8 weeks.
Definition and epidemiology of Graves Disease?
A clinical triad of hyperthyroidism due to diffuse thyroid enlargement, infiltrative ophthalmopathy, and localised infiltrative dermopathy in a minority of patients.
Affects women 7 times more frequently than men. Peak incidence between 20-40. Strong genetic component (30-40% MZT).
Describe the autoantibodies related to Graves’ disease:
Thyroid stimulating immunoglobulin: specific to Graves, binds TSHR triggers T3/4 release.
Thyroid growth stimulating immunoglobulin: Binds TSHR and induce thyroid follicular epithelium proliferation.
TSH-binding inhibitor immunoglobulin competes with TSH, may inhibit or excite receptor.
What 4 mechanisms contribute to infiltrative ophthalmopathy?
Marked mononuclear (T-cell) infiltration
Inflammatory oedema ( AB against orbital preadipocyte fibroblasts)
Accumulation of ECM
Fatty infiltration
How do most patients with simple goitres present?
With compressive symptoms related to the size of the goitre.
Although they often have elevated TSH, they are usually euthyroid. The TSH is elevated due to impaired synthesis of thyroid hormone.
Solitary thyroid nodules occur in what percentage of the population?
What percentage of these are malignant?
1-10% of the (US) population have solitary thyroid nodules.
1% of these are malignant.
Risk of malignancy in thyroid nodules increase with what factors?
Solitary nodules rather than multiple nodules Nodules in younger (<40) patients Nodules in men A history of head and neck radiotherapy Cold nodules.
What are thyroid adenomas?
Discrete, solitary masses derived from follicular epithelium. Most are non-functional and they are rarely precursors to malignancy.
What is a “cold” thyroid nodule? What proportion of these prove to be malignant?
How is the definitive diagnosis made?
Non-functioning adenomas of the thyroid, they take up less radioactive iodine than the surrounding tissue.
Less than 10% of these prove to be malignant. Because capsular integrity is a fundamental distinguishing feature, diagnosis can really only be made after excision.
Percentage breakdown of thyroid cancer:
Risk factors for thyroid cancer:
Papillary carcinoma: 80%
Follicular carcinoma: 5-15%
Anaplastic carcinoma: less than 5%
Medullary carcinoma: 5%
The major risk factor is ionising radiation, especially in the first two decades of life. Iodine deficiency is linked to higher frequency of follicular carcinomas.
What genetic mutations underlie thyroid oncogenesis?
GoF mutations in MAP (Mitogen-activated protein) and the PI3 Kinase/AKT pathways. These lead to constitutive cell activation in the absence of TSH.
The former is associated more closely with Papillary tumours, the latter with Follicular tumours.
What additional genetic mutations may contribute to anaplastic thyroid carcinoma’s aggression?
In addition to PI Kinase 3CA and RAS mutations, anaplastic thyroid carcinomas may also exhibit p53 and b-catenin mutations.
Epidemiology of Papillary carcinoma?
Papillary carcinoma accounts for 85% of thyroid cancer.
It occurs most commonly between the ages of 25-50 and are strongly associated with previous ionising radiation exposure.
What is the clinical course of Papillary thyroid cancer?
Most lesions present as “cold” thyroid nodules, though a few may present with cervical nodal metastases. They are indistinguishable from benign nodules on examination, though additional features like hoarseness, cough, dysphagia, or dyspnoea suggest advanced disease.
10-year survival for papillary thyroid carcinoma?
Exceeds 95%; unfavourable factors include older age, extrathyroidal extension, and distant metastases.
Epidemiology of Follicular carcinoma?
Follicular carcinoma accounts for 5-15% of thyroid cancers. They are three fold more common in women with a peak incidence between 40-60 years.
Iodine deficiency increases risk.
What is the clinical course of Follicular thyroid cancer?
Most present as slow growing, painless, “cold” nodules. Haematogenous metastases to bone, liver, and lungs are common.
Prognosis depends on stage and extent of invasion. Therapy involves surgical resection and radioablative therapy. Thyroid hormone may be given to downregulate TSH.
10-year survival for Follicular carcinoma of the thyroid?
Minimally invasive disease = 90%
Metastatic disease = 50%.
What type of neoplasm are Medullary carcinomas?
Why do they deserve mention?
They are NE tumours and secrete not only calcitonin but also serotonin, ACTH, and VIP. Because of this they may present with paraneoplastic syndromes.
Though 70% are sporadic, the remainder occur in the setting on MEN-2 or familial medullary thyroid carcinoma.
