Biochemistry Flashcards
Describe the thyroid gland
- Soft gland, lower neck, anterior to trachea, below thyroid cartilage of the larynx
- Makes thyroxine and T3
- Has 2 lobes connected by the isthmus
- Can’t palpate unless enlarged
Describe the histology of the thyroid
- Follicles (cuboidal epithelium) are filled with colloid (TFCs) - where thyroid hormones are made
- Lined with columnar epithelium: thyroid follicular cells make thyroglobulin
- Interspersed C-cells make calcitonin
- Adjacent to thyroid gland are the parathyroid glands
What are the thyroid hormones?
- Tetraiodothyronine = T4
- Triiodothyronine = T3
Thyronines are made from thyroglobulin.
Describe the process of thyroid hormone synthesis
- TFC make thyroglobulin (Tg) under control of TSH (activated by TSHR) and secrete into colloid
- Iodide is trapped by TFCs and transported into colloin
- Tg provides source of tyrosines
- Thyroid peroxidase (TPO) on luminal membrane of TFCs iodinates tyrosines
- TFCs endocytose Tg from luminal border - hydrolysis of Tg releases T4 into blood
- Deiodination of T4 to T3
- T3R is nuclear hormone receptor - DNA binding and transcription
What is the pituitary-thyroid hormone axis?
Negative feedback of T4/T3 on pituitary TSH and hypothalamic TRH
- Low T4 > high TSH (hypo-)
- High T3 > suppressed TSH (hyper-)
What is primary hyperthyroidism?
Thyroid gland releases too much T3 and T4
What is secondary hyperthyroidism?
Pituitary gland releases too much TSH or hypothalamus releases too much TRH.
What are the causes of thyrotoxicosis/hyperthyroidism?
- Grave’s disease (60-80%): young people, antibody stimulation of TSH receptor, autoimmune
- Multinodular goitre: older patients
- Solitary toxic nodule (5%): solitary benign adenoma, produces T3 and T4
- Drugs: interferon (HepC), amiodarone (arrhythmia)
What is the mechanism of neonatal hyperthyroidism?
Thyroid stimulating antibodies (in Graves disease) can cross the placenta and stimulate the thyroid gland of the foetus.
What are the most common complications of hyperthyroidism?
AF and osteoporosis
Describe the role of iodine in the production of thyroid hormones
T3 and T4 are produced by the iodination of tyrosine residues bound to thyroglobulin in the thyroid follicles. Iodide is taken up by the thyroid gland and is under the control of the pituitary hormone, TSH.
What is the role of thyroid hormones?
They are deiodinated in the liver and kidney (peripheral tissues) and have a role in metabolism including oxygen consumption, CO and HR. Also, they are important for growth, brain development and sexual maturation.
Which hormones are released from where?
Hypothalamus - TRH
Anterior pituitary - TSH
Thyroid - T3, T4
What are the causes of primary autoimmune hypothyroidism?
- Chronic autoimmune thyroiditis (Hashimoto’s) - more common in women.
- Primary atrophic hypothyroidism: diffuse lymphocytic infiltration of the thyroid > atrophy > no goitre
How do you distinguish secondary hypothyroidism?
Due to a TSH deficiency caused by pituitary or hypothalamic disease. TFT’s show low free T4 and low TSH levels.
What are the causes of primary hypothyroidism?
- Iodine deficiency
- Post-thyroidectomy or radioiodine treatment
- Drug-induced: anti-thyroid drugs, amiodarone, lithium, iodine
- Subacute thyroiditis: temporary hypothyroidism after hyperthyroid phase
Describe Hashimoto’s Thyroiditis
- T-cell infiltration, destruction of thyroid tissue
- Can’t see follicles, just a sheet of lymphocytes
- May cause firm goitre in early stages
- Autoantibodies to TPO, Tg
- Women > men 10:1, age 40+
What is sub-clinical hypothyroidism?
- Early thyroid failure
- Raised TSH, T3 + T4 still maintained
- May be symptomatic, though symptoms often non-specific and hard to judge
- Very common
What types of thyroid carcinoma are there?
- Papillary carcinoma (70%) - follicular epithelium
- Follicular carcinoma (20%)- follicular epithelium
- Anaplastic carcinoma (3%)
- Lymphoma (2%)
- Medullary cell carcinoma (5%) - calcitonin producing C-cells
Describe papillary carcinoma
Can be multifocal as can invade lymphatics within the thyroid. Most common in middle-aged women. Most common site of metastasis is to local lymph nodes in neck (nodal metastasis at first)
How does Grave’s disease cause hyperthyroidism?
More common in women
Circulating IgG autoantibodies binding and activating G-protein coupled thyrotropin receptors > thyroid enlargement and increased hormone production
What are the triggers and associated conditions of Grave’s disease?
Triggers: stress, infection, childbirth
Associated: vitiligo, T1DM, Addison’s
What are the causes of secondary hypothyroidism?
- Pituitary infarction (Sheehan’s syndrome) - secondary to post-partum haemorrhage
- Pituitary tumour
