Thyroid Disease Flashcards
What is the histology of the thyroid gland?
Made up of follicles;
- Colloid (formed of thyroglobulin and iodine)
- Surrounded by parafolliciular cells
How does iodine enter the colloid of the follicular lumen?
- Iodide transported from the bloodstream into follicular cell via I/Na co-transporter
- Exocytosed into the follicular lumen and oxidised to iodine by thyroid peroxidase
How is T3 and T4 formed in the follicular lumen?
- Tyrosine residues on thyroglobulin are iodinated
- Mono/di-iodinated tyrosine combine to form T3/T4
What enzyme is responsible for the iodination of thyroglobulin?
TPO - Thyroid Peroxidase
What is the composition of T3 and T4?
T3 - MIT+DIT
T4 - 2xDIT
How does T3 and T4 enter the circulation
- Endocytosed into the follicular cell
- Cleaved from thyroglobulin via lysosome
- Diffuse into circulation
What plasma proteins to T3 and T4 bind to?
Thyroid-binding globulins, albumin and transthyretin
How is biologically active free T3 formed?
- Most circulating thyroid hormone is T4 which is de-iodinated in the periphery by tissues which require thyroid hormone activity
How is the secretion of thyroid hormone regulated?
- Hypothalamus releases Thyrotropin Releasing Hormone (TRH)
- Stimulates the anterior pituitary to release Thyroid Stimulating Hormone (TSH)
- Stimulates thyroid to produce T3 and T4, which negatively feedback
How do thyroid hormones elicit a response in target cells?
Diffuse into cells and bind to nuclear receptors which act as transcription factors for certain genes.
What is the general action of thyroid hormones?
Increased metabolism and glucose uptake
What is the action of thyroid hormones on carbohydrate, lipid and protein metabolism?
- Increased gluconeogenesis and glycogenolysis
- Increased lipolysis
- Increased proteolysis
What is the action of thyroid hormones on the CV/resp system?
Increased HR, CO and RR
What are the common causes of hyperthyroidism?
- Graves disease (most common)
- Multinodular goitre
- Thyroid adenoma
What is the pathophysiology of Graves disease?
Autoimmune condition, producing antibodies of the TSH receptor. Stimulates the thyroid to produce T3 and T4, negative feedback of TSH does not affect thyroid hormone production.
What are the clinical features of hyperthyroidism (specify those specific to Graves disease)?
Hypermetabolism:
- Weight loss
- Diarrhoea
- Sweating
Increased CV output:
- Tachycardia
- Palapatations
- Hypertension
GRAVES
- Opthalmopathy: Bulging, dry, bloodshot eyes
- Dermopathy of shins: Scaly thickening skin
What investigations should be ordered and what results seen in hyperthyroidism?
- Low TSH
- High free T4
Positive TSH receptor antibody in Graves
What are the management options for hyperthyroidism?
- Thioamides - carmibazole and proplythiouracil
- Beta blockers to reduce CV symptoms
- Radioactive iodine
- Thyroidectomy (results is permanent hypothyroidism)
What is the mechanism of action of thioamide drugs?
Carmibazole and propylthiouracil
- TPO (thyroid peroxidase) inhibitor
- Reduced iodination of thyroglobulin, therefore production of T3 ad T4
What is are the risks of thioamide drugs?
Agranulocytosis causing infection - watch out for fever or sore throat
What is the mechanism and risks of radioactive iodine?
Taken up by the thyroid and destroys the granular tissue via beta emission.
Stay away from others due to radiation risk, and results in hypothyroidism.
What are the two types of goitre?
Diffuse - hypertrophy of the whole thyroid
Nodular - Formation of nodules, can be malignant
What is the diagnosis and treatment of thyroid carcinomas?
Fine needle aspiration of nodules. Surgical excision and radioactive iodine therapy.
What are the causes of hypothyroidism?
- Hashimotos thyroiditis
- Thyroidectomy or radio-iodine therapy
- Iodine deficiency
- Secondary hypothyroidism relating to AP/hypothalamus (rare)
What is the pathophysiology of Hashimotos thyroiditis?
Autoimmune condition producing TPO (thyroid peroxidase antibodies). Causing inflammation of the thyroid and decreased T3 and T4 production due to reduced iodination of thyroglobulin by TPO.
What is the clinical presentation of hypothyroidism?
- Weight gain
- Intolerance to cold
- Heavy menstruation
- Dry, thin hair
- Periorbital and peripheral oedema
What investigation and results would give a diagnosis of hypothyroidism (Hashimotos)?
- High TSH
- Low free T4
- High TPO antibody
What is the treatment of hypothyroidism?
Oral levothyroxinetaken daily
What is the most common cause of congenital hypothyroidism?
Genetic defect to the TSH receptor
What is Pendred syndrome?
Congenital hypothyroidism. Autosomal recessive genetic condition causing deficiency in Pendrin which transports iodine to the colloid.
