Endocrine Topic 6 - Thyroid Gland Flashcards
How is hyperthyroidism treated?
- Thionamides - carbizamole, propylthiouracil
- Carbizamole - drug of choice, absorbed well from gut, converted to methimazole via 1st pass metabolism, half life = 12-15 hours
- Propylthiouracil - less active, shorter half-life, higher dose needed - 2nd line or in pregancy
- Beta-blockers e.g. propanolol - reduces sympathetic symptoms, no hormonal effect
- Potassium iodide - reduced TH released acutely
- Radioactive iodine
- Surgery - thyroidectomy (partial or total)
Describe the location of the thyroid gland
- Anterior neck, C5-T1
- Behind sternohyoid and sternothyroid muscle
- Visceral compartment of neck (with trachea, oesophagus and pharynx) - bound by the pre-tracheal fascia
What are the risk factors for hypothyroidism?
- Female
- Age
- Genetic predisposition (autoimmune)
- Drugs e.g. lithium
What change occurs in the follicles when they become active?
Epithelial cells - Cuboidal/squamous to columnar when active
Describe the pathophysiology of autoimmune hypothyroidism
- Infiltration of CD4+ and CD8+ T cells, autoantibodies blocking TSH receptor/attacking thyroid peroxidase/Tg
- Progressive destruction of thyroid follicular tissue
How is thyroid hormone release stimulated?
- Thyroid releasing hormone (TRH) secreted by hypothalamus, stimulates thyroid stimulating hormone (TSH) release from the anterior pituitary
- TSH binds to G protein coupled receptor on follicular cells, activated cAMP and phospholipase C
- cAMP mediates actions - increased Tg iodination, microvilli number and length, endocyotsis of colloid droplets, TH release, iodine influx, cellular metabolism, protein (including Tg) synthesis and DNA synthesis
- Increases TH stores, within 1 hours increases TH release
Describe the innervation of the thyroid gland
Sympathetic trunk, doesn’t control hormone secretion
Why is propylthiouracil used to treat hyperthyroidism in pregnancy?
Carbimazole (usually drug of choice) has adverse effects on newborns - skin conditions
How is hyperthyroidism diagnosed?
- Biochemical proof of suppressed TSH and high free thyroid hormone
- Anti-TSH receptor/Tg/TPO antibodies
- ESR - inflammation
- Ultrasound - increased vascularisation of thyroid (Grave’s)
- Radioactive iodine uptake test with PET scan
How is hypothyroidism treated?
- Levothyroxine
- 1.7-2.0 micro g/kg/day on empty stomach
- Avoid taking with PPI, ferrous sulphate or calcium - chelate, won’t be absorbed (incomplete gastric absorption)
- Start low in elderly/cardiac disease - increase HR quickly, could have ischaemic heart disease
- Long half-life
- Travels bound to protein, metabolised to triiodothyronine (T3)
- Goal = normalise symptoms and TSH (normal level is disputed)
Describe the action of thyroid hormone
- Nuclear receptors - cytosolic T3 transported to the nucleus, binds to thyroid receptors alpha and beta, proteins synthesised
- T3 acts as ligan for TR - transcription factor, alters gene expression
- Determinants of brain and somatic development (foetal)
- Skeletal (increases in bone tumours), cardiovascular (increases HR), increases metabolic rate
What are the functional units of the thyroid gland?
- Follicles - epithelial structures
- Single layer of cuboidal epithelium with basement membrane, colloid in centre
- Store thyroglobulin (iodinated glycoprotein) - storage form of T3/4
What are the risks for hyperthyroidism?
- Autoimmune disease
- Female
- Pregnancy
- Drugs e.g. amidarone
How does thyroglobulin become converted to active hormone?
- Colloid enveloped by microvilli on cell surface (endocytosis) to form colloid vesicles within cells, fuse with lysosomes
- Enzymes in lysosomes break down iodinated thyroglobulin, releasing T3/4
- T3/4 pass across basal cell membrane into capillary (T4>T3)
What causes hypothyroidism?
- Primary - high TSH, low T4
- Autoimmune Hashimoto thyroiditis
- Iodine deficiency
- Drugs e.g. lithium
- Congenital hypothyroidism
- Post-radioactive iodine
- Post-thyroiditis
- Secondary - low TSH, low T4
- Pituitary or hypothalamic disease
Define goitre
Swelling of the neck due to enlargement of the thyroid - hypothyroid, hyperthyroid or euthyroid with nodular disease
Describe dermopathy in Grave’s disease
- Infiltrative dermopathy, waxy discoloured induration of the skin (peau d’orange)
- Begins in feet/lower legs, spreads upwards in advanced cases
Compare hypo- and hyperthyroidism
- Hypothyroidism = low TH
- More common and more difficult to treat
- Hyperthyroidism = excess TH
List the signs/symptoms of hypothyroidism
- Weight gain
- Depression
- Lethargy
- Constipation
- Cold intolerance
- Poor concentration
- Hoarseness
- Menorrhagia
- Bradycardia
- Dry skin
- Coarse, thin hair
- Anaemia
- Slow relaxing reflexes
- May have goitre
- Pale, puffy face
- Lose lateral 1/3 of eyebrows
What causes hyperthyroidism?
- Autoimmune - Grave’s disease
- Toxic adenoma - benign hormone-producing tumour
- Multinodular goitre
- Thyroiditis (transient)
- Excess administration of thyroxine (? weight loss) - high T4, low TSH
How does radioactive iodine function to treat hyperthyroidism?
- Destroys thyroid tissue by beta emission
- May worsen eye disease
- Defer conception (at least 4 months), pregnancy = contraindication
- Hypothyrodism is main side effect - may be transient
Describe the arterial supply of the thyroid gland
- Superior and inferior thyroid artery (left and right)
- Superior is 1st branch of external carotid - supplies superior and anterior parts
- Inferior is branch of thyrocervical trunk, from subclavian artery - supplies posterior and inferior parts
Describe the mechanism of action of thionamides
- Reduce TH synthesis
- Inhibit iodide oxidation (inhibit thyroid perioxidase)
- Inhibit iodination of tyrosine
- Inhibit coupling of DI/MIT
- Slow effect
- Propylthiouracil - reduces conversion of T4 to T3, reduces action of T3 acutely
What causes Hashimoto’s thyroiditis?
- Autoantibodies against thyroid perioxidase, thyroglobulin and TSH
- Activation of CD8+ T cells in response to cell mediated immune response affected by CD4+ T cells - thyrocyte destruction
- Type 4 hypersensitivity
Describe the venous drainage of the thyroid gland
- Superior, middle and inferior thyroid veins - form venous plexus
- Supeior and middle drain to internal jugular vein
- Inferior drains to brachiocephalic vein
How is hypothyroidism diagnosed?
Measure - free T4, TSH, thyroid autoantibodies
Describe circulating thyroid hormone
- Free 0.5%, bound 99.5%
- Free is active and regulated
- Bound is bound to thyroid binding globulin, transthyretin and albumin
- T4 converted to T3 by deiodination from outer ring in periphery
- Catalysed by selenodiodinase enzymes (D1 in liver, kidney, muscle, D2 in brain, pituitary)
What is Grave’s disease?
Autoimmune condition, thyroid stimulating antibody
Describe the embryonic origin of the thyroid gland
- Endodermal origin, forms in floor of primitive pharynx near base of tongue (thyroglossal duct)
- Moves down through neck (and hyoid bone) to adult anatomical position
- Foramen caecum at back of tongue is embryological remnant
What are the potential complications of thyroidectomy?
- Haemorrhage - thyroid is very vascular
- Recurrent laryngeal palsy (hoarseness)
- Permanent hypocalcaemia (PTH damage)
- Hypothyroidism
Describe the gross structure of the thyroid gland
- L and R lobes (+ pyramidal lobe sometimes - anatomical variant) - R bigger, joined by isthmus
- Weight 15-25g - varies with I2 intake, increases during puberty, pregnancy, lactation
- Very vascularised
Compare T3 and T4
- T4 - higher quantity released
- Less active, like a prohormone
- T3 - more active form, formed by peripheral deiodination of T4
How is colloid produced in thyroid follicles?
- Synthesise glycoprotein
- Protein from RER, sugar added in Golgi
- Convert iodide to iodine
- Iodine + glycoprotein = thyroglobulin
Describe the structure of T3/4
- T4 - 2 tyrosine and 4 iodine
- T3 - 2 tyrosine and 2 iodine
What is the function of the thyroid gland in calcium homeostasis?
- Thyroid C/parafollicular C cells - in follicles and between follicles
- Secrete calcitonin - decreases serum Ca2+
What are the complications of Grave’s disease?
- Dysthyroid eye disease
- Dermopathy
- Thyroid acropachy
Describe Grave’s ophthalmopathy
- Swelling in retrobulbar area due to glycosaminoglycan accumulation
- Lid retraction/lag and periorbital oedema
- Proptosis (protrusion), diplopia, nerve compression
- Potentially sight threatening
What are the signs/symptoms of classical thyrotoxicosis?
- Weight loss
- Tremor
- Heat imbalance
- Diarrhoea
- Tachycardia
- Hypertension
- Palpitations
- Sweating
Describe the synthesis of thyroid hormones
- Need iodine - seawater, fruit, vegetables
- Oral iodine converted to iodide in GI tract and absorbed
- Iodide transported into follicular cells against chemical gradient on basolateral membrane by sodium iodide transporter (thyroid symporter) - active transport, inhibited by perchlorate
- Iodide diffuses to apex, prendrine transports into vesicles at apical membrane
- Oxidation of iodide to iodine in vesicles, catalysed by thyroid peroxidase
- Binds to tyrosine residues on thyroglobulin = organification
- Formatioin of di/mono-iodotyrosine (T3/4), endocytosis of thyroglobulin into cell
What is thyroid acropachy?
- Rare
- Digital clubbing, swelling of digits and toes - periosteal reaction of extremity bones
- Usually with ophthalmopathy and dermopathy
