Endocrine Topic 6 - Thyroid Gland

Question 1

How is hyperthyroidism treated?

Answer 1

• 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)

Question 2

Describe the location of the thyroid gland

Answer 2

• Anterior neck, C5-T1
• Behind sternohyoid and sternothyroid muscle
• Visceral compartment of neck (with trachea, oesophagus and pharynx) - bound by the pre-tracheal fascia

Question 3

What are the risk factors for hypothyroidism?

Answer 3

• Female
• Age
• Genetic predisposition (autoimmune)
• Drugs e.g. lithium

Question 4

What change occurs in the follicles when they become active?

Answer 4

Epithelial cells - Cuboidal/squamous to columnar when active

Question 5

Describe the pathophysiology of autoimmune hypothyroidism

Answer 5

• Infiltration of CD4+ and CD8+ T cells, autoantibodies blocking TSH receptor/attacking thyroid peroxidase/Tg
• Progressive destruction of thyroid follicular tissue

Question 6

How is thyroid hormone release stimulated?

Answer 6

• 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

Question 7

Describe the innervation of the thyroid gland

Answer 7

Sympathetic trunk, doesn’t control hormone secretion

Question 8

Why is propylthiouracil used to treat hyperthyroidism in pregnancy?

Answer 8

Carbimazole (usually drug of choice) has adverse effects on newborns - skin conditions

Question 9

How is hyperthyroidism diagnosed?

Answer 9

• 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

Question 10

How is hypothyroidism treated?

Answer 10

• 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)

Question 11

Describe the action of thyroid hormone

Answer 11

• 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

Question 12

What are the functional units of the thyroid gland?

Answer 12

• Follicles - epithelial structures
  
  • Single layer of cuboidal epithelium with basement membrane, colloid in centre
  • Store thyroglobulin (iodinated glycoprotein) - storage form of T_3/4

Question 13

What are the risks for hyperthyroidism?

Answer 13

• Autoimmune disease
• Female
• Pregnancy
• Drugs e.g. amidarone

Question 14

How does thyroglobulin become converted to active hormone?

Answer 14

• 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 T_3/4
• T_3/4 pass across basal cell membrane into capillary (T₄>T₃)

Question 15

What causes hypothyroidism?

Answer 15

• 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

Question 16

Define goitre

Answer 16

Swelling of the neck due to enlargement of the thyroid - hypothyroid, hyperthyroid or euthyroid with nodular disease

Question 17

Describe dermopathy in Grave’s disease

Answer 17

• Infiltrative dermopathy, waxy discoloured induration of the skin (peau d’orange)
• Begins in feet/lower legs, spreads upwards in advanced cases

Question 18

Compare hypo- and hyperthyroidism

Answer 18

• Hypothyroidism = low TH
  
  • More common and more difficult to treat
• Hyperthyroidism = excess TH

Question 19

List the signs/symptoms of hypothyroidism

Answer 19

• 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

Question 20

What causes hyperthyroidism?

Answer 20

• Autoimmune - Grave’s disease
• Toxic adenoma - benign hormone-producing tumour
• Multinodular goitre
• Thyroiditis (transient)
• Excess administration of thyroxine (? weight loss) - high T_4, low TSH

Question 21

How does radioactive iodine function to treat hyperthyroidism?

Answer 21

• 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

Question 22

Describe the arterial supply of the thyroid gland

Answer 22

• 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

Question 23

Describe the mechanism of action of thionamides

Answer 23

• 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 T_3, reduces action of T₃ acutely

Question 24

What causes Hashimoto’s thyroiditis?

Answer 24

• 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

Question 25

Describe the venous drainage of the thyroid gland

Answer 25

* Superior, middle and inferior thyroid veins - form venous plexus * Supeior and middle drain to internal jugular vein * Inferior drains to brachiocephalic vein

Question 26

How is hypothyroidism diagnosed?

Answer 26

Measure - free T_4, TSH, thyroid autoantibodies

Question 27

Describe circulating thyroid hormone

Answer 27

* 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)

Question 28

What is Grave's disease?

Answer 28

Autoimmune condition, thyroid stimulating antibody

Question 29

Describe the embryonic origin of the thyroid gland

Answer 29

* 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

Question 30

What are the potential complications of thyroidectomy?

Answer 30

* Haemorrhage - thyroid is very vascular * Recurrent laryngeal palsy (hoarseness) * Permanent hypocalcaemia (PTH damage) * Hypothyroidism

Question 31

Describe the gross structure of the thyroid gland

Answer 31

* 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

Question 32

Compare T3 and T4

Answer 32

* T4 - higher quantity released * Less active, like a prohormone * T3 - more active form, formed by peripheral deiodination of T₄

Question 33

How is colloid produced in thyroid follicles?

Answer 33

* Synthesise glycoprotein * Protein from RER, sugar added in Golgi * Convert iodide to iodine * Iodine + glycoprotein = thyroglobulin

Question 34

Describe the structure of T_3/4

Answer 34

* T₄ - 2 tyrosine and 4 iodine * T₃ - 2 tyrosine and 2 iodine

Question 35

What is the function of the thyroid gland in calcium homeostasis?

Answer 35

* Thyroid C/parafollicular C cells - in follicles and between follicles * Secrete calcitonin - decreases serum Ca²⁺

Question 36

What are the complications of Grave's disease?

Answer 36

* Dysthyroid eye disease * Dermopathy * Thyroid acropachy

Question 37

Describe Grave's ophthalmopathy

Answer 37

* Swelling in retrobulbar area due to glycosaminoglycan accumulation * Lid retraction/lag and periorbital oedema * Proptosis (protrusion), diplopia, nerve compression * Potentially sight threatening

Question 38

What are the signs/symptoms of classical thyrotoxicosis?

Answer 38

* Weight loss * Tremor * Heat imbalance * Diarrhoea * Tachycardia * Hypertension * Palpitations * Sweating

Question 39

Describe the synthesis of thyroid hormones

Answer 39

* 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 (T_3/4), endocytosis of thyroglobulin into cell

Question 40

What is thyroid acropachy?

Answer 40

* Rare * Digital clubbing, swelling of digits and toes - periosteal reaction of extremity bones * Usually with ophthalmopathy and dermopathy