Thyroid

Question 1

Draw an diagram and explain the feedback mechanisms involved in the secretion of thryoid hormone

Answer 1

Refer to notes-
TRH synthesized in the paraventriuclar nucleus- enters portal blood in median eminance, binds to GPCR on thyrotrophs- increases Ca- releases TSH
TSH- blood system to thryoid gland and binds to GPCR on basolateral membrane and triggers everthing!!
Secretion of T4 and some T3 inhibits hypothalamus and pituitary and has peripheral actions

Question 2

Draw diagram of formation and secretion of thyroglobulin

Answer 2

1. Oxidation of iodide to iodine that can then combine directly with tyrosin (promoted by peroxidase after/in apical membrane)
2. Organification of thyroglobulin: iodine binds with tyrosine molecules in TG with iodinase enzyme… MIT+I = DIT etc
3. Storage of TG (up to 30 T4 inside)
   Release: cleavage of TG (enters via pinocytosis then cleavage with T4/3 released and DIT/MIT recycled)

Question 3

How is thyroid hormone transported?

Answer 3

70% bound to thyroxine binding globulin and some bindes to prealbumin and albumin

Question 4

Describe with the help of a diagram how thyroid hormone has its effects

Answer 4

Retinoid x receptor- changes transcription
Carbs: increased gluconeogenesis, incred glycogenolysis
Protein: increased synthesis and proteinolysis (muscle wasting)
Lipid: increased liplysis and decreased serum cholesterol (via increased LDL receptor on hepatocytes)
GIT: Increased motility and juices
Cardiovascular: cardiac output, widened pulse pressure, increased HR, heart strength, increased resp
Metabolism: Increased BMR/mitochondria/NaK ATPase

Question 5

Why do people with thryoid disease lose weight?

Answer 5

Increased basal metabolic rate

Increased gut motility and associated hyperdefecation and malabsorption

Question 6

How does hyperthyroidism lead to AF?

Answer 6

Thryoid hormone has ionotropic and chronotropic effects because it:
Increases transcription of Ca ATPase on SR, transcription of myosin and transcription of beta adrenorecptors
Increased stimulation increases firing rate in SA node
Over stimulation overwhelms the normal electrical impulses and causes diorganised firing and contraction therefore AF

Question 7

Why do beta blockers work to alleviate the sx of hyperthyroidism?

Answer 7

Many sx caused by upregulation in beta adrenergic receptors

Propranolol also has effect on 5- monoiodinase that converts T4 to T3

Question 8

What is thyrotoxicosis?

Answer 8

The state of thyroid hormone excess when tissues are exposed to high levels causing generalised acceleration of metabolic processes (not necessarily caused by hyperthyroidism- thyroiditis, exogenous thyroid hormone etc)

Question 9

What is thyroid storm?

Answer 9

Infection in poorly managed thyrotoxicosis
Sx: confusion, fever, agitation, tachy, AF,
Tx: rehydrate, broad spectrum antibiotic, propranolol and dosium ipodate

Question 10

What are the causes of hypothyroidism?

Answer 10

Primary: iodine deficiency, autimmune sugery, drugs, congenital
Secondary- result of disorder of ant pituitary
Tertiary: hypothalamus disorder
Sx: dry/course skin, tiredness, weakness, feeling cold, hair loss, cognition, weight gain with poor appetite

Question 11

What is the cause of: dry/course skin, tiredness, weakness, feeling cold, hair loss, cognition, weight gain with poor appetite
DDx? Ix? Tx?

Answer 11

Hypothyroidism
Ddx: depression , alzheimers, anaemia
Ix: Serum TSH (increased) then serum T4 and radioactive iodine uptake
Tx: Levothyroxine for life

Question 12

What are the causes of hyperthyroidism?

Answer 12

Primary: graves, too much iodine/synthetic T4, cacner thyroiditis
Secondary: Pituitary adenoma
Sx: heat intolerance, sweating, palpitations, tremor, tachy, diffuse goitre (G), opthalmopathy (graves), pretibial myxoederma (G)

Question 13

What is the cause of: heat intolerance, sweating, palpitations, tremor, tachy, diffuse goitre, opthalmopathy, pretibial myxoederma
Ddx? Ix? Tx?

Answer 13

Hyperthyroidsim
Ddx: toxic nodular disease, subacute thyroiditis, cocain/amphetamine use, cancer psychological disorder
Ix: TSH (down in primary), T4 (increased), radioactive iodine uptake
Tx: Radioactive iodine
thyroid surgery
prolonged antithyroid durg therapy (risk of rash and agranocytosis)

Question 14

What is phaeochromocytoma?

Answer 14

Catecholamine producing tumours of the SNS (paraganglionoma is extra adrenal phaeochromocytoma)
Sx: pain, palpiation, perspiration and hypertension
Dx: 24hr catecholamine +plasma catecholamines and T2 weighted MRI
Ddx: hypertension, panic attacks, substance use
Tx: remove the tumour, medical is alpha blockers +/- beta blockers

Question 15

How does neomercazole work?

Answer 15

Carbimazole, inhibits thyroperoxidase so inhibts the iodination of tyrosil resides in thyroglobulin
Side effects: nausea, headache, arthralgia, mild gastric distress, rashes and pruitis as well as BONE MARROW DEPRESSION!!!

Question 16

What is the triad of Graves disease?

Answer 16

hyperfunctional enlargement of thyroid
infiltrative opthalmopathy with resulting exopthalmos
Localised infiltrative dermopathy (pretibial)

Question 17

What antibodies would you see in Graves disease?

Answer 17

Against TSH

1) Thyroid stimulating immunoglobulin (mimics)
2) Thyroid growth stimulating Ig (proliferation)
3) TSH binding inhibitor Ig (antagonist)

Question 18

Explain the infiltrative opthalmopahty seen in Graves

Answer 18

Infiltration of retroorbital space/connective tissues by T cells which causes inflammatory oedema and swelling of muscles > accumulation of ECM components and increased number of adipocytes (which also have TSH receptor… increases inflammation)
Eye moves forward

Question 19

What autantibodies would you expect in Hashimoto’s thyroiditis?

Answer 19

Against thyroglobulin and thyroid peroxidase (TPO) which is possibly caused by abnormal regulatory T cells, exposure of normally sequestered thyroid antigen

Question 20

What happens in Hashimoto’s thyroiditis?

Answer 20

Induction of thyroid autoimmunity is accompanied by progressive depletion of thyrocytes by apoptosis and replacement of the thyroid parenchyma (CD8+ T cells, cytokine- macrophages or marked by antibodies) by mononuclear cell infiltration and fibrosis.

Causes hyperthyroidism and ultimately hypothyroidism