Hyperthyroidism

Question 1

What are the effects of T3/T4?

Answer 1

BMR: increases the basal metabolic rate.
Metabolism: it has anabolic effects at low serum levels and catabolic effects at higher levels.
Growth: increases release and effect of GH and IGF-1.
Cardiovascular: increases the heart rate and contractility through increasing sensitivity to catecholamines.

Question 2

How is thyroid hormone synthesised (general)?

Answer 2

Tyrosine synthesised in body and iodine gained from diet is used. Glycoprotein thyroglobulin used as base with synthesis occuring in central colloid.

Question 3

Describe preparation of thyroid hormone synthesis

Answer 3

1. Iodide enters the cell across the basolateral membrane via a sodium symporter. This process is driven by secondary active transport mediated by a Na+/K+-ATPase pump.
2. At the luminal membrane, iodide is activated by thyroperoxidase (TPO) before entering the colloid via the ion exchanger Pendrin.
3. Thyroglobulin, containing tyrosine, is produced by Golgi complexes and the endoplasmic reticulum in the follicular cells. The thyroglobulin/tyrosine complex is exocytosed across the luminal membrane into the colloid.

Question 4

Describe synthesis stage of thyroid hormone synthesis

Answer 4

1. Within the colloid, one iodide may attach to a tyrosine (attached to a thyroglobulin) to form monoiodotyrosine (MIT). This reaction is catalysed by TPO.
2. A second iodide may attach to MIT to form di-iodotyrosine (DIT).
3. Coupling of MIT and DIT yield the thyroid hormones. One MIT and one DIT gives triiodothyronine (T3) while two DITs give thyroxine (T4).

Question 5

Describe release stage of thyroid hormone synthesis

Answer 5

When stimulated (by TSH) the surrounding follicular cells phagocytose a portion of the colloid. Once within the follicular cell, this vesicle is subject to lysosomes which act to release the T3/T4 from Tg. The thyroid hormones T3/T4 may then diffuse into the blood stream. Any remaining MIT and DIT is deiodinated (a reaction catalysed by iodinase) and recycled.

Question 6

What is Graves’ Disease?

Answer 6

An autoimmune disorder where anti-TSH receptor antibodies are made which bind to and stimulate the TSH receptor causing excess thyroid hormone release. Appears as a smooth goitre.

Question 7

What are symptoms of Graves’ Disease?

Answer 7

Perspiration, facial flushing, muscle wasting, shortness of breath, breast enlargement/gynaecomastia, loss of weight, rapid pulse, warm palms, oligo/amenorrhoea, myxoedema, exophthalmos. goitre, warm skin, palpitations, tachycardia, increased appetite, diarrhoea, tremor, clubbing of fingers, muscular weakness

Question 8

How is exophthalmos caused?

Answer 8

Antibodies bind to muscles behind the eyes cause hypertrophy and an appearance of protrusion

Question 9

Define pretibial myxoedema

Answer 9

The swelling (non-pitting) that occurs on the shins of patients with Graves’ disease. It is growth of excess soft tissue (hypertrophy). Also caused by antibodies.

Question 10

What is a radiological and a physical feature of Graves’ Disease?

Answer 10

Diffuse enlargement and engorgement of thyroid gland. Diffuse goitre of moderate size and uniform radioiodine uptake.

Question 11

What are features of Pummer’s Disease

Answer 11

Characterised by a toxic nodular goitre. Caused by a Benign adenoma that is overactive at making thyroxine so no autoimmune features seen. Scintigram shows a hyperfunctioning adenoma as unsymmetric enlargement of thyroid with one section taking up much more radioiodine than others.

Question 12

What are the effects of thyroxine on the sympathetic nervous system?

Answer 12

Sensitises beta adrenoceptors to ambient levels of adrenaline and noradrenaline. Thus there is apparent sympathetic activation such as tremors, palpitations, lid lag and tachycardia.

Question 13

How is a thyroid storm diagnosed?

Answer 13

Any 2 of the following features being present:

1. Hyperpyrexia > 41oC
2. Accelerated tachycardia (>170) / arrhythmia
3. Cardiac failure
4. Delirium / frank psychosis
5. Hepatocellular dysfunction; jaundice

Question 14

What are outcome statistics for thyroid storm?

Answer 14

Is a medical emergency and needs aggressive treatment. 50% mortality if left untreated.

Question 15

What are treatment options for hyperthyroidism?

Answer 15

1. Surgery (thyroidectomy)
2. Radioiodine
3. Drugs

Question 16

What are the 4 classes of drugs used in the treatment of hyperthyroidism?

Answer 16

1. The thionamides (thiourylenes; anti-thyroid drugs)
   - propylthiouracil (PTU)
   - carbimazole (CBZ)
2. Potassium Iodide
3. Radioiodine
4. β-blockers

First 3 reduce thyroid hormone synthesis while beta blockers reduce symptoms

Question 17

Describe mechanism of action of thionamides

Answer 17

Used in daily treatment of hyperthyroidism. Inhibits thyroid peroxidase and hence T3/4 synthesis and secretion. Has biochem effect in hours but clinical effect takes weeks to show. May be coupled with propanolol to reduce symptoms like palpitations and tremors.

Question 18

What are some unwanted actions of thionamides?

Answer 18

1. Agranulocytosis (usually reduction in neutrophils) - rare and reversible on withdrawal of drug.
2. Rashes (relatively common)

Question 19

What 2 things should be remembered in follow-up?

Answer 19

1. Usually aim to stop anti-thyroid drug treatment after 18 months
2. Review patient periodically including thyroid function tests for remission/relapse

Question 20

What is the role of beta blockers?

Answer 20

Control of symptoms in the interim while other treatment options work. Non-selective beta blockers used to have a widespread effect.

Question 21

How is iodide used in treatment?

Answer 21

Potassium iodide prescribed in quantities above 30 times DRA. Acts via Wolff-Chaikoff effect, inhibiting thyroperoxidase and hydrogen peroxide formation as well as iodination of thyroglobulin. Vascularity and size of gland will reduce in 10-14 days. Hyperthyroid symptoms reduce in 10-14 days.

Question 22

What are the 4 risks of surgery?

Answer 22

1. Risk of voice change
2. Risk of also losing parathyroid glands
3. Scar
4. Anaesthetic

Question 23

What is the role of radioiodine and how is it administered?

Answer 23

Radioactivity blocks thyroid hormone synthesis. Taken by swallowing a capsule containing about 370 MBq (10 mCi) of the isotope I (131).

Question 24

When is radioidoine contraindicated?

Answer 24

In pregnant and breastfeeding women. Children and pregnant mums must be avoided for a few days after treatment.

Question 25

What else can radioiodine be used for?

Answer 25

For scans only (not treatment), 99-Tc pertechnetate is an option.

Question 26

What 4 symptoms is viral thyroiditis characterised by?

Answer 26

Painful dysphagia
Hyperthyroidism
Pyrexia
Thyroid inflammation

Question 27

What is a natural history of viral thyroiditis?

Answer 27

Virus attacks thyroid gland causing pain and tenderness
Thyroid stops making thyroxine and makes viruses instead
Thus no iodine uptake (ZERO)

Question 28

What are the consequences of viral thyroiditis?

Answer 28

No new thyroxine made and instead stored thyroxine is released. Thus is toxic with zero uptake and 4 weeks later when stored thyroid is exhausted, hypothyroid.

Question 29

Summarise sequence of viral thyroiditis

Answer 29

After viral attack:

1. Neck becomes painful
2. All stored thyroxine released
3. Free T4 levels rise
4. TSH levels drop
5. 1 month hyperthyroidism but NO new thyroxine is being synthesised
6. Patient becomes hypothyroid – gland stops making thyroxine and just replicates virus
7. Hypothyroidism lasts a second month
8. After 3 months, there is slow recovery

Question 30

What is postpartum thyroiditis?

Answer 30

Similar to viral thyroiditis but no associated pain and only occurs after pregnancy. Caused by modulations of the immune system that occur during pregnancy.