Hyperthyroidism Flashcards
-> Function of endocrine glands: Summarise the function of the key endocrine glands, including the synthesis, regulation and physiological effects of their hormones. -> Endocrine disorders: Describe the clinical features and treatment options of endocrine disorders.
1
Q
Which endocrine cells release TSH?
A
- Thyrotrophs within the anterior pituitary gland
2
Q
Which cells respond to TSH?
A
- Follicular cells of the thyroid gland
3
Q
How is iodine pumped into follicular cell of the thyroid gland?
A
- Sodium-iodine symporter (secondary active transport)
4
Q
How is iodide pumped from the follicle into the colloid?
A
- Pendrin pumps within the apical membrane
5
Q
How is iodine activated into iodide?
A
- Under the action of thyroid peroxidase in the presence of hydrogen peroxide
6
Q
Where does iodination occur within the thyroid gland?
A
- Within the colloid
7
Q
What are the two direct products of iodination of thyroglobulin within the colloid?
A
- Monoiodotyrosine (MIT) or Diiodotyrosine (DIT) molecules
8
Q
Which thyroid pro-hormone is iodinated?
A
- Thyroglobulin
9
Q
Which thyroglobulin residues are iodinated?
A
- Tyrosine residues
10
Q
How is triiodothyronine (T3) formed?
A
- Coupling of MIT and DIT
11
Q
How is tetraiodothyronine / thyroxine (T4) formed?
A
- Coupling of DIT molecules
12
Q
Which thyroid hormone is active?
A
- T3
Tetraiodothyronine (Thyroxine, T4) is a prohormone converted by deiodinase enzyme into the more active metabolite triiodothyronine (T3)
13
Q
Which structures are directly inhibited by thyroxine (fT4) via negative feedback mechanisms?
A
- Anterior pituitary gland (thyrotrophs)
- Hypothalamic neurones (secreting TRH)
14
Q
What is the effect of thyroxine (fT4) on the heart rate?
A
- Sensitives beta adrenoreceptors to ambient levels of adrenaline and noradrenaline
- This increases the heart rate ( tachycardia and tremor in hands) → Lid lag
15
Q
What are the common forms of hyperthyroidism (4)?
A
- Grave’s Disease (Autoimmune Disease)
- Plummer’s Disease (Non-Autoimmune Disease)
- Viral (de Quervain’s) thyroiditis
- Post partum thyroiditis
16
Q
What is the pathophysiology of Grave’s disease (autoimmuune hyperthyroidism)?
A
- TSH Immunoglobulins binds to TSH receptors in the thyroid gland
- Stimulation of TSH receptors subsequently result in smooth goitre formation and hyperthyroidism
17
Q
What are the clinical signs of Grave’s disease (3)?
A
- Elevated fT4
- Elevated fT3
- Insufficient TSH
18
Q
What are the clinical features of Grave’s disease (10)?
A
- Respiration, facial flushing
- Muscle wasting
- Shortness of breath
- Heat intolerance
- Weight loss - despite increased appetite
- Localised myxoedema
- Tremor
- Sweating
- Palpitations
- Exophthalmos (proptosis)
Antibodies bind to muscles behind the eye and cause exophthalmos
19
Q
What is pretibial myxoedema?
A
- The swelling that occurs on the shins (legs) of patients with Grave’s disease: growth of soft tissue
Not to be confused with myxoedema = hypothyroidism
20
Q
What type of goitre is shown in a patient with Plummer’s disease (non-autoimmuune hyperthyroidism)?
A
-
Toxic nodular goitre
- Benign nodules of the thyroid gland (not autoimmune associated)
21
Q
What are the clinical signs of Plummer’s disease (3)?
A
- Elevated fT4
- Elevated fT3
- Insufficient TSH
22
Q
What are the clinical features of Plummer’s disease (8)?
A
- Weight loss - despite increased appetite
- Shortness of breath
- Palpitations
- Tachycardia
- Sweating
- Heat intolerance
- Diarrhoea
- Lid lag and other sympathetic features
23
Q
What are the four main features of viral (de Quervain’s) thyroiditis?
A
- Painful dysphagia
- Hyperthyroidism (The thyroid gland is tender and palpable)
- Pyrexia (fever)
- Thyroid inflammation
24
Q
How is hyperthyroidism induced in individuals with viral (de Quervain’s) thyroiditis?
A
- Round follicle is damaged, subsequently causing stored thyroxine within the colloid to be released
25
Describe the pattern of iodine uptake in an individual with viral (de Quervain’s) thyroiditis.
* There is **no iodine uptake** as the thyroid gland stops making thyroxine
26
How is hypothyroidism caused in individuals with viral (de Quervain’s) thyroiditis?
* Four weeks upon the onset of viral thyroiditis, **stored thyroxine is depleted**
27
How is viral (de Quervain’s) thyroiditis managed?
* A further month after hypothyroidism occurs, resolution occurs (like in all viral diseases)
* Patient then becomes **euthyroid** again.
28
What type thyroid scan is conducted to identify the type of goitre in hyperthyroidism (Grave's or Plummer's)?
* **Iodine-123** scan
29
Which radioisotope is administered for a thyroid scan?
* Tc-99
30
How is Grave's disease diagnosed (distinguished from Plummer's disease) (2)?
* Positive **anti-TSH** **receptor** antibody blood test
* Radioactive iodine uptake test
## Footnote
Diffuse goitre of moderate size and uniform radioiodine uptake
31
Which part of the thyroid gland uptakes iodine-123 in Plummer's disease?
* The **toxic nodular goitre**
* The inactive thyroid gland is suppressed due to the adenoma.
32
What are the long term treatment options of hyperthyroidism (3)?
* **Surgery**
* **Radioiodine**
* **Anti-thyroid drugs**
33
What are the associated risks with a thyroidectomy?
* Risk of **voice change**
* Risk of also **losing parathyroid glands**
* **Scar**
* **Anaesthetic**
34
Which nerve is at risk of damage during a thyroidectomy?
* The **recurrent laryngeal nerve**
35
Which isotope is used in radioiodine?
* **Iodine 131**
* Emits radiation for 10 days therefore avoid pregnant individuals
36
What are the 3 main classes of drugs used in the treatment of hyperthyroidism?
1. Thionamides
1. Potassium Iodide
1. Beta-blockers
37
How long should anti-thyroid drugs typically be prescribed for?
18 months
38
What class of drug is the main anti-thyroid?
* **Thionamides**
* Propylthiouracil (PTU)
* Carbimazole (CBZ)
39
What is the mechanism of action of thionamides?
* **Inhibition of thyroid peroxidase and peroxidase transaminase**, therefore **reduce** iodine activation and iodination of thyroglobulin into **MIT & DIT**
40
Which enzyme is inhibited by thionamides?
Thyroid peroxidase
41
Why does it take 3-4 weeks for the clinical effects of anti-thyroid hormones to become apparrent?
* There is a months **store of thyroxine**
42
Which co-drug is prescribed alongside thionamides? Why?
* **Propanolol** rapidly reduces **tremors & tachycardia**
43
What are the unwanted actions of thinamides (2)?
* **Agranulocytosis** (reduction in neutrophils) - neutropenia increases risk of sepsis
* **Rashes** (common)
## Footnote
Agranulocytosis is reversed witht he withdrawl of the drug
44
Which drug should be pre-operatively administered in hyperthyroid patients?
Potassium Iodide - induces Wolff-Chaikoff effect (10 days)
45
What effect does KI have in hyperthyroid patients (3)?
* **Inhibits hydrogen peroxide** generation and thyroid peroxidase
* **Reduces vascularity and size of gland** (atrophy of thyroid gland)
* **Inhibits the iodination of thyroglobulin** by inducing the Wolff-Chaikoff effect
46
Which effect demonstrates the auto-regulatory function of iodine control?
* Wolff-Chaikoff effect
47
What is the Wolff-Chaikoff effect?
* An **autoregulatory function**, whereby an **excess ingestion of iodine inhibits thyroid peroxidase activity** and thus **reducing iodothyronine production** within thyroid follicular cells, **independent from the serum-level of thyroid-stimulating hormone (TSH)**
48
What purpose do beta-blockers have in terms of hyperthyroidism treatment?
* Alleviate the symptoms concerned with **arrhythmia**
49
What is the role performed by beta blockers in thyrotoxicosis?
* Reduces heart rate and beta adrenoreceptor sensitivity
50
What are the main clinical features of a thyroid storm (5)?
* **Hyperpyrexia** \> 41 oC
* Accelerated **tachycardia** / arrhythmia
* **Cardiac failure**
* **Delirium** / frank psychosis
* Hepatocellular dysfunction; **jaundice**
51
What are the main treatment options for a thyroid storm (3)?
* Thyroidectomy
* Radioiodine
* Drugs
52
What are the short term drug options of a thyroid storm (2)?
* Beta - blockers
* Thionamides
