Drugs used in Thyroid Disorders

Question 1

Which hormone is released by the hypothalamus and controls thyroid hormone secretion?

Answer 1

Thyrotropin-Releasing Hormone (TRH).

Question 2

Which hormone is released by the pituitary gland and controls thyroid hormone secretion?

Answer 2

Thyroid Stimulating Hormone (TSH)

Question 3

How are TRH and TSH secretions controlled?

Answer 3

Negative feedback by T4 and T3

Question 4

What is thyroid peroxidase enzyme’s role in thyroid hormone biosynthesis?

Answer 4

1. Oxidation of iodide
2. Iodination of tyrosyl residues to form mono or di-iodo tyrosyl residues, also known as organification

Question 5

What is the half life of T3 and T4?

Answer 5

T3 - about a day, T4 about a week

Question 6

State 5 causes of hypothyroidism

Answer 6

1. Hashimoto thyroiditis
2. pitituary failure
3. hypothalamus failure
4. congenital
5. IODINE DEFICIENCY

Question 7

What would be expected of the TSH and T4 levels in a person with primary hypothyroidism?

Answer 7

High TSH, Low T4

Question 8

What would be expected of the TSH and T4 levels in a person with subclinical hypothyroidism?

Answer 8

Higher than normal TSH, normal T4

Question 9

Name 5 symptoms of hypothyroidism

Answer 9

Fatigue/lethargy
Mental slowness
Dry skin
Weight gain
Irregular menses
Hair loss
Cold intolerance

Question 10

What drugs are commonly used to manage hypothyroidism?

Answer 10

Levothyroxine and Liothyronine

Question 11

What precipitates myxedema coma and how would a patient with myxedema coma present?

Answer 11

Myxedema:
hypothyrodism
= insufficient T3/4 produced
= decrease metabolic rate
= low turnover rate of protein breakdown and metabolism
= glycosaminoglycans (hyaluronic acid, chondrotitin sulfate) accumulate in EXTRAcellular space
= retention of water within glycosaminoglycans, and decreased collagen synthesis
= non pitting edema and dry skin

Precipitated by: systemic illness (infection, heart attack)

long standing untreated hypothyrodism –> myxedema coma

Symptoms:
- altered mental status
-low body temperature
- hypoglycemia
- low blood pressure.

Question 12

How often do we monitor TSH levels after initiating levothyroxine treatment?

Answer 12

6 to 8 weeks

Question 13

What could cause persistently elevated TSH levels after initiation of treatment?

Answer 13

Poor medication compliance, malabsorption, drud/food interactions, inadequate dosing,

Question 14

How does cholestyramine (lipid lowering medication) interfere with levothyroxine absorption?

Answer 14

cholestyramine
= bile acid sequesterant
= bind to bile acids in GIT
= forms insoluble complex
= levothyroxine cannot be absorbed in the intestines into the blood stream
= decreased efficiency of levothyroxine

Question 15

How does estrogen interfere with levothyroxine absorption?

Answer 15

increase estrogen
= increase production of thyroid binding globulin (TBG)
= TBG binds to levothyroxine
= decrease free levothyroxine (T4) concentration in the blood

Question 16

How would you expect levothyroxine requirements to change as one ages?

Answer 16

older individuals
= decrease metabolism
= levothyroxine degraded slower
= decreased levothyroxine required when older

Question 17

How would you expect levothyroxine requirements to change during pregnancy?

Answer 17

Increase by about 30% - 50% early in pregnancy

Question 18

How should levothyroxine be dosed in patients with ischemic disease and why?

Answer 18

levothyroxine increases metabolism
= has inotropic (contraction) and chronotropic (rate) effects
= can cause acute coronary disease if started at a full dose in HF patients
= should do slow upward titration till euthryrodism is achieved

Question 19

Name 5 symptoms of hyperthyroidism

Answer 19

Increased motor activity, metabolism, increased heat production (flushed, warm moist skin),Increased appetite, weight loss with insufficient intake,
Increased heart rate, anxiety, nervousness

Question 20

What would be expected of the TSH and T4 levels in a person with hyperthyroidism?

Answer 20

Low TSH, High T4

Question 21

Name 3 classes of drugs that are used to downregulate thyroid hormone levels in patients suffering from hyperthyroidism

Answer 21

1. Anti thyroid drugs - Thioamides (carbimazole, propylthiouracil, thiamazole)
2. iodine (Lugol’s solution / Potassium iodide),
3. Radioactive iodine therapy (I131)

Question 22

What is the mechanism of action thioamides?

Answer 22

thioamides
1. propylthiouracil
2. carbimazole

thioamides (propylthiouracil) inhibit thyroid peroxidase
= prevent deiodination
= decrease T3/4 levels

carbimazole and propylTHIOuracil
= inhibit coupling of iodotyrosyl residues

Question 23

What are the advantages carbimazole has over PTU?

Answer 23

Less frequent dosing, and lesser hepatotoxicity.
PTU has a black box warning due to its hepatotoxic effect.

Question 24

What are some important adverse effects of thioamides that we need to look out for?

Answer 24

1. Agranulocytosis = body does not have enough neutrophils
   (do FBC if signs of infection appear)
2. Cholestatic jaundice due to liver damage or bile duct injury (carbimazole)
3. Liver failure (PTU) –> hepatotoxicity (since it is a black box label)

Question 25

What are anti-thyroid drugs commonly used to treat?

Answer 25

1. hyperthyrodism (eg. graves disease)
2. thyroid storm

Question 26

Which of the thioamides is prescribed during the first trimester of a pregnancy?

Answer 26

PTU is preferred in the first trimester. Switch to carbimazole after first trimester

Question 27

What is iodide used to treat?

Answer 27

Thyroid storm (an hour after anti thyroid drugs) It prevents the release of thyroid hormones.
In preparation for thyroidectomy, reduces size and vascularity of the gland,
Endemic goiter (iodine deficiency) as iodine replacement

Question 28

How long does iodides take to have an onset of action?

Answer 28

24 to 48 hours

Question 29

What are the signs and symptoms of iodism?

Answer 29

Metallic taste, gastrointestinal discomfort (diarrhoea, vomiting), lacrimation, severe headache, sore teeth and gums

Question 30

Which radioactive iodine isotope is used for diagnosis of toxic nodular goiter and which is used in the treatment?

Answer 30

123I (diagnosis) and 131I (treatment)

patient given small dose of radioactive iodine
= absorbed by the thyroid gland
= in toxic MNG, there is somatic mutation of TSH receptors
= some nodules will take up more iodine than normal
= the nodules that do not take up iodine are malignant

Question 31

How does radioactive iodine therapy work?

Answer 31

Radioactive iodine is rapidly and efficiently trapped by the thyroid sodium-iodide transporter, into the follicular cells, from which it is slowly liberated. Destructive β particles act almost exclusively on the follicular cells to destroy them , with little or no damage to surrounding tissue.

Question 32

Does 123I emit beta rays?

Answer 32

No, only 131I. 131I emits goth beta and gamma rays

Question 33

What advantage does radioactive iodine therapy have over thyroidectomy?

Answer 33

No hospitalisation, low cost, ease of administration (oral), low rate of complications.

Question 34

What are the contraindications for radioactive iodine therapy?

Answer 34

Pregnancy, Extra caution in patients with active (moderate to severe Graves’ ophthalmopathy) as it may worsen the condition

Question 35

Can radioactive iodine therapy be con-administered with thioamides?

Answer 35

No, must stop thioamides at least 3 days before. Been found to otherwise reduce effectiveness of RAI

Question 36

How could beta blockers help in a thyroid storm?

Answer 36

Beta blockers limit the positive ionotropic and chronotropic effects of thyroid hormones, slightly decrease T4 conversion to T3.

Question 37

What is the utility of glucocorticoids in thyroid disorders?

Answer 37

They are useful in a thyroid storm as they can reduce the conversion of T4 to T3. Used in Graves’ ophthalmopathy to reduce inflammation and swelling.