Pharm - Thyroid/Antithyroid

Question 1

Cardiovascular function of thyroid hormone

Answer 1

Increased CO

Decreased vascular resistance

Question 2

Metabolic function of thyroid hormone

Answer 2

Increase BMR, heat production, O2 consumption, and LDL receptor expression

Question 3

Respiratory function of thyroid hormone

Answer 3

Increase respiratory rate

Question 4

Bone/Skin function of thyroid hormone

Answer 4

Bone growth
Epidermis and dermis
Hair and nails
Sweat glands

Question 5

CNS function of thyroid hormone

Answer 5

CNS development and responsiveness

Question 6

Growth function of thyroid hormone

Answer 6

Promotes growth

Required for fetal development

Question 7

Skeletal muscle function of thyroid hormone

Answer 7

Required for muscle function

Question 8

Describe the regulation of thyroid hormone synthesis

Answer 8

The HPT axis controls thyroid hormone synthesis.
TSH from the anterior pituitary stimulates thyroid hormone production. Iodine and thyroglobulin combine to make MIT and DIT (organificaiton) and then are coupled within the colloid to form T3 and T4. Both steps are catalyzed by TPO.

Question 9

How are thyroid hormones transported in the blood?

Answer 9

Bound to thyroxine-binding globulin (T3 and T4) and transthyretin (T4 only)
Only the unbound hormone is active

Question 10

What effect does pregnancy have on thyroid hormone transport?

Answer 10

Increased estrogen associated with pregnancy increases the TBG levels, thus decreasing the amount of free T4, decreasing the biological activity

Question 11

How is T4 converted to T3?

Answer 11

Deiodinase enzymes: Type 1 activates T4 to T3 in the liver and kidney. Type 2 activates T4 to T3 intracellularly in target tissues.

Question 12

What are the two major disorders of the thyroid gland?

Answer 12

Hypothyroidism: Hashimotos thyroiditis
Hyperthyroidism: Grave’s disease

Question 13

Diagnose a patient with Low T4/T3 and high TSH

Answer 13

Hypothyroidism: most likely Hashimotos thyroiditis

Question 14

Diagnose a patient with High T4/T3 and low TSH

Answer 14

Hyperthyroidism: Could be pituitary adenoma, Grave’s disease

Question 15

What are the treatment options for hypothyroidism

Answer 15

Levothyroxine: synthetic T4 (Drug of choice)
Liothyronine: synthetic T3

Question 16

What is a major pharmacokinetic difference between Levothyroxine and Liothyronine?

Answer 16

Levothyroxine has a slow onset whereas Liothyronine is rapid onset. This allows levothyroxine to be taken once daily, unlike liothyronine which requires multiple doses per day.

Question 17

When would you use liothyronine instead of levothyroxine?

Answer 17

In cases when rapid action is required such as myxedema coma or preparing a patient for radioiodine therapy

Question 18

Once T4 therapy is begun, how long does it take for improvement?

Answer 18

Improvements should begin in about 2 weeks
TSH levels reach steady state in about 6 weeks
Full recovery can take months

Question 19

How is T4 therapy monitored?

Answer 19

TSH levels are checked to assess therapeutic efficacy

Question 20

What risks are associated with over replacement of T4?

Answer 20

Hyperthyroidism
Risk of atrial fibrillation
Increased bone loss in post-menopausal women

Question 21

What are the major types of drug interaction with levothyroxine?

Answer 21

Inhibitors of absorption: Ca/Fe supplements, fiber, cholestyramine, ciprofloxacin, antacids
Increased metabolism: Rifampin, carbamazepine, phenytoin, phenobarbital, St. John’s wort
Increased TBG: pregnancy, cirrhosis, estrogen therapy

Question 22

How is hypothyroidism treated in pregnant patients?

Answer 22

TSH receptors in pregnant patients do not respond to beta-hCG agonism like normal patients. They require increased dose of levothyroxine, regular TSH monitoring to support fetal development

Question 23

What is myxedema coma?

Answer 23

Severe hypothyroidism can cause impaired mental status, hypothermia, hypotension, bradycardia, hypoglycemia and hypoventilation.
Usually triggered by acute event
30-40% mortality

Question 24

What is the treatment for myxedema coma?

Answer 24

IV levothyroxine and/or liothyronine
Mechanical ventilation
Electrolytes
Correction of hypothermia

Question 25

What are the therapies used to treat hyperthyroidism?

Answer 25

``` Beta blockers (symptomatic relief) Antithyroid drugs Iodide Radioactive iodine therapy Surgery ```

Question 26

How does propranolol help with hyperthyroidism?

Answer 26

Prevents palpitations, tremor, anxiety and heat intolerance associated with increased adrenergic response of hyperthyroidism

Question 27

What are the contraindications for beta blockers?

Answer 27

Asthma, COPD, heart failure

Question 28

What are the two antithyroid drugs?

Answer 28

Propylthiouracil (PTU) | Methimazole (MMI)

Question 29

What is the mechanism of action of PTU and MMI?

Answer 29

They inhibit synthesis of thyroid hormones by inhibiting TPO (affects organification and coupling steps)

Question 30

What is the onset time for PTU and MMI?

Answer 30

3-4 weeks because these drugs do not affect the pre-existing stored T3/T4. Once stores are depleted, PTU and MMI begin to show effect.

Question 31

What is one major difference between action of PTU and MMI?

Answer 31

PTU partially inhibits peripheral conversion of T4 to T3, MMI does not

Question 32

Therapeutic use of PTU and MMI

Answer 32

Hyperthyroidism in Grave's disease Adjunt to radioiodide therapy to improve recovery Control hyperthyroidism leading up to surgery

Question 33

What adverse effects are associated with PTU and MMI?

Answer 33

Pruritus, rash, uticaria (treated with antihistamines) Joint pain Fever Rare: PTU is associated with hepatotoxicity, ANCA-positive vasculitis, agranulocytosis MMI is associated with teratogenicity and agranulocytosis

Question 34

When is MMI indicated and when is PTU indicated?

Answer 34

MMI preferred for non-pregnant patients | PTU is preferred for pregnant patients during the first trimester (then switch to MMI)

Question 35

What are the two preparations of iodide treatment?

Answer 35

Saturated potassium iodide (SSKI) | Potasium iodide-iodine (Lugol's solution)

Question 36

What effects does high dose iodide have?

Answer 36

Inhibits thyroid hormone synthesis Acute inhibition of homrone secretion (Thyroid storm) Decreases vascularity of thyroid gland

Question 37

What is the Wolff-Chaikoff effect?

Answer 37

Iodide acts in negative feedback to inhibit organification by TPO. This is useful for treating people involved with nuclear disasters to prevent radioiodine uptake

Question 38

What are the indications for iodide treatment?

Answer 38

Severe hyperthyroidism/ Thyroid storm Adjunctive therapy with radioactive iodine Adjunctive therapy with antithyroid drugs in Graves disease Preoperative for thyroidectomy

Question 39

What are the indications of radioactive iodine treatment?

Answer 39

Treatment of choice for Graves disease and toxic nodular goiter

Question 40

What is the mechanism of action of radioactive iodine?

Answer 40

Concentrated in the thyroid gland Emits beta particles which act directly on parenchymal cells leading to follicular cell necrosis, ablation of the thyroid.

Question 41

How does radioactive iodine treatment differ for elderly patients, coronary artery disease, or those intolerant of hyperthyroid symptoms

Answer 41

Must be pretreated with antithyroid (MMI) for 4-6 weeks to establish euthyroid state

Question 42

What are the adverse effects of radioactive iodine treatment?

Answer 42

Radiation thyroiditis | Exacerbation of Graves ophthalmopathy

Question 43

What are the contraindications of radioactive iodine treatment?

Answer 43

Pregnancy | Severe opthalmopathy

Question 44

What are the indications for thyroid surgery?

Answer 44

Patients with large goiters cause airway obstruction Patients who refuse radioiodine therapy and antithyroid drugs Patients with severe opthalmopathy Patients resistant to other therapies

Question 45

What are patients undergoing thyroidectomy at risk of developing?

Answer 45

Thyroid storm | Prevented by pre-treating with antithyroid drugs

Question 46

Which hyperthyroid treatment is most effective? Thionamides, radioiodine, surgery

Answer 46

All are equally effective

Question 47

What is thyroid storm?

Answer 47

A rare, life-threatening condition (10-30% mortality) | Exaggeration of hyperthyroid symptoms: tachycardia, hyperpyrexia, agitation, delirium, psychosis

Question 48

What is the treatment for thyroid storm?

Answer 48

``` Propranolol PTU Iodide Dexamethasone (blocks peripheral conversion of T4 to T3) Cholestyramine (block reabsorption) ```

Question 49

What is a common drug that can induce thyroid disease?

Answer 49

Amiodarone

Question 50

How does amiodarone cause thyroid disease?

Answer 50

It contains iodine that is released during metabolism. This causes Wolff-Chaikoff effect leading to destructive thyroiditis

Question 51

How is amiodarone induced hypothyroidism treated?

Answer 51

T4 supplementation

Question 52

How is amiodarone induced hyperthyroidism treated?

Answer 52

Anti-thyroid drugs, radioiodine, surgery are used to treat in cases of pre-existing multinodular goiter or Graves Glucocorticoids are used to treat inflammation if the toxic effect is due to destructive thyroiditis, release of preformed T4/T3

Question 53

What is the treatment strategy for thyroid carcinoma?

Answer 53

Total thyroidectomy followed by radioiodine ablation to destroy any residual carcinoma and metastases

Question 54

How is iodine uptake stimulated before radioiodine ablation therapy?

Answer 54

Withdraw levothyroxine for 4-6 weeks Levothyroxine withdrawal with liothyronine administration IV injection of rTSH