Thyroid Diseases (Cut off for Exam 1)

Question 1

Hypothyroid

Answer 1

• Hashimoto’s thyroiditis
• Non-responsive to TSH
• Thyroid hormone deficiency
• Small thyroid
• Replacement therapy

Question 2

Hyperthyroid

Answer 2

• Grave’s disease
• Abnormal activation of TSH receptor
• Thyroid hormone excess
• Large thyroid (goiter)
• Block production

Question 3

Thyroid Hormones

Answer 3

• T4 - inactive
• T3 - active
• T4 = reservoir to maintain steady state levels of T3
• Both act as negative feedback to reduce TSH levels

Question 4

Thyroid Gland

Answer 4

• Consists of follicle cells that surround colloid

- Thyroglobulin - protein that is stored in the colloid and is the source for T3 and T4

Question 5

Iodide

Answer 5

• Accumulated in thyroid
• Thyroperoxidase enzyme oxidzies iodide
• Then binds it with thyroglobulin protein residues
• MIT + DIT = T3, DIT + DIT = T4

Question 6

Thyroid Hormones

Answer 6

• > 99.9% protein bound in plasma
• Includes thyroid binding globulin (TBG), albumin, and transthyretin
• Only free T3 and T4 can enter cells and only T3 is active
• The binding ensures large reservoirs, slow clearance, and slow responses to change

Question 7

T3 + Entering Cell

Answer 7

• Once T3 has entered, it binds to thyroid hormone receptors
• This then binds to DNA and alters gene expression of proteins that influence metabolism, cardiac function, and GI function

Question 8

T3 Regulates….

Answer 8

• Basal metabolic rate
• Cardiac Function
• Intestinal Food Processing

Question 9

If T3 decreases then…

Answer 9

• Basal metabolism decreases which causes the oxidation of glucose to ATP => feeling cold and weight gain
• Decreased catecholamine sensitivity which decreases beta adrenergic receptors and causes bradycardia
• Decreased gut mobility which causes constipation

Question 10

Hypothyroid Diseases + Symptoms

Answer 10

• Congenital deficiency => dwarfism, mental retardation (screened at birth)
• Hashimoto’s thyroiditis - autoimmune disease Ab against TSH receptor, causes T3 and T4 to go down by thyroid not responding to TSH

Question 11

Hypothyroidism Treatment

Answer 11

-Replacement therapy with T4, T3, or a mixture

MOA: mediated by stimulating thyroid hormone receptors in target tissues

Question 12

Treating hypothyroidism causes…

Answer 12

• Increased metabolism and ATP synthase
• Increased heart rate and contractility - B1 adrenergic receptors and NA-K ATPase pump
• Increased gut motility

Question 13

LT4 Site of Action

Answer 13

• Liver
• Heart
• GI

Question 14

LT4 MOA

Answer 14

• LT4 is deiodinated to T3 which binds to thyroid hormone receptors
• These thing bind DNA and alter gene expression

Question 15

LT4 Pharmacological Benefit

Answer 15

• Increase metabolism

- Increase cardiac and GI function

Question 16

T4 Replacement

Answer 16

• Takes 6 weeks or more to show an effect
• T4 binding sites must be saturated first before adequate levels of free T4 are available to be absorbed by target tissues

Question 17

Are LT4 generic formulations equivalent?

Answer 17

• Highly controversial
• One study reported 177 adverse events when switching form brand to generic
• Lack of consensus for design of bioequivalence study

Question 18

Levothyroxine Drug Interactions

Answer 18

• Cholestyramine: decrease oral bioavailability, decreases total T4, seperate by 4-6 hours
• Ethinylestradiol: increases protein binding, increases total T4, may need a higher LT4 dose
• Phenobarbital/Rifampin: increases metabolism, decreasing total T4, increase LT4 dose
• Proton Pump Inhibitor: Decreases oral bioavailability, decreasing total T4, increase LT4 dose

Question 19

Causes/Symptoms of Hyperthyroidism

Answer 19

• T4 replacement therapy that is too high
• Grave’s Disease - autoimmune disease Ab activates TSH receptor (acts as agonist)
• Multinodular goiter

Question 20

Hyperthyroidism Treatment

Answer 20

• Block T3 and T4 synthesis
• Destroy thyroid gland
• Surgical resection
• Some symptomatic relief can be achieved with beta blockers
• PTU and MMI used to inhibit TPO and decrease T3/T4 synthesis