Thyroid Diseases (Cut off for Exam 1) Flashcards
1
Q
Hypothyroid
A
- Hashimoto’s thyroiditis
- Non-responsive to TSH
- Thyroid hormone deficiency
- Small thyroid
- Replacement therapy
2
Q
Hyperthyroid
A
- Grave’s disease
- Abnormal activation of TSH receptor
- Thyroid hormone excess
- Large thyroid (goiter)
- Block production
3
Q
Thyroid Hormones
A
- T4 - inactive
- T3 - active
- T4 = reservoir to maintain steady state levels of T3
- Both act as negative feedback to reduce TSH levels
4
Q
Thyroid Gland
A
- Consists of follicle cells that surround colloid
- Thyroglobulin - protein that is stored in the colloid and is the source for T3 and T4
5
Q
Iodide
A
- Accumulated in thyroid
- Thyroperoxidase enzyme oxidzies iodide
- Then binds it with thyroglobulin protein residues
- MIT + DIT = T3, DIT + DIT = T4
6
Q
Thyroid Hormones
A
- > 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
7
Q
T3 + Entering Cell
A
- 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
8
Q
T3 Regulates….
A
- Basal metabolic rate
- Cardiac Function
- Intestinal Food Processing
9
Q
If T3 decreases then…
A
- 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
10
Q
Hypothyroid Diseases + Symptoms
A
- 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
11
Q
Hypothyroidism Treatment
A
-Replacement therapy with T4, T3, or a mixture
MOA: mediated by stimulating thyroid hormone receptors in target tissues
12
Q
Treating hypothyroidism causes…
A
- Increased metabolism and ATP synthase
- Increased heart rate and contractility - B1 adrenergic receptors and NA-K ATPase pump
- Increased gut motility
13
Q
LT4 Site of Action
A
- Liver
- Heart
- GI
14
Q
LT4 MOA
A
- LT4 is deiodinated to T3 which binds to thyroid hormone receptors
- These thing bind DNA and alter gene expression
15
Q
LT4 Pharmacological Benefit
A
- Increase metabolism
- Increase cardiac and GI function
16
Q
T4 Replacement
A
- 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
17
Q
Are LT4 generic formulations equivalent?
A
- Highly controversial
- One study reported 177 adverse events when switching form brand to generic
- Lack of consensus for design of bioequivalence study
18
Q
Levothyroxine Drug Interactions
A
- 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
19
Q
Causes/Symptoms of Hyperthyroidism
A
- T4 replacement therapy that is too high
- Grave’s Disease - autoimmune disease Ab activates TSH receptor (acts as agonist)
- Multinodular goiter
20
Q
Hyperthyroidism Treatment
A
- 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
