(5) GI & Endo: Thyroid etc (3.1-3.4)

Question 1

What cell type is responsible for iodine uptake and thyroid hormone production?

Answer 1

What cell type is responsible for iodine uptake and thyroid hormone production?

Question 2

How is iodide transported into the thyroid follicular cell?

Answer 2

Na+/I- symporter

Question 3

Where is thyroglobulin found?

Answer 3

Thyroid follicu-LAIR lumen

Question 4

Name 3 functions of thyroid peroxidase

Answer 4

(1) Oxidation of I^- → I₂
(2) Organification of thyroglobulin
(3) Coupling of iodinated tyrosine residues

Question 5

In what compartment is thyroid hormone cleaved off of thyroglobulin?

Answer 5

Follicular cell’s cytoplasm

Question 6

Is T3 or T4 more potent?

Answer 6

T3

Question 7

What enzyme converts T4 to T3 in the peripheral tissues?

Answer 7

5’ deiodinase

Question 8

Broadly, what can we attribute the symptoms of hyperthyroidism to?

Answer 8

↑ β-adrenergic receptors

(⇒ Hypermetabolic and hyperadrenergic state)

Question 9

Which thyroid disorder causes exophthalmos?

Answer 9

Graves disease

Question 10

Adverse Effects (3) : I¹³¹ ablation therapy

Answer 10

(1) Hypothyroidism
(2) Exacerbation of hyperthyroidism
(3) Exacerbation of Graves ophthalmopathy
* (Exacerbation of ophthalmopathy MOA: Rapid reduction in thyroid hormone ⇒ ↑ TSH ⇒ Binds pre-adipocytic fibroblasts ⇒ ↑ Glycosaminoglycan and adipose deposition)*

Question 11

MOA: Propylthiouracil

Answer 11

(1) Inhibits TPO
(2) Inhibits 5’ deiodinase

Question 12

MOA: Methimazole

Answer 12

Inhibits TPO

(TPO: thyroid peroxidase enzyme; involved in iodide oxidation & organification)

(Methimazole is 10x more potent than Propylthiouracil and is usually the DOC. The exception is in FIRST trimester of pregnancy)

Question 13

MOA: β-blockers (in treating hyperthyroidism)

Answer 13

(1) β-blocker
(2) Inhibit 5’ deiodinase

Question 14

MOA: Glucocorticoids (in treating hyperthyroidism)

Answer 14

Inhibits 5’ deiodinase

Question 15

Which pharmacologic treatment of hyperthyroidism is particularly effective against Graves’s ophthalmopathy?

Answer 15

Glucocorticoids

(Glucocorticoids induce lymphocyte apoptosis and ∵ ↓ production of autoantibodies ⇒ ↓ Fibroblast proliferation ⇒ ↓ Ophthalmopathy)

Question 16

Treatment: Thyroid storm

Answer 16

(1) β-blockers
(2) Methimazole
(3) Glucocorticoids
* (Methimazole preferred over PTU∵ of increased efficacy)*

Question 17

Adverse Effects (3) : Propylthiouracil (unique from methimazole)

Answer 17

(1) Hepatotoxicity
(2) Maculopapular rash
(3) ANCA-associated vasculitis

Question 18

Name 3 adverse effect that Propylthiouracil and Methimazole share

Answer 18

(1) Agranulocytosis
(2) Aplastic anemia
(3) Drug-induced lupus

Question 19

Treatment: Hypothyroidism (in a first-trimester pregnant woman)

Answer 19

Propylthiouracil

(Methimazole is contraindicated in the first trimester due to teratogenicity, whereas PTU is contraindicated in second and third trimester due to risk of hepatotoxicity)

Question 20

Name a T4 analog

Answer 20

Levothyroxine

Question 21

Treatment: Radioactive iodine exposure

Answer 21

Anions

(Such as perchlorate, pertechnetate, and thiocyanate which inhibit the Na+/I- symporter)

Question 22

Suffix: Biphosphonates

Answer 22

“-dronate”

Question 23

Biphosphonates have a chemical structure similiar to what molecule?

Answer 23

Pyrophosphate

Question 24

Name 3 ways biphosphonates affect osteoclasts

Answer 24

(1) Inhibit bone adherence
(2) Inhibit recruitment/development
(3) Induce apoptosis

Question 25

Other than osteoporosis, what can biphosphonates be used to treat?

Answer 25

(1) Hypercalcemia (2) Paget's Disease * (_Note_: Calcitonin has similar indications, but is the second line)*

Question 26

**Adverse Effects** (3) : Biphosphonates

Answer 26

(1) Corrosive esophagitis (2) Osteonecrosis of jaw (3) Hypocalcemia

Question 27

What is the mechanism of estrogen therapy in the treatment of osteoporosis?

Answer 27

Inhibit osteoclast **_precursor_** development

Question 28

What drug is an estrogen agonist in bone but antagonist in the breast and uterus?

Answer 28

Raloxifene

Question 29

How does parathyroid hormone stimulate osteoclasts?

Answer 29

↑ RANKL on Osteo**_b_**lasts *(⇒ Osteoclast activation)*

Question 30

**MOA**: Denosumab

Answer 30

anti-RANKL antibody

Question 31

Does calcitonin bind receptors on osteoclasts or osteoblasts?

Answer 31

Osteo**_c_**lasts

Question 32

How does Calcitonin reduce serum calcium?

Answer 32

(1) Inhibits osteoclasts (2) ↓ Renal Ca2+ reabsorption

Question 33

Name two hormones which upregulate RANKL

Answer 33

(1) PTH (2) Calcitriol

Question 34

Name two mechanisms of negative feedback on PTH

Answer 34

(1) ↑ Ca2+ (2) ↑ Calcitriol * (A rare instance where ↑ intracellular Ca2+ inhibits exocytosis)*

Question 35

What effect does the RANK-RANKL interaction have on osteoclasts?

Answer 35

(1) Differentiation (2) Activation * (RANKL is upregulated by PTH, whereas osteoprotegrin is upregulated by Calcitriol)*

Question 36

What effect does PTH have on osteoblasts?

Answer 36

**Maturation** of pre-OB → OB *(The net effect of PTH is bone resorption. Vit. D also stimulates OB maturation)*

Question 37

What effect does PTH have on renal electrolyte handling?

Answer 37

(1) ↑ Ca2+ reabsorption (2) ↑ PO42- excretion

Question 38

Name 3 ways PTH elevates serum [Ca2+]

Answer 38

(1) Activates osteoclasts (2) ↑ Renal Ca2+ reabsorption (3) Activates Vitamin D

Question 39

**MOA:** Teriparatide

Answer 39

PTH analog

Question 40

Identify an important physiologic distinction between Teriparatide and endogenous PTH

Answer 40

(1) _Teriparatide_: Net bone formation (2) _Parathormone_: Net bone resorption * (Pulsatile Teriparatide ⇒ bone formation. Constant dosing would likely instead lead to bone resorption)*

Question 41

Indication: Teriparatide

Answer 41

Osteoporosis

Question 42

What are the source(s) of Vitamin D3?

Answer 42

(1) Dairy products (2) UVB radiation * (Vit. D3 = Cholecalciferol. The 3 of Vit. D3 to remember Cholecalciferol starts with the third letter of alphabet)*

Question 43

What are the source(s) of Vitamin D2?

Answer 43

Plants

Question 44

Describe how dietary Vitamin D is converted into the active form

Answer 44

(1) **25**-hydroxylated in the **liver** (2) **1**-hydroxylated in the **kidney** * (∴ Calcitriol would be indicated over Vit. D2/D3 in the setting of renal/liver disease)*

Question 45

What effect does Calcitriol have on renal electrolyte handling?

Answer 45

(1) ↑ Ca²⁺ reabsorption (2) ↑ PO₄^2- reabsorption

Question 46

What effect does Calcitriol have on GI electrolyte handling?

Answer 46

(1) ↑ Ca²⁺ reabsorption (2) ↑ PO₄^2- reabsorption

Question 47

**Indication**: Topical Vit. D

Answer 47

Psoriasis *(Vit. D plays an important role in T-cell homing to skin ∴ topical Vit. D exerts immunomodulatory effects)*

Question 48

Name 2 endocrine etiologies of hypocalcemia treated with Calcitriol

Answer 48

(1) Hypothyroidism (2) Hypoparathyroidism

Question 49

**MOA**: Cinacalcet

Answer 49

Activates CaSR in parathyroid gland * (CaSR = calcium-sensing receptor)* * (⇒ reduced secretion of PTH and ∴ is helpful against renal osteodystrophy secondary to CKD)*

Question 50

**Indication**: Cinacalcet

Answer 50

Hyperparathyroidism

Question 51

**MOA**: Sevelamer

Answer 51

Reduces absorption of PO₄^2- in GI tract *(It is a non-absorbable oral formulation)*

Question 52

**Indication**: Sevelamer

Answer 52

Hyperphosphatemia *(Secondary to chronic kidney disease)*

Question 53

**Suffix**: Glucocorticoids

Answer 53

"-sone"

Question 54

Where is the glucocorticoid receptor found?

Answer 54

Cytoplasm

Question 55

What inflammatory enzyme do glucocorticoids inhibit?

Answer 55

Phospholipase A₂ *(By upregulating Lipocortin = Annexin)*

Question 56

What transcription factor do glucocorticoids inhibit?

Answer 56

NF-κB *(∴ Inhibiting production of inflammatory cytokines and activation of B and T cells)*

Question 57

How do glucocorticoids prevent leukocyte migration?

Answer 57

Inhibit adhesion molecules *(∴ Also increase WBC count ∵ fewer WBCs are attached to endothelium and more are freely floating in blood)*

Question 58

What cell type are glucocorticoids most effective at inducing apoptosis in?

Answer 58

T_H *(Induce apoptosis of B-cells, T-cells, and eosinophils)*

Question 59

Name 5 metabolic effects of glucocorticoids

Answer 59

(1) Insulin resistance (2) ↑ Gluconeogenesis (3) ↑ Glycogenesis (4) ↑ Proteolysis (5) ↑ Lipolysis

Question 60

Name 4 physical symptoms of Cushing's syndrome

Answer 60

(1) Moon facies (2) Central adipose tissue (3) Muscle wasting (4) Skin thinning

Question 61

What CNS effects can glucocorticoids cause?

Answer 61

Psychosis

Question 62

What electrolyte abnormality can glucocorticoids cause?

Answer 62

Hypokalemia *(Due to mineralocorticoid effects)*