Endo Part 6

Front 1

osteitis fibrosa cystica (excess PTH) ~~

Back 1

too much bone resorption

Front 2

too little bone deposition is seen in 2 dz's:

Back 2

1. osteogenesis imperfecta
- defects in bone matrix formation

2. Ricket's/osteomalacia
- severe Vit. D deficiency

Front 3

features of osteitis fibrosa cystica:

(2)

Back 3

1. excessive osteoclast activity via excess PTH

2. ~~fractures and kidney stones

Front 4

features of Paget's Dz:

(5)

Back 4

1. improper resorption AND deposition
(~~improper osteoblast and osteoclast activity)

2. => areas of thin bone with other areas of thick bone

3. thickened areas are still weaker than nl bone

4. anywhere, but skull/spine/pelvis m.c.

5. NORMAL serum Ca2+

Front 5

bone matrix is made up of:

Back 5

collagen

Front 6

osteogenesis imperfecta =

Back 6

inherited defect in either 1 of 2 collagen genes

=> inadequate formation of collagen

=> defective collagen impairs mineralization

Front 7

features of osteogenesis imperfecta =

(2)

Back 7

1. diminished bone mass/strength

2. => multiple fractures and deformities in childhood

Front 8

features of Rickets / osteomalacia:

(3)

Back 8

1. defective mineralization of bone matrix

2. bone deformities

3. reduced mechanical strength

Front 9

3 causes of Rickets or osteomalacia:

Back 9

1. Vit. D deficiency

2. Phosphate deficiency

3. both together

Front 10

osteoporosis =

Back 10

decrease in BOTH bone matrix AND bone mineralization

- "skeletal fragility characterized by reduced bone mass and microarchitectural deterioration"

Front 11

***features of osteoporosis:***

(2)

Back 11

1. ~~decreased osteoblast activity

2. ~~increased osteoclast activity

Front 12

normal BMD =

(bone mineral density)

Back 12

T-score between +1 and =1

(within 1 SD of the mean of controls)

Front 13

osteopenia =

Back 13

T-score between -1 and -2.5 SD

Front 14

osteoporosis =

Back 14

T-score less than -2.5 SD

Front 15

***1 SD down = ***

Back 15

**2 times** the risk for fracture

=> -3 SD = 8x risk of fracture

Front 16

women always have lower bone density than men; furthermore,

Back 16

the decrease in bone density is more dramatic past 40 y.o.

Front 17

osteoporosis starts in:

Back 17

childhood

Front 18

amenorrhea ~~ osteoporosis because:

Back 18

amenorrhea = dec. EST

dec. EST = dec. bone mineralization/mass

check

Front 19

you have higher Vit D/Ca2+ requirements during:

(2)

Back 19

preg,

puberty

Front 20

Ca2+ absorption hits a ________ wrt Vit D levels

Back 20

peak

- past 1,25-D of 40, your Ca2+ absorption actually decreases

Front 21

**non-modifiable risk factors of osteoporosis:**

(5)

Back 21

1. previous fracture as adult (esp. hip)

2. history of osteoporotic fracture in a 1st degree relative

3. Female

4. age

5. dementia/poor health/frailty

Front 22

**modifiable risk factors of osteoporosis:**

(6)

Back 22

1. current smoker

2. LOW weight (< 127 lbs)

3. EST deficiency

4. low lifelong Ca2+ intake

5. high alcohol (3 or more drinks per day)

6. history of other diseases causing secondary osteoporosis

Front 23

difference between primary and secondary osteoporosis:

Back 23

primary ~~ aging,

secondary ~~ direct cause, like Vit. D deficiency

Front 24

endo causes of secondary osteoporosis:

(5)

Back 24

1. hyperPTH

2. Cushing’s syndrome

3. hyperthy

4. hypogonadism (=> dec. EST)

5. hyperprolactinemia (=> dec. EST)

Front 25

4 malignant causes of secondary osteoporosis:

Back 25

1. Myeloma

2. Leukemia

3. Lymphoma

4. Mastocytosis

Front 26

when evaluating osteopenia/osteoporosis, definitely get bone mineral density scans of:

Back 26

hip and spine

Front 27

7 routine laboratory tests when evaluating osteopenia/osteo

Back 27

1. serum Ca2+

2. P

3. AP

4. BUN

5. TSH

6. CBC

7. 25-OH


(rule out secondary disease.)

Front 28

5 indications for BMD measurement:

Back 28

1. postmenopausal women < 65 yrs with one or more risk factors in addition to menopause

2. ALL women > 65 yrs (and men > 70 yrs)

3. postmenopausal women presenting with fractures

4. women considering therapy for osteoporosis if BMD testing would facilitate the decision

5. women who have been on postmenopausal HRT for long periods

Front 29

BMD testing should not be done unless:

Back 29

it will influence a treatment decision

Front 30

2 indications for treatment with anti-osteoporotic drugs:

Back 30

1. postmenopausal women and men >50 with a prior vertebral or hip fracture

2. postmenopausal women and men >50 with T-score of -2.5 or lower at the hip or spine

Front 31

Estrogen replacement keeps BMD elevated, but:

Back 31

it has significant risk for BC

Front 32

SERM's =

Back 32

selective estrogen receptor modifiers

Front 33

best SERM =

Back 33

Raloxifene

- EST-antagonist in the breast, EST agonist for bone

=> anti-osteoporosis without exacerbating breast cancer

Front 34

bisphosphonates =

Back 34

long-term inhibitors of bone resorption

- bind hydroxyapatite, inhibit osteoclast activity

Front 35

4 bisphosphonates approved for osteoporosis:

Back 35

1. Alendronate

2. Risedronate

3. Ibandronate

4. Zoledronic acid

Front 36

2 inhibitors of RANK ligand:

Back 36

1. Osteoprotegerin
(decoy r' for RANKL - takes it out of circulation)

2. Denosumab
- FDA-approved

Front 37

**what does preventing binding of RANK ligand do?**

Back 37

prevents osteoclast activation

Front 38

Teriparatide =

Back 38

AA fragment of PTH that activates **osteoblasts**

=> new bone formation

Front 39

calcitonin =

Back 39

direct inhibitor of osteoclasts

Front 40

which anti-osteoporotic meds are best for reducing fractures?

(3)

Back 40

1. bisphosphonates

2. Denosumab

3. Teriparatide

Front 41

GnRH pulse frequency increases at:

(4)

Back 41

1. night

2. puberty

3. mid-menstrual cycle

4. after menopause

Front 42

GnRH pulse frequency decreases with:

(3)

Back 42

1. starvation

2. illness

3. sex steroid feedback

Front 43

function of LH at the gonads:

Back 43

secretion of sex steroids

Front 44

function of FSH at the gonads:

Back 44

development of gametes

Front 45

3 gonadal peptides:

Back 45

1. Anti-Mullerian protein

2. Inhibin A

3. Inhibin B

Front 46

what does Anti-Mullerian peptide do?

Back 46

causes regression of Mullerian ducts in male fetus

(Mullerian ducts become fallopian tubes' male genitalia ~~ Wolfiann ducts)

Front 47

what do Inhibins A and B do?

Back 47

inhibit FSH production at the pituitary

- no role for Inhibin A in men

Front 48

gonadal steroids = Test and EST; 98% bound to:

Back 48

Sex Hormone Binding Globulin (SHBG)

Front 49

TEST is metabolized to EST by:

Back 49

aromatase

Front 50

TEST is metabolized to DHT by:

Back 50

5-alpha reductase

Front 51

**role of EST in bones:**

Back 51

maintains bone density

Front 52

hypogonadism =

(2)

Back 52

1. loss of sex hormone secretion or function

2. loss of gametes
(mature germ cells)

Front 53

physiologic causes of hypogonadism:

(4)

Back 53

1. menopause

2. energy restriction (loss)
- dieting, starving, anorexia nervosa

3. severe illness

4. ?aging

Front 54

menopause =

Back 54

exhaustion of egg supply

=> cessation of menstruation

Front 55

hormones in menopause:

(3)

Back 55

1. low EST

2. low Progesterone

3. high FSH

Front 56

pulsatile infusion of GnRH is used to:

(2)

Back 56

induce puberty or treat central hypogonadism

- **continuous GnRH will suppress puberty**

Front 57

presentation of *congenital* hypogonadism =

Back 57

abnl development of sexual organs

Front 58

presentation of childhood hypogonadism =

Back 58

simply fewer sex hormones

(hypogonadal)

Front 59

presentation of hypogonadism during puberty =

Back 59

lack of secondary sex characteristics

(hair, growth, genital enlargement)

Front 60

presentation of hypogonadism in adults =

Back 60

dec. libido, infertility, dec. energy

- amenorrhea, osteoporosis in women

Front 61

female genitalia does NOT depend on:

Back 61

gonadal hormones

- a hypogonadal female will have nl internal and external genitalia

Front 62

Kallman’s syndrome =

Back 62

congenitally-absent GnRH

- olfactory nerve fails to migrate through cribiform plate, GnRH neurons don’t migrate to hypothalamus, causing **failure to initiate puberty** and anosmia

Front 63

**physical sign of hypogonadism in males in puberty:**

Back 63

long arms/legs, short trunk

Front 64

5 risks of EST replacement:

Back 64

1. VTE

2. stroke

3. heart dz

4. Breast cancer

5. endometrial cancer (dec'd with concurrent progesterone)

- risks are mostly dose-related

Front 65

2 ABSOLUTE contraindications for EST:

Back 65

1. EST-dependent cancer (breast, endometrial)

2. history of thrombotic disease

Front 66

what form of TEST supplementation/medication is NOT recommended?

Back 66

ORAL

Front 67

***sex hormone levels are susceptible to:***

Back 67

MANY transient systemic effects (nutrition, illness, meds)

Front 68

what kind of hormone is insulin?

Back 68

a PEPTIDE hormone

- starts as pre-pro-insulin

- works through ER, then Golgi, then secretory vesicles (where C-peptide is cleaved)

- stored in insulin granules

Front 69

apart from sugar, these 3 things also stimulate insulin release:

Back 69

1. arginine and leucine

2. parasymp. release of ACH

3. incretins (GI-derived hormones)

Front 70

mechanism of glucose releasing insulin:

(7)

Back 70

1. glucose enters Beta cells via GLUT2

2. generates ATP via glycolysis

3. ATP-sensitive K+ channels close

4. membrane depolarizes

5. voltage-gated Ca2+ channels open

6. Ca2+ enters cell

7. insulin granules fuse with memb. to release insulin into the blood

Front 71

imp. feature of GLUT2's:

Back 71

LOW affinity

=> don't need a lot of glucose to cause insulin release

Front 72

3 key features of an insulin r':

Back 72

1. 2 alpha chains, 2 penetrating Beta chains, linked by disulfide bonds

2. = tyrosine kinase
- transfers P from ATP to tyrosine residues on intracellular proteins

3. binding alpha subunits cause Beta subunits to autophophorylate
=> phos. of intracellular proteins

Front 73

insulin acts mainly on:

(3)

Back 73

1. liver

2. muscle

3. adipose cells

- called insulin-DEPENDENT organs

Front 74

insulin at the liver decreases:

(2)

Back 74

1. glycogenolysis

2. GNG

Front 75

insulin at the liver increases:

(4)

Back 75

1. glucose P'n

2. glycolysis

3. glycogen synthesis

4. FA synthesis

Front 76

insulin at the muscle:

(4)

Back 76

1. inhibits glycogenolysis

2. increases glucose uptake into muscle
(via GLUT4 translocation to memb.)

3. increases glycogen synthesis

4. inc. prot. synthesis

Front 77

insulin at adipose tissue:

(4)

Back 77

1. inc. glucose uptake
(via GLUT4)

2. inc. glycolysis

3. dec. release of FFA's

4. inc. FA conversion into TG's
(by increasing LPL activity)

Front 78

3 effects of insulin:

Back 78

1. increase glycogenesis in the liver

2. increase glycogenesis, protein synthesis in the muscle

3. inc. FFA conversion into TG's at adipose tissue

Front 79

effects of glucagon:

(3)

Back 79

1. decreased glucose uptake into cells

2. increased protein breakdown

3. increased lipolysis
=> inc. FFA's
(=> ketogenesis in absence of glucose)

Front 80

exocrine ~~

Back 80

ducts

- whereas endocrine secretes directly into blood

Front 81

functional unit of the endocrine pancreas =

Back 81

islets of Langerhans

Front 82

**histo feature of islets:**

Back 82

salt and pepper nucleus

- salt = light nucleus
- pepper = dark chromatin

- also seen in tumors of islet cell proliferation

Front 83

glucagon is released from the:

Back 83

alpha cells

at the periphery

Front 84

somatostatin is synthesized in:

Back 84

D cells,

sparsely scattered throughout islet

Front 85

breakdown of incidence of DM1 vs DM2:

Back 85

DM1 = 10%,

DM2 = 90%

Front 86

features of DM1:

(15)

Back 86

1. onset <20 y.o.

2. **abrupt onset**

3. **often presents with DKA already**

4. AI

5. markedly-decreased Beta-cell mass

6. markedly reduced circulating insulin level

7. insulinitis/lymphocytes

8. fibrosis if late

9. genetics = AR

10 ~~ HLA-DR3, DR4

11. GAD-positive

12. WIDELY-fluctuating glucose levels on the same day

13. acetone fruity breath

14. AMS

15. environment has no bearing

Front 87

**body can compensate for Beta-cell destruction incredibly well; won't see DM1 effects until:

Back 87

90% of the Beta-cells are gone

Front 88

9 features of DM2:

Back 88

1. onset >20

2. **gradual, often asymptomatic**

3. **~~obesity, HTN, CV dz**

4. stronger genetic correlation than DM1

5. increased insulin until pancreas becomes exhausted

6. circulating insulin level can be normal or even elevated

7. **amyloid deposition**

8. can also see fibrosis

9. **GRADUAL increase in blood glucose, over years**

Front 89

where does amyloid deposition of DM2 come from?

Back 89

amylin, a peptide hormone secreted with insulin

- note: you can see amyloid deposition in elderly, but it's not necessarily DM2

Front 90

pancreatic endocrine tumors can be:

Back 90

functioning or nonfunctioning

Front 91

2 syndromes with which pancreatic endocrine tumors are associated:

Back 91

1. MEN1

2. VHL dz

Front 92

cytologic atypia is not reliable for:

Back 92

distinguishing between benign and malignant tumors

- seen in both

Front 93

a dx of malignancy requires:

(2)

Back 93

1. direct invasion into peripancreatic tissues

OR

2. the presence of mets

Front 94

features of Insulinoma:

(6)

Back 94

1. m.c.

2. benign

3. *functioning*

4. can induce *severe hypoglycemia**
(secretion NOT influenced by blood glucose level)

5. small (<3 cm)

6. tx of choice = surgery
(can be hard to localize though)

Front 95

features of gastrinoma:

(4)

Back 95

1. next m.c.

2. G-cells are not endemic to islets

3. cause ZE Syndrome

4. ~malignant

Front 96

ZE Syndrome:

Back 96

gastrinoma (made up of G cells) releases excess gastrin

=> severe peptic ulcers of duodenum and jejunum

Front 97

features of glucagonoma:

(4)

Back 97

1. rare

2. mostly malignant

3. **large, invade surrounding structures**

4. ~~ mild diabetes, necrolytic migratory erythema, anemia, venous thrombosis, and severe inf's

Front 98

features of somatostatinoma:

(3)

Back 98

rare, malignant

associated with mild diabetes, gallstones, steatorrhea, hypochlorhydria

Front 99

features of VIPoma:

(6)

Back 99

1. rare

2. explosive watery diarrhea

3. hypokalemia

4. hypochlorhydria

5. usually large

6 usually malignant

Front 100

acinar pattern ~~

Back 100

sac-like

Front 101

ductal pancreatic tumors are far more common than endocrine pancreatic tumors, but:

Back 101

endocrine ones are far more aggressive

Front 102

"functioning" endocrine pancreatic tumor depends on:

Back 102

whether it can secrete the product

Front 103

main feature of microadenomas of the endocrine pancreas (<0.5 cm):

Back 103

UNIVERSALLY benign

Front 104

3 meds for Insulinoma:

Back 104

1. Diazoxide
(inhibits insulin secretion)

2. Octreotide

3. small frequent meals

Front 105

remember that endocrine pancreatic tumors can occur with:

Back 105

MEN1

+ pituitary tumor, +PT gland hyperplasia/adenoma

Front 106

both DM1 and DM2 can present with:

Back 106

dehydration,

due to diuretic effect of glucose leaving kidneys