Endo Part 3

Front 1

"corticosteroid" =

Back 1

**any** steroid hormone made in the adrenal cortex

- includes mineralocorticoids like aldo and glucocorticoids like cortisol

Front 2

ACTH starts as:

Back 2

POMC,

a pro-hormone

Front 3

ACTH has some ________-__________________ properties

Back 3

skin-darkening

Front 4

6 nl effects of cortisol:

Back 4

BIG FIB

1. inc. BP

2. inc. Insulin R

3. inc. GNG/lipolysis/proteolysis


4. dec, Fibroblast activity

5. dec. Inflammatory/Immune responses

6. dec. Bone formation (dec. osteoblast activity)

Front 5

***key step of ACTH***

Back 5

converts cholesterol into Pregnenolone

- Pregnenolone is the precursor to aldosterone, cortisol, AND androgens

Front 6

androgens =

Back 6

sex hormones

(EST can be derived from TEST)

Front 7

features of cortisol deficiency:

(6)

Back 7

1. fatigue

2. anorexia/wt loss

3. hypoglycemia

4. hyponatremia (dilutional)

5. poor stress tolerance - acute vascular collapse

6. hyperpigmentation/dark buccal spots (primary adrenal dz only)

Front 8

features of mineralocorticoid deficiency:

(4)

Back 8

1. hypovolemia/postural hypotension

2. hyperkalemia

3. hyponatremia

4. met. acidosis

(excess of mineralocorticoids will result in the opposite)

Front 9

features of androgen deficiency:

(2)

Back 9

lack of pubic and axillary hair (females)

- in males, proportion of androgens made in the adrenal gland is miniscule - won't see sex hair loss in men uless testes (or pit.) are involved

Front 10

dec. aldo =>

Back 10

increased renin/AII

Front 11

most important cause of secondary adrenal insufficiency =

Back 11

MEDS

(taking glucocorticosteroids to fix primary OR secondary adrenal cortex insufficiency)

Front 12

rapid ACTH stim. test results and meaning:

(Cosyntopin = synth. ACTH)

Back 12

1. flat line in response to ACTH (i.e. NO cortisol production) ~~ primary adrenal insufficiency

2. *small* increase in cortisol production ~~ secondary insufficiency

3. (nl response = rise of cortisol to 25-30)

Front 13

why is cortisol production small in response to ACTH stim test in secondary adrenal insufficiencies?

Back 13

b/c lack of ACTH (remember, it's a secondary dz) means that cortisol-producing cells have atrophied (not being used)

=> continuous admin. of ACTH will see that line increase more, as ACTH is trophic and will start to make cortisol-producing cells grow as it's continually present

Front 14

m.c.c. of adrenal insufficiency =

second m.c.c. =

Back 14

21-OH deficiency;

11-OH deficiency

Front 15

what is the significance of the enzyme 21-hydroxylase?

Back 15

***upstream, responsible for production of aldosterone AND cortisol***

Front 16

a deficiency in 21-hydroxylase causes:

Back 16

shift of production from aldo and cortisol to ANDROGENS

- a **congenital** deficiency - a **type of CAH**

Front 17

if deficiency of 21-OH is severe, androgen symps =

(2)

Back 17

1. masculinization of female genitalia in female infants

2. sexual precocity in boys

Front 18

if deficiency of 21-OH is partial, androgen symps =


(2)

Back 18

1. hirsutism (excessive hair in parts of the body where it doesn't belong, e.g. beard),

2. irregular menses

- in *adult* women only

- mild symps at best in men

Front 19

severe deficiency of 21-OH shows these aldo symps:

(3)

Back 19

1. polyuria

2. volume depletion

3. hyperkalemia

- in infancy

Front 20

mineralocorticosteroids act to:

Back 20

control fluid and electrolyte balance, by promoting reabsorption of Na+ and secreting K+

- **excess of mineralocorticosteroids => water retention and edema => HTN**

- insufficiency of mineralocorticosteroids therefore shows water loss => hypotension/hypovolemia

Front 21

problem with mineralocorticoid excess or deficiency doesn't have to involve:

Back 21

aldo

- could be a precursor problem

Front 22

***remember that primary adrenal insufficiency affects BOTH:***

Back 22

cortisol AND aldo production

(BOTH are decreased)

Front 23

6 symps of hypercortisolism:

Back 23

1. muscle wasting/weakness

2. easy bruising/poor wound healing

3. osteoporosis/fractures

4. central obesity

5. glucose intolerance

6. psychiatric disturbances

Front 24

dexamethasone mimics:

Back 24

cortisol

=> should suppress cortisol in a nl pt, due to negative feedback on pituitary and hypothalamus

Front 25

big difference between pit. tumor that produces excess ACTH and an ectopic ACTH production:

Back 25

with pit. tumor, administering high dose of dexamethasone will decrease cortisol levels, since there will be SOME negative feedback on the pituitary
(ACTH-producing pituitary tumor tissue still retains some normal properties and the level of ACTH can be suppressed by the nl cortisol fb mechanism)

- but with ectopic ACTH production, there is NO pathway for dexamethasone to negatively feed back
=> ACTH levels remain high
=> cortisol continues to be produced

Front 26

when measuring cortisol, ALWAYS take:

Back 26

24-hour urine sample

Front 27

Cushing's Syndrome =

Back 27

excess cortisol

Front 28

Cushing's dz =

Back 28

SPECIFICALLY ACTH-producing tumor in the pit. that results in Cushing Syndrome symps

- = secondary hypercortisolism
- m.c.c of CSynd

Front 29

symps of Cushing's Dz:

(10)

Back 29

1. HTN

2. wt. gain

3. moon facies

4. truncal obesity

5. buffalo hump

6. insulin R / hyperglycemia

7. skin changes (thinning, striae)

8. osteoporosis

9. amenorrhea

10. immune suppression

Front 30

treatment for ACTH-producing pit. tumor:

(3)

Back 30

1. removal of pit. tumor

2. bilateral adrenalectomy

3. drug therapy: blockers of ACTH secretion from tumor OR steroid biosynthesis OR steroid action

Front 31

treatment of primary adrenal tumor that's producing excess cortisol:

(2)

Back 31

1. surgical resection
(not very successful for carcinomas)

2. drug therapy: blockers of steroid biosynthesis, adrenolytic drugs

Front 32

treatment of Ectopic ACTH Syndrome:

(3)

Back 32

1. removal/ablation of primary tumor
(surgery, X-ray)

2. Drug therapy: block steroid biosynthesis

3. bilateral adrenalectomy

Front 33

2 drugs that decrease ACTH secretion by a pit. tumor:

Back 33

1. Cabergoline

2. Pasireotide

Front 34

2 drugs that inhibit steroidogenesis:

Back 34

1. Ketoconazole

2. Aminoglutethimide

Front 35

2 drugs that inhibit gluco and mineralocorticoid function AT target tissues:

Back 35

1. Mifepristone

2. Spironolactone

Front 36

4 factors determining the severity of iatrogenic Cushing's Syndrome:

Back 36

1. effective dose of glucocorticoid given

2. duration of glucocorticoid treatment
(the shorter the better)

3. pharmacokinetics of the glucocorticoid
(longer-acting drugs are generally worse)

4. tissue distribution of the glucocorticoid
(systemic distribution is worse than localized or topical)

Front 37

glucocorticoid meds _____________ ACTH

Back 37

suppress

- via cortisol's neg. fb loop on hypothalamus, pit.

Front 38

the longer the half-life of a glucocorticoid med, the greater:

Back 38

the ACTH suppression

=> more atrophy of cortisol-producing cells

Front 39

the problem with long-term adrenal suppression (as via glucocorticoid course):

Back 39

recovery of cortisol-producing cells can take months

Front 40

to Minimize adverse effects of glucocorticoid med course:

(5)

Back 40

1. limit therapy to the lowest dose and duration required to control the underlying dz

2. use alternative anti-inflammatory or immunosuppressive drugs when possible

3. select shorter half-life steroids and use alternate day dosing intervals when possible

4. use *topical* steroid preparations instead of systemic therapy when appropriate

5. GRADUALLY TAPER glucocorticoid med discontinuation, to allow recovery of pit. and adrenal function

Front 41

3 hormone classes that are absolutely necessary for normal BP regulation:

Back 41

1. glucocorticoids,

2. mineralocorticoids,

3. catecholamines

Front 42

removal of an aldosterone-producing tumor does not always cure HTN b/c a substantial fraction of these patients also have:

Back 42

Essential HTN

Front 43

the most supportive physical finding of the presence of a pheochromocytoma in b/w paroxysms =

Back 43

postural hypotension due to intravascular volume depletion

Front 44

2 RAA effects on BP:

Back 44

1. direct AII effect on vascular tone (constricts blood vessels)

2. indirect effect of aldo on volume (increases V)

Front 45

features of Primary Mineralocorticoid Excess:

(4)

Back 45

1. <5% of HTN cases

2. characterized by Na+ retention with concomitant plasma volume inc.

3. hypokalemia due to excessive K+ excretion

4. ***has to be distinguished from Essential HTN pts who are taking diuretics***
- need to take them off diuretics in order to see if Primary Mineralocorticoid Excess is going on

Front 46

4 things that increase renin release:

Back 46

1. Na+ depletion

2. upright posture

3. hypovolemia

4. B2-adrenergic stimulation

Front 47

5 things that decrease renin:

Back 47

1. salt loading

2. lying down

3. ADH

4. aldosterone

5. ANF

Front 48

3 things that increase aldosterone release:

Back 48

1. inc. K+

2. inc. ACTH

3. inc. AII

Front 49

Primary hyperaldo ~~ LOW:

Back 49

plasma renin;


Secondary hyperaldo ~~ HIGH plasma renin

Front 50

2 things that decrease aldo release:

Back 50

1. ANF

2. age

Front 51

primary hyperaldostronism => K+ loss and Na+ retention; the latter =>

Back 51

dec. renin, => dec. AII

Front 52

4 potential causes of Secondary Hyperaldo:

Back 52

1. renovascular HTN

2. diuretic use

3. renin-secreting tumor

4. coarctation of the aorta

Front 53

3 possible causes of low PRA and low PAC at the same time:

Back 53

1. CAH

2. Cushing's Syndrome

3. Liddle's syndrome

Front 54

if you confirm Primary Hyperaldo, the next step is:

Back 54

adrenal CT scan

Front 55

4 causes of secondary hypermineralocorticoidism:

Back 55

1. renovascular HTN

2. renin-secreting tumor

3. accelerated HTN

4. EST therapy

Front 56

renal artery stenosis = less volume going by JG cells =>

Back 56

excessive release of renin on that side

(will see tons of renin in renal VEIN - duh)

Front 57

RAAS antagonists are VERY effective at:

Back 57

lowering renal HTN

Front 58

4 types of RAAS antagonists:

Back 58

1. renin inhibitors

2. ACEI's

3. AT1 r' blockers (inhibit AII from binding zona glomerulosa to release aldo)

4. aldo r' antagonists

Front 59

b/c Pheochromocytomas are rare and difficult to find, the key to diagnosing them is:

Back 59

a high index of suspicion

Front 60

***pts with pheochromocytoma will have ________________ of ________________________***

Back 60

**paroxysms of SEVERE HTN**

Front 61

paroxysm =

Back 61

sudden attack

- in the case of pheochromocytoma, looks like wild swing in BP

Front 62

5 symps during a HTN paroxysm:

(aka hyperadrenergic episode)

Back 62

5 P's

1. Pressure (way up)

2. Pain (HA)

3. Perspiration

4. Palpitations (tachy)

5. Pallor

Front 63

4 symps b/w HTN paroxysm:

Back 63

1. inc. sweating

2. cold hands and feet

3. wt. loss

4. constipation


(think some combination)

Front 64

rule of 10 regarding pheochromocytoma:

(4)

Back 64

10% are bilateral

10% occur in children

10% originate in the sympathetic ganglia outside the medulla

10% are malignant
(nly benign)

Front 65

5 screening tests for Pheochromocytoma:

Back 65

1. plasma catecholamines

2. urinary catecholamines

3. urinary metabolites

4. 3 reps of plasma or urine tests

5. suppression test - use Clonidine to stimulate NOR - check

**do NOT use stimulation test**

Front 66

what imaging do you get to try and see a pheochromocytoma?

Back 66

MRI

- will be DARK on T1, like water, b/c it's highly vascular

Front 67

if the MRI is negative but urine samples still suggest pheochromocytoma, it might be ectopic (10%); imaging to order =

Back 67

PET scan

Front 68

if a pheochromocytoma is bilateral, the ONLY medical recourse is:

Back 68

surgery to remove them

Front 69

med treatment of pheo, apart from surgery:

Back 69

combo of alpha and Beta-blockers is often effective to control HTN and cardic arrythmias

Front 70

4 lobes of the thyroid gland:

Back 70

1. pyramidal (on top)

2. isthmus (in the middle)

3. right

4. left

Front 71

nl dimensions of the thyroid gland:

Back 71

2.5 x 2.5 x 4.0 cm

Front 72

thyroid hormones are formed via:

Back 72

organification

- within the follicular cells of the thyroid gland

- see Sheet

Front 73

organification =

Back 73

adding Iodine to tyrosine residues of thyroglobulin

Front 74

2 features of thyroxine (T4):

Back 74

1. ~~80% of secreted thyroid

2. t1/2 = 7 days

Front 75

2 features of triiodo-thyronine (T3):

Back 75

1. 20% of secreted thyroid

2. half-life = 1 day

Front 76

"labile" =

Back 76

liable to change; easily altered

Front 77

thyroid hormone r's are found within the nuclei of:

Back 77

almost everywhere in the body

- main effects are on CV, GI, and CNS

- generally stimulatory for gene expression

Front 78

***the 4 B's of T3 function:***

Back 78

1. inc. BMR 
(via Na+/K+ ATPase, => O2 consumption, RR, body Temp)

2. Brain/CNS maturation

3. B-adrenergic effects (inc. HR, SV, CO)

4. Bone growth (with GH)

Front 79

T4 is converted to T3 via:

Back 79

deiodinases type I and II

esp. in the liver

Front 80

blood tests of thyroid function measure:

(6)

Back 80

TSH

T4 or free T4

T3 or free T3

AB's

Front 81

2 options to measure INTRINSIC activity of the thyroid gland:

Back 81

1. Radioactive iodine uptake (RAIU)

2. Thyroid scan

Front 82

RAIU measures:

(2)

Back 82

1. active transport and

2. organification of iodine

- the PERCENT of uptake at 4 and 24 hrs is m'd

Front 83

what does the thyroid scan do?

Back 83

localizes rates of active transport of iodine

- seen via IMAGE
- nl thyroid scan shows UNIFORM tracer distribution

Front 84

95% of the time, hypothyroidism is:

Back 84

PRIMARY

- i.e. caused by thyroid gland dysfunction, failure, or absence

Front 85

hypothyroidism occurs more often in:

(2)

Back 85

1. women

2. elderly

- MUCH more common than hyperthyroidism

Front 86

4 specific causes of hypothyroidism:

Back 86

1. Hashimoto's thyroiditis
(AI destruction of tissue)

2. post-surg/radx ablation

3. meds

4. iodine deficiency (globally)

Front 87

which meds can cause hypothyroidism, and how?

(3)

Back 87

1. Li2+

2. Amiodarone

3. Interferon

=> decreased thyroid production

Front 88

5 features of Hashimoto's thyroiditis:

Back 88

1. also called chronic lymphocytic thyroiditis

2. = AI destruction of thyroid tissue
(m.c.c. of hypothy)

3. ~~ high TPO (anti-thyroid) AB's

4. ~~lymphocytic infiltration

5. big, diffuse gland, until later stages
(i.e. looks like hyperthy at first, but then gland atrophies)

Front 89

Subacute (deQuervain) Granulomatous Thyroiditis =

Back 89

granulomatous thyroiditis that follows *viral* infection

- presents with TENDER thyroid

- but self-limited - does NOT progress to hypothyroidism (i.e. mild, transient hypothyroidism)

Front 90

non-specific lymphocytic thyroiditis is also called:

(2)

Back 90

1. *Painless thyroiditis

2. *Postpartum thyroiditis

= transient hyperthy followed by hypo, then nl

Front 91

classic course of thyroiditis:

(3 phases)

Back 91

1. hyperthyroidism, given release of preformed T3/T4 into blood
- TSH levels dec. in response
- first 3 months

2. hypothy, as gland "rests"
- T3/T4 dec.
- 4-6 mths

3. T3/T4 naturally reach nl levels, as gland recovers
- 12 months in

Front 92

in general, symps of hypothyroidism are due to:

(2)

Back 92

1. slowing of metabolism and target organ function

2. accum. of GAG's
=> myxedema (doughy)

Front 93

10 symps of hypothyroidism

(apart from wt gain, cold intolerance,

Back 93

1. myxedema
(esp. in larynx and tongue, => deep voice, large tongue)

2. slowing of mental activity

3. muscle weakness

4. dec. sweating

5. bradycardia with dec. CO
=> SOB, fatigue

6. oligomenorrhea

7. hypercholesterolemia

8. constipation (gut slows down)

9. dry skin/hair, brittle nails

10. paresthesias/delayed reflexes

Front 94

if hypothyroidism develops gradually, the symps and signs may be:

Back 94

overlooked

- severity may become evident in retrospect, after treatment begins

Front 95

TSH > 10 =

Back 95

OVERT primary hypothyroidism

Front 96

labs of overt primary hypothyroidism:

(3)

Back 96

1. high TSH

2. low T4

3. low/nl T3

Front 97

labs of subclinical primary hypothyroidism:

(3)

Back 97

1. high TSH

2. nl T4

3. nl T3

Front 98

abs of overt secondary hypothyroidism:

(3)

Back 98

1. low/nl TSH

2. low T4

3. low/nl T3

Front 99

treatment of hypothyroidism =

Back 99

Levothyroxine

- oral, synthetic form of T4

- different colors ~~ different doses

Front 100

how often do you measure TSH after starting treatment with Levothyroxine?

Back 100

every 6-8 weeks, with dose adjustments as indicated, until TSH is in nl reference range

Front 101

Hypothyroidism in preg:

(3)

Back 101

1. demand for thyroid hormone increases in early in pregnancy by 30%

2. mother must be able to meet this demand, as fetal thyroid development does not begin until 12th week

3. untreated overt hypothyroidism can be devastating for pregnancy outcome and for offspring
(~~mental retardation, growth deformities)

Front 102

4 causes of hypothyroidism in infants:

Back 102

1. absent/underdeveloped thyroid

2. hypopit.

3. defects in thyroid hormone synthesis or action

4. mom's hypothyroidism
(baby thyroid doesn't develop until 12th week)

Front 103

8 signs/symps of hypothyroidism in infants:

Back 103

1. delayed growth/development
(increased wt for given ht)

2. poor feeding

3. sluggish, poor muscle tone (“floppy”)

4. hoarse cry

5. protruding tongue

6. delayed bone age

7. prolonged neonatal jaundice

8. poor cognition

Front 104

severe hypothyroidism =>

Back 104

myxedema coma

Front 105

4 symps of myxedema coma:

Back 105

1. bradycardia

2. hypotension

3. hypothermia

4. hypoventilation

=> stupor, coma

Front 106

myxedema coma is usually seen in:

(2)

Back 106

chronic non-compliance or undiagnosed hypothyroidism,

**after precipitating event**

Front 107

3 potential precipitating events of myxedema coma:

Back 107

1. severe illness, e.g. infection, stroke, hemorrhage

2. surgery,

3. sedatives, anesthetics

Front 108

**clue to diagnosis of myxedema coma = **

Back 108

neck scar from prior thyroid surgery

Front 109

myxedema coma has a high mortality; treatment =

(3)

Back 109

1. UC

2. aggressive supportive care

3. thyroid hormone

Front 110

for hyperthy, think:

Back 110

PRIMARY ONLY

- either endogenous or exogenous

Front 111

exogenous hyperthy ~~

(2)

Back 111

excess supplementation (iatrogenic)

or surreptitious use

Front 112

3 major causes of excess thyroid hor. production:

Back 112

1. Graves’ Dz (70%)

2. Toxic Multinodular Goiter (20%)

3. Toxic Adenoma

("toxic" means it's producing thyroid hormone but NOT under control of TSH)

Front 113

excess *release* of preformed thyroid is most often due to:

Back 113

thyroiditis

Front 114

in general, symps of hyperthyroidism are due to:

(2)

Back 114

1. accelerated metabolism and

2. target organ hyperfunction

Front 115

11 symps of hyperthy:

(apart from wt loss and heat intolerance/sweating)

Back 115

1. tachycardia, inc. CO

2. arrhythmias, esp. in the elderly

3. tremor, anxiety, insomnia, heightened emotions

4. *staring gaze w/ lid lag*

5. diarrhea with malabsorption
(gut speeds up)

6. oligomenorrhea

7. bone resorption with hypercalcemia
=> osteoporosis

8. dec. muscle mass/weakness

9. hypochol

10. hyperglycemia
(thyroid hor causes GNG, glycogenolysis)

11. fine hair

Front 116

next step in evaluating hyperthy =

Back 116

identify underlying etiology

Front 117

in hypothyroidism, the treatment (thyroid hormone) is the same regardless of the cause; in hyperthy,

Back 117

the underlying etiology determines the clinical course

Front 118

4 tests useful for evaluating hyperthy:

Back 118

1. RAIU

2. thyroid scanning

3. AB testing
(elevated TSI/TSH-R Ab often seen in Graves)

4. Thyroglobulin level
(useful if exogenous thyroid hormone ingestion is suspected)

Front 119

Grave's Dz =

Back 119

AI dz in which Thyroid-Stimulating Ig's (TSI) activate the TSH r' in thyroid cells

Front 120

6 features of Grave's:

Back 120

1. YOUNG WOMEN

2. toxic, diffuse, symmetrical, BIG goiter

3. ***with bruits, thrills***

4. ophthalmopathy
(due to prolif. of SM, fibroblasts behind the eye)

5. Grave's dermopathy (pretibial myxedema)

6. acropachy (finger clubbing due to new bone formation)

Front 121

4 effects of Grave's ophthalmopathy:

Back 121

1. proptosis (exophthalmos)

2. chemosis (swelling)

3. EOM entrapment

4. optic nerve damage

Front 122

path of Toxic Multinodular Goiter:

Back 122

nodules gradually acquire autonomy over many years

Front 123

features of TMG:

(4)

Back 123

1. usually elderly

2. F > M

3. asymmetric, nodular gland

4. compressive symptoms can occur with growth
(think airway compromise)

Front 124

4 treatment for hyperthy:

Back 124

1. anti-thyroid drugs
- first-line for Grave's

2./3. Radioactive Iodine/ Surg
- first-line for toxic nodules

4. ancillary/adjunctive Drugs:

Front 125

surgery is NOT:

Back 125

a common treatment for hyperthy (since Grave's makes up 70% of cases)

Front 126

2 anti-thyroid drugs:

Back 126

1. Methimazole

2. Propylthiouracil (PTU)

Front 127

Methimazole and PTU work by blocking:

(4)

Back 127

1. thyroid peroxidase

2. thus, organification of iodide

3. Coupling of iodotyrosines (MIT, DIT)

4. peripheral T4 to T3 conversion

- goiter shrinkage is minimal at first; need to wait several weeks for full effect

Front 128

2 common SE's of Methimazole and PTU:

Back 128

1. rash

2. muscle/joint pain

Front 129

2 serious SE's of Methimazole and PTU:

Back 129

1. liver damage
- tell pts to report abd pain, vomiting

2. agranulocytosis
- fever, sore throat

Front 130

2 ancillary/adjunctive drugs for hyperthy:

Back 130

1. Iodine, steroids
(severe cases)

2. B-blockers
(symp relief)

Front 131

1 major and 1 minor drawback of using radioactive Iodine to treat hyperthy:

Back 131

major: cause HYPOthy

minor: exacerbates Grave's ophthalmopathy

Front 132

counterintuitive effect of iodine as adjunctive drug:

Back 132

*inhibits* thyroid hormone synth/release within 2-7 days


= Wolff-Chaikoff effect of high iodine exposure

- NOT for long-term therapy

Front 133

thyroid storm =

Back 133

SEVERE hyperthy

= surge of catecholamines and massive hormonal excess

Front 134

symptoms of thyroid storm:

(3)

Back 134

1. fever,

2. AMS

3. CV collapse

Front 135

3 precipitants of thyroid storm:

Back 135

1. surgery

2. child-bearing

3. iodine load

Front 136

treatment of thyroid storm:

(5)

Back 136

1. high-dose PTU

2. iodine (2 hrs after PTU)

3. propranolol

4. dexamethasone

5. treat UC