Endo Part 2

Front 1

hypopituitarism is a spectrum:

Back 1

starts with deficiency in secretion of ONE hormone,

through 2+,

into panhypopituitarism (which means post. pit. is included)

Front 2

2 clues to hereditary hypothalamic issue:

Back 2

1. cleft lip/palate,

2. *single* upper central incisor

Front 3

3 KEY features of hypopituitarism:

Back 3

1. symps develop slowly/insidiously

2. acquired dz's tend to affect multiple hormones
(starting with GH, then LH/FSH)

3. ALL hypopit's are treatable

Front 4

isolated cases of ____ and __________ are semi-common

Back 4

GH;

LH/FSH

Front 5

features of hypopit. in children:

(8)

Back 5

1. history of short stature

2. trauma/hypoxia

3. hypoglycemia in neonates

4. **micropenis**

5. **decreased growth velocity**

6. **delayed or absent puberty**

7. **midline defects**
(~~brain, SC)

8. TSH/ACTH deficiency

Front 6

most specific symp of hypopit. in adults =

Back 6

LH/FSH deficiency

Front 7

features of GH deficiency:

(2)

Back 7

1. increased adipose

2. reduced strength/muscle mass

Front 8

features of LH/FSH deficiency:

(2)

Back 8

1. oligo- or amenorrhea in women

2. loss of libido, ED in men

Front 9

features of TSH deficiency:

(4)

Back 9

1. cold intolerance

2. constipation

3. dry skin

4. hair loss

Front 10

features of ACTH deficiency:

(2)

Back 10

1. weight loss

2. postural hypotension

Front 11

Prolactin deficiency =>

Back 11

inability to lactate in women

Front 12

2 labs that suggest pit. LH/FSH deficiency:

Back 12

1. low estradiol, low TEST

2. low or *inappropriately nl* LH/FSH

Front 13

2 labs that suggest pit. TSH deficiency:

Back 13

1. low T3, T4

2. low or *inappropriately nl* TSH

Front 14

2 labs that suggest pit. ACTH deficiency:

Back 14

1. low *morning* cortisol

2. low or *inappropriately nl* ACTH

Front 15

"inappropriately nl" ~~

Back 15

if you have missing cortisol, ACTH should inc. dramatically

- if it's in the nl range, that's inappropriate

Front 16

hallmark of endo: if a hormone is unequivocally low,

Back 16

go with that diagnosis;


but if it's not quite low but close, try stimulate it

- and if it's high, try to suppress it

Front 17

stimulation test works well for:

Back 17

ACTH
(induce low sugar state, it should increase - if it doesn't, something's wrong

=> diagnosis)

Front 18

treatment for LH/FSH deficiency:

(3)

Back 18

1. W: estrogen/progestin (pills, patch)

2. M: TEST (gel, patch, shots)

3. *both:* LH/FSH injections for fertility

Front 19

treatment for TSH deficiency:

(1)

Back 19

Levothyroxine (daily pill)

Front 20

treatment for ACTH deficiency:

(3)

Back 20

1. hydrocortisone

2. prednisone

3. dexamethaxasone (pills)

Front 21

in adults, GH Deficiency is usually due to:

Back 21

pituitary tumor,

so it usually exists with other pituitary deficiencies

- treatment is expensive

Front 22

7 features of GHD in children:

Back 22

1. severity determines age of onset

2. standing height <2 SD from the mean

3. ~~10th-25th percentile

4. delayed dentition
(arrangement of teeth in their particular order)

5. delayed puberty

6. delayed bone age

7. micropenis

Front 23

what's the most important imaging in GHD?

Back 23

MRI,

to assess structural dz

Front 24

2 features of GHD in adults:

Back 24

1. usually in 30's or 40's

2. nonspecific symps
(dec. energy, mood, exercise performance)

Front 25

5 signs/labs of GHD in adults:

Back 25

1. dec. muscle mass

2. dec. bone density
(~~ inc. fracture risk)

3. inc. central adiposity

4. inc. LDL cholesterol, dec. HDL => atherogenesis

5. impaired cardiac function

Front 26

diagnosis of GHD:

(3)

Back 26

1. IGF-1 level should be low
(< 2.5th percentile most convincing)

2. provocative (stimulating) testing is usually necessary
- Insulin-induced hypoglycemia should result in a burst of GH release

3. when multiple other pituitary deficits are present, low IGF-1 level may suffice

Front 27

treatment of GHD =

Back 27

recombinant hGH

- injections

- also used to treat select causes of short stature in children, e.g. Prader-Willi

Front 28

goals of hGH treatment in children:

(3)

Back 28

1. **linear growth**

2. restore body composition

3. continue until final height, epiphyseal closure, or both

Front 29

goals of hGH treatment in adults:

(3)

Back 29

1. improve strength

2. restore body composition

3. improve quality of life

Front 30

risks of hGH treatment:

(3)

Back 30

1. Na/H20 retention

2. Glucose intolerance

3. Mitogenic effects (triggers mitosis)
?Increased cancer

Front 31

effects of Na/H20 retention:

(2)

Back 31

1. arthralgias, myalgias, edema

2. carpal tunnel syndrome

Front 32

disorders of GH Responsiveness =

(dz that's a little different from GHD but with similar effects)

Back 32

GH r' mutation => GH R, insensitivity

=> Laron dwarfism

- almost NO cancer, DM

Front 33

in general, the main causes of hypopituitarism are:

(3)

Back 33

1. genetic/familial

2. pituitary tumors

3. other forms of pituitary damage

Front 34

in general, diagnosis of hypopit. =

(3)

Back 34

1. m'g target organ hormones (e.g. TEST)

2. m'g pituitary hormones,

3. in some cases, stimulatory testing

Front 35

treatment for hypopit. =

Back 35

replacing missing hormone(s),

*usually the target-organ hormones rather than pituitary hormones*

Front 36

samples of endocrine testing are taken from:

(2)

Back 36

1. serum/plasma

2. urine (though serum better)

Front 37

the reference range for many hormones depends on:

(3)

Back 37

WHEN, HOW, and in WHOM the samples are collected

Front 38

3 types of hormonal patterns:

Back 38

1. circadian/diurnal patterns
- tied to sleep-wake cycles
- e.g. cortisol in the morning

2. episodic pulsations
- tied to food, exercise, sleep
- e.g. GH inc's after eating

3. positional changes
- aldosterone inc's when upright, decreases when recumbent

Front 39

most hormones, especially steroid and thyroid hormones, circulate as:

(2)

Back 39

“bound” and free forms

Front 40

note: protein/peptide hormones and catecholamines are not associated with proteins, i.e. they:

Back 40

*circulate freely* only

Front 41

bound form =

Back 41

hormone + carrier proteins

Front 42

unbound/free form =

Back 42

*biologically active* form

=> the form that exerts hormonal action

- is often the minority form

Front 43

the total hormone measurement is affected not only by changes in the hormone itself, but also by:

Back 43

changes in the proteins that are binding the hormones

Front 44

4 things to take into account when you take the hormone measurement:

Back 44

1. meds

2. when they last ate

3. what time of day it is

4. how you're collecting

Front 45

remember: symps reflect the amount of hormone:

Back 45

*available* to act at the target organ

(i.e. amount of *free* hormone)

Front 46

total hormone measurements reflect Bound + Free;

If results are abnormal, ask:

Back 46

“do symptoms match free hormone level?"

"If not, is concentration of the *carrier protein* affected?”

Front 47

if hormone is low (deficiency), perform:

Back 47

stimulation studies

- if high (excess): perform suppression studies

Front 48

"analytes" =

Back 48

what you're measuring

Front 49

end-organ analytes for GH, ACTH, LH/FSH, and TSH:

(4)

Back 49

1. IGF-1, IGF binding proteins

2. cortisol

3. estradiol, TEST

4. T3, free T3, T4, free T4

Front 50

end-organ analytes for ADH:

Back 50

1. Na+

2. osmolality (serum, urine)

Front 51

things that inhibit GH synthesis:

(4)

Back 51

1. Somatostatin

2. cortisol

3. malnutrition

4. hyperglycemia

many others

Front 52

3 causes of GH synthesis/release:

Back 52

1. deep sleep

2. exercise

3. eating

- GH stimulates GNG at the liver

Front 53

diagnosing GH excess:

(3)

Back 53

1. IGF-1/IGFBP-3 complex

2. multiple samples of GH over 24 hours

3. glucose suppression test
(glucose should cause GH suppression)

Front 54

secondary endocrine dysfunction:

Back 54

the endocrine gland is “fine”,

*but is receiving too much or too little tropic hormone*

- for most, the problem is one with the pituitary

Front 55

look at both sets of test results (tropic and secretory hormones) to distinguish between:

Back 55

Primary from Secondary dz

Front 56

wrt endocrine secretory hormone and pituitary hormone levels, PRIMARY Hyperfunction ~~

(2)

Back 56

1. increased endocrine gland secretory hormone (e.g. T3)

2. decreased pituitary (e.g. TSH)

Front 57

what are the levels of endocrine secretory hormone and pituitary in SECONDARY hyperfunction?

(2)

Back 57

1. increased or inappropriately nl secretory hormone (e.g. T3)

2. INC. or inappropriately nl pituitary hormone (TSH)

(think through these, drawing TSH/T3 examples)

Front 58

wrt endocrine secretory hormone and pituitary hormone levels, primary hypofunction ~~

(2)

Back 58

1. dec. levels of secretory hormone

2. inc. levels of pituitary hormone

Front 59

secondary hypofunction ~~

(2)

Back 59

1. dec. endocrine secretory hormone

2. dec. pituitary hormone

Front 60

ADH and OXY are synthesized in the:

Back 60

magnocellular neurons of the supra-optic and paraventricular nuclei of the hypothalamus

- stored in post. pit. as prohormones

Front 61

functions of OXY:

(2)

Back 61

1. inc. uterine SM contraction

2. milk ejection
(stimulated by suckling)

Front 62

there are no known OXY:

Back 62

dz's

Front 63

2 important VP r's, V1 and V2;

V1 function ~~

Back 63

**vasoconstriction**

Front 64

V1 r's are found in SM of:

Back 64

cardiac, vascular, GI, and uterus.

- low affinity (need lots of ADH/VP to see effect)

Front 65

main function of V2 r's ~~

Back 65

water retention

- high affinity

Front 66

V3 function ~~

Back 66

stimulating ACTH from pituitary

Front 67

ADH binding to V2 r's stimulates:

Back 67

AQ2's to lumen of collecting duct , to reabsorb water

Front 68

osmotic regulation is very sensitive; osm. is monitored by:

Back 68

hypothalamic osmoreceptors ant. to the 3rd ventricle

- 1% increase in serum osm. => release of ADH

- conversely, suppress ADH when serum osm. is low/dilute

Front 69

pressure regulation of the body is achieved via:

Back 69

carotid sinus, carotid baro-r's

- tonically inhibit ADH

=> hypotension causes release of inhibition => exponential increase in ADH

(5-10% dec. in blood volume is required before ADH inhibition is released)

Front 70

sensory regulators of ADH:

(3)

Back 70

1. thirst
(need to sense higher serum osm. than osmotic sense)

2. nausea
(potent and rapid)

3. pain/emotional stress

Front 71

"diabetes" =

Back 71

excess pee

Front 72

diabetes insipidus =

Back 72

excess urinary loss of water

Front 73

cause of DI =

(2)

Back 73

deficiency of ADH or insensitivity to it

Front 74

dx of DI =

Back 74

1. plasma hyper-osm w/

2. urinary hypo-osm.

- ***in practice:
hypernatremia and HIGH serum osm. w/ inappropriately LOW urine Na+ and osm***


(i.e. high Na+ in the blood, low Na+ osm. in the urine)

Front 75

formula for osm:

Back 75

Osm = 2 Na + BUN/2.8 + glucose/18

Front 76

nl serum osm. =

Back 76

289

Front 77

polyuria =

Back 77

peeing >3 L per day

Front 78

4 major causes of polyuria:

Back 78

1. diuresis

2. primary polydipsia

3. nephrogenic DI: renal insensitivity to AVP

4. Central DI

Front 79

features of nephrogenic DI:

(5)

Back 79

1. hypercalcemia

2. hypokalemia

3. s/ts induced by drugs (lithium, ampho B, gentamicin, cisplatin…)

4. or renal dz

5. AVPR2 or AQP inactivating muts

Front 80

outpt diagnosis of DI =

Back 80

water deprivation test

Front 81

water deprivation test explained:

Back 81

no water intake in a nl pt should cause an inc. in ADH

- but in CDI, ADH will NOT be released

- so when/if hypernatremia occurs, test for urinary hyponatremia

- dx of DI if: HIGH serum sodium and osm with inappropriately LOW urine sodium and osm

Front 82

to determine whether DI is central or nephrogenic, add:

Back 82

dDAVP (ADH analog)

- if serum and urine Na+ start improving (back to normal), that means it's Central DI

- if not, it indicates problem with kidney r's => nephrogenic DI

Front 83

treatment of Central DI =

Back 83

dDAVP (ADH analog)

Front 84

SE's of dDAVP =

Back 84

HA, nausea, flushing

Front 85

***dDAVP turns off the fountain (peeing out water), but don't forget to:***

Back 85

fill the tank (i.e. drink water to replenish)

Front 86

SIADH = opposite of CDI =

Back 86

inappropriate water retention

Front 87

dx of SIADH =

Back 87

hypoNa+ with inappropriate urinary Na+ loss

AFTER THE EXCLUSION of other causes of hyponatremia

Front 88

5 features of SIADH:

Back 88

1. hyponatraemia with low plasma osm.

2. urine osm. > plasma osm.

3. inappropriate renal sodium excretion > 20 mmol/l

4. absence of hypotension, hypovolemia and edema-forming states

5. nl renal, adrenal and thyroid function

Front 89

symps of SIADH range from:

Back 89

none to gradual (HA's, nausea) to sudden onset confusion, se'z or coma (water intoxication

Front 90

tx of SIADH without CNS symps:

(2)

Back 90

1. fluid restriction

2. Demeclocycline
(a tetracycline)

Front 91

tx of SIADH w/ CNS symps:

(2)

Back 91

1. NS or 3% Saline

2. loop diuretics

Front 92

2 new V2 antagonists:

Back 92

1. Conivaptan IV

2. Tolvaptan po

Front 93

with SIADH, always follow:

Back 93

serum sodium CLOSELY

Front 94

In CHRONIC hyponatremia, a rapid increase in sodium can cause:

Back 94

CPM

- do not exceed a correction rate of 10 mmol per day

- for known acute hyponatremia, can add more, faster

Front 95

CPM often presents as:

(4)

Back 95

1. lethargy

2. ataxia

3. Locked-in Syndrome

4. sez's


- esp. in alcoholics

Front 96

adrenal cortex color:

Back 96

yellow

Front 97

adrenal medulla color =

(INNER)

Back 97

dark red/brown

Front 98

the medulla is derived from the neural crest, which means:

Back 98

it's basically NEURAL tissue

- neural crest also forms the sympathetic ganglia

Front 99

3 layers of the adrenal cortex:

Back 99

zona glomerulosa

fasciculata

reticularis

Front 100

3 features of the zona glomerulosa:

Back 100

1. spheres (glomeruli) of cells

2. produces aldosterone

3. responsive to ANII

Front 101

features of the zona fasciculata:

(3)

Back 101

1. vertical cords of pale cells

2. produces cortisol, androgen

3. responsive to ACTH

Front 102

pale cells are pale b/c they are filled with:

Back 102

lipid,

the precursor to steroid hormone synth.

Front 103

zona reticularis:

(3)

Back 103

1. irregular array of darker cells

2. also produces cortisol, androgen

3. also responsive to ACTH

Front 104

the medulla is composed of ______________ cells, which are _______________________________

Back 104

chromaffin cells,

post-ganglionic sympathetic cells

Front 105

the medulla synthesizes:

Back 105

catecholamines

- secretes them into blood

Front 106

the entire adrenal gland is highly:

Back 106

vascular

Front 107

the adrenal cortex and medulla are different tissues and have distinct diseases; the cortex is affected by many different processes, while the medulla is only ever affected by:

Back 107

neoplasms

Front 108

2 types of pathology that are NOT common in the adrenal gland:

Back 108

inf. and hemorrhage

Front 109

Addison dz =

Back 109

a primary CHRONIC adrenal insufficiency

- due to destruction of >90% of adrenal tissue

- whether by mets or AI or TB (globally)


Hyperpigmentation and hyperkalemia distinguish primary adrenal insufficiency (e.g. Addison’s) from secondary adrenal insufficiency

Front 110

Conn Syndrome =

Back 110

= primary HYPERaldosteronism

- can be caused by functional adenoma

Front 111

Cushing's dz =

Back 111

excessive cortisol

Front 112

Congenital Adrenal Hyperplasia = hyperfunction dz of:

Back 112

excessive androgen production

Front 113

2 features of CAH:

Back 113

1. group of AR disorders

2. ~~lack of steroid hormone synthetic **enzymes**
(e.g. 21-hydroxylase, 11-OH)

Front 114

primary adrenal hyperplasia is the result of:

Back 114

congenital lack of a synthetic enzyme

Front 115

secondary adrenal hyperplasia is the result of:

Back 115

inc.'d trophic factor (ACTH, renin/AII)

- **secondary adrenal hyperplasia** m.c. than primary**

Front 116

pathogenensis of CAH:

Back 116

lack of 21-hydroxylase means no production of aldosterone OR cortisol

=> production shifts to androgens

=> virilization (development of male characteristics in a female or precociously in a boy)

Front 117

***what can easily cause adrenal atrophy?***

Back 117

MEDS

- taking glucocorticoids makes adrenal glands "useless"

=> meds use same neg. fb as cortisol

=> decreased ACTH release

=> nl cortisol-releasing cells atrophy b/c they aren't being used/stimulated by ACTH

(if therapy is withdrawn acutely, the atrophic adrenal glands won't be able to pick up the need so fast =>=> primary acute adrenal insufficiency)

Front 118

gross of adrenal adenoma:

(3)

Back 118

solid, encapsulated, yellow

Front 119

histo of adrenal adenoma:

(3)

Back 119

1. pale

2. lipid-laden

3. well-differentiated cells

Front 120

if the adenoma is functional (i.e. releases cortisol),

Back 120

ACTH will decrease

=> nl adrenal glands not being used

=> atrophy

Front 121

adrenal adenomas can be function or NON-functional; when they're functional,

Back 121

ONE hormone is produced

Front 122

both adenomas and carcinomas of the adrenal gland are:

Back 122

RARE

Front 123

histo of adrenal carcinoma =

Back 123

variable (well-differentiated to anaplastic)

Front 124

remember that if neoplasms are functional, the increase in the hormone that they produce is a:

Back 124

PRIMARY problem, b/c it's still part of the gland

Front 125

3 m.c. CA's that mets to the adrenal gland:

Back 125

1. lung

2. breast

3. melanoma

Front 126

females tend to get AI disorders more:

Back 126

than men

Front 127

adrenal AI disorders have AB against adrenal tissue; 50% of cases show:

Back 127

ONLY adrenal gland involvement;

50% show mult. gland involvement

Front 128

early histo of AI adrenitis =

Back 128

lymphoid (lymphocyte) infiltrates in cortex

Front 129

histo of chronic AI adrenitis =

Back 129

fibrosis of cortex

- **medulla is spared**

Front 130

gross of TB inf of adrenal gland:
(tuberculous adrenitis)

(2)

Back 130

1. early the gland enlarges;

2. later the gland atrophies

Front 131

histo of TB adrenitis:

Back 131

granulomas

(epitheliod mΦ's +/- multinucleate giant cells)

Front 132

hemorrhage of adrenal gland occurs with:

(3)

Back 132

1. Anti-coagulant therapy

2. DIC

3. bacterial sepsis (= Waterhouse - Friderichsen Syndrome)

Front 133

pathogenesis of adrenal hemorrhage:

Back 133

bilateral adrenal hemorrhage →

acute hemorrhagic necrosis →

1° acute adrenal insufficiency

Front 134

Waterhouse-Friderichsen Syndrome =

Back 134

N. meningitidis septicemia

=> hypotension, DIC

=> massive adrenal hemorrhage, skin purpura (dark)

=> **primary ACUTE adrenal insufficiency,** death
(^vs. Addison's)

Front 135

5 ways to get Cushing's:

Back 135

1. medical glucocorticoids

2. pit. adenoma that => inc. ACTH release
=> adrenal cortical hyperplasia

3. adrenal cortical adenoma

4. adrenal cortical carcinoma

5. ectopic inc. in ACTH (e.g. SCC of the lung)

Front 136

only path that hits adrenal medulla =

Back 136

neoplasm

Front 137

neuroblastoma =

Back 137

peds version of pheochromocytoma,

but w/o HTN

Front 138

pheochromocytoma =

Back 138

neoplasm of chromaffin cells which secrete catecholamines → HTN

Front 139

rule of 10 with pheochromocytoma:

(4)

Back 139

10% are bilateral,

10% are malignant,

10% occur in children,

10% extra-adrenal

Front 140

pheochromocytoma is a surgically-

Back 140

correctable form of HTN