Adrenal Pathophysiology (5/16) Flashcards Preview

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Flashcards in Adrenal Pathophysiology (5/16) Deck (50):
1

List diseases of the Zona Fasciculata

Cortisol Xs: Cushings

Cortisol Deficiency: Addison's

2

List disease of Zona Glomerulosa

Primary Hyperaldosteronism

3

List disease of the Zona Reticularis

Androgen Excess

4

List disease of the adrenal medulla

Pheochromocytoma (tumor that secrete XS catecholamines)

5

Dfine Cushing's Syndrome

Having excess cortisol secretion (regardless of cause/source)

6

What is the most common cause of cushings syndrome?

Iatrogenic from exogenous glucocorticoid use

7

What are the pathophys changes in HPA axis with cushings?

1. Loss of diurnal variation of cortisol secretion (cortisol peaks are higher and taller)
2. Autonomy from ACTH control (ie loss of feedback regulation)
3. XS cortisol secretion

8

What is Cushing's Disease?

Pituitary adenoma that secretes too much ACTH

9

What is ectopic ACTH syndrome

Ectopic ACTH is being produced by a tumor outside the pituitary. Most common in lung and bronchi. Very severe

10

What are some basic metabolic derangements due to XS corticosteroids?

1. Carb metab: stimulates gluconeogenesis leading to hyperglycemia

2. Fat metab: inc lipgenesis leads to inc FFAs and insulin resistance (obesity is the most common finding in Cushings)

3. Protein metab: Inc gluconeo-->catabolism (uses muscle)

11

What is the most common finding in cushings?

Obesity (also diabetes, hypertension, menstrual abnormalities, muscle weakness etc)

12

What are some phyiscal effects of fat metab?

Dewlap (double chin), Buffalo hump (fat bad at back of neck), supraclavicular fat pads

13

What are some effects of cortisol excess?

-Impaired immunity
-Inc clotting factors
-Cataract formation
-Proximal myopathy
-Osteoporosis
-Redistribution of body fat
-Hypertension, cardiomyopathy, inc thromboemobolic events
-Thin skin, easy brusing, striae, acne, hyperpigmentation, hirsutism
-Psychiatric disturbances
-Hypokalemia
-Inc testosterone in females
-Menses abnormalities
-Marked virillization in women worrisome for malginant adnreal tumor

14

Describe ACTh dependent cushings

Characterized by bilateral adrenal hyperplasia

15

Describe ACTH independent cushings

Adenoma makes cortisol

16

What do you measure if there is loss of diurnal variation cortisol secretion?

Measure late night salivary cortisol. Measures free cortisol. Beware of pts with night shift/disturbed sleep/wake cycle

17

What do you measure if there is autonomy from ACTH control?

1mg dexamethasone suppression test. DST measures loss of feedback inhibition. Dex is a synthetic glucocorticoid so it should suppress ACTH and cortisol levels. If it doesn't, then you have ACTH being produced elsewhere or from an ACTH producing adenoma.

-indicates inappropriate secretion, does not indicate source of cortisol

-Dex is taken at 11pm and cortisol is measured at 8am

-Normal: cortisol <2mcg/dL after dex

18

What do you measure if there is an excess of cortisol?

24 hr urinary free cortisol measurements. Cushings is more likely if cortisol >3x upper limit of normal

19

If a pts urine cortisol is markedly elevated and cortisol is elevated after DSH. ACTH is also elevated. What is the source of cushings?

Pituitary adenoma (inc ACTH, cortisol despite DST)

20

If ACTH is low

Cushings from adrenal source

21

If ACTH is normal or elevated

Pituitary or ectopic source

22

ACTH is suppressed

Source is exogenous glucocorticoids

23

How do we localize the source?

imaging

24

How do we treat cushings?

Depends on source

-Cure unilateral adrenal adenoma with adrenalectomy
-Use ketoconazole, metyrapone or bilateral adrenalectomy if required

25

How long does it take for symptoms to go away post treatment?

Up to 12 mo, not all sequelae completely resolve, esp psychiatric complications

26

Name a disease of cortisol deficiency

Addison's (adrenal cortical failure)

27

How much of cortex is destroyed prior to presentation in addisons?

90%

28

What hormone is elevated in addisons?

ACTH

29

What ion deficiencies can you have?

Hyponatremia and hyperkalemia

30

What bp abnormality will you have?

Hypotension

31

What are the clinical characteristics of addison;s?

Hyperpigmentation from increased ACTH
Weight loss
Muscle or joint pains
Fatigue
Nausea, abdominal pain
Hypoglycemia can occur

32

What is the etiology of primary adrenal insufficiency (aka Addison's)

-Autoimmune destruction of 60% of the adrenal cortex
-Infectious from TB, fungus, HIV etc
-Bilateral hemorrhage/infarction: anticoag, trauma, embolic, meningococcemia etc=waterhouse-friderichsen syndrome
-Metastatic cancer
-Drugs, including those that inc cortisol metab

33

How do we diagnose Addison's?

-Early AM cortisol 20mcg/dL excludes adrenal failure.

34

What is a good initial short term treatment?

Dexamethasone because it will not interfere with cortisol assay. If pt is hypotensive with a strong clinical suspicion, treat with glucocorticoids first and make the diagnosis later

35

What is an adrenal crisis

Acute deficiency in cortisol and mineralocorticoids. CAn be life threatening and masquerade as other conditions

36

What are the clinical characteristics of an adrenal crisis?

Hypotension, shock, fatigue, weakness, fever, lethargy, abdominal pain, anorexia, hypoglycemia

37

What are some causes of adrenal crisis?

-New primary adrenal failure
-Known adrenal insufficiency with acute illness or under-replacement of meds
-Acute withdrawal of high dose glucocorticoids
-Pituitary apoplexy

38

How do we treat adrenal crisis (short term)?

-1-3 liters saline IV over 12-24 hrs
-Dexamethasone 4mg IV
-Monitor electrolytes
-Monitor bP

39

What are the two types of polyglandular syndromes and why do we care?

-We care because addisons can be associated with polyglandular syndromes
-Type 1: hypoparathyroidism, mucocutaneous candidiasis, primary hypogonadism
-Type 2: T1D, autoimmune thyroiditis, vitiligo, hypogonadism

40

What is primary hyperaldosteronism?

Mineralocorticoid excess

41

What are the associated issues with hyperaldosteronism?

Hypertension, hypokalemia (though it is possible that this is normal...still aldosterone causes the collecting duct transporters to secrete k+ in exchange for Na+), mild hyernatremia, metabolic alkalosis, muscle weakness

42

What causes hyperaldosteronism?

Adrenal adenoma producing aldosterone or bilateral adrenal hyperplasia

43

Who should be screened for primary hyperaldosteronism?

-<30 y.o with hyperT, no obesity or fam hx
-Persons with unexplained hypokalemia and hyperT
-Persons with resistant hyperT
-Persons with an adrenal incidentaloma and hyperT (ie find it accidentally)

44

How do we diagnose hyperaldosteronism?

-Early morning aldosterone:renin ratio
-Ratio >20 suggestive, but not diagnostic
-Aldosterone >15 and suppressed renin suggestive
-Once biochemical diag is certain, do CT or MRI
-If pos imaging, further testing req: salt loading to demonstrate inappropriate aldosterone secretion, *adrenal vein sampling prior to surgery

45

What is adrenal vein sampling

-MEasure aldo and cortisol concentrations in each vein and IVC
-Distinguishes between uni adenoma and bilateral adrenal hyperplasia
-For lateral dis, the aldosterone concentration needs to be 4x greater than the contralateral side

46

What is the treatment of primary hyperaldosteronism?

-Unilateral aldosterone secreting adenoma: surgical resection
-Bilateral adrenal hyperplasia: mineralocorticoid antag

47

What are the symp of androgen excess?

-Woman: hirsutism, male pattern baldness, menstrual irreg
-Men: Gonadotrophin sec disrupted

48

What is an adrenal adenoma relationship to androgen excess?

Adrenal adenomas rarely cause androgen xs, they usually cause cortisol xs

49

What can cause androgen excess?

-ACTH dependent cushings can cause elevation in testosterone and DHEAS
-If you see a woman with acute onset virilization-->think this

50

What does the adrenal medulla secrete?

Catecholamines