Lecture 92, 94 - Adrenal Disorders + Adrenal Steroid Pharm

Question 1

labs of primary adrenal insufficeincy

Answer 1

Low cortisol;

High ACTH, CRH

Question 2

etiologies of acute adrenal insufficiency

Answer 2

massive hemorrhage
Tumors
Drugs (ketoconazole, Etomidate)
abrupt withdrawal of glucocorticoids

Question 3

etiolgoes of chronic adrenal insuffieicny

Answer 3

TB Adrenalitis

Auto immune (APS 1 – APECED, APS 2)

XLALD

CAH

Question 4

what is APECED (APS1)

defect to what gene?

Answer 4

Autoimmune polyendocrinopathy candidiasis ectodermal dystrophy

AIRE gene

Question 5

what is APS2?

Answer 5

Genes: AD with incomplete penetrance
More Common than APS1

Hallmark: Adrenal Insufficiency + Thyroid Disease (Hypo or Hyper)

Question 6

what is XLADL

manifestation

Answer 6

XL genetic mutation to ATP binding casettes which code for proteins necessary to break down long chain fatty acids

CNS, AI

Question 7

what is the most common defect of Congential Adrenal Hyperplasia

how may it presetnt early in life?

Answer 7

21 Alpha Hydroxylase

most common cause of salt wasting adrenal crisis in the first two weeks of life

Question 8

in 21 alpha hydroxylase deficincey – what features may present in females

Answer 8

virulizing effects

Question 9

labs of secondary adrenal failure

Answer 9

Labs: Low Cortisol; Low ACTH (CRH)

Question 10

what is the most common etiology for secondary adrenal failure?

Answer 10

Pituitary/Hypothalamic Tumor

Question 11

hyperpigmentation is present in ______ adrenal fuction.. why?

Answer 11

If Primary AI – Hyperpigmentation (bc ACTH –> MSH)

Question 12

serum electrolyte values of AI

what changes to the CBC?

Answer 12

Low adolsterone –

Hyponatremia
Hyperkalemia
Hypoglycemia
Hypercalcemia – cortisol nomrally decreases intestinal calcium
Eosinophilia (cortisol is toxic to eosinophils)

Question 13

gold standard for diagnosis of AI

other good test ?

Answer 13

ACTH Stimulation Test – GOLD STANDARD

Primary – no rise in cortisol

Secondary – some response to cortisol

Morning cortisol check:
Cortisol should be high in the morning. If Low, check ACTH to determine if primary or secondary

Question 14

Treatment for AI

Answer 14

Hydrocortisone – but this is short acting and requires multiple injections per day

Fludrocortisone – Mineralocorticoid and Glucocortisol effects

DHEA – replacement of Androgens for Women

Question 15

what is cushing’s syndrome

what is cushing’s disease

Answer 15

syndrome – excess cortisol production

Disease – ACTH producing adenoma

Question 16

Causes of Cushing’s Syndrome

Answer 16

Unilateral Adrenal Adenoma;

Bilateral Adrenal Hyperplasia (usually bilateral)

Question 17

three tests to help dx cushing’s

Answer 17

Dexamethasone Suppression Test (ACTH doesn’t decrease)

24 hour urine – increased

Late night salivary cortisol – higher than it should be

Question 18

clinical features of cushing’s

Answer 18

muscle weakness and thin extremitiis

Moon facies, buffalo hump, truncal obesity

high insulin

abdominal stira

HTN

Osteoporsis

Immune suppression; poor wound healing

Question 19

Hyperaldosteronism

what is conn syndrome?
what is the most common cause?

Answer 19

Most common cause: bilateral adrenal hyperplasia

Conn syndrome – adrenal adenoma over producing aldosterone

Question 20

Clinical presesntation of hyperaldosterone

Answer 20

hypernatremia; HTN
Hypokalemia
weakness, cramps, periodic paralysis

Question 21

best way to diagnose and locate hyperaldosterone

Answer 21

CT – 1/3 of time its unilateral; if B

Adrenal Vein Sampling – -the gold standard

Question 22

treamtnet for hyperaldosterone

unilateral vs bilateral

Answer 22

Surgery – if unilateral

If Bilateral -- Medical: Spironolactone, Eplerenone

Question 23

what is a pheochromocytoma

Answer 23

Catecholamine producing tumor of the adrenal medulla
“attacks” of release of catecholamines;

Symptoms can be paroxysmal

Question 24

classic triad of symptoms of pheo

other sx:

Answer 24

HA, Diaphoresis, Palpitations

HTN, Diaphoresis, Palpitations

Question 25

diagnosis of pheo

Answer 25

measure Metanephrines

Clonidine suppression test

Question 26

4 familial forms of pheo

Answer 26

VHL

NF1

MEN2A

MEN2B

Question 27

MEN 2a vs MEN2B –

what is the associated mutation

Answer 27

RET gene

Question 28

Treatment of Pheo –

Answer 28

alpha and beta blockers A before B)

CCBs

Metyrosine

Surgery

Question 29

which glucocorticoid agonist has the highest anti-inflammatory potency ?

whaich has the highest NA retntion potency?

Answer 29

anti-inflammatory Dexamethasone

9 alpha Fluorocortisol – highest Na Retention potency;

Question 30

indications for glucocorticoid use

Answer 30

Hormone Replacement Therapy

Suppress Inflammation and Immune Responses

Question 31

what are the primary targets of Cortisol in the periphery

Answer 31

Liver and Kidneys –

Question 32

what is the difference between 11B HSD 1 and 11B HSD 2

Answer 32

Glucocorticoid Receptor Rich Tissues: Express High level of 11 Beta HSD Type 1: converts cortisol to active form (cortisone –> Cortisol)

Mineralocorticoid Receptor Rich Tissues: Express High level of 11 Beta HSD Type 2: converts cortisol to inactive form (cortisone)

Question 33

indications for glucocorticoid antagonists

Answer 33

Severe Hypercoretisolism

Persistent Hypercortisolism following surgery

Cushings disease

Question 34

Synthesis inhibitors of Glucocorticoids

Answer 34

Ketoconazole –

Mitotane –

Metyrapone

Question 35

Mineralocorticoid Receptor Agonists

Answer 35

Fludrocortisone

Question 36

MR Antagonists

Answer 36

Spironolactone (+ Eplerenone) –