2-6: 5/12: Adrenal Insufficiency

Front 1

Adrenal Insufficiency:
AKA
Presentation

Back 1

Addison's Syndrome

Specific: Volume depletion, hyperkalemia, hyperpigmentation

General: fatigue, weakness, weight loss, GI complaints, low BP

PRESENTATION IS VARIABLE

Front 2

Primary vs Secondary AI
GC function
MC function ([Na+], [K+], blood volume)
ACTH levels (pigmentation)
Pituitary function

Back 2

Primary:
Lose GC
Lose MC (sodium + volume loss; potassium retention)
High ACTH (lack negative feedback; hyperpigmentation)
Normal pituitary fn

Secondary:
Loss GC
MC okay (no hyperkalemia)
LOW ACTH (no hyperpigmentation)
Hypopituitarism

Front 3

Why does primary AI result in hyperpigmentation?

Back 3

ACTH receptor and alpha-MSH receptors come from same receptor line
When tons of ACTH, ACTH will bind alpha-MSH receptors

Front 4

Autoimmune adrenalitis:
Effects
Antibodies Present
Affiliated Syndromes

Back 4

Major cause of AI

Adrenal Ab's (21-OHase Ab)

May be part of polyglandular autoimmune syndrome

PRIMARY AI

Front 5

Polyglandular Autoimmune Syndromes:
Type I vs Type II

Back 5

Type I:
APECED
Autoimmune polyendocrinopathy
Chronic mucocutaneous candidiasis
Ectodermal dysplasia (abnormal development of the skin, hair, nails, teeth, or sweat glands)

Results in hypopara, AI, and hypogonadism

Type 2:
HLA-related
Affects multiple endocrine systems, most commonly AI, thyroid, and DM I

PRIMARY AI

Front 6

Cause of AI in undeveloped countries

Back 6

Tb
Fungal
CMV
HIV

PRIMARY AI

Front 7

Waterhouse-Friederichson Syndrome is an example of ___________ which can result in _____.

Back 7

Adrenal hemorrhage (in pts with meningococcal sepsis) and can result in AI

(Clues of adrenal hemorrhage: hypotn, shock, abdominal/flank pain, fever, DROP IN Hg)

PRIMARY AI

Front 8

Metastatic Causes of AI (cancer types)

Back 8

BrCa
Lung Ca

PRIMARY AI

Front 9

What drugs interfere with adrenal function?

Back 9

Ketoconazole (antifungal)
Etomidate (anesthetic)

PRIMARY AI

Front 10

Congenital Adrenal Hyperplasia:
Relevance to AI

Back 10

Impaired production of cortisol

PRIMARY AI

Front 11

Adrenoleukodystrophy:
Relevance to AI

Back 11

Defect in oxidation of FA's in peroxisomes-->elevated serum levels of long chain FA's-->accumulation in cell membranes

leads to PRIMARY AI

Front 12

Familial Glucocorticoid Deficiency

Back 12

Defect in MCR-2 (Melanocortin Receptor--an ACTH receptor), can't make cortisol
Can make ACTH
Zona glomerulosa not affected, so can make MC

PRIMARY AI

Front 13

Causes of Secondary AI

Back 13

EXOGENOUS GLUCOCORTICOIDS
(Suppress HPA axis, adrenals atrophy)

Pituitary/CNS tumors (visual changes, thunderclap tumors)
Hemorrhage into tumors
SHEEHAN'S SYNDROME

Front 14

Cortrosyn stimulation testing:
Describe
Normal values?
How would results vary based on time since onset of secondary AI?

Back 14

Cortrosyn stimulation testing (CST):
Large dose of ACTH (CST) then measure cortisol
normal peak >18-20

If primary AI, will have below 18-20
NOT GOOD FOR SECONDARY AI OF RECENT ONSET bc they'll look nrml (non-atrophied zona fasciculata

If it's been a while from onset, shouldn't get an increase in cortisol (atrophy!)

Front 15

How would you screen for secondary AI?

Back 15

Insulin tolerance:
Hypoglycemia = stress-->stimulates HPA
Give IV insulin to induce hypoglycemia (<45 gm/dl)

(not that safe, use one below)
OR

Metyrapone testing (blocks last step in cortisol synthesis):

Normally 11-deoxy cortisol low but if block it's conversion to cortisol, cortisol levels will fall, inc'd CRH, inc'd ACTH, inc'd 11-deoxy cortisol
(11-DOC)

If have a problem in pit gland, give metyrapone at bedtime, measure in morning CRH would be low, 11-DOC doesn't go up

Front 16

How do ACTH levels vary with primary/secondary AI?

Back 16

If primary AI, ACTH HIGH

If secondary AI, low or inappropriately nl

Front 17

Glucocorticoids:
Use
AE's
Examples (include MC affinity)

Back 17

Use: Treat AI

AE's: signs of Cushing's, problems when steroids are withdrawn (can take a year to recover!)

Prednisone
Cortisol, Cortisone (binds MC)
Dexameth (doesn't bind MC as much affinity as Cortisol)

Front 18

Fludrocortisone:
Mechanism
Use

Back 18

Fludrocortisone; potent synthetic MC
Use: Primary AI (need to stimulate MC's)

Note: some GC drugs have MC props at high doses

Front 19

Traditional dosing of glucocorticoid replacement is based on ________.

Back 19

Circadian rhythms and daily fluctuations of cortisol levels

So higher dose in AM, lower dose in PM

(no good method for biochemical monitoring so if pt feels good, dose is okay)

Front 20

What is adrenal crisis?
Causes?
Treatment?
More prominent in Primary or Secondary AI? Why?

Back 20

Presentation of AI as hypotensive shock unresponsive to fluid resuscitation and pressors

Could be due to loss of HPA fn, abrupt withdrawal of HPA Suppression tx
Omission of adrenal replacement tx in known AI
Failure to increase adrenal replacement when necessary for acute stress (Surgery, Illness)

More common in primary Ai bc of combined GC and MC deficiencies

Tx:
Stress dose steroids for serious illness or sx, doses tapered as pt improves (2-4x usual dose of steroids)

Pts should wear Medic-alert bracelet!