Endo - Adrenal Gland

Front 1

What are the parts of the Adrenal Gland?

Back 1

Adrenal Cortex
Adrenal Medulla

Front 2

What are the zones of the Adrenal Cortex?
- what does each produce?

Back 2

1. Outer Zona Glomerulosa - 15%
- produces mineralcorticoids (aldosterone)

2. Zona Fasciculata - 75%
- prduces glucocorticoids (cortisol)

3. Inner Zona Reticularis - 10%
- produces sex steroids (DHEA-S)

Front 3

Adrenal Medulla
- what is it made up of?
- how does it form?
- what does it produce?
- what tumors can form here?

Back 3

- Made up of Chromaffin Cells

- Chromaffin Cells migrate along with sympathetic nerve ganglia and invaginate into the embryonic adrenal cortex to form the medulla

- produces catecholamines: epinephrine, noerpinephrine, dopamine

- pheochromocytoma (from adrenal medulla)
OR
- paraganglioma (along sympathetic chain from base of skull to pelvis; same cells but "extra-adrenal")

Front 4

Adrenal Insufficiency
- Due to destruction of what part???
- How does it present?

Back 4

= destruction of adrenal cortex

Presents acutely as adrenal crisis or in chronic fashion

Front 5

What is Primary v Secondary AI?
- what is the cause of each?

Back 5

Primary: Addison's Disease
- loss of glucocorticoids and mineralcorticoids
- due to AUTOIMMUNE (most common)

Secondary: Hypothal/Pit problem
- loss of only glucocorticoids (bc loss of CSH/ACTH, but NO problem with renin/angiotensin system that makes mineralcorticoids)
- due to suppression of H/P axis due to HIGH-DOSE GLUCOCORTICOID THERAPY (most common)

Front 6

What are Poly Glandular Autoimmune Syndrome Type I and Type II?
- which is more common?
- pop?
- sx?

Back 6

= autoimmune disorders assoc'd with Primary Adrenal Insufficiency (Addison's)

TYPE I:
- children (5-20 y.o.)
- hypoparathyroidism
- chronic mucocutaneous candidiasis (reason for presenting)
- adrenal insufficiency

TYPE II:
- more common
- adults (>20 y.o.)
- adrenal insufficiencty
- autoimmune thyroid disease (e.g., Hashimoto's or Grave's)
- Type I diabetes
****No candidiasis or hypopara

Front 7

What are some of the causes of Secondary Adrenal Insufficiency?
- main cause?

Back 7

- main cause: high-dose glucocorticoid tx
- other causes also lead to hypopituitarism:
-- mass lesions
-- pit surgery
-- pit radiation
-- apoplexy (bleeding)
-- hypothalamic diseases

Front 8

What are the clinical manifestations of Adrenal Insufficiency?

Back 8

- weakness, fatigue
- GI sx
- salt cravings**
- postural dizziness**
- hypotension**
(**due to decreased aldosterone)
- HYPERPIGMENTATION

Front 9

What is the cause of hyperpigmentation in Adrenal Insufficiency?
- which AI??

Back 9

- problem in adrenals --> lose negative feedback on ACTH --> increased ACTH (which binds to melanocytes) --> hyperpigmented

**When PRIMARY AI

Front 10

What are 4 sx ONLY due to Primary AI???

Back 10

- hyperpigmentation
- vitiligo
- salt craving
- hyperkalemia

Front 11

In what form of adrenal insufficiency is hyponatremia a symptom?
- why??

Back 11

BOTH!!
- Primary: lose aldosterone
- Secondary: normal aldosterone, but low cortisol, so increased ADH --> retain fluids --> dilute --> hyponatremia

Front 12

How do you perform lab exams (dx) on patients with Adrenal Insufficiency?
- what are the downfalls of each test?
- what is the gold standard?

Back 12

1. Morning serum cortisol:
AI = < 3 mcg/dL
normal = > 19 mcg/dL
*Highest cortisol 6AM-8AM
(problem: some patients don't follow normal daily cortisol fluctuations)

2. Cosyntropin test
*****GOLD STANDARD*****
- cosyntropin = synthetic ACTH
- IV or IM, then measure cortisol 30-60 min later
- AI = < 18-20 mcg/dL
- normal = > 18 mcg/dL
**Works for primary OR secondary... secondary too bc adrenals atrophied, so even synthetic ACTH doesn't stim cortisol secretion
(problem: false negatives bc if recent onset of secondary AI, adrenals are not yet atrophic)

3. Serum ACTH > 100 pg/ml = primary AI
Serum ACTH < 100 = secondary AI

Front 13

What is the treatment for Adrenal Insufficiency?

Back 13

**Smallest glucocorticoid dose to relieve patient's sx
- hydrocortisone
OR
- prednisone

*Add mineralcorticoid if PRIMARY AI
- fludrocortisone (= synthetic aldosterone)

***Medic-Alert Bracelet

Front 14

Adrenal Cushing Syndrome
- Cause of Adrenal Cushing? How?

Back 14

Cause
- adenoma
- adrenocortical carcinoma
.... both have autonomous overproduction of cortisol --> ACTH suppression
... adrenocortical carcinomas may also overproduce androgens --> masculinization of females

Front 15

Cushing Syndrome
- dx?
- tx?

Back 15

Dx:
- abnormal 24-hour urine-free cortisol
- overnight dexamethasone suppression test
- LOW ACTH
- adrenal mass seen on CT/MRI

Tx:
- surgery (unilateral adrenalectomy)
- possible adjuvant tx (chemo; adrenolytic agents like mitotone)
***Replacement glucocorticoids for ~1 year while second adrenal gland recovers after unilateral adrenelectomy

Front 16

Primary Hyperaldosteronism
- clinical sx?
- main reason for visit to Dr?

- other clinical sx...

Back 16

- hypertension (main reason for Dr visit)
- hypokalemia
- HIGH aldosterone; LOW renin
***Most patients asymptomatic

.... other sx due to HYPOKALEMIA:
- muscle weakness, cramping, polyuria, polydipsia... can lead to Nephrogenic DI

Front 17

What percent of hypertensive patients have primary hyperaldosteronism?

Back 17

1%

Front 18

In Primary Hyperaldosteronism, why is renin low???
In what case would renin be high?

Back 18

Adrenal tumor/hyperplasia causing overproduction of aldosteron --> negative feedback on kidneys' renin production....
- aldosterone high
- renin low

If major renal hypoperfusion, JG cells in afferent arteriorles cause increase in renin --> converts angiotensinogen to ang I --> ACE converts ang I to ang II (vasonstriction) --> stims adrenals to secrete aldosterone --> kidneys retain Na and water
- renin high
- aldosterone high

Front 19

Primary Hyperaldosteronism
- causes?
- most common?
- main difference in presentation btwn the causes?

Back 19

1. Conn's Syndrome = adrenal adenoma (almost always benign; rarelyyy carcinoma)
- 70%

2. Hyperplasia (both adrenals)
- 30%

**patients with adenoma are younger (<50 y.o.), have more severe HTN and more severe hypokalemia

Front 20

Primary Hyperaldosteronism
- screening tests?
- gold standard??
- confirmatory tests?

Back 20

1. Serum Potassium <3.6 meq/l
(BUT not all patients are hypokalemic)

2. 24 hour urine potassium >30 meq/day
(NOT USED bc affected by salt intake --> increases urine K)

3. Aldosterone/Renin RATIO
***Gold Standard***
- must be off diuretics, ACE inhibitors, spirinolactone for 2, 2, 6 wks
- if ratio <20, NOT Hyperaldosteronism (sensitivity 100%)
- if ratio >20, Hyperaldosteronism strongly suggested, but must do more tests... (specificity 80%)

CONFIRMATORY TESTS
- must show aldosterone doesn't suppress with high salt

1. HIGH SALT DIET
Hyperaldosteronism =
- must have high urine sodium (complied with diet)
- must have high urine aldosterone

2. SALINE INFUSION (immediate, not as good as high salt diet)
Hyperaldosteronism =
high plasma aldosterone!

Front 21

For Primary Hyperaldosteronism, how do you differentiate between adenoma and hyperplasia?
- why is this important?

Back 21

Important bc treatment different for each...

1. CT scan of adrenals (or MRI - same results)
2. Iodocholesterol scan
3. If nothing works, adrenal venous sampling (~100% accurate in differentiation)
- cath both L and R adrenal veins (via percutaneous femoral route)
- measure serum cortisol from each (to make sure cath is IN adrenal vein)
- measure serum aldosterone from each
--> if L = R, BILATERAL HYPERPLASIA
--> if L>R (or vice versa), UNILATERAL ADENOMA

Front 22

What is the treatment for Primary Hyperaldosteronism?

Back 22

ADENOMA
- Surgery
(must correct BP and serum K at least 2 weeks before)
*HTN persists in 30%, but milder

HYPERPLASIA
- Na-restricted Died
- Pharmacotherapy
--- K-sparing agents (spirinolactone, amiloride, triamterene)
--- Calcium Channel Blockers
--- ACE Inhibitors
--- Diuretics (thiazides)

Front 23

Pheochromocytoma
- what is?
- sx?
(most common sx?)

Back 23

= tumor producing autonomous catecholamines
- usually adrenal tumor
- occasionally paraganglioma (extra-adrenal)

Sx:
- Hypertension (most common - 60% sustained; 40% paroxysmal)
- Spells - sx typical to THAT patient; sudden onset- last few mins-hrs (sweating, palpitations, headache, anxiety attack, etc.)
- Crisis - any manifestation of obtundation (shock, DIC, seizures, rhabdomyolysis, acute renal failure, death)

- weight loss
- nausea/vomiting
- constipation
- orthostatic hypotension
- arrhythmias, angina, cardiomyopathy
- polycythemia
- fever

Front 24

What is the "rule of 10"?

Back 24

= facts about pheochromocytoma:

- 10% are extra-adrenal (thorax, bladder, cervix)
- 10% bilateral
- 10% familial
- 10% malignant
- 10% occur in children
- 10% can recur after surgery

Front 25

Familial Pheochromocytoma
- inheritance?
- often found in combo with what other genetic syndrome?

Back 25

- 10% of pheochromocytomas
- autosomal dominant
- can be alone OR with MEN 2A or 2B (NOT MEN 1)
- bilateral pheochromocytomas are more often familial

Front 26

MEN1
MEN 2A
MEN 2B
- which are associated with familial pheochromocytomas??

Back 26

MEN 1: (3Ps)
- pituitary adenoma
- parathyroid (hyperparathyroidism)
- pancreatic islet cell tumors (gastrinomas)

MEN 2A:
- pheochromocytoma***
- medually thyroid carcinoma
- hyperparathyroidism

MEN 2B
- pheochromocytoma***
- medullary thyroid carcinoma
- mucosal neuromas
- marfanoid body habitus

Front 27

What other diseases are pheochromocytomas often associated with?

Back 27

- Familial Pheochromocytoma (10%)
- MEN 2A, MEN 2B
- Von Recklinghousen's Disease (neurofibromatosis)
- Von Hippel Lindau Syndrome

Front 28

Pheochromocytoma
- diagnosis?
- best test??

Back 28

1. 24-hour urine catecholamines (epi, NE, dopamine) AND their metabolites (metanephrines)
- PHEO = >2-fold increase above upper normal limit
***best test!!!

2. Plasma catecholamines -- not a good test! these are stress hormones, so anything stressful (even the test itself) can lead to false positives

3. Plasma Free Metanephrines
- false positives

**Once dx confirmed, must locate tumor (adrenal or paraganglioma)

Front 29

CT v. MRI for dx of pheochromocytoma??

Back 29

CT - most widely applied for anatomic localization

MRI - best to distinguish pheo from incidentaloma (pheo has hyperintense signal on T2)

- similar sensitivity

- if both are negative but pt has severe HTN (must be paraganglioma):
- whole body MRI
- I-123 MIBG scan (compound similar to NE that is taken up by tumor)

Front 30

Tx of Pheochromocytoma
- recurrence?
- follow-up?
- remaining sx?

Back 30

SURGERY
****must do pre-op preparations to prevent HTN crisis!!!! Bc just touchin the tumor will release tons of catecholamines
- give Alpha-Blockers until BP normalizes
- THEN if pt becomes tachycardic, give Beta-Blockers (cant give these first bc would get unopposed alpha stim - alpha constricts blood vessels)

Follow up:
- recurrence of pheo = 10%
- check 24-hr urine catecholamines and metanephrines yearly for 5 years
- 30% remain hypertension (but less severe)

Front 31

Adrenal Incidentaloma
- what is?
- frequency?

Back 31

= adrenal mass found serendipitously
**Most are non-functional, benign

- found in up to 15% of autopsies
- found in 1-4% abdom CTs

Front 32

What are functional adrenal adenomas?

Back 32

- glucocorticoid secretion (20%)
- catecholamine secretion (10%)
- mineralcorticoid secretion
- androgen secretion
- estrogen secretion (RARE)

Front 33

What are malignant adrenal masses?

Back 33

Adrenocortical Carcinoma
- 2-12% adrenal incidentalomas
- most are BIG
- 2/3 secrete horones
**FNAB cannot distinguish benign from malignant adrenal tissue

Metastasis to Adrenals
- from lung, breast, colon, stomach, kidney, melanoma, lymphoma
- Risk of finding on is LOW without known extra-adrenal malignancy
- If known extra-adrenal malig, metast risk is 8-38%
**FNABs can distinguish metasts from adrenal tissue

Front 34

Adrenal Incidentaloma
- work up??

Back 34

Work-Up
- 24-hr urine catecholamines and metanephrine OR plasma free metanephrines in ALL patients
- If HTN, screen for hyperaldosteronemia and plasma renin activity
- Screen for Cushings - overnight dexamethasone suppression test
- Check androgens and estrogens

Front 35

Adrenal Incidentaloma
- Management?
- Follow-up?

Back 35

Management:
- SURGERY if hormonally active
- SURGERY if > 4cm
- FNAB if known extra-adrenal malignancy (must first rule out pheochromocytoma bc unopposed alpha)

Follow-Up
- If <4 cm and nonfunctional --> observation
- Repeat biochemical workup yearly for at least 4 years
- Repeat CT/MRI 3-6 mo, 12 mo, 24 mo
- If tumor grows --> SURGERY