Hypercortisolism

Question 1

What is the definition of Cushing’s syndrome?

Answer 1

Complex resulting from prolonged supraphysiological concentrations of glucocorticoids

Question 2

What is the width of the abdominal striae?

Answer 2

Greater than 1 cm

Question 3

What causes the thin skin and poor wound healing with Cushing’s?

Answer 3

Inhibition of fibroblasts

Question 4

What muscles are particularly weak with Cushing’?

Answer 4

Proximal muscles

Question 5

What are the two causes of insulin resistance with Cushing’s?

Answer 5

DM2 or impaired glucose tolerance

Question 6

What are the supraclavicular findings of Cushing’s disease?

Answer 6

Fullness

Question 7

What are the three endogenous causes of Cushing’s?

Answer 7

Primary (adrenal issue)
Secondary (increased ACTH)
Tertiary (increased CRH)

Question 8

What is the most common cause of Cushing’s?

Answer 8

Iatrogenic exogenous steroid administration

Question 9

ACTH independent cause of Cushing’s = ?

Answer 9

Exogenous or primary

Question 10

What are the ACTH dependent causes of Cushing’s?

Answer 10

Pituitary or hypothalamic causes

Question 11

What is the most common cause of ACTH dependent Cushing’s?

Answer 11

Pituitary microadenoma (true Cushing’s disease) from a mutated corticotroph cell

Question 12

What are the common causes of ectopic ACTH production?

Answer 12

Bronchial or thymic carcinoid

SCLC

Question 13

What are the ACTH levels of ectopic production of ACTH relative to Cushing’s disease?

Answer 13

5-10x greater than pituitary ACTH overproduction

Question 14

What other findings are common with ectopic ACTH production? (2)

Answer 14

• Hirsutism from adrenal androgen production

- hyperpigmentation from ACTH precursor

Question 15

True or false: ectopically producing ACTH tumors cause hyperpigmentation

Answer 15

True

Question 16

What are the two breakdown products of POMC?

Answer 16

ACTH

MSH

Question 17

Are ectopic ACTh secreting tumors fast or slow onset?

Answer 17

Fast

Question 18

Which are more common: adrenal adenoma or carcinomas? Are these usually unilateral, or bilateral?

Answer 18

Unilateral adenoma

Question 19

What are the two major etiologies of bilateral adrenal disease?

Answer 19

Micronodular hyperplasia

Macronodular hyperplasia

Question 20

What are the three major steps of diagnosing Cushing’s?

Answer 20

1. Confirm hypercortisolemia
2. Determine subtype
3. Localize source of overproduction

Question 21

Why is testing for Cushing’s done as an outpatient?

Answer 21

Increased stress in the hospital may give false positives

Question 22

What are the three major tests that can be done to assess for hypercortisolemia?

Answer 22

• 24 hour urinary free cortisol excretion
• 2300 salivary or serum cort
• Low dose dexamethasone suppression test

Question 23

How is the low dose dexamethasone test performed?

Answer 23

Give Cort at 2300, return at 0800 to check ACTH levels

Question 24

What are the ranges for normal, borderline, and high 24 hr urinary cortisol collection concentrations?

Answer 24

Less than 50 mcg: unlikely
50-150 = borderline
More than 150 = likely

Question 25

True or false: a normal 24 urine collection test usually rules out Cushings

Answer 25

False-- may have a secretory type Cushing's

Question 26

What, besides Cushing's, will cause an abnormally elevated 24 hours UFC?

Answer 26

Pseudo Cushing's

Question 27

How can the 24 hour urine cortisol test be made more accurate?

Answer 27

done x4 over a month

Question 28

What is pseudo-cushing's? Causes?

Answer 28

Underlying issue that stimulates that HPA axis - EtOH-ism - Depression - Severe stress/surgery/infection

Question 29

What is the medication that causes a decreased clearance of cortisol?

Answer 29

Carbamazepine

Question 30

What is the best test to do on patients who may have pseudo-Cushing's?

Answer 30

Overnight low-dose Dexamethasone suppression test

Question 31

Why is the midnight salivary cortisol testing useful to diagnose Cushing's?

Answer 31

Should be very low at this time, but Cushing's will disrupt the normal diurinal pattern

Question 32

What are the ranges of the midnight salivary test for Cushing's?

Answer 32

- less than 5 mcg = no - 5-7.5 mcg = indeterminant - More than 7.5 = likely cushing

Question 33

What are the ranges of serum cortisol for the low dose dexamethasone test?

Answer 33

Normal = less than 2 mcg/dL Indeterminant = 3-10 mcg/dL More than 10 = Likely Cushing's

Question 34

Hypercortisolemia + low ACTH = what?

Answer 34

Adrenal pathology

Question 35

High ACTH + high cortisol levels = ?

Answer 35

Pituitary, hypothalamic, or ectopic pathology

Question 36

What is the best way to assess for a pituitary problem causing hypercortisolemia? Adrenal? Ectopic?

Answer 36

- Pituitary = MRI the head - Adrenal = CT the abo - Ectopic = CT the chest

Question 37

What is the treatment for adrenocortical adenomas? What are the complications that can arise from this?

Answer 37

- Surgical resection | - Atrophy of contralateral gland or pituitary corticotroph atrophy, leading to hypocortisolism

Question 38

How malignant is adrenal carcinoma? Prognosis? Treatment?

Answer 38

Highly malignant Poor Surgical debulking, RT, non-specific chemo

Question 39

What are the three etiologies of ACTH dependent Cushing's?

Answer 39

Pituitary, Hypothalamic, or ectopic tumor secreting ACTH

Question 40

What are the two tests that can be performed to determine if a small pituitary mass is secreting ACTH?

Answer 40

- Inferior petrosal sinus sampling | - High dose dexamethasone test

Question 41

What is the dose for low and high dose dexamethasone?

Answer 41

1 vs 8 mg

Question 42

What is the role of the high dose dexamethasone test?

Answer 42

Pituitary will show partial suppression of ACTH, but ectopic will NOT

Question 43

What is done with inferior petrosal sinus sampling?

Answer 43

Give CRH Comparing the concentration of ACTH in the sinus vs the concentration of ACTH in the periphery--helps localize source of ACTH

Question 44

What is the anatomic site of where the pituitary drains?

Answer 44

Petrosal sinus

Question 45

What is the outcome of the Inferior pituitary sinus sampling test that will identify it as a pituitary source?

Answer 45

If IPS : P ratio is more than 2:1, then it is a pituitary source

Question 46

What are the options for treating Cushing's disease?

Answer 46

Irradiation Surgery Adrenal surgery Drug therapy

Question 47

What is the indication of performing bilateral adrenalectomies in patients with an ACTH secreting pituitary adenoma?

Answer 47

If cannot remove the pituitary problem, then remove the source of cortisol

Question 48

What is the mortality rate of pituitary surgery?

Answer 48

1%

Question 49

What are the complications of pituitary surgery?

Answer 49

Anterior pituitary deficits | DI from post op swelling

Question 50

What are the downsides of stereotactic radiosurgery on the pituitary? (2)

Answer 50

Slow therapeutic response | Post radiation panhypopituitarism

Question 51

What is the use and MOA of aminoglutethimide?

Answer 51

Anticonvulsant that blocks the conversion of cholesterol to pregnenolone, Leads to Decreased cortisol, aldosterone, and androgens

Question 52

What is the use and MOA of ketoconazole?

Answer 52

Antifungal used to lock 11 beta hydroxylase to decrease cortisol, aldosterone, DHEA

Question 53

What is the use and MOA of mitotane?

Answer 53

Blocks 11 beta hydroxylase | Decreases all cortical adrenal stuffz

Question 54

What is the treatment for an ectopic site of ACTH production that is not well localized?

Answer 54

RT/chemo Bilateral adrenal adrenalectomy Meds