Hypercortisolism Flashcards

1
Q

Pathologic hypercortisolism may be caused by either

A

a pituitary or nonpituitary (ectopic) ACTH secreting neoplasm or by benign or malignant adrenal tumors.

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2
Q

sypmtoms of ACTH Dependent Hypercortisolism

A

• weight gain • facial fullness/plethory • supraclavicular fat • diabetes • osteoporosis • BP • Myopathy • Neuropsych disoerders • edema • hypogonadism • androgen excess

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3
Q

________neoplasms have a much higher set point for glucocorticoid negative feedback and diurnal rhythm is disrupted.

A

ACTH-secreting

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4
Q

The earliest biochemically-detectable finding of hypercortisolism is the

A

lack of nadir of cortisol secration late at night

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5
Q

What is the pathophysiology behind ACTH Dependent Hypercoricolism?

A

ACTH secreating tumor in the pituitary acting independent of negative feedback

see adrenal gland hyperplasia and increased cortisol secreation with low CRH

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6
Q

• Incidentally discovered • Intermittent cortisol excess • Hypertension • Hyperglycemia/metabolic syndrome • Osteoporosis • Vertebral compression Fx • Very long duration, 10-40 yrs.

A

signs of Adrenal dependent hypercorticolism

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7
Q

due to a solitary benign or malignant tumor and sometimes bilateral adrenal nodular disease. As expected, ACTH is low in these patients due to cortisol negative feedback and, as a result, the contralateral adrenal is usually small

A

ACTH-independent (adrenal-dependent) hypercortisolism

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8
Q

Whats the difference btwn ACTH dependent and adrenal dependent cushings?

A

see image

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9
Q

How do pts with ACTH INDEPENDENT cushings present different than Dependent?

A

have very mild hypercortisolism and usually present with incidentally discovered adrenal nodules (during abdominal imaging studies for unrelated symptoms) without overt clinical evidence of cortisol excess

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10
Q

What types of things can lead to hypercorticolism that are more related to physiologic adaptions?

A

• Stress • Alcohol • Neuropsych disorders • Starvation

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11
Q

What signs/symptoms should raise your index of suspicion for Cushing syndrome?

A

Weight gain (unexplained) in truncal distribution

Increased supraclavicular and dorsocervical fat accumulation

Facial rounding and plethora

Proximal muscle weakness

Hirsutism/androgen excess in women

Wide violaceous striae

Cutaneous wasting (skin fold thickness in dorsum of hand <2 mm)

Easy bruising Neuropsychiatric problems

Cognitive difficulty, depression, psychosis Growth retardation (children)

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12
Q

What diagnosis may raise your suspicion for Cushing syndrome?

A

Diabetes/Hypertension/Metabolic syndrome Approximately 0.5-1.0% of this patient population Osteoporosis: 3% of patients with osteoporosis

Adrenal nodules; 10-30% of patients with incidental adrenal nodules

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13
Q

You suspect a pt has Cushings syndrome and excluced the cause to be d/t glucocorticoid medicine, what three tests could you perform next? which is the most accurate?

A

Late night salivary cortisol level

overnight low-dose dexamethasone suppression test

24 hours free cortisol

(written in order of most to least accurate)

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14
Q

How is teh overnight dexamethesone suppression test performed?

A

Overnight low-dose (1 mg) dexamethasone suppression test Simple, sensitive test for Cushing: 1 mg dexamethasone is given orally at 11pm with measurement of cortisol the following morning: normal suppression= cortisol <1.8 µg/dL (50 nmol/L). Particularly sensitive in patients with adrenal nodules, but there are many false positives limiting specificity

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15
Q

Your pt you suspected of cushings has abnromally high cortisol levels, what is your next step?

A

Measure ACTH levels!

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16
Q

What does it mean if your patient that has elevated cortisol levels has normal or elevated ACTH levels?

A

likely have ACTH DEPENDENT Cushings; get MRI of pituitary

17
Q

Your attending informs you your pt came it with symproms of Cushings; both cortisol and ACTH levels were elevated and asks you what does this mean and how do we proceed?

A

means pts has ACTH dependent Cushings

get MRI of pituitary; if abnromal = CUSHIGS diesease

if normal, do bilateral petrosal sinus sampling to check for pituitary ACTH gradient

18
Q

You perform a bilateral petrosal sinus pituitary gradient for pts with ACTH dependent cushings that has normal pituitary MRI, what are we looking for?

A

see a pituitary gradient means you have cushings disease

no gradient, we have occult ectopic ACTH production

19
Q

If you have elevated coritsol and low ACTH levels, what is our Dx?

What is our next step?

A

ACTH INdependent Cushigns syndrome, get adrenal CT

20
Q

What is the Tx for Cushings Disease?

A

The best treatment for Cushing syndrome always depends on an accurate differential diagnosis. Surgery: Remove the offending tumor (pituitary/adrenal) Pituitary surgery has 70-85% remission rate w/ experienced surgeons, but 10- 20% recurrence rate over 10 years

21
Q

When is bilateral adrenalectomy recommend for pts with Cushings

A

indicated in patients who have failed other modalities of treatment; definitive therapy but confers decreased quality of life issues associated with life-long dependence on steroid (glucocorticoid and mineralocorticoid) support; also concern regarding re-growth of the pituitary tumor (as a result of loss of glucocorticoid negative feedback)—this is called Nelson’s syndrome

22
Q

When is radiotherapy recommend for Cushings?

When is it not?

A

Used in pituitary Cushing as adjunctive therapy after failed surgery; modest success rates (15-50%) in inducing a remission of hypercortisolism and there is a high incidence of hypopituitarism within 5-10 years after pituitary radiation

***Not indicated in adrenal Cushing

23
Q

Pituitary-directed somatostatin receptor analog (agonist) – This somatostatin analog is used specifically for the treatment of Cushing’s disease in patients for whom pituitary surgery is not an option or has not been curative. T

A

Pasireotide:

24
Q

Side effects of paseriotide

A

diarrhea, nausea, hyperglycemia, headache

25
Q

Adrenal steroid inhibitor: available with compassionate use; 11-beta hydroxylase inhibitor

A

Metyrapone:

26
Q

potent inhibitor of glucocorticoid and progesterone receptor

used for Cushings when surgery has failed

A

Mifepristone