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Flashcards in Hypercortisolism Deck (26)
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 Pathologic hypercortisolism may be caused by either 

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


sypmtoms of  ACTH Dependent Hypercortisolism

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


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



The earliest biochemically-detectable finding of hypercortisolism is the 

lack of nadir of cortisol secration late at night


What is the pathophysiology behind ACTH Dependent Hypercoricolism?

ACTH secreating tumor in the pituitary acting independent of negative feedback

see adrenal gland hyperplasia and increased cortisol secreation with low CRH


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

signs of Adrenal dependent hypercorticolism


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

ACTH-independent (adrenal-dependent) hypercortisolism 


Whats the difference btwn ACTH dependent and adrenal dependent cushings?

see image


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

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


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

• Stress • Alcohol • Neuropsych disorders • Starvation


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

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) 


What diagnosis may raise your suspicion for Cushing syndrome?

 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 


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?

Late night salivary cortisol level

overnight low-dose dexamethasone suppression test

24 hours free cortisol

(written in order of most to least accurate)


How is teh overnight dexamethesone suppression test performed?

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


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

Measure ACTH levels!


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

likely  have ACTH DEPENDENT Cushings; get MRI of pituitary


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?

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


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

see a pituitary gradient means you have cushings disease 

no gradient, we have occult ectopic ACTH production


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

What is our next step?

ACTH INdependent Cushigns syndrome, get adrenal CT


What is the Tx for Cushings Disease?

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


When is bilateral adrenalectomy recommend for pts with Cushings

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


When is radiotherapy recommend for Cushings?

When is it not?

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 


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



Side effects of paseriotide

diarrhea, nausea, hyperglycemia, headache 


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



potent inhibitor of glucocorticoid and progesterone receptor 

used for Cushings when surgery has failed