Hypercortisolism Flashcards
What is the definition of Cushing’s syndrome?
Complex resulting from prolonged supraphysiological concentrations of glucocorticoids
What is the width of the abdominal striae?
Greater than 1 cm
What causes the thin skin and poor wound healing with Cushing’s?
Inhibition of fibroblasts
What muscles are particularly weak with Cushing’?
Proximal muscles
What are the two causes of insulin resistance with Cushing’s?
DM2 or impaired glucose tolerance
What are the supraclavicular findings of Cushing’s disease?
Fullness
What are the three endogenous causes of Cushing’s?
Primary (adrenal issue)
Secondary (increased ACTH)
Tertiary (increased CRH)
What is the most common cause of Cushing’s?
Iatrogenic exogenous steroid administration
ACTH independent cause of Cushing’s = ?
Exogenous or primary
What are the ACTH dependent causes of Cushing’s?
Pituitary or hypothalamic causes
What is the most common cause of ACTH dependent Cushing’s?
Pituitary microadenoma (true Cushing’s disease) from a mutated corticotroph cell
What are the common causes of ectopic ACTH production?
Bronchial or thymic carcinoid
SCLC
What are the ACTH levels of ectopic production of ACTH relative to Cushing’s disease?
5-10x greater than pituitary ACTH overproduction
What other findings are common with ectopic ACTH production? (2)
- Hirsutism from adrenal androgen production
- hyperpigmentation from ACTH precursor
True or false: ectopically producing ACTH tumors cause hyperpigmentation
True
What are the two breakdown products of POMC?
ACTH
MSH
Are ectopic ACTh secreting tumors fast or slow onset?
Fast
Which are more common: adrenal adenoma or carcinomas? Are these usually unilateral, or bilateral?
Unilateral adenoma
What are the two major etiologies of bilateral adrenal disease?
Micronodular hyperplasia
Macronodular hyperplasia
What are the three major steps of diagnosing Cushing’s?
- Confirm hypercortisolemia
- Determine subtype
- Localize source of overproduction
Why is testing for Cushing’s done as an outpatient?
Increased stress in the hospital may give false positives
What are the three major tests that can be done to assess for hypercortisolemia?
- 24 hour urinary free cortisol excretion
- 2300 salivary or serum cort
- Low dose dexamethasone suppression test
How is the low dose dexamethasone test performed?
Give Cort at 2300, return at 0800 to check ACTH levels
What are the ranges for normal, borderline, and high 24 hr urinary cortisol collection concentrations?
Less than 50 mcg: unlikely
50-150 = borderline
More than 150 = likely
True or false: a normal 24 urine collection test usually rules out Cushings
False– may have a secretory type Cushing’s
What, besides Cushing’s, will cause an abnormally elevated 24 hours UFC?
Pseudo Cushing’s
How can the 24 hour urine cortisol test be made more accurate?
done x4 over a month
What is pseudo-cushing’s? Causes?
Underlying issue that stimulates that HPA axis
- EtOH-ism
- Depression
- Severe stress/surgery/infection
What is the medication that causes a decreased clearance of cortisol?
Carbamazepine
What is the best test to do on patients who may have pseudo-Cushing’s?
Overnight low-dose Dexamethasone suppression test
Why is the midnight salivary cortisol testing useful to diagnose Cushing’s?
Should be very low at this time, but Cushing’s will disrupt the normal diurinal pattern
What are the ranges of the midnight salivary test for Cushing’s?
- less than 5 mcg = no
- 5-7.5 mcg = indeterminant
- More than 7.5 = likely cushing
What are the ranges of serum cortisol for the low dose dexamethasone test?
Normal = less than 2 mcg/dL
Indeterminant = 3-10 mcg/dL
More than 10 = Likely Cushing’s
Hypercortisolemia + low ACTH = what?
Adrenal pathology
High ACTH + high cortisol levels = ?
Pituitary, hypothalamic, or ectopic pathology
What is the best way to assess for a pituitary problem causing hypercortisolemia? Adrenal? Ectopic?
- Pituitary = MRI the head
- Adrenal = CT the abo
- Ectopic = CT the chest
What is the treatment for adrenocortical adenomas? What are the complications that can arise from this?
- Surgical resection
- Atrophy of contralateral gland or pituitary corticotroph atrophy, leading to hypocortisolism
How malignant is adrenal carcinoma? Prognosis? Treatment?
Highly malignant
Poor
Surgical debulking, RT, non-specific chemo
What are the three etiologies of ACTH dependent Cushing’s?
Pituitary, Hypothalamic, or ectopic tumor secreting ACTH
What are the two tests that can be performed to determine if a small pituitary mass is secreting ACTH?
- Inferior petrosal sinus sampling
- High dose dexamethasone test
What is the dose for low and high dose dexamethasone?
1 vs 8 mg
What is the role of the high dose dexamethasone test?
Pituitary will show partial suppression of ACTH, but ectopic will NOT
What is done with inferior petrosal sinus sampling?
Give CRH
Comparing the concentration of ACTH in the sinus vs the concentration of ACTH in the periphery–helps localize source of ACTH
What is the anatomic site of where the pituitary drains?
Petrosal sinus
What is the outcome of the Inferior pituitary sinus sampling test that will identify it as a pituitary source?
If IPS : P ratio is more than 2:1, then it is a pituitary source
What are the options for treating Cushing’s disease?
Irradiation
Surgery
Adrenal surgery
Drug therapy
What is the indication of performing bilateral adrenalectomies in patients with an ACTH secreting pituitary adenoma?
If cannot remove the pituitary problem, then remove the source of cortisol
What is the mortality rate of pituitary surgery?
1%
What are the complications of pituitary surgery?
Anterior pituitary deficits
DI from post op swelling
What are the downsides of stereotactic radiosurgery on the pituitary? (2)
Slow therapeutic response
Post radiation panhypopituitarism
What is the use and MOA of aminoglutethimide?
Anticonvulsant that blocks the conversion of cholesterol to pregnenolone,
Leads to Decreased cortisol, aldosterone, and androgens
What is the use and MOA of ketoconazole?
Antifungal used to lock 11 beta hydroxylase to decrease cortisol, aldosterone, DHEA
What is the use and MOA of mitotane?
Blocks 11 beta hydroxylase
Decreases all cortical adrenal stuffz
What is the treatment for an ectopic site of ACTH production that is not well localized?
RT/chemo
Bilateral adrenal adrenalectomy
Meds
