Diagnosing Cushing’s Syndrome:

Not as Easy as it Seems

Theodore C. Friedman, M.D., Ph.D.
Professor of Medicine-Charles Drew
University
Professor of Medicine-UCLA
Magic Foundation
Symposium on Cushing’s Syndrome
February 22, 2009
Las Vegas, NV
 States of Glucocorticoid
Excess
• ACTH-dependent States
a. Pituitary Adenoma (Cushing’s Disease) 90-95%
b. Ectopic ACTH Syndrome
• ACTH-independent States
a. Adrenal adenoma
b. Adrenal carcinoma
• Exogenous Sources
Glucocorticoid intake
• Psychiatric Conditions (Pseudo-Cushing Disorders)
a. Depression
b. Alcoholism
• Pregnancy
Pseudo-Cushing States
High Cortisol Secretion Rate
without Convincing Clinical
Features of Cushing Syndrome
Eucortisolemic Cushing
Syndrome
Clinical Manifestations of Cushing
Syndrome without evidence of increased
cortisol levels
– Exogenous glucocorticoid administration
– Episodic (periodic) Cushing syndrome-common
– Recently cured Cushing syndrome
Need to Distinguish Early or Mild
Cushing’s from Other Diseases
• Cushing’s is considered rare, but may not be that
rare.
• It is vastly under diagnosed.
• Other diseases that have some symptoms/signs in
common with Cushing’s (PCOS or Metabolic
Syndrome) are more common, but present
differently from Cushing’s. The treatment is
different for these other diseases
• A strategy needs to be developed to diagnose
Cushing’s syndrome.
Is Cushing’s Syndrome Rare?
• Probably under-diagnosed
• Catargi et al. JCEM 2003, 88:5808-200 consecutive overweight
patients with type 2 diabetes, but no other stigmata of
hypercortisolism. 4 (2%) patients were found to have Cushing’s
syndrome and another 7 are being evaluated.
• Kadioglu et al. Endo Society 2004 86: P2-455- 100 consecutive
obese patients. Cushing’s syndrome was diagnosed in 11%.
• Nishikawa et al. Endo Society 2004 86: P3-437- 1020 patients
with hypertension. 11 had Cushing’s syndrome and 10 had
subclinical Cushing’s syndrome (2%).
• These studies may have missed mild Cushing’s syndrome and
may actually be low.
• Maybe Cushing’s syndrome is not so rare
Do all diseases progress from
mild to severe?
Rapid onset

Linear

Delayed onset
 Should Cushing’s be
Diagnosed Early?
• Cushing’s patients are miserable.
• Effective treatment (surgery) exists
• Lack of medicine for it, less pharmaceutical
funding.
• Most doctors are not familiar with Cushing’s
syndrome and may only be familiar with
severe cases.
 How to Diagnose
Cushing’s Syndrome
• Careful history and physical
• Change in weight and body habitus
• Look at old pictures
• Not all patients have all signs and symptoms, especially “early”
and “periodic” patients.
• Most published data compared severe Cushing’s with normals.
• Important to diagnose early before devastating sequelae
develop.
• Initial diagnosis most difficult aspect of Cushing’s syndrome.
• “Gestalt” with as much information as possible
• Periodic Cushing’s common, so one positive test may be worth
more than 10 negative tests
• Make the diagnosis before proceeding to the differential
diagnosis??
IMPORTANT SYMPTOMS
• Wired at night
• Trouble sleeping-trouble falling asleep or
frequent awakenings
• Severe fatigue-new onset
• Abrupt weight gain-without other cause such as
decreased activity or depression
• Decreased ability to exercise
• Menstrual abnormalities
• Cognitive changes- “brain fog”
• Decreased Libido
• Symptoms of adrenal insufficiency-joint pains,
can’t get out of bed, nausea and vomiting
• Depression, anxiety, mood-swings
 IMPORTANT SIGNS
• Central obesity
• Muscle atrophy
• Thin skin
• Buffalo hump
• Round, red face
• Bruising
• Extra hair growth
• Acne
• Loss of hair on head
• Stretch marks
 Signs/Symptoms
• Most patients don’t have all these
signs/symptoms
• Many doctors may have only seen 1
case of Cushing’s and textbooks may
show only severe cases.
The Diagnosis of Cushing’s Syndrome: An Endocrine
Society Clinical Practice Guideline
J Clin Endocrinol Metab. May 2008, 93(5):1526–1540

• Lynnette K. Nieman
• Beverly M. K. Biller
• James W. Findling
• John Newell-Price
• Martin O. Savage
• Paul M. Stewart
• Victor M. Montori
The Diagnosis of Cushing’s Syndrome: An Endocrine
Society Clinical Practice Guideline
J Clin Endocrinol Metab. May 2008, 93(5):1526–1540

• 1st line recommended tests

– UFC
– Low dose or overnight dexamethasone test
– Night-time salivary cortisols
• Testing for Cushing’s syndrome in patients with
multiple and progressive features compatible with the
syndrome
• Patients with an abnormal result see an
endocrinologist and undergo a second test, either
one of the above or, in some cases, a serum
midnight cortisol or dexamethasone-CRH test.
The Diagnosis of Cushing’s Syndrome: An Endocrine
Society Clinical Practice Guideline
J Clin Endocrinol Metab. May 2008, 93(5):1526–1540

• Patients with 2 or more normal results

should not undergo further evaluation.
• Recommend additional testing in
patients with discordant results, normal
responses suspected of cyclic
hypercortisolism, or initially normal
responses who accumulate additional
features over time.
The Diagnosis of Cushing’s Syndrome: An Endocrine
Society Clinical Practice Guideline
J Clin Endocrinol Metab. May 2008, 93(5):1526–1540

• We recommend against any further testing for Cushing's

syndrome in individuals with concordantly negative results on
two different tests (except in patients suspected of having the
very rare case of cyclical disease)
• Rarely patients have been described with episodic secretion of
cortisol excess in a cyclical pattern with peaks occurring at
intervals of several days to many months. Because the DST
results may be normal in patients who are cycling out of
hypercortisolism, these tests are not recommended for patients
suspected of having cyclic disease. Instead, measurement of
UFC or salivary cortisol may best demonstrate cyclicity. In
patients for whom clinical suspicion is high but initial tests are
normal, follow-up is recommended with repeat testing, if
possible to coincide with clinical symptoms.
FIG. 1. Algorithm for testing patients suspected of having Cushing's
syndrome (CS)
 Hypothesis
• Patients with full-blown Cushing’s syndrome started out with mild
Cushing’s syndrome.
– It would be advantageous to diagnose these patients when they
have mild disease before they are affected by hypercortisolemia.
• There are many case reports of patients with periodic Cushing’s
syndrome.
• Some of these patients have hypercortisolism at regular intervals as
documented by symptoms and laboratory measurements.
• Many patients report “highs” and” lows”even if not regular.
• There has been no series examining the frequency of mild or
periodic/episodic Cushing’s syndrome.
• Thus, we hypothesized that a high percentage of consecutive patients
presenting with signs and symptoms of hypercortisolism have episodic
and/or mild Cushing’s syndrome.
Episodic, Cyclical, Periodic
• Periodic and cyclical refer to changes in
cortisol levels that occur on a regular
predictable basis.
• Episodic refers to high cortisol levels
that are random.
• Most of my patients are episodic.
 WEB AGE
• MOST FOUND ME FROM THE INTERNET
• Cushing’s-help.com (I hosted several “chats”
including Jan 2009*)
• Most went to numerous other
Endocrinologists, including Cushing’s
specialists
• Told “Your arms aren’t thin enough for
Cushing’s” or were dismissed with 1 normal
test
• In most cases, patient suspected Cushing’s,
in spite of doctor telling them it’s unlikely
* Chat in January and new chat in February: Chat 2
Confirmed Cushing’s Patients
– 66 patients
– 61 females, 5 males
– 62 Caucasians, 2 Hispanic, 1 Black, 1 Pacific Islander
– Median age 38.5 years
– BMI was 35.9 ±8.5 kg/m2 (mean ± SD)
– Average weight gain was 67.7 ±40.2 pounds
– Patients were considered for Cushing’s syndrome if they
had a rapid, unexplained weight gain and associated
symptoms of hypercortisolism including adult-onset
hirsutism and acne, menstrual irregularities and proximal
muscle weakness.
– All subjects reported that their symptoms were more
severe at certain times suggesting episodic hypercortisolism
 Cushing’s excluded
– 54 subjects
– 52 females, two males
– All Caucasians
– Median age 36 years
– BMI was 32.9 ±8.0 kg/m2
– Average weight gain was 48.3 ±35 pounds
– Cushing’s syndrome was excluded by lack of
progression of symptoms and lack of biochemical
evidence.
– Many were diagnosed with other conditions,
including growth hormone deficiency
 Symptoms/ Signs
SYMPTOMS/ SIGNS CUSHINGS NON-CUSHINGS
Mild Depression 36/66 28/54
Fatigue 59/66 42/54
Menstrual Irregularities 33/47 24/40
Insomnia 57/66 37/54
Hirsuitism 34/59 15/52
Striae 36/66 23/54
Acne 47/66 22/54
Bruising 26/66 21/54
Cognitive problems 41/66 27/54
 24-Hour Urinary Free
Cortisol (UFC)
• Integration of plasma cortisol throughout the day
• “Good” assays (using HPLC or mass spectroscopy) have a
normal range of 10-34 μg, with higher levels for men.
• Normal range of many older assays is 20-100 μg /day
indicating some non-specificity or interference of the assay
• PseudoCushings patients may have normal values in newer
assays, but elevated levels in older assays.
• Many Cushing’s patients have normal values in the new
assay
• My data demonstrates that most Cushing’s patients are
periodic, therefore patients need to collect multiple
collections hopefully when they have high cortisol.
• May be normal if subject is high at night and low during the
day.
 Women
Men

UFC: Cushing's
UFC> 34 micrograms/day=(50/66)
UFC< 34 micrograms/day=(57/66)
200-470

180

160

140
micrograms/day

120

100

80

60

40

20

0
0 10 20 30 40 50 60
Cushing's Patients
 Women
Men

UFC: non-Cushing's
One UFC > 34 micrograms/day= (13/51)
One UFC < 34 micrograms/day= (50/51)
90-145

80

70

60
micrograms/day

50

40

30

20

10

0
0 10 20 30 40 50
non-Cushing's Patients
10 hr urine Cortisol/Creatinine

• Corcuff, et al. Clinical Endocrinology 48:1998, 503-

508.
• Night-time (from 10 PM to 8 AM) UFC excretion
(correct for g of creatinine)
• 16 nmol/umol was the cutoff
• Helpful in subjects with high night time cortisol
excretion and low daytime cortisol excretion
• Correcting for US units 16 ug/g is a reasonable cut-
off
• I need to tabulate our data, but this is a reasonable
approach.
 Urinary 17-OH
Corticosteroids (17-OHS)
• One of the earliest tests
• Went out of favor about 10 years ago and has been
(incorrectly) replaced by UFC.
• UFC is probably better for full-blown Cushing’s
compared to obese and normal subjects.
• 17-OHS may be better for picking up mild cases.
• Can use the same collection for both, so its
worthwhile to measure 17-OHS in addition to UFC.
• Can also express results per gram of creatinine to
correct for obesity
 Women
Men

17 OHS: Cushing's
One 17 OHS > 6mg/day=(52/63)
One 17 OHS < 6mg/day=(53/63)
30-95

25

20
mg/day

15

10

0
0 10 20 30 40 50 60
Cushing's Patients
 Women
Men

17 OHS: non-Cushing's
One 17 OHS > 6mg/day= (15/50)
One 17 OHS < 6mg/day= (48/50)
16-32
14

12

10
mg/day

0
0 10 20 30 40 50
non-Cushing's Patients
 Women
Men

17 OHS/g Cr: Cushing's

One 17 OHS/g Cr > 3.6 micrograms/g=(45/61)
One 17 OHS/g Cr < 3.6 micrograms/g=(45/61)
14-60

12

10
micrograms/day

0
0 10 20 30 40 50 60
Cushing's Patients
 Women
Men

17 OHS/g Cr: non-Cushing's

One 17 OHS/g Cr > 3.6 micrograms/g= (15/50)
One 17 OHS/g Cr < 3.6 micrograms/g= (46/50)
12.0

10.0

8.0
micrograms/day

6.0

4.0

2.0

0.0
0 10 20 30 40 50
non-Cushing's Patients
Diurnal Plasma Cortisol Test
• Normal individuals and patients with pseudo-Cushing
states have a pronounced diurnal rhythm of cortisol
with the highest values in the morning and lower
values at night.
• Patients with Cushing syndrome lack their diurnal
variation of cortisol.
• Papanicolaou et al. (JCEM, 1998, 83:1163-1167)
compared morning and nighttime plasma cortisol in
97 patients with proven Cushing syndrome and 31
patients with pseudo-Cushing states.
• A midnight plasma cortisol greater than 7.5 μg/dL
makes Cushing’s syndrome likely.
• Patients taking oral estrogens (or birth control pills)
will have an increase in their CBG and a falsely high
serum cortisol level.
• Pretty good test, but hard to arrange.
 Midnight plasma cortisol

Papanicolaou et al. (JCEM, 1998, 83:1163-1167)

 Women
Men

Night Cortisol: Cushing's

Night cortisol > 7.5 micrograms/dL= (26/57)
Night cortisol < 7.5 micrograms/dL= (31/57)
30

25

20
micrograms/dL

15

10

0
0 10 20 30 40 50 60
Cushing's Patients
 Women
Men

Night Cortisol: non-Cushing's

night cortisol > 7.5 micrograms/dL=(11/44)
night cortisol < 7.5 micrograms/dL=(33/44)
16

14

12
micrograms/dL

10

0
0 10 20 30 40 50
non-Cushing's Patients
Diurnal Salivary Cortisol Test
• Salivary cortisol levels reflect plasma cortisol
levels.
• Midnight plasma cortisol measurement requires
blood-drawing and may be difficult to obtain in an
outpatient setting.
• Measured by a company in Wisconsin called ACL.
Also Esoterix
• Uses a "Salivette" in which the patient chews on a
cotton tube for 2-3 minutes. The samples are
stable for a week at room temperature and
salivary cortisol is independent of the rate of
saliva production.
Diurnal Salivary Cortisol Test (2)

• 36/39 patients with Cushing

syndrome had a salivary
cortisol > 3.6 nmol/L (0.13
μg/dl).
• 38/39 normal volunteers had
a value ≤ 3.6 nmol/l (mean
1.2 nmol/L) and 37/39
patients with rule/out Cushing
syndrome had a value ≤ 3.6
nmol/l (mean 1.6 nmol/L).
 Women
Men

Salivary Cortisols: Cushing's

salivary cortisol > 4.3 nmol/L=(43/64)
salivary cortisol < 4.3 nmol/L=(58/64)
20-80

18

16

14

12
nmol/L

10

0
0 10 20 30 40 50 60
Cushing's Patients
 Women
Men

Salivary Cortisols: non-Cushing's

One salivary cortisol> 4.3 nmol/L=(9/53)
One salivary cortisol< 4.3 nmol/L=(53/53)
16-22
14

12

10
nmol/L

0
0 10 20 30 40 50
non-Cushing's Patients
Both UFC and Salivary Cortisol are
unlikely to pick-up mild Cushing’s
• Serum cortisol less than 20 μg/dl (lower in
evening when CBG is lower) is mainly (but
not exclusively) bound to CBG and therefore
little free cortisol is present in the blood.
• This results in little increase in salivary
cortisol or UFC.
• At serum cortisol concentrations exceeding
this cut-off, then salivary cortisol and UFC will
rise dramatically.
 Salivary cortisol:
Conclusions
• Convenient for periodic patients as the
patient can collect many samples easily
• Try to have the patient collect when high
symptoms, but I’m finding that multiple
collections (up to 8) is probably the best
approach
• No better or worse than UFC for picking up
mild cases.
 Overnight dexamethasone test
• Give 1 mg of dexamethasone at midnight- collect 8 am plasma cortisol
• Cushing’s patients resistant to glucocorticoid feedback.
• Old cut-off 5 mg/dL, new cut-off 1.8, 2 or 3 mg/dL. Value greater than
that consistent with Cushing’s syndrome.
• Cortisol assay isn’t that good at low values
• May get falsely high values if on oral estrogens.
• Only half of classic Cushing’s patients have the genetic defects leading to
resistance to dexamethasone-probably lower in mild/episodic patients
(Bilodeau et al. 2006 20: 2871-2886 Genes & Dev.)
• Friedman, T.C. (2006) An Update on the Overnight Dexamethasone
Suppression Test for the Diagnosis of Cushing’s Syndrome: Limitations in
Patients with Mild and/or Episodic Hypercortisolism. Experimental and
Clinical Endocrinology and Diabetes 216: 356-360.
 Overnight dexamethasone test

14

12
0800 h cortisol (μg/dL)

10

0
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17

Patient #
Overnight dexamethasone test
• Conclusion: test useless for excluding Cushing’s
syndrome.
• If someone has a high value after dexamethasone, may
help with the diagnosis of Cushing’s syndrome, but
those patients usually are severe and can be diagnosed
anyway
• If patient suppresses to overnight dexamethasone,
adrenal adenoma or ectopic is unlikely.
• I am now doing a prospective study using 0.25 mg of
overnight dexamethasone, 1 mg of dexamethasone and
the 2 mg/2 day dexamethasone test.
• All my patients suppress on the 2 mg/2 day test
• 0.25 mg may be helpful, but so far a lot of overlap
between Cushing’s and Cushing’s excluded.
Dexamethasone-CRH test
• Patients with pseudo-Cushing’s states show a diminished
response to exogenous CRH and a greater inhibition of cortisol
production by glucocorticoids than patients with Cushing’s
syndrome.
• Yanovski et al. (JAMA 1993, 269:2232-2238) studied 39
patients with surgery confirmed Cushing’s syndrome and 19
patients with pseudo-Cushing states. Both groups of patients
had UFC between 90-360 ug/day (nl 20-100 ug/day).
• Dexamethasone (0.5 mg) is given every 6 hours for 8 doses,
starting at noon. The last dose is given at 6 A.M, 2 hours
before the CRH test. Ovine CRH (1 mg/kg) is then given at 8
A.M. Plasma samples were analyzed for cortisol and ACTH at 4
basal time points (-15, -10, -5 and 0) and at 5, 15, 30, 45 and
60 minutes after oCRH.
Dexamethasone-CRH test
• Using a cutoff of 1.4 mg/dL, a plasma cortisol drawn
15 minutes after oCRH administration (following
dexamethasone suppression) was able to completely
separate patients with pseudo-Cushing states from
those with Cushing syndrome. This was much better
than just performing a oCRH test or dexamethasone
test alone.
• Subsequently, many articles have shown the test is not
foolproof
• Timing is crucial.
• Has not been tested in mild or periodic patients.
• The dex-CRH test is expensive and time consuming. I
found that most of my patients with mild Cushing’s
syndrome had low cortisol values following the test.
 Pituitary MRI
• In literature approximately 50% of patients with Cushing
disease have a visible tumor on MRI (older, non-dynamic,
lower power MRIs).
• 10% of normal volunteers have MRIs consistent with a
pituitary adenoma (Hall et al. Ann. Intern. Med., 1994,
120:817-820).
• Now 3 Tesla doing dynamic MRIs can pick up small tumors
are done.
• Patients without Cushing’s syndrome or with adrenal/
ectopic Cushing’s can have a pituitary incidentaloma.
• Friedman, T.C., Zuckerbraun, E., Lee, M.L., Kabil, M.S.,
Shahinian, H.K. (2007) Dynamic Pituitary MRI Has High
Sensitivity and Specificity for the Diagnosis of Mild
Cushing’s Syndrome and Should be Part of the Initial
Workup. Hormone and Metabolic Research 39:451-456.
23 of 24 patients had had a MRI consistent with a pituitary lesion

Pituitary MRI
12

10
Tumor size (mm)

Pt #
 Pituitary MRI-Cushing’s Syndrome-excluded
10

8
Tumor size (mm)

Pt #
 Pituitary MRI
• 23 of 24 patients had had a MRI consistent with a pituitary lesion
(21 with a microadenoma, two with pituitary asymmetry).
• Only 3 of 20 patients (2 patient did not have MRIs) in the
Cushing’s excluded group had a pituitary lesion on dynamic MRI.
• Dynamic pituitary MRI had the highest sensitivity and negative
predictive value of any testing modalities and its specificity and
positive predictive value were similar to that of other tests.
• A negative MRI goes a long way in excluding Cushing’s
syndrome, except in the patient with adrenal or ectopic Cushing’s
syndrome, who usually has more severe hypercortisolism and is
usually easy to diagnose.
• Positive MRI is helpful, but still needs biochemical evidence for
hypercortisolism.
Dynamic Pituitary MRI

Coronal T1-weighted Coronal T1-weighted

Static MRI (Contrasted) Dynamic MRI (Contrasted)
 Pituitary MRI
• 3T MRI with dynamic is the best-picks up small tumors and
gives more specificity
• Need to send MRI to neurosurgeons as radiologists often miss
small tumors.
• Still no way to distinguish between Cushing’s tumors and
incidentalomas on MRI.
• Size is not helpful. Cushing's tumors are often very small:1-3
mm.
• Do not have to perform during a high
• Quality of MRI’s still vary, make sure yours is a good one
• I think the test is very helpful as it adds useful information to
the clinician. Goes against dictum of diagnose Cushing’s
syndrome before performing tests previously reserved for
determining type of Cushing’s.
 Adrenal Imaging
• Patients with severe pituitary Cushing’s can
have adrenal enlargement.
• I hypothesized that adrenal MRIs or CTs would
show adrenal enlargement that would help with
the diagnosis.
• Did not find adrenal imaging helpful for the
diagnosis of hypercortisolism
• Helpful for determining the type of Cushing’s
syndrome (discussed later)
 Unhelpful tests
• Morning cortisol (Friedman, T.C. and Yanovski, J.A.
(1995) Morning Plasma Free Cortisol: Inability to
Distinguish Patients with Mild Cushing Syndrome
from Patients with Pseudo-Cushing States. J.
Endocrinol. Invest. 18:696-701)
• Morning ACTH
• Late afternoon cortisol
• Insulin tolerance test
• CRH test
 Periodic Cushing’s
• Data shows that all patients are periodic to some
degree
• May account for many patients incorrectly diagnosed
as normal.
• Marked by mostly normal (or low) cortisol levels with
some high values accounting for the signs and
symptoms of Cushing’s syndrome
• Can be all types of Cushing’s syndrome, but in my
hands, it’s pituitary.
• Very difficult to diagnose and exclude
 Periodic Cushing’s (2)
• My approach is to measure 3-8 UFCs and 17-OHS
and 3-8 salivary cortisols in patients with a high
degree of suspicion and symptoms of periodicity.
• Multiple serum midnight cortisols and 10 hr urine
cortisols can also be done
• The patient should keep a diary of symptoms to
correlate with cortisol values.
• Patients should try to collect urines/saliva when high
symptoms.
• If all urines /saliva are normal, it makes active
Cushing’s syndrome unlikely at that time.
• Patients should be followed and re-examined at a
future time.
 Periodic Cushing’s (3)
• I agree with the Endocrine Society recommendations
and like to see 2 different tests high.
• The higher the test, the more likely Cushing’s is
• Patients with mild/episodic Cushing’s seem to have
as many symptoms and as poor a quality of life as
full-blown-may be due to daytime lows.
Conditions with Normal Cortisol Levels
which May Mimic Cushing’s Syndrome:

What else gives you a rapid weight gain,

striae, trouble sleeping, fatigue, acne,
irregular periods??
• Obesity-not associated with other stigmata
• Syndrome X (Insulin Resistance)
• Polycystic Ovary Syndromes
• Growth Hormone Deficiency (different
symptoms and testable)
 Cushing’s vs Metabolic
Syndrome/Polycystic Ovary
Syndromes
• Rapid new onset weight gain in Cushing’s
• Sleep disturbances, depression, striae, fatigue,
bruising
• Measure testosterone level (low in Cushing’s)-
Pall et al. (2008) Testosterone and Bioavailable
Testosterone Help to Distinguish Between Mild
Cushing’s Syndrome and Polycystic Ovarian
Syndrome. Hormone and Metabolic Research.
40:813-8.
• Measure fasting insulin level-low value argues
against metabolic syndrome
 Cushing’s vs Syndrome X/Polycystic Ovary
95% Sensitivity
70% Specificity Total Testosterone
3

Syndromes
2.5

2
nmol/L

Upper limit of normal range

1.5

1.39 nmol/L cut-point

0.5

Cushing's Syndrome PCOS

 How to tell if you are in a
high cortisol phase
• Trouble sleeping
• Worsening acne
• Worsening ‘brain fog”
• If diabetes-higher glucose (especially after
carbohydrate meals)
• If hypertension-higher blood pressure
• Signs of low cortisol-joint pains, can’t get out
of bed, nausea and vomiting-do not test!
 How to tell if you are in a
high cortisol phase
• In the future, hopefully we will have a
cortisolometer.
• Like a glucometer-gives instant cortisol
levels with a finger prick.
 Mild Cushing’s-Conclusions
• Important to make the diagnosis of Cushing’s
Syndrome early-before ravages of disease
have affected the patient.
• Careful history and physical (patient may not
have all the classic findings)
• Many tests may be normal
• Unclear which is the “earliest” test to be
abnormal.
• Wait only until ample evidence for Cushing’s
is obtained.
 CONCLUSIONS
• Almost all patients are episodic
• Most patients are mild
• Less pseudo-Cushing’s with new UFC assay
• No single tests diagnoses everyone
• Overnight dex testing is not helpful
• 17-OHS may pick up some patients and
should be done in conjunction with UFC
• Pituitary MRI helpful
• Difficult to diagnose
 RECOMMENDATIONS
• Careful history and physical
• At least 3 UFC and 17-OHS
• At least 3 11 pm salivary cortisols
• Make diagnosis if two distinct values are high
• Have patient keep a diary and try to collect
when “high”
• Be careful interpreting serum cortisols on
birth control pills
On to Determining the
Type of Cushing’s

See next PowerPoint

Thanks to:
Dianne Andrews
Magic foundation
All my patients
Surgeons:Ian McCutcheon, M.D., Hrayr Shahinian, M.D.,
Hae Dong Jho, M.D., Ph.D. , Sandeep Kunwar, M.D., Ed
Phillips, M.D., Manfred Chiang, M.D.
Assistants: Lynne Drabkowski and Erik Zuckerbraun, M.D.
 For more help
• Chat with Dr. Friedman on Cushing’s: Chat 1 and Chat 2

• National geographic show on Cushing’s:

http://www.cushings-help.com/media.htm

• Dr. Friedman’s website: http://goodhormonehealth.com/

• Dr. Friedman’s email or to schedule an appointment:

mail@goodhormonehealth.com