Transcript Document

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
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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
• Thus, 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%) patietns 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
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• 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
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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
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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 Endocrinologist,
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 its unlikely
Confirmed Cushing’s Patients
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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
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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
Mild Depression
Fatigue
Menstrual Irregularities
Insomnia
Hirsuitism
Striae
Acne
Bruising
Cogni tive problems
CUSHINGS
36/66
59/66
33/47
57/66
34/59
36/66
47/66
26/66
41/66
NON-CUSHINGS
28/54
42/54
24/40
37/54
15/52
23/54
22/54
21/54
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 g, with higher levels for men.
• Normal range of many older assays is 20-100 g /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
micrograms/day
140
120
100
80
60
40
20
0
0
10
20
30
40
Cushing's Patients
50
60
Women
Men
UFC: non-Cushing's
One UFC > 34 micrograms/day= (13/51)
One UFC < 34 micrograms/day= (50/51)
90-145
80
micrograms/day
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60
50
40
30
20
10
0
0
10
20
30
non-Cushing's Patients
40
50
10 hr urine Cortisol/Cr
• 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 tabulating 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 17OHS 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
mg/day
20
15
10
5
0
0
10
20
30
40
Cushing's Patients
50
60
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
mg/day
10
8
6
4
2
0
0
10
20
30
non-Cushing's Patients
40
50
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
micrograms/day
10
8
6
4
2
0
0
10
20
30
40
Cushing's Patients
50
60
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
micrograms/day
10.0
8.0
6.0
4.0
2.0
0.0
0
10
20
30
non-Cushing's Patients
40
50
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 pseudoCushing states.
• A midnight plasma cortisol greater than 7.5 g/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
micrograms/dL
25
20
15
10
5
0
0
10
20
30
40
Cushing's Patients
50
60
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
micrograms/dL
12
10
8
6
4
2
0
0
10
20
30
non-Cushing's Patients
40
50
Diurnal Salivary Cortisol Test
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Salivary cortisol levels reflect plasma cortisol levels.
Midnight plasma cortisol measurement requires blooddrawing and may be difficult to obtain in an outpatient setting.
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Measured by a company in Wisconsin called ACL. Also
Esoterix
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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)
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36/39 patients with Cushing syndrome had a
salivary cortisol > 3.6 nmol/L (0.13 g/dl).
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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
nmol/L
12
10
8
6
4
2
0
0
10
20
30
40
Cushing's Patients
50
60
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
nmol/L
10
8
6
4
2
0
0
10
20
30
non-Cushing's Patients
40
50
Both UFC and Salivary Cortisol are unlikely to pickup mild Cushing’s
• Serum cortisol less than 20 g/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
0800 h cortisol (g/dL)
12
10
8
6
4
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Patient #
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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.
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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).
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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 full-proof
• 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
Tumor size (mm)
10
8
6
4
2
0
Pt #
Pituitary MRI-Cushing’s Syndrome-excluded
10
9
Tumor size (mm)
8
7
6
5
4
3
2
1
0
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
Static MRI (Contrasted)
Coronal T1-weighted
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, its 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 (2)
• 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-blownmay be due to daytime lows.
Conditions with Normal Cortisol Levels
which May Mimic Cushing’s SyndromeWhat else gives you a rapid weight gain,
striae, trouble sleeping, fatigue, acne,
irregular periods??
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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
Total Testosterone
Cushing’s vs Syndrome
X/Polycystic Ovary
Syndromes
95% Sensitivity
70% Specificity
3
2.5
• Rapid new onset weight gain in Cushing’s
• Sleep disturbances, depression, striae,
fatigue, bruising
• Measure testosterone level (low in
Cushing’s)
• Measure fasting insulin level-low value
argues againstCushing's
metabolic
syndromePCOS
Syndrome
nmol/L
2
Upper limit of normal range
1.5
1.39 nmol/L cut-point
1
0.5
0
How to tell if you are in a high
cortisol phase
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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
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Almost all patients are episodic
Most patients are mild
Less pseudoCushing’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
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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
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:
http://www.blogtalkradio.com/CushingsHelp/va/2009/01/30/i
nterview-with-Dr-Ted-Friedman-DR-F
• 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:
[email protected]