Download adrenal insufficiency

ADRENALS
& INCIDENTALOMAS
The Adrenal
Physiology 
Adrenal Insufficiency, Primary
& Secondary
Adrenal Incidentaloma
Adrenal Physiology
Steroid Biosynthesis
 Glucocorticosteroids
 Aldosterone
 Androgen
Steroid Biosynthesis
Zona Fasiculata
Cortisol Production
• 10-20 mg/day
• Controlled Primarily By ACTH
• Negative and Positive Feedback
Between Cortisol and ACTH at
Pituitary and Hypothalamic Levels
Hypothalamic-Pituitary Adrenal Axis
CRH
Hypothalamus
Pituitary
ACTH
Adrenal
Cortisol
ACTH
Cortisol
= Stimulation
= Inhibition
Cortisol
Davidsons 22nd Ed, 2015
Steroid Biosynthesis
Zona Fasiculata
Zona Glomerulosa
Aldosterone Production
• 100-150 ug/day
• Stimulated by the Renin-Angiotensin System
 Decreased Perfusion Pressure
• Hyperkalemia Stimulates and Hypokalemia
Inhibits Aldosterone Secretion
• ACTH Acutely May Stimulate Aldosterone
Secretion
Steroid Biosynthesis
Zona Fasiculata
Zona Glomerulosa
Zona Reticularis
Androgen Synthesis
• ACTH: Capable of Stimulating Adrenal
Androgens
However,
• Dissociated From Cortisol Production in Many
Physiological and Pathological Situations
Adrenal Physiology
Steroid Biosynthesis
 Glucocorticosteroids
 Aldosterone
 Androgen
Catecholamine Production
Case 1:
42 Year Old Female Admitted for Abd Pain,
Nausea, Vomiting x 5 Days
 Lightheaded on Standing x 6 Months;
Fatigue x 2 Years; Amenorrhea x 3 Years
 PE: 108/60  76/40; P 120; Diffuse
Hyperpigmentation with Buccal
Discoloration
 Lab: Na 128, K+5.7, Cl 110, Bicarb 19
Adrenal Insufficiency:
Clinical Manifestations
Clinical Manifestations
“…a morbid state, the leading and
characteristic features of which are
anemia, general languor and debility,
remarkable feebleness of the heart’s
action, irritability of the stomach and a
peculiar change of color of the skin,
occurring in connection with a diseased
condition of the suprarenal capsules”
Physiologic Functions
• Glucocorticoid Production
• Mineralcorticoid Production
• Androgen Production
General
 Fatigue
 Generalized Weakness
 Anorexia
 Weight Loss
 Diffuse Myalgias and Arthralgias
Davidsons 22nd Ed, 2015
Hypoglycemia
• Hypoglycemia Can Occur After
Prolonged Fasting Or Several
Hours After a High-CHO Meal
• Rare in Adults in the Absence of
Infection, Fever, or Alcohol
Gastrointestinal Complaints
• Nausea, Occasionally Vomiting
• Diarrhea That May Alternate With
Constipation
• Vomiting and Abdominal Pain Often
Herald Adrenal Crisis
• Cause of GI Symptoms Unknown
Hyperpigmentation
• Seen in Primary Adrenal Insufficiency Only
• Caused by High ACTH Concentrations
Auricular-Cartilage Calcification
• Calcification of the Auricular Cartilages
Occurs in Primary or Secondary Adrenal
Insufficiency
• Occurs Mostly in Males
Calcification of Auricular Cartilage
in Addison’s Disease
Psychiatric Manifestations
Impairment of Memory
Depression
Psychosis
Physiologic Functions
• Glucocorticoid Production
• Mineralcorticoid Production
• Androgen Production
Mineralocorticoid Deficiency:
 Salt Craving
 Increased Thirst for Ice Cold Liquids
 Hyperkalemia With a Mild Hyperchloremic
Acidosis
 Hyponatremia:
Inappropriate ADH Secretion Due To
Cortisol Deficiency; Salt Wasting
Cardiovascular
• Hypotension
• Postural Dizziness or Syncope
• The Presence of Hypertension Is Strong
Evidence Against a Diagnosis of
Adrenal Insufficiency
Adrenal Physiology
Steroid Biosynthesis
 Glucocorticosteroids
 Aldosterone
 Androgen
Sexual Dysfunction
• Decreased Axillary and Pubic Hair
and Loss of Libido Are Common in
Women
• Amenorrhea in 25% of Women
Diagnosis
• Are the Adrenals Functioning?
• If Not, Why Not?
Diagnosis
Are the Adrenals Functioning?
- Cortisol Concentration
- Adrenal Stimulation Testing
Always Remember Hormone Pairs 
Get The ACTH Level!!!
Hypothalamic-Pituitary Adrenal Axis:
Primary Adrenal Insufficiency
CRH
Hypothalamus
Pituitary
ACTH
Cortisol
ACTH
Cortisol
= Stimulation
= Inhibition
Cortisol
Adrenal
Adrenal
Baseline Cortisol Concentration
•
Highest Cortisol Concentration Between
4:00 - 8:00 AM
•
< 3ug/dl  Insufficiency
•
< 10 ug/dl  Suggests Adrenal Insufficiency
•
But…. If Corticosteroid-Binding Globulin
Deficiency, Interpretation May Be Incorrect
Cosyntropin Stimulation Test
 250 ug ACTH, IV or IM
 Cortisol Measured 30 and 60 Minutes Later
 Level > 18-20 ug/dl  Normal
 Can Be Done At Any Time During The Day
Davidsons 22nd Ed, 2015
In a patient who is already receiving
glucocorticoids:
The short ACTH stimulation test can be
performed
• first thing in the morning, more than 12
hours after the last dose of glucocorticoid
• or
• the treatment can be changed to a
synthetic steroid such as dexamethasone
(0.75 mg daily), which does not crossreact in the plasma cortisol immunoassay
Diagnosis
• Are the Adrenals Functioning?
• If Not, Why Not?
Davidsons 22nd Ed, 2015
Primary Adrenal Insufficiency: Etiology
Autoimmune
80%
Drugs
Infection
Hemorrhage
Metastases
Autoimmune Adrenalitis
• Most Common Cause In Industrialized
Nations
• Caused by Autoantibodies That React
With Several Steroidogenic Enzymes
(Cyp21a2)
• Can Be Isolated or Associated With
Autoimmune Polyglandular Syndromes
Primary Adrenal Insufficiency: Etiology
Autoimmune
80%
Infection
Hemorrhage
Drugs
Metastases
Infectious Causes
• Disseminated TB: Most Common Cause
Worldwide
• Fungal Infections
• HIV: Directly Or Through Opportunistic
Infections
• Syphilis
• Tuberculosis causes adrenal calcification,
visible on plain X-ray or ultrasound scan
Primary Adrenal Insufficiency: Etiology
Autoimmune
80%
Infection
Hemorrhage
Drugs
Metastases
Hemorrhage
• Sepsis: Meningococcemia or
Pseudomonas Aeruginosa
• Anticoagulant Therapy
Primary Adrenal Insufficiency: Etiology
Autoimmune
80%
Drugs
Infection
Hemorrhage
Metastases
Drugs
•
•
•
•
•
•
•
Rifampin
Megestrol Acetate
Barbiturates
Phenytoin
Ketoconazole
Aminogluthemide
Metyrapone
Primary Adrenal Insufficiency
Autoimmune
80%
Infection
Hemorrhage
Drugs
Metastases
Metastases
Metastases To Adrenal Glands Common
However,
Metastases To Adrenal Glands An
Uncommon Cause Of Adrenal Insufficiency
Treatment
• Chronic Adrenal Insufficiency
• Acute Adrenal Insufficiency
Chronic Treatment
• Hydrocortisone: Short Acting
• Cortisone Acetate: Short Acting, But Needs
Liver Conversion to Become Active
• Prednisone: Long Acting
• Dexamethasone: Very Long Acting
Steroid Preparations
Steroid
Half Life
(minutes)
Hydrocortisone
Cortisone
Prednisolone
Prednisone
Dexamethasone
Glucocorticoid Mineralocorticoid
Potency
Potency
90
30
230
60
1.0
0.8
4.0
3.5-4.0
1.0
0.8
0.8
0.5
280
25.0-30.0
0.0
Davidsons 22nd Ed, 2015
Chronic Treatment
 Increase the dose in Stress / last TT Pregnancy
 Supra-physiologic GC replacement (doses > 30
mg HC will affect bone metabolism
 Wear a bracelet or necklace to identify Adrenal
Insufficiency
 Carry a Dexamethasone Emergency kit when
traveling
Hydrocortisone
• 15 mg AM, 5 mg at 6 PM
Monitoring of Response
• Clinical Monitoring
• ACTH Not Reliable
• 24 Hour Cortisol Excretion 
Between-Individual Variability
Mineralcorticoids Replacement
• Only in Primary Adrenal Disease
• Fludrocortisone (9 α-fluoroHydrocortisone) : 50-100 mcg/day
• Monitor Electrolytes and Perhaps
Plasma Renin Activity
Androgen Replacement in Women
• Controversial
• Lack of energy – despite optimised GC &
MC replacement
• Women with features of androgen
deficiency, including loss of libido
• DHEA 25-50 mg OD
• Complications: Acne, Hirsuitism
Treatment
• Chronic Adrenal Insufficiency
• Acute Adrenal Insufficiency
Treatment
High Dose IV Drip Steroids (300 mg
Hydrocortisone Daily)
IV Fluids (Isotonic)
Treatment of Precipitating Illness
Davidsons 22nd Ed, 2015
Case 2
73 Year Male Admitted to CCU With CHF;
Hx CAD, DM, HTN, Dyslipidemia
Hx of Low Back Pain, Treated at Local Pain
Clinic x 4 Months

PE: Pale, Frail, P112, RR 28, BP 110/60,
Bilateral Rales, S3, LE Edema

Lab: Cortisol (random) 6 mg/dl; ACTH 14 pg/ml
Hypothalamic-Pituitary Adrenal Axis
Secondary Adrenal Insufficiency
CRH
Hypothalamus
Pituitary
ACTH
Cortisol
Adrenal
Cortisol
ACTH
= Stimulation
= Inhibition
Cortisol
Primary Adrenal Insufficiency
 Hyperpigmentation
 Dehydration
 Hypotension
 Hyperkalemia
 Hyponatremia
 Hypoglycemia
SECONDARY OR TERTIARY
ADRENAL INSUFFICIENCY
 Hyperpigmentation Is Not Present
 Dehydration Is Not Present
 Hypotension Is Less Prominent
 Hyperkalemia Is Not Present
 Hyponatremia May Be Present
 Hypoglycemia Is More Common
Secondary Adrenal Insufficiency:
Causes
•
•
•
•
Exogenous Corticosteroids
Isolated ACTH Deficiency
Isolated CRH Deficiency
Lesions of the Hypothalamus or
Pituitary Gland (Tumor, Infection,
Granulomas)
• Postpartum (Sheehan Syndrome)
Secondary Adrenal Insufficiency:
Diagnosis
• Recent Onset  Adrenal Glands May
Respond To ACTH Stimulation
• Time Needed for the Adrenal Glands
to Become Unresponsive Varies
Testing In Adrenal Insufficiency
Adrenal Insufficiency
Normal
Serum Cortisol mg/dl
ACTH pg/ml @ 8 AM
Primary Secondary
Recent Onset
20 Adrenal
Insufficiency
Long-Standing
20 Adrenal
Insufficiency
10 Adrenal
Insufficiency
0
= Normal Range
30
60
Time minutes
Secondary Adrenal Insufficiency
The Best Way To Stimulate Endogenous
ACTH…
Insulin Tolerance test
Metyrapone Stimulation Test
CRH Stimulation Test
Insulin Tolerance Test (ITT)
The Gold Standard Test
 Glucose Level <40 mg/dl After Insulin IV
 Cortisol Level > 18-20 ug/dl
 This Test Should Not Be Done In Patients
With Seizures or Severe Cardiac Disease
The Metyrapone Test
ACTH
11 Deoxycortisol
Metyrapone
Cortisol
CRH Stimulation Test
• Used to Distinguish Hypothalamic and
Pituitary Causes of Secondary AI
• IV Bolus of CRH (1ug/kg/bw)
• Blood Samples at –15, 0, 5, 10, 15, 30, 45,
60, 90, and 120 min for ACTH & Cortisol
Adrenal Insufficiency:
Evaluation of Patient at Risk
(History of Steroid Administration)
Serum Cortisol (6-8 am)
Cortrosyn Stimulation Test (≥ 18 ug/dl)
Insulin Tolerance Test (≥ 18 ug/dl)
Metyrapone Test
CRH Stimulation Test
Diagnosis of Adrenal Insufficiency
in Critical Illness  “Relative”
Insufficiency
Evaluation of Adrenal Insufficiency in
Critical Illness
Glucocorticoid secretion increases
during critical illness, yet the increase
may not be detected if only total
cortisol concentrations are measured.
Serum free cortisol measurements
may be helpful to avoid unnecessary
glucocorticoid therapy.
These assays are not yet widely
available.
Hamrahian AH; Oseni TS; Arafah BM N Engl J Med 2004 15;350:1629-38.
Evaluation of Adrenal Insufficiency in
Critical Illness: A Reasonable Approach
Critical Illness:
Random Cortisol
< 15 ug/ml
15-34 ug/ml
> 34 ug/l
Adrenal Insuff
Cortrosyn Stim
Test
Adrenal Insuff
Unlikely
Likely   Free Cortisol
& Treat
< 9 ug/ml
≥ 9 ug/ml
Evaluation of Adrenal Insufficiency in
Critical Illness: The Bottom Line
While some critically ill patients
may have functional adrenal
insufficiency, there is currently no
consensus on diagnostic criteria
or indications for treatment.
Cooper MS; Stewart PM NEJM 2003; 348:727-34
Case 3
67 y/o Female Referred For An Adrenal Nodule
Noted On A CT Done For Evaluation Of Abd
Pain
 Hx HTN x 5 Years  Controlled On
Monotherapy
 Hx DM  Controlled On Metformin and SU
 No Hypokalemia
 PE Unremarkable; BP 132/78
Adrenal Incidentaloma
Epidemiology
 Figures Vary From O.4-6% Of CT Scans
 2.1% Of Autopsy Series
 Incidence Increases With Age; 7% After 70
 Seen More Commonly In Women
NATIONAL INSTITUTES OF HEALTH
Management of the Clinically Inapparent Adrenal Mass (Incidentaloma). Final
Statement. July 16, 2002
Adrenal Incidentaloma
IS IT MALIGNANT?
IS IT HYPERSECRETORY?
Major Causes
Benign Adenoma
Cyst
Myelolipoma
50%
10%
10%
 Pheochromocytoma
10%
Metastases
Adrenal Cancer
6-30%
0.01%
The incidental adrenal mass. Am J Med 1996
Adrenal Carcinoma
• Virilization (Production Rate of
Androgen Is High)
• Recent Onset of Symptoms (Months)
Is It Malignant?
• Size
• Radiological Findings
IS IT MALIGNANT?
• Masses > 6 cm Usually Are Treated Surgically
• Masses < 4 cm Are Generally Monitored
• Masses Between 4 And 6 cm:
Criteria Other Than Size Should Be
Considered In Making The Decision To
Monitor Or Proceed To Surgery
National Institutes Of Health
Management Of The Clinically Inapparent Adrenal Mass (Incidentaloma) 2002
Is It Malignant?
• Size
• Radiological Findings
Computed Tomographic Scans
• Attenuation On CT Scan Is Measured In
Hounsfield Units (HU)
• Lipid-Rich Masses Are Usually Benign
• Lipid-Rich Lesions Have Low Attenuation
• Low Attenuation Lesions Have Low HU
Values
Computed Tomographic Scans
• Unenhanced CT:
Adenomas: < 10 HU
Malignancies: > 18 HU
Sensitivity: 73% Specificity: 96%
• Delayed Enhanced CT:
Adenomas: < 30 HU
Malignancies: > 30 HU
Sensitivity 95% And Specificity: 100%
MRI
• Equally Effective As CT
• Adenomas Are Iso-Intense With The
Liver On T2-weighted Images
• Carcinomas Have A Hyper-Intense
Signal Compared With The Liver
Fine-Needle Aspiration Biopsy
CANNOT Distinguish A Benign
Adrenal Mass From Adrenal
Carcinoma
Other Tests…
• Iodinated Cholesterol Derivative (NP-59):
Show Uptake In Functioning Lesions
• I-131 Metaiodobenzyl Guanidine (MIBG):
Evaluating Pheochromocytoma
• Positron Emission Tomography (PET):
Not Enough Data
IS IT HYPERSECRETORY?
Cortisol
Catecholamines
Mineralcorticoids
Androgens
Patients
1004
Non-Secretory
854 (85%)
Sub-Clinical Cushings Syndrome (SCC) 92 (9.2%)
Pheochromocytoma
42 (4.2%)
Aldosterone-Producing Adenoma
15 (1.6%)
Journal of Clinical Endocrinology & Metabolism 85 (2) 637-644, 2000
Subclinical Hypercortisolism
Absence Of The Stigmata Of
Cushing’s Syndrome
Hypercortisolism
• 24 Hour Urinary Free Cortisol
• Positive: More Than 3-4 Times The
Upper Limit Of Normal Range
Problems With 24 Hour Urine
Free Cortisol
Mildly Elevated Levels Can Be Seen In
Anxiety, Depression, Alcoholism
When the 24 UFC Is Not
Conclusive……..
Dexamethasone Suppression
Test
1 mg Dexamethasone At 11 pm 
Measure Cortisol At 8 am
Normal: Cortisol < 5 ug/dl
Specificity Is Reduced In Acute Or
Chronic Illness
Subclinical Hypercortisolism
Two Of The Following:
 Increased Urinary Free Cortisol (UFC)
 Unsuppressed Serum Cortisol Levels
After 1-mg Overnight Dexamethasone
 Low ACTH Levels
 No Clinical Signs Of Cushing Syndrome
Mantero F, Masini AM, Opocher G, Giovagnetti M, Arnaldi G. Horm Res
47:284–289, 1997
Is There A Problem With SCS?
Increased Incidence Of:
 HTN
 Obesity
 DM
 IGT
 Increased CV Risk
 Bone Disease
Patients
1004
Non-Secretory
854 (85%)
Sub-Clinical Cushings Syndrome (SCC) 92 (9.2%)
Pheochromocytoma
42 (4.2%)
Aldosterone-Producing Adenoma
15 (1.6%)
Journal of Clinical Endocrinology & Metabolism 85 (2) 637-644, 2000
Pheochromocytoma
19-76% Of Pheochromocytomas Not
Diagnosed Until After Death
80% Of Patients With Unsuspected
Pheochromocytomas Who Underwent
Surgery Or Anesthesia Died
Not Possible To Determine Which Will
Present With Crisis
Not Possible To Determine The Malignant
Potential Of Pheochromocytoma
Hypertension In
Pheochromocytoma
• Paroxysmal in 48%
• Persistent in 29%
• Normal in 13%
Other Symptoms
• Attacks of Headaches (80%)
• Palpitations (64%)
• Diaphoresis (57%)
Symptomatic Triad Of Headache, Sweating,
And Tachycardia In A Hypertensive Patient
 Sensitivity 90.9% And Specificity 93.8%
Pheochromocytoma
Therefore….
It Is Reasonable To Screen All Patients
With Adrenal Incidentalomas For
Pheochromocytoma
How To Screen…
• Urine Collection Of Catecholamines
Or The Metabolites
• Plasma Collection Of
Catecholamines And Metabolites
Which Is Better?
Catecholamine-Secreting Tumors Histologically
Proven In 31 of 340 Patients:
 Sensitivity Of Plasma Free Metanephrine 97%
Specificity 98%
 Sensitivity Of Urinary Total Metanephrine
And Catecholamines 90%; Specificity 85%
Sawka et al. JCEM 88(2): 553-558. 2003.
Pheochromocytoma
Plasma-Free Metanephrines Are Recommended
As The Test Of Choice For Excluding Or
Confirming The Diagnosis Of
Pheochromocytoma
NATIONAL INSTITUTES OF HEALTH
Management of the Clinically Inapparent Adrenal Mass (Incidentaloma). Final Statement. July
16, 2002
Patients
1004
Non-Secretory
854 (85%)
Sub-Clinical Cushings Syndrome (SCC) 92 (9.2%)
Pheochromocytoma
42 (4.2%)
Aldosterone-Producing Adenoma
15 (1.6%)
Journal of Clinical Endocrinology & Metabolism 85 (2) 637-644, 2000
Signs and Symptoms
in Primary Hyperaldosteronism
 Hypertension
 Headache
 Weakness And/Or Fatigue
 Paresthesias
 Muscle Cramps
 Polyuria, Polydipsia, Nocturia
 Arrhythmias
Signs, Symptoms, and Laboratory Data
in Primary Hyperaldosteronism
 Hypertension
 Hypokalemia
 Headache
 No Other Cause For
 Weakness/ Fatigue
Hypertension Or
Hypokalemia
 Metabolic Alkalosis
 Hyperaldosteronism
 Hyporeninemia
 Paresthesias
 Muscle Cramps
 Polyuria/ Polydipsia
 Arrhythmias
In the Past…
• Hypokalemia Was Considered Common
In Primary Hyperaldosteronism
• The Evaluation Was Difficult
(Discontinuing All Antihypertensive
Medications)
Now…
• Patients With PA Can Be Normokalemic
• Not Necessary To Stop All Medications
• Screening Is Easier
Aldosterone-Producing
Adenoma
Serum Potassium And Aldosterone /Plasma
Renin Activity Ratio Should Be Determined
To Evaluate For Primary Aldosteronism
NATIONAL INSTITUTES OF HEALTH
Management of the Clinically Inapparent Adrenal Mass (Incidentaloma). Final Statement.
July 16, 2002
Aldosterone/PRA Ratio
• Normals And Patients With Essential
Hypertension  < 20
• Primary Aldosteronism  > 30
• > 90% Sensitivity And Specificity
Medications and PAC/PRA
• Impossible To Interpret PAC/PRA On
Spironolactone
• ACE Inhibitor: A Normal Test Does Not
Exclude The Diagnosis ( PRA)
• ACE Inhibitor: A Positive Test Increases
The Specificity Of The Diagnosis
Other Medications
•  Blockers Suppress PRA, But Do Not
Alter PAC/PRA
• Diuretics Increase PRA (Hypovolemia),
But Do Not Alter the Ratio
Adenoma (APA) vs Hyperplasia (IHA)
• Very High PAC/PRA  Adenoma
• Increased 18-OH-Corticosterone 
APA if >100 mg/dl and IHA if <50 ng/dl
• Adrenal Vein Sampling Sometimes
Indicated
Decision Matrix of the Incidental Adrenal
Mass on CT or MRI Scan
Solid Or With Cystic Degeneration
>6 Cm
Evaluate
Biochemically
And Operate
Pure Cyst
Remove Fluid
<6 Cm
Evaluate
Biochemically
Biochemically
Active
Operate
Biochemically
Inactive
Clear
Bloody
Observe
Evaluate
Biochemically
And Follow
As For Solid
Tumor
Repeat Scan In
3, 6, 18, and 36
Months
Larger
Evaluate
Biochemically
And Operate
Unchanged
Observe
Follow Up
• Will The Mass Become Malignant?
• Will The Mass Become Hypersecretory?
Incidental Adrenal Mass
Risk of Progression
Adrenal Hyperfunction:




Unlikely If Lesion < 3 cm
Cortisol Hypersecretion Most Likely Disorder
4% After 1 Year
9.5% Within 3 Years  None Thereafter
Mass Enlargement:
8% After 1 Year
 18% After 5 Years
 Most Enlargement Occurred Within 3 Years

Barzon et al J Clin Endocrinol Metab 1999
Follow Up
An Approach: Perform An Overnight 1mg
Dexamethasone Suppression Test And
Plasma Free Metanephrines Yearly Or
Earlier If Clinically Indicated
The Risk Of Tumor Hyperfunction Appears
To Plateau After 3 Years
National Institutes Of Health: Management Of The Clinically Inapparent
Adrenal Mass (Incidentaloma). Final Statement. July 16, 2002
The Adrenal: Take Home Points
 Sx’s Adrenal Insufficiency Non-Specific
Screen With Cortisol 6:00 - 8:00 am
< 3ug/dl  Insufficiency
 ACTH and Cortrosyn Stim Test
 In ICU Setting: Free Cortisol & Cortrosyn Stim
< 15 Random or Increase < 9 After ACTH 
Treat
Take Home Points…
Incidental Adrenal Mass
Size and HU units Important
>6 cm  Surgical Removal (After w/u)
Exclude Hypersecretion:
24 Urine Free Cortisol
Plasma Free Metanephrines
Potassium and Aldo/Renin
The Metyrapone Test
• Metyrapone: 750 mg Q 4 Hours x 24 Hrs
• 08:00 Cortisol Measured Day 2
• Cortisol < 7ug/dl and 11Deoxycortisol
> 10ug/dl
The Mayo Clinic Study
• 342 Patients With Adrenal Incidentaloma
Retrospectively Evaluated
• Tumor Diameter Averaged 2.5 cm.
• Most Malignant Tumors Measured > 5 cm.
• Removing All Tumors > 4 cm Would Have
Removed Eight Benign Tumors For
Every Carcinoma
Incidentally discovered adrenal tumors: an institutional perspective.
Herrera MF; Grant CS; van Heerden JA; Sheedy PF; Ilstrup DM. Surgery
1991 Dec;110(6):1014-21
The Adrenal Incidentaloma
Survey
• Multicentric, Retrospective Survey
• Review Of Adrenal Incidentalomas From
1980-1995
• 1004 Cases Of Asymptomatic IncidentallyFound Adrenal Masses
J Clin Endo & Meta 85: 637-644 2000
Problems With the DST
• Decreasing Dexamethasone Absorption
• Increased Dexamethasone Metabolism
• Increased Concentration of CBG
(Estrogen and Pregnancy)
Management
• Hypersecretory With Symptoms And Signs:
Adrenalectomy
• Silent Pheochromocytoma: Adrenalectomy
• Adrenalectomy Is An Option For An
Individual With Hypertension And
Aldosterone Excess
Chronic Treatment
Dose May Need to Be Increased in
Obese Patients Or If On Drugs That
Accelerate Hepatic Metabolism
General Aspects
Small, But Mighty….
• 2 to 3 cm Wide, 4 to 6 cm Long, ~ 1 cm Thick
• Weight: 4-5 gm
• Highly Vascular Organs  11% of Cardiac
Output
General Aspects
Small, But Mighty….
• 2 to 3 cm Wide, 4 to 6 cm Long, ~ 1 cm Thick
• Weight: 4-5 gm
• Highly Vascular Organs  11% of Cardiac
Output
The Size….
The Mayo Clinic Study (n= 342)
The Adrenal Incidentaloma Survey in
Italy (n = 1004)
 Malignant Tumors > 6 cm
Herrera MF et al: Incidentally discovered adrenal tumors: an institutional perspective. Surgery 1991;
110(6):1014-21. J Clin Endo & Meta 85: 637-644 2000
Benign Adenoma
Adrenal Carcinoma
Resources:
Davidson’s 22nd Edition, 2015
Harrison’s 18 th Edition
Net resources