approach to adrenal incidentalomas
DESCRIPTION
Approach to Adrenal Incidentalomas. Moayad Assiri Urology R4 KAUH. Definition. Prevalence. Causes led to it discovery. DDx. Diagnostic approach -Hormonally. -Imaging. -? FNA. Management approach. - PowerPoint PPT PresentationTRANSCRIPT
Approach to Adrenal Incidentalomas
Moayad Assiri
Urology R4
KAUH
Definition. Prevalence. Causes led to it discovery. DDx. Diagnostic approach -Hormonally. -Imaging. -? FNA. Management approach. F\U. Summary. References.
(Clinically inapparent adrenal masses.)
adrenal tumor not suspected prior to radiological studies led to it discovery.
A disease of modern technology. J Endocrinal Metab
Clin North Am 1997
Except: -Pt w known non adrenal malignant tumor. -pt known HTN.
Definition
Incidence of adrenal masses is 9 - 12% in autopsies.
Incidence of AI is 2- 5 %.
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Rt > lt . Bil 2 – 10 %. NATIONAL INSTITUTES OF HEALTH
Management of the Clinically Inapparent Adrenal Mass (Incidentaloma). Final Statement. July 16, 2002
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Adrenal Incidentalomas Study - Chi Mei Medical Center
1998 Jan – 2002 Dec Abdominal CT scan 70,101 in 5 years 127 cases of AI in 256 cases of adrenal
tumors Incidence of AI: 0.18% Hormonally active: 4%
Mayo clinic 1985-1990 61,054 CT scans performed . Adrenal mass in 2066 pts ( 3.4%). 16.5% were present incidental ( <1 cm ). Overall, AI 259 pts ( 0.4% ) 50% metastatic ca. 25% other known lesions. 7.5% symptomatic tumors.
Prevalence of Adrenal Incidentalomas on CT Imaging
Study Year Number of Scans Number with Mass Frequency)%(
Abecassis et al, Toronto, Canada
1985 1,459 19 1.3
Belldegrun et al,Boston, MA
1986 12,000 88 0.7
Caplan et al,LaCrosse, WI
1994 1,779 33 1.9
Glazer et al,St. Louis, MO
1982 2,200 16 0.7
Herrera et al,Rochester, MN
1991 61,054 259 0.4
Prinz et al,Chicago,IL
1982 1,423 4 0.3
TOTAL)average( 79,915 419 (0.9)
Cheng & Shen 2003 70101 127 0.18
Causes led to discover IA
342 cases, 136 men and 206 women
Reasons for CT scan: nonspecific abdominal pain, 60% known abdominal or thoracic disease, renal problems, musculoskeletal pain
Acta Endocrine (copenh)1989
Age-dependent occurrence of adrenal adenomas
1% in age < 30 y. 3 -7 % in age > 50 y. Compensatory growth in response to local
ischemic damage of arteriosclerotic disease Higher number of diagnostic procedures performed
in aged patients N Engl J
Med, 1990
Increases with Age
Age-dependent occurrence of adrenal cortical adenomas autopsy studies with total of 57,262 subjects
0
2
4
6
8
0~9 10~19 20~29 30~39 40~49 50~59 60~69 >70
Age(y)
Endocrine and Metabolism Clinics of North America 2000; 29)1(:159-185
Clinical characteristics
Per definition ,NO clinical symptoms or signs of adrenal disease should be present at the time of Dx.
More detailed Q and careful PE might reveal evidence of subtle hormonal excess;
-recent w.t gain -skin atrophy. -episodic of headaches.
Àdrenal incidentaloma
Majority are neither function nor malignant 70-90%. The malignant tumors may and may not
secrete hormonal. The 3 mains hormone-producing tumors:1. Cortisone producing adenoma SCCS 11%.2. Pheochromocytoma 7%.3. Aldoestrone producing adenoma 2%.
PREVALENCE OF ADRENAL INCIDENTALOMAS IN DIFFERENT SERIES
_______________________________
Type of Tumor Mantero et al Al-SIE Othorst _______________________________________________ Nonhypersecretory tumors 76.0 74.0 70-94Hypersecretory tumors Cortisol-secreting adenomas 14.0 9.2 0-14 Aldosteronomas 1.0 1.4 0-7 Pheochromocytomas 3.4 4.2 0-11Adrenal carcinomas 1.0 4.0 0-25Myelolipomas 2.0 3.0 7-15Cysts 1.0 1.9 4-22Ganglioneuromas 1.0 1.5 0-6Metastases Unselected patients 1.0 0.7 0-21 Oncological patients 32-73 ________________________________________AI-SIE: Adrenal Incidentaloma Study Group of the Italian Society of Endocrinology
Prevalence (%)
Endocrine and Metabolism Clinics of North America 2000; 29)1(:107-126
Adrenal cancer
Benign Adenoma 50%
Cyst 10%
Myelolipoma 10%
Pheochromocytoma 10%
Metastases 6-30%
Adrenal Cancer 0.01%
The incidental adrenal mass. Am J Med 1996
Benign nonfunctioning
Adenoma Adrenolipoma Amyloidosis Cyst / Pseudocyst
Ganglioneuroma Granuloma
Infection Hamartoma
HemangiomaLeiomyoma
Lipoma Myelolipoma
Malignant nonfunctioning
Angiosarcoma
Ganglioneuroblastoma Leiomyosarcoma Malignant schwannoma Metastatic carcinoma Malignant melanoma
Malignant lymphoma Adrenocortical
carcinoma
Endocrine and Metabolism Clinics of North America 2000; 29)1(:159-185
Differential Diagnosis of Adreanl Incidentalomas
Hyperfunctioning mass
- Pheochromocytoma - Preclinical Cushing’s syndrome - Primary aldosteronism - Nodular hyperplasia - Congenital adrenal hyperplasia - Masculinizing or feminizing tumor - Primary malignancy (Adrenocortical carcinoma)
Pseudoadrenal mass
- Mistaken vasculature - Liver
- Lymph nodes - Pancreatic mass - Spleen - Renal mass - Stomach mass - Technical artifact
Differential Diagnosis of Adreanl Incidentalomas
Endocrine and Metabolism Clinics of North America 2000; 29)1(:159-185
After incidental discovery of an adrenal mass, 2 questions should be addressed
Functional status hormonally active even in the absence of a classic clinical presentation
Malignant potential any chance that the mass is malignant
Important consideration
Trying not to miss important pathology.
Trying no to subject the pt to unnecessary procedure or surgery.
Cost effect.
1-Endocrinology investigation
significant endocrine activity increase with increase tumor size
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<2cm
2-2.9cm
3-3.9cm
4-5.9cm
>6cm
hormonally inactive hormonally active
Subclinical Cushing’s Syndrome
Most frequent hormonal abnormality (5 – 20%)
Autonomous cortisol secretion without stigmata of Cushing’s syndrome
Diagnostic criteria not yet clearly defined
• 10-20 mg/day
• Controlled Primarily By ACTH
• Negative and Positive Feedback Between Cortisol and ACTH at Pituitary and Hypothalamic Levels
Dx
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
Dexamethasone Suppression Test
Low-dose: 1mg dexamethasone at 2300, followed by assay of cortisol at 0800 the following day– Cortisol > 3 mcg/dl suggests autonomous secretion
High-dose: 8 mg dexamethasone at 2300 with assay of cortisol at 0800 the next day– Cortisol > 1 mcg/dl indicates autonomous secretion– Reduces false positives
“Intermediate-dose”: 2 – 3 mg dexamethasone at 2300, followed by cortisol at 0800– Cortisol > 3 mcg/dl reportedly suggestive of autonomy
Easier to perform overnight suppression rather than 2-day oral load
Association with Metabolic Syndrome?
1990’s Italian multiinstitutional study collection 1004 patients with adrenal incidentaloma– 41% prevalence HTN– 10% prevalence DM– 28% prevalence obesity
May contribute to, and worsen, hypertension, obesity , diabetes, dyslipidemia and osteoporosis
Pheochromocytoma
Approximately 5-7 % of adrenal incidentalomas.
0.5% among screened hypertensive pt’s
Can be clinically silent and not suggested by history
Mixed recommendations on diagnostic testing
Dx
24-h Urinary fractionated catecholamine excretion or free metanephrines.
• 24 hour urine fractionated metanephrines recommended by some as first diagnostic test
• Especially in incidentalomas without radiographic features suggestive of pheochromocytoma
• Sensitivity and specificity between 91 – 98% • Increased even further when fractionated
catecholamines added
Plasma Free Metanephrines
Plasma free metanephrines
– Used when imaging characteristics and other pre-test probability of pheochromocytoma are high, but 24 hr urine normal
– Due to high sensitivity (97 – 100%) but low specificity (85 – 89%, ) of test
– Negative result quite effective at ruling out
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.
Aldosteronism (Conns Sx)
Quite rare cause <1%– Most have already been diagnosed before
become large enough to be detected by CT/MRI
Should be evaluated in all hypertensive patients with incidentaloma
Serum potassium not sufficient, but should be included– Common to have normokalemia with
aldosterone producting adrenal tumor 7 – 38%.
Hypertension Headache Weakness And/Or Fatigue Paresthesias Muscle Cramps Polyuria, Polydipsia, Nocturia Arrhythmias
Signs and Symptomsin Primary Hyperaldosteronism
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
Dx
Plasma aldosterone/plasma renin activity ratio greater than 30 highly suggestive– Especially with plasma aldosterone >15 ng/dl
Confirm with aldosterone suppression test– IV 0.9 NS infusion – 2L over 2 hrs, with supine
aldosterone >10 suggestive– Can also do 24 hour urinary aldosterone while
patient orally ingests 5000 mg sodium/day x 3 days
Urinary aldosterone >14 mcg/24º
Appropriate screening tests should be performed if the patient has clinical features that are suggestive of increased adrenal function
Diagnosis Suggestive Clinical Features Laboratory Tests
Pheochromocytoma Hypertension, Paroxysmal Symptoms (eg, palpitation, diaphoresis, headache, pallor, tremor)
24-hr urine:fractionated metanephrines fractionated catecholaminesBlood:fractionated metanephrines
SC Cushing's syndrome (SCCS)
Central obesity, proximal muscle weakness, thin skin, supraclavicular fat pad, facial plethora
For patients lacking symptoms of CS:1-mg overnight dexamethasone suppression test
Diagnosis Suggestive Clinical Features
Laboratory Tests
Primary aldosteronism
Hypertension, hypokalemia
Plasma aldosterone concentration Plasma renin activity
Adrenocortical carcinoma
Mass effect symptoms, symptoms related to excess glucocorticoid, mineralocorticoid, androgen, or estrogen secretion
Serum dehydroepiandrosterone sulfateMeasures of clinically indicated steroid
Stepwise diagnostic approach
Step I :
1- 24-h Urinary catecholamine excretion or free metanephrines.
2- Serum cortisol after dexamethasone suppression 1mg at 11 pm PO.
3-HTN , Serum K and – PAC\PRA ratio.
Stepwise diagnostic approach
Step II : confirmatory test.
1- MRI . CT scan or 123-I-MIBG scintigraphy or 131 I-MIBG.
2- high-dose dexamethasone 8mg suppression test. If +ve
.CRH test analysis of diurnal cortisol secretion , and 24-h urine free cortisol.
3- confirm with aldosterone suppression test.And 24-h urine aldosterone .
Step III. Revaluation
-repeat screening tests after 2 years in patient with a tumor size of > 3 cm.
Stepwise diagnostic approach
2 -Imaging
Imaging Characteristics
CT Scan– Hounsfield Scale
Measures xray attenuation
Each number represents a shade of grey, with air and bone
Water as zero Air = -1000 Bone = +1000
Hounsfield Units for Relative Densities of Various SubstancesSubstance Hounsfield units(H)
-1,000 Air
-50 Fat
0 Water
+40 Soft tissue )i.e., muscle(
+100 to +400 Calculus
+1,000 Bone
Hounsfield units = units of x-ray attenuation used in CT. each pixel is assigned a value on a scale from -1,000 to +1,000.
CT scan
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 HUMalignancies: > 18 HU
Sensitivity: 73% Specificity: 96%
Delayed Enhanced CT: Adenomas: < 30 HU Malignancies: > 30 HU
Sensitivity 95% And Specificity: 100%
Adrenocortical carcinoma
Size large, typically > 4 cmShape irregular with unclear marginsTexture inhomogenous with mixed densities compared with liverLaterality usually solitary and unilateralCT > 10 HU without contrast and >30-40 HU 30 min after contrast administrationMRI hyperintense to liver on T2-weighted imagePresence of necrosis, hemorrhage, or calcifications-- commonGrowth usually rapid
Adrenal cancer CT
Contrast-enhanced CT scan through the abdomen of a 56-year-old man reveals a complex solid and cystic, calcified mass (arrow) in the right suprarenal fossa extending into the adjacent liver. The tumor proved at surgery to be a carcinoma of the adrenal cortex. .
Malignant Potential
Imaging phenotype and mass size are two major predictors of malignancy
Additional test that may be preformed to predict malignancy include image-guided needle biopsy and iodocholesterol scintigraphy
Hormonal evaluation is not predictive of malignancy
Approximately 41% of 1,891 published cases of adrenocortical carcinoma, was not hormone-secreting
size
The probability that an AI is ACC is increases with increasing size of the lesion.
90% of all ACC is > 6 cm in size.
The prevalence of ACC related to size of tumor 2% in tumors < 4 cm. 6% in tumors 4-6 cm. 25% in tumor > 6 cm.
Resection all tumor > 4 cm- 8 benign tumors removed for each cancer resected.
Imaging Phenotypes of Adrenal Incidentalomas
Adrenal cortical adenomas
Size small, typically < 3 cmShape round to oval with smooth marginsTexture homogenous and low density compared with liverLaterality usually solitary and unilateralCT < 10 HU without contrast and <37 HU 30 min after contrast administrationMRI isointense to liver on T2-weighted imagePresence of necrosis, hemorrhage, or calcifications-- rareGrowth usually stable size over time or very slow growth
Adrenal adenoma hypodense
Abdominal CT showing a 1.5-cm round hypodense left adrenal cortical adenoma (arrow).
PheochromocytomaSize large, typically > 3 cmShape round to oval with smooth marginsTexture inhomogenous with cystic texture Laterality usually solitary and unilateralCT >10 HU without contrast and >40 HU 30 min after contrast administration, usually vascular, marked enhancement MRI marked hyperintense compared with liver on T2-weighted imagePresence of necrosis, hemorrhage, or calcifications-- hemorrhage and cystic necrotic areas commonGrowth very slow
Pheochromocytoma silent Abdominal CT showing an 8-cm left adrenal mass (arrow) discovered incidentally. Note the vascular and inhomogenous imaging characteristics of this mass. Biochemical evaluation was consistent with a clinically silent pheochromocytoma, which was confirmed at surgery..
MRI of the abdomen shows a 4.5-cm right adrenal pheochromocytoma (arrows). Upper panel: T1-weighted image. Lower panel: T2-weighted image shows increased signal intensity typical of a pheochromocytoma.
Metastasis
Size variable, frequently < 3 cmShape round to irregular with unclear marginsTexture inhomogenousLaterality often bilateralCT > 10 HU without contrast and >40 HU 30 min after contrast administration, usually vascular, enhancement on tumor rim MRI hyperintense compared with liver on T2-weighted imagePresence of necrosis, hemorrhage, or calcifications-- hemorrhage and cystic necrotic areas commonGrowth usually slow
Imaging CharacteristicsAdenoma Adrenocortical
CarcinomaPheochromocytoma
Metastasis
Size < 3 cm diameter >4 cm diameter >3 cm diameter Usually <3 cm
Shape Round, smoothMargins
Irregular, no clear margins
Round/oval, clear margins
Oval/irregular, unclear margins
Texture Homogenous Heterogenous, mixed densities
Heterogenous, cystic
Heterogenous, mixed densities
Lateralize Solitary, unilateral
Solitary, unilateral
Solitary, unilateraly Bilateral
CT Attenuation
<10 HU >25 HU >25 HU >25 HU
CT Washout at 10 minutes
>50% <50% <50% <50%
T2 MRI Appearance )compare to liver(
= + +++ +
Necrosis, Ca, hemorrhage
Rare Common Common Occasional
Growth rate Slow Rapid Slow Variable
Nuclear Imaging PET – most useful in
patients with oncologic history and incidentaloma– 100% sensitive
determining both metastasis and benign adenomas based on adrenalectomy studies
Radionuclide Scintigraphy
Schlamp A et al. )2007( Recurrent adrenocortical carcinoma after laparoscopic resectionNat Clin Pract Endocrinol Metab 3: 191–195 doi:10.1038/ncpendmet0391
CT and fluorodeoxyglucose(FDG)-PET scans of the tumor before and after primary surgery
MIBG – used to confirm suspicion of pheochromocytoma, little utility in eval of incidentalomas in general
NP-59 – radiolabeled cholesterol derivative, preferentially taken up by adrenal adenomas– Unilateral uptake suggests
functional adenomas, and may be useful in screening for subclinical cushing’s syndrome
3 -Fine-needle aspiration biopsy
(FNA) cannot distinguish a benign adrenal mass from the rare adrenal carcinoma.
It can distinguish between an adrenal tumor and a metastatic tumor.
FNA may be indicated : when there is a suspicion of cancer outside the adrenal
gland, or in the patient undergoing a staging evaluation for a
known cancer. ? Infection. NATIONAL INSTITUTES OF HEALTH
Management of the Clinically Inapparent Adrenal Mass (Incidentaloma). Final Statement. July 16, 2002
Tumors that most commonly metastasize to adrenals are carcinomas of lung, breast, kidney and gastrointestinal tract, melanoma or lymphoma
FNA is not free of S.E .
• FNA is not useful in the routine evaluation.
• Pheochromocytoma should always be excluded before attempting FNA biopsy of an adrenal mass
NATIONAL INSTITUTES OF HEALTHManagement of the Clinically Inapparent Adrenal Mass (Incidentaloma).
Final Statement. July 16, 2002
Bilateral masses
Analyses from two large adrenal incidentaloma studies with 887 and 202 patients showed that bilateral masses were found in 10 to 15 percent of cases.
Bilateral adrenal masses can be seen with – metastatic disease, – congenital adrenal hyperplasia, – cortical adenomas, lymphoma, – infection (eg, tuberculosis, fungal), – hemorrhage, – ACTH-dependent Cushing's, – pheochromocytoma, – amyloidosis, – infiltrative disease of the adrenal glands, and – ACTH-independent bilateral macronodular adrenal
hyperplasia
Adrenalectomy?
Individualized approach
The decision to operate on pt should be based on :
Suspicious of the presence of malignancy. Evidence of function of the tumor. Pt age . Pt preference .
Adrenalectomy?
Recommended for: all patients with mass size > 6 cm, pheochromocytoma, aldosteronism, and Cushing’s syndrome
Aldosteronism and CS can be treated medically, but surgical approach favored
MedicalSpironolactone
Inhibits sodium-postassium exchange in the distal tubule, normalizes serum K and may lower blood pressure.
4 – 6 cm masses– Either surgical approach or close follow-up
considered reasonable
*Strongly consider adrenalectomy:– if imaging phenotype suspicious,– increase in size > 1 cm during f/u, – or development of hormonal hyperfunction during
f/u.
Considered in SCS, especially in pt’s < 40 or 50 y/o, and those with disorders attributable to hypercortisolism
- Caution for postoperative adrenal insufficiency in SCS patients taken to adrenalectomy.
No difference between open and laparoscopic approaches
Complication rate of ~3%Special consideration : -Poor surgical patient – FU. -Not possible or difficult FU – Sx.
Izaki H et al. Indications for laparoscopic adrenalectomy for non-functional adrenal tumor with hypertension: usefulness of
adrenocortical scintigraphy. Int J Urol 2006:13(6):677-81.
342 pts AI. 52 patients underwent adrenalectomy 5 patients had malignancy: 4 adrenocortical carcinomas and one
metastasis 1.2% of 342 had cancer No malignancy < 5 cm in diameter 287 of 342 had follow-up; 90% at one year None had extension of tumor or hormonal
excess Herrera et al, Surgery
Conclusions: (1) Hormonal screening on patients with an
AI > 1 cm, (2) any patient with a hyper-secretory state
should undergo adrenalectomy, (3) advise adrenalectomy on AIs > 4 cm and (4) comparison CT scans at 3 month intervals
for those choosing observation only of their AI < 4 cm
Herrera et al, Surgery
National survey on AI Purpose: To evaluate AI based on imaging
size alone Strict exclusion criteria 1004 enrolled; 584 women and 420 men All patients underwent CT scan or MRI
Montero, JCEM
85% underwent hormonal evaluation Results: 9.2% had SCS, 1.6% had an aldosteronoma
and 4.2% had pheochromocytomas All these patients underwent adrenalectomy A total of 380 patients underwent
adrenalectomy.
Montero, JCEM
Table 4 Histological picture in relation with gender, age, and mass size )CT measurement(. Mantero, JCEM
Conclusions: (1) An AI > 4 cm is 93% sensitive for
detecting all malignancies and (2) Pain at presentation may be
associated with a malignant outcome
Mantero, JCEM
The Mayo Clinic Study
432 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
Incidentaloma Follow-Up
No single approach is proof yet.
1st Follow up 3 - 6 m with another FU at 12 m.
Repeat hormone screening after 12m.
Then annually. 2 -3 y
IA 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 ThereafterMass Enlargement: 8% After 1 Year 18% After 5 Years Most Enlargement Occurred Within 3 Years
Barzon et al J Clin Endocrinol Metab 1999
Summary
Relatively common – prevalence ~ 2 – 5 %.– Increases with age, so expected to increase further in
future. 1 in every 4000-1.6 million adrenal tumors are malignant Up to 20% are hyperfunction.
All patients with incidentaloma need hormonal eval-24º urinary metanephrines-Midnight dexamethasone suppression test-PAC\PRA ratio in pt’s with underlying HTN or
hpokalemia.No optimal radiologic test to distinguish between benign and
malignant tumors
Summary
FNA of little value.
Sx indicated for hyperfunction masses , size >6cm and possibility of malignancy .
Malignant tumors more likely to be > 4 cm Nearly all masses <4 cm are benign
No consensus on follow-up
References
AI-SIE: Adrenal Incidentaloma Study Group of the Italian Society of Endocrinology
Acta Endocrine (copenh)1989
N Engl J Med, 1990
Endocrine and Metabolism Clinics of North America 2000; 29(1):159-185
NATIONAL INSTITUTES OF HEALTHManagement of the Clinically Inapparent Adrenal Mass(Incidentaloma).Final Statement. July 16, 2002
Endocrine and Metabolism Clinics of North America 1997
Barzon et al J Clin Endocrinol Metab 1999
References
Endocrine and Metabolism Clinics of North America 2000; 29(1):107-126
Mantero F, Masini AM, Opocher G, Giovagnetti M, Arnaldi G. Horm Res 47:284–289, 1997
Sawka et al. JCEM 88(2): 553-558. 2003.
Izaki H et al. Indications for laparoscopic adrenalectomy for non-functional adrenal tumor with hypertension: usefulness of adrenocortical scintigraphy. Int J Urol 2006:13(6):677-81.
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