Dr Tsang Yi Po Department of Surgery Pamela Youde Nethersole Eastern Hospital
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Dr Tsang Yi PoDepartment of SurgeryPamela Youde Nethersole Eastern HospitalJoint Hospital Surgical Grand Round 2013
Management of Adrenal Incidentaloma
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Introduction
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Introduction • Mass lesion in adrenal gland >1cm• Discovered incidentally during radiologic exams for
other medical condition• Prevalence ~4-6% in general population• Prevalence increases with age
– 20-29 years old: 0.2%– >70 years old: 7%
Bovio et al. J Endocrinol Invest 2006Young. N Engl J Med 2007
Boland et al. Radiology 2008
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Introduction
Hypersecreting ?
Malignant?
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Introduction • Causes Differential diagnoses Prevalence (%) Size (cm)Non-functioning adenoma 70-80 1-4Hypersecreting tumours
Cortisol secretingAldosterone secretingPhaeochromocytoma
~2010-201-35-10
Variable
Other adrenal tumoursMyelolipomaCysts
5-10<5
Variable
Primary adrenal carcinomas <5 Usually >4
Metastasis from other malignancy 1-5 Variable, usually
<3Infection / granulomas <1 Variable
Young. N Engl J Med 2007Anagnostis et al. Hormones 2009
Ridho et al. Acta Med Indones 2009 Terzolo et al. Eur J Endocrinol 2011
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Introduction • Hormonal evaluation• Imaging
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Hormonal evaluation
Subclinical Cushing’s syndromePhaeochromocytomaConn’s syndrome
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Subclinical Cushing’s syndrome (SCS)• For all patients with incidentaloma• Features
– Most frequent endocrine dysfunction in patients with adrenal incidentalomas
– Lack typical signs / symptoms but may have metabolic disturbances
• Difficult demonstration of SCS in clinical practice – Spectrum and heterogenicity of clinical presentation – may
be overlooked– Flexible approach with biochemical test and clinical
judgement
Anagnostis et al. Hormones 2009Terzolo et al. Eur J Endocrinol 2011
Chiodini. J Clin Endocrinol Metab 2011
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SCS• Blood (screening)
– Overnight dexamethasone suppression test (ONDST) – 1mg oral dexamethasone nocte
• Threshold: 50nmol/l or 1.8µg/dl• Values
– <50nmol/l or <1.8µg/dl – clearly exclude Cushing’s– >138nmol/l or >5µg/dl – likely Cushing’s– 50-138nmol/l or 1.8-5µg/dl – indeterminate (DDx: alcoholism,
stress, obesity, depression etc.)• Sensitivity: 91%
• Urine (screening)– 24-hr urinary free cortisol (UFC)
• Normal: <250nmol/24hr
Young. N Engl J Med 2007Anagnostis et al. Hormones 2009
Terzolo et al. Eur J Endocrinol 2011
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SCS• Confirmatory test
– Low dose dexamethasone suppression test (LDDST) – 0.5mg oral dexamethasone Q6H for 48hrs
• For indeterminate results after ONDST• Check serum cortisol / 24hr UFC• Normal if serum cortisol <50nmol/l or >50% fall in serum
and/or urine cortisol• Sensitivity 98%, specificity 80-98%
Young. N Engl J Med 2007Anagnostis et al. Hormones 2009
Terzolo et al. Eur J Endocrinol 2011
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Phaeochromocytoma • For all patients with incidentaloma• Urine (screening)
– 24hr urine fractionated metanephrines and catecholamines– Sensitivity / specificity: 90-98%
• Blood (screening)– Plasma free metanephrines if urine test normal and high
suspicion– Sensitivity: 96-100%, specificity 85-89%
• Normal screening tests exclude diagnosis
Sawka et al. J Clin Endocrinol Metab 2003Young. N Engl J Med 2007
Terzolo et al. Eur J Endocrinol 2011
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Conn’s syndrome• For all hypertensive and/or hypokalaemia patients
with incidentaloma• Blood (screening)
– Ambulatory morning plasma aldosterone (PA) + plasma renin activity (PRA)
aldosterone / renin ratio (ARR) ≥20 confirm diagnosis (PA ng/dl; PRA ng/ml/hr)
• Confirmatory test– Aldosterone suppression test
• Saline infusion test• 24hr urinary aldosterone excretion test with high salt diet
– Adrenal venous sampling
Young. N Engl J Med 2007Terzolo et al. Eur J Endocrinol 2011
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Imaging
Ultrasound Computed tomographyMagnetic resonance imagingPositron emission tomographyScintigraphyImage guided fine needle aspiration
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Ultrasound • Advantage
– Good reliability for mass size and growth
– Non-invasive– No radiation
• Drawbacks– Operator dependent– Difficult visualisation
especially if obesity / overlying gas
– Cannot differentiate between benign and malignant masses
• Sensitivity: 65% for <3cm and 100% for >3cm
• Larger role in follow-up Fontana et al. Urology 1999Friedrich-Rust et al. Am J Roentgenol 2008
Terzolo et al. Eur J Endocrinol 2011
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Computed tomography (CT)• Cornerstone of imaging studies• Features of malignancy
– Calcifications – Heterogenicity / tumour necrosis– Irregular border– Invasion / displacement of adjacent structures– Size
Anagnostis et al. Hormones 2009Nieman. J Clin Endocrinol Metab 2010
Terzolo et al. Eur J Endocrinol 2011Palmeiro et al. SEDIA 2012
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CT – Plain • Hounsfield unit (HU)
– Up to 70% of adenoma – abundant fat
– Benign lesion <10HU• Sensitivity 96-100%• Specificity 50-100%
– Indeterminate lesions >10HU • Need further characterisations• 30% adenoma with >10HU
– Lipid-poor Another parameter
Boland et al. Am J Roentgenol 1998Hamrahian et al. J Clin Endocrinol 2005
McDermott et al. Best Pract Res Clin Endocrinol Metab 2012Palmeiro et al. SEDIA 2012
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CT – Contrast • Delayed washout
– Washout at 10-15min– >50% washout: typical in
adenoma– <50% washout (i.e. more
contrast retention): malignancy / phaeo-chromocytoma
– Sensitivity 98%, specificity 100%
– Cost-effective
Caoili et al. Am J Roentgenol 2000Pena et al. Radiology 2000
Terzolo et al. Eur J Endocrinol 2011Palmeiro et al. SEDIA 2012
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Magnetic resonance imaging (MRI)• Characteristics Type T1 T2Non-functioning adenoma
Hypo-/Iso-intenseliver Iso-intenseliver
Hypersecreting tumoursCortisol secretingAldosterone
secreting
Phaeochromocytoma
Hypo-/Iso-intenseliverHypo-/Iso-intenseliverHyper-/Iso-intenseliver
Hyper-intensePrimary adrenal carcinomas Hyper-intense
Metastasis Iso-intenseliverMyelolipoma Hypo-intenseCysts Heinz-Peer G et al. Am J Roentgenol 1999
Anagnostis et al. Hormones 2009Terzolo et al. Eur J Endocrinol 2011
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MRI – Chemical shift imaging• Detect lipid content in adrenal tissue• Differentiate adenoma (lipid-rich) from non-adenoma• Lipid-rich adenoma: loss of signal intensity in out-of-
phase image – Compare with spleen (to avoid confounding of liver
steatosis) – Sensitivity: 84-100%; specificity: 92-100%
• Comparable to CT in sensitivity / specificity– No additional benefit to CT
Outwater et al. Am J Roentgenol 1995Israel et al. Am J Roentgenol 2004
Haider et al. Radiology 2004Aron et al. Best Pract Res Clin Endocrinol Metab 2012
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Positron emission tomography (PET)• 2-[fluorine-18]-fluoro-2-deoxy-D-glucose (18F-FDG)
– Increase glucose uptake by malignant lesions• Highly accurate for differentiation between benign
and malignant lesions– Sensitivity 93-100%, specificity 80-100%
• Necrotic / haemorrhagic lesions poor FDG uptake false negative
– Further improves sensitivity / specificity if +CT– Further improves yield of CT scan
Metser et al. J Nucl Med 2006Caoili et al. Acad Radiol 2007
Boland et al. Am J Roentgenol 2009Groussin et al. J Clin Endocrinol Metab 2009
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PET• Maximum standardised uptake
value (SUVmax) < 1.60 highly predictive of benign lesions
• Indicated if inconclusive CT findings
• Drawbacks– Not reliable for lesions < 1cm– Cannot differentiate among
malignant lesions
Metser et al. J Nucl Med 2006Caoili et al. Acad Radiol 2007
Boland et al. Am J Roentgenol 2009Groussin et al. J Clin Endocrinol Metab 2009
Boland. Am J Roentgenol 2011
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Scintigraphy • [I-131]-6-beta-iodomethyl-norcholesterol (NP-59) /
[Se-75]-selenomethyl-19-norcholesterol scan– Morphological and functional imaging of cortex– Bind to specific low-density lipoproteins stored in
adrenocortical lipid droplets – Normal uptake: 5days after tracer injection
• Hypersecretion of cortisol / aldosterone / sex hormone: uptake before 5days
• Malignancies (primary / secondary): cold masses as most not secreting
– Sensitivity: 71-100%, specificity: 50-100%
Gross et al. J Nucl Med 1994Ilias et al. Endocr Relat Cancer 2007
Anagnostis et al. Hormones 2009
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Scintigraphy• [I-123]-metaiodo-benzylguanidine (MIBG) scan
– Morphological and functional imaging of medulla– Noradrenaline analogue taken up by phaeochromocytoma
cells– Sensitivity: 91-97%, specificity: 87-98%
• Octreotide scan– Lower sensitivity than MIBG scan
Jacobson et al. J Clin Endocrinol Metab 2010
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Fine needle aspiration (FNA)• Not recommended • Cannot differentiate adenoma from carcinoma• Associates with complications: 2.8-14%
– Pneumothorax– Bleeding
• Haemothorax • Adrenal haematoma• Haematuria
– Hypertensive crisis due to bleeding in phaeochromocytoma– Needle track seeding of tumour cells
Young. N Engl J Med 2007Anagnostis et al. Hormones 2009
Terzolo et al. Eur J Endocrinol 2011
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Summary – Imaging Imaging modalities Sensitivity
(%)Specificity (%) Features
USG65 (<3cm); 100 (>3cm)
Operator dependentCannot differentiate nature of lesion
Plain CT – HU 96-100 50-100 Malignancy: Higher HU
Contrast CT – Washout 98 100
Malignancy: Less washout, heterogenous, invasion, size
MRI – Chemical shift imaging
84-100 92-100 Malignancy: Persistent signal intensity
PET 93-100 80-100 Malignancy: More FDG uptake
Scintigraphy NP-59MIBG
71-10091-97
50-10087-98
Malignancy: Cold lesionsFunctioning: More tracer uptake
Image guided FNA 81-96 99-100Cannot differentiate adenoma from carcinomaComplications
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Risks of adrenal incidentaloma
Hypersecreting ?
Malignant?
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Malignant potential• Size: Chance of malignancy
<4cm 4-6cm >6cm
NIH Consens State Sci Statements 2002Bulow B et al. Eur J Endocrinol 2006
2% 6% 25%
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Hormonal oversecretion• Autonomous hormonal oversecretion <1%
– Most common: cortisol secretion SCS– Very rare: catecholamine (phaeochromocytoma) /
aldosterone (Conn’s syndrome)
HypersecretingNon-functioning
Barzon et al. Eur J Endocrinol 2003Terzolo et al. Eur J Endocrinol 2011
Cushing's syndromePhaeochromocytoma Conn's syndrome
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Management
SurgeryFollow-up
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Follow-up and indication for surgery• Malignant potential
– No consensus / specific recommendations on serial imaging protocol
– Recommend CT scan at 6, 12, 24months– To closely monitor tumour behaviour through imaging
• Suspicious of malignancy on imaging • Size >4cm (risk of malignancy starts to increase significantly
when size >4cm)• Size ≥1cm / year on imaging
NIH Consens State Sci Statements 2002Grumbach et al. Ann Intern Med 2003
Young. N Engl J Med 2007Zeiger et al. Endocr Prac 2009
Terzolo et al. Eur J Endocrinol 2011
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Follow-up and indication for surgery• Hormonal hypersecretion
– Recommend hormonal evaluation annually for 4years– Hormonal profile normal at diagnosis can become
autonomous during subsequent 4years– Risks of hyperfunction plateau after 4years
NIH Consens State Sci Statements 2002Grumbach et al. Ann Intern Med 2003
Young. N Engl J Med 2007Zeiger et al. Endocr Prac 2009
Terzolo et al. Eur J Endocrinol 2011
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Adrenalectomy • Laparoscopic adrenalectomy
– Gold standard since 1992– Advantages vs open surgery
• Less blood loss• Lower morbidity• Shorter hospital stay• Faster functional recovery
Gagner et al. N Engl J Med 1992Lai G et al. Surg Oncol 2003
Grumbach et al. Ann Intern Med 2003Terzolo et al. Eur J Endocrinol 2011
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Adrenalectomy
Karanikola et al. Tohoku J Exp Med 2010Nigri et al. Surgery 2013
Lee et al. Ann Surg Oncol 2013
• No consistent superiority between different laparoscopic approaches (anterior or lateral transperitoneal; posterior retroperitoneal)– Bulky / malignant – transperitoneal
• Metastasis / vascular pedicle especially for large tumour– Unilateral benign tumour – mostly posterior retroperitoneal
• Direct access to adrenal without handling of intraperitoneal organs
• Avoidance of previous intraabdominal adhesions – Bilateral – transperitoneal
• Can assess both lesions at the same time without the need to reposition the patient
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Adrenalectomy • Contraindications for minimal invasive surgery
– Local tumour invasion of surrounding tissue or metastatic disease
– Size >12cm
Ramacciato et al. Surg Endosc 2008Zografos et al. JSLS 2009
Karanikola et al. Tohoku J Exp med 2010Carter et al. Endocr Pract 2012
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Young. N Engl J Med 2007
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End