an approach to the adrenal incidentaloma aimgp clinic lecture series katina tzanetos, 2007
TRANSCRIPT
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An Approach to the An Approach to the Adrenal IncidentalomaAdrenal Incidentaloma
AIMGP Clinic Lecture SeriesKatina Tzanetos, 2007
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ReferencesReferences Arnaldi, G. et. Al. Adrenal Incidentaloma. Braz J Bio Res;
33: 2000. Bornstein, S. (moderator) et al. Adrenalcortical Tumours:
Recent Advances in Basic Concepts and Clinical Management. Ann Int Med. 1999; 130: 759.
Grumback, M. et al. Management of the Clinically Inapparent Adrenal Mass. Ann Int Med. 2003; 138: 424.
Pacak, K. et al. Recent Advances in Genetics, Diagnosis, Localization, and Treatment of Pheochromocytoma. Ann Int Med. 2001; 132: 315.
Westphal, S. Diagnosis of Pheochromocytoma. Am J Med Sci. 2005; 329: 18.
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Case StudyCase Study
70 y.o. female who had a CT of the abdomen post-appendectomy for post-operative fever that subsequently resolved
Incidental finding of a 3-cm mass on her right adrenal gland
Pt feels well with no specific complaints at 3-months post-surgery
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Take a minute to discuss…Take a minute to discuss…
What is your differential diagnosis for this mass?
What aspects of the history and physical examination would you focus on in this patient?
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Take a minute to discuss…Take a minute to discuss…
On further questioning: After a thorough history and physical examination
she is completely asymptomatic and your physical exam is unremarkable.
What investigations would you order? What advice would you give the patient? What sort of follow-up would you recommend?
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Incidentaloma –Incidentaloma –Prevalence and CausesPrevalence and Causes
Prevalence:– Autopsy series:
3% in those > 50 y < 1% for those < 30 y and 7% in those > 70 y
– CT series: 1-5% of patients imaged
Causes: – Adrenal cortex: adenoma, nodular hyperplasia, carcinoma– Adrenal medulla: pheochromocytoma, ganglioneuroma– Metastases or primary lymphoma– Other: lipoma, neurofibroma, fibroma, hemangioma,
angiosarcoma, cysts, amyloid, cryptococcosis, granuloma
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Incidentaloma –Incidentaloma –Prevalence and CausesPrevalence and Causes
Of those investigated:– Malignant:
Frequency of cancer varies among series from 0-35%
In largest series of 1000 pts, 47 pts had clinically-silent cancer
– Functioning: Among those with no symptoms, > 70% are non-
functioning
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Incidentaloma - ApproachIncidentaloma - Approach
Main purpose of history, physical and lab investigations is to determine:
Is the tumour producing hormones?Is the tumour likely to be malignant?
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Hormonal Evaluation -Hormonal Evaluation -PheochromocytomaPheochromocytoma
90% are located in the adrenals 5% incidence of malignancy, but high risk of
cardiovascular morbidity and mortality Predisposition to pheochromocytoma: MEN-2,
von Hippel Landau disease, Neurofibromatosis Classic triad of symptoms: headache, palpitations
and sweating– In pt with hypertension, symptom complex has
specificity of 93.8% and sensitivity of 90%
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Hormonal Evaluation - Hormonal Evaluation - PheochromocytomaPheochromocytoma
Substance Sensitivity Specificity
Plasma free metanephrines 99% 89%
Plasma catecholamines 85% 80%
Urine catecholamines 83% 88%
Urine total metanephrines 77% 94%
Urine VMA 63% 94%
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Hormonal Evaluation - Hormonal Evaluation - PheochromocytomaPheochromocytoma
Plasma metanephrines recommended as initial test due to uniquely high sensitivity
False-positive result can be refuted by further testing – Beyond scope of this talk, but consider false-positive in
those with only marginal increase in plasma metanephrines
– See article by Pacak et al for details
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Hormonal Evaluation - Hormonal Evaluation - Glucocorticoid-Secreting MassGlucocorticoid-Secreting Mass
Cortisol is most common substance to be secreted by incidentalomas
Even more common than obvious Cushing’s Syndrome, is subclinical hypercortisolism – Isolated abnormalities that are not automatically
thought of as indicative of Cushings (e.g. syndrome X alone, hypertension alone etc.) or biochemical increases in cortisol with no clinical abnormalities
– Natural history and consequences unclear
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Hormonal Evaluation – Hormonal Evaluation – Cushing’s SyndromeCushing’s Syndrome
Controversy as to best screening test. Can use (note sensitivity and specificity quoted at 100% of the other):
– 24-hr urinary cortisol excretion Sensitivity 45-71% Specificity 73% Definitely abnormal: 3-fold (or more) increase above normal
– 1-mg overnight dexamthasone suppression test Sensitivity 54% specificity 41%
– Circadian rhythm studies promising: High salivary or plasma cortisol at 11pm Sensitivity: serum 96% salivary 93% Specificity: serum 77% salivary 96% (may be much lower
under certain circumstances, e.g. stress, sleep disturbance)
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Hormonal Evaluation – Hormonal Evaluation – Cushing’s SyndromeCushing’s Syndrome
At our institution (special thanks to Dr. R. Silver and Dr. B. Perkins):
– 1-mg overnight dexamethasone suppression (given low pre-test probability)
normal value for cortisol set at 50 to increase sensitivity but at cost of specificity
– 24-hr urine for free cortisol if pt has a high pre-test likelihood of a false positive results (obesity, ETOH, depression) or a higher pre-test suspicion based on clinical assessment
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Hormonal Evaluation – Hormonal Evaluation – Aldosterone-Secreting MassAldosterone-Secreting Mass
Unlikely in absence of hypertension Normokalemia does not exclude (7-38% of pts
with aldosteronism are normokalemic) If pt is hypertensive or hyperkalemic, screen with
aldosterone: renin ratio measured in upright position
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Hormonal Evaluation – Sex-Steroid Hormonal Evaluation – Sex-Steroid Producing TumourProducing Tumour
Carcinomas can produce androgens and have defective steroid biosynthesis enzymes, causing elevated steroid precursors – Ask about virilization or feminization– Measure DHEA-S, urinary 24-hour 17-ketosteroid
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Features Suggestive of MalignancyFeatures Suggestive of Malignancy
Size less than 4 cm likely benign – > 60% are benign adenomas and < 2% are adrenal
carcinomas Size greater than 6 cm increases likelihood of
malignancy– 25% are adrenal carcinomas
Other helpful radiographic features suggestive of malignancy: high CT attenuation (radiograph absorption), border irregularity, non-homogeneity, fast growth rate
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Management of IncidentalomasManagement of Incidentalomas
Remove all tumours that:– Are functioning– Are larger than 4 cm– Have suspicious CT features– Grow rapidly in size
Follow all others– With a repeat CT at 3-6m period then q1y for 3y– Repeat hormonal evaluation after 1 year, then q 1-2y– Length of hormonal follow-up that is ideal has not been
determined
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Back to the Case…Back to the Case…
You review the patient’s CT scan with the radiologist and are re-assured that she has no radiographic high-risk features
After completing a thorough screening evaluation it is all negative
You re-assure the patient At 6m, a repeat CT is unchanged and at 1 year, a
repeat hormonal evaluation is non-worrisome