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An Approach to the Adrenal Incidentaloma AIMGP Clinic Lecture Series Katina Tzanetos, 2007.

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Presentation on theme: "An Approach to the Adrenal Incidentaloma AIMGP Clinic Lecture Series Katina Tzanetos, 2007."— Presentation transcript:

1 An Approach to the Adrenal Incidentaloma AIMGP Clinic Lecture Series Katina Tzanetos, 2007

2 References 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.

3 Case 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

4 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?

5 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?

6 Incidentaloma – Prevalence and Causes Prevalence: – Autopsy series:  3% in those > 50 y 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

7 Incidentaloma – Prevalence 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

8 Incidentaloma - Approach Main purpose of history, physical and lab investigations is to determine: Is the tumour producing hormones? Is the tumour likely to be malignant?

9 Hormonal Evaluation - Pheochromocytoma 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%

10 Hormonal Evaluation - Pheochromocytoma SubstanceSensitivitySpecificity Plasma free metanephrines99%89% Plasma catecholamines85%80% Urine catecholamines83%88% Urine total metanephrines77%94% Urine VMA63%94%

11 Hormonal Evaluation - Pheochromocytoma 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

12 Hormonal Evaluation - Glucocorticoid-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

13 Hormonal Evaluation – Cushing’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)

14 Hormonal Evaluation – Cushing’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

15 Hormonal Evaluation – Aldosterone-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

16 Hormonal Evaluation – Sex-Steroid Producing 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

17 Features 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

18 Management 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

19 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

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