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Adrenal incidentalomas

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The term adrenal incidentaloma (AI) is usually defined as an adrenal mass unexpectedly detected through an imaging procedure performed for reasons a priori unrelated to adrenal dysfunction or suspected dysfunction. The preferred approach to their management in terms of diagnosis, follow-up, and treatment remain controversial despite a state-of-the-science conference sponsored by the U.S. National Institutes of Health. Although most experts’ recommendations tend to be relatively minor variations of the conference’s approach, dissenting voices have been heard. Despite their frequent appearance, the challenge remains to recognize and treat the small percentage of AI that do pose a significant risk, either because of their hormonal activity or because of their malignant histology, while leaving the rest alone. Although the differential diagnosis of an incidentally discovered mass is quite extensive, most AIs are non-secreting cortical adenomas. The noninvasive differentiation of benign and malignant lesions depends upon imaging characteristics, and sometimes radiologic diagnosis can be definitive, but often it is not, Among function lesions, autonomous cortisol production seems to be the most common and may be associated with increased cardiovascular risk and clinical features of the “metabolic syndrome.” Follow-up of cases in which a specific diagnosis is not made initially involves assessment for growth and development of hormonal function, but even here, controversy about the extent of evaluation persists.

Introduction

The term adrenal incidentaloma (AI) is usually defined as an adrenal mass unexpectedly detected through an imaging procedure performed for reasons a priori unrelated to adrenal dysfunction or suspected dysfunction. First described more than three decades ago,2, 3, *4 AI has become a common clinical problem, one that poses a challenging management dilemma.5 The challenge is to recognize and treat the small percentage of AI that do pose a significant risk, either because of their hormonal activity or because of their malignant histology, while leaving the rest alone. The preferred approach to their management in terms of diagnosis, follow-up, and treatment remain controversial despite a state-of-the-science conference sponsored by the National Institutes of Health (NIH).1 Although most experts’ recommendations tend to be relatively minor variations of the conference’s approach, dissenting voices have been heard.1, 6, 7, 8, 9, 10, 11, *12, 13, *14 In fact, even the definition is subject to some controversy around the specifics of the phrase a priori. Does the known presence of extra-adrenal cancer itself constitute an appropriate exclusion criterion? What about the fact that the complaints for which the diagnostic imaging was performed may turn out later to be caused by the adrenal mass? Nevertheless, the individual practitioner is left with a myriad of potential hormonal and radiological tests and strategies from which to choose.

Section snippets

The magnitude of the problem

The identification of an adrenal mass as an incidental finding is common.15 It is difficult to know the true prevalence of this entity, because of varied definitions and variability in methods and circumstances of detection i.e., the reasons for the imaging study. The characteristics of the population studied and the radiological techniques used determine the prevalence of clinically inapparent adrenal masses. Thus, estimates of prevalence vary. Prevalence at autopsy ranges from 1.4% to 2.9%.

Differential diagnosis

Although the differential diagnosis of an incidentally discovered mass is quite extensive as shown in Table 1, most AIs are non-secreting cortical adenomas. A systematic review conducted for the NIH State of the Science Conference used a very broad definition of AI and reported that adenomas accounted for 41% of adrenal incidentalomas, metastases 19%, adrenocortical carcinoma 10%, myelolipoma 9%, and pheochromocytoma 8%, with other usually benign lesions, such as adrenal cysts, comprising the

Adrenocortical carcinoma

Clinically diagnosed cases of primary adrenal carcinoma are rare; the estimated prevalence of adrenal carcinoma in the general population is approximately 12 in 1,000,000. These cases have a very poor prognosis. Mean survival is approximately 18 months and 5-year survival is usually <20%. This would suggest that early diagnosis and definitive treatment is critical.17 However, the frequency of adrenal cancer found in series of adrenal incidentalomas, though varying widely, ranges as high as 25%.

Evaluation by imaging techniques

The noninvasive differentiation of benign and malignant lesions depends upon imaging characteristics.22 Although sometimes radiologic diagnosis can be definitive, two important points must be made about studies of imaging techniques (and these points apply to studies of other diagnostic tests). First, studies report sensitivity and specificity in the aggregate. Therefore a study has an accuracy on the average, but may not be correct in any given case. Second, initial descriptions are typically

Evaluation of hormonal functioning

Hypersecretion of glucocorticoids, mineralocorticoids, sex steroids, or catecholamines can produce clinical syndromes, each associated with morbidity and premature mortality. When a hormonal disorder is suspected clinically, appropriate, i.e., targeted, diagnostic testing can proceed apace. However, one should not infer the absence of endocrine activity by the AI solely because of the absence of clinically recognizable signs and symptoms. Biochemical detection of hormonal dysfunction can be

Surgical treatment

One thing can be said for surgery in the case of the incidentally discovered adrenal mass. It is definitive and thus, offers the ultimate solution to the diagnostic and therapeutic dilemma of an adrenal incidentaloma, albeit at the cost of some risk to the patient. When a lesion is found to be hormonally active, surgical treatment can be curative, or at least ameliorative. For lesions whose hormonal activity is clear, appropriate preoperative, intraoperative, and postoperative management can be

Follow-up of incidentalomas

Among the most controversial issues is that of follow-up. Follow-up is done for two reasons: (1) to determine if there is rapid increase in size of a benign-appearing mass, a finding that would prompt surgery to remove a lesion that may be a cancer; and (2) to detect appearance or progression of hormonal activity of the incidentaloma, a finding that would prompt surgery to avert complications of hormonal excess. The most appropriate follow-up strategy is not clear. Most incidentalomas don’t

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