Management of the Clinically Inapparent Adrenal Mass (Incidentaloma)

The adrenals are triangular glands that sit atop each kidney. They influence or regulate the body's metabolism, salt and water balance, and response to stress by secreting various hormones. Based on autopsy studies, adrenal masses are among the most common tumors in humans. At autopsy, an adrenal mass is found in at least 3% of persons older than age 50 years. Most adrenal masses cause no health problems. A small proportion, however, can lead to many serious hormonal diseases; approximately 1 of every 4000 adrenal tumors is malignant. Clinically inapparent adrenal masses are discovered inadvertently during diagnostic testing or treatment for other clinical conditions that are not related to suspicion of adrenal disease; thus, they are commonly known as incidentalomas. The definition of incidentaloma excludes patients undergoing imaging procedures as part of staging and work-up for cancer. Improvements in abdominal imaging techniques and technologies have increased detection of adrenal incidentalomas. Increasing clinical and scientific interest is reflected in a 20-fold increase in publications about this condition over the past three decades. When detected, clinically inapparent adrenal masses raise challenging questions for physicians and their patients. Diagnostic evaluation determines whether the lesion is hormonally active or nonfunctioning and whether it is malignant or benign. The test results will influence whether the mass is removed surgically or treated nonsurgically. Because the prevalence of these masses increases with age, appropriate management of adrenal tumors will be a growing challenge in our aging society. Over the past three decades, new information has become available regarding the epidemiology, biology, screening, treatment, and follow-up of adrenal tumors. For example, recent refinements in the field of minimally invasive surgery have made laparoscopic adrenalectomy a more frequently used method for removing adrenal masses. Recent reports suggest that up to 20% of patients with adrenal incidentaloma have some form of subclinical hormonal dysfunction and may represent a population at higher risk for metabolic disorders and cardiovascular disease. It is important to determine whether groups of patients with subclinical disease benefit from treatment. The psychological effect of the patient's knowing that he or she harbors an adrenal incidentaloma, an incompletely understood clinical problem, merits investigation. A 2.5-day National Institutes of Health (NIH) state-of-the-science conference, Management of the Clinically Inapparent Adrenal Mass (Incidentaloma), was convened on 46 February 2002 to explore and assess the current knowledge regarding adrenal incidentalomas, so that health care providers and the general public can make informed decisions about this important public health issue. After 1.5 days of expert presentations and questions and public discussion by members of the panel and the audience of interested attendees on incidental adrenal masses, an independent, nonfederal panel weighed the evidence and drafted a statement that was presented on the third day of the conference. Expert presentations and the panel's statement addressed the following questions: 1) What are the causes, prevalence, and natural history of clinically inapparent adrenal masses? 2) Based on available scientific evidence, what is the appropriate evaluation of a clinically inapparent adrenal mass? 3) What criteria should guide the decision on surgical versus nonsurgical management of these masses? 4) If surgery is indicated, what is the appropriate procedure? 5) What is the appropriate follow-up for patients for each management approach? and 6) What additional research is needed to guide practice? The panel's draft statement was posted on the NIH Consensus Program Web site (consensus.nih.gov) on 6 February 2002. The primary sponsors of this meeting were the National Institute of Child Health and Human Development and the NIH Office of Medical Applications of Research. Cosponsors included the National Cancer Institute and the National Institute of Diabetes and Digestive and Kidney Diseases. 1. What are the Causes, Prevalence, and Natural History of Clinically Inapparent Adrenal Masses? Clinically inapparent adrenal masses are detected incidentally with imaging studies conducted for other reasons. They may be clinically important because some are caused by adrenal cortical carcinomas (estimated prevalence, 4 to 12 per million), which have a high mortality rate. The other clinical concern is hormone overproduction from pheochromocytomas, aldosteronomas, and subclinical hypercortisolism, which may be associated with morbidity if untreated. Prevalence of Clinically Inapparent Adrenal Masses In autopsy series, the prevalence of clinically inapparent adrenal masses is about 2.1%. Because of increased use of noninvasive high-resolution imaging technology, clinically inapparent adrenal masses are being recognized more often. Estimates range from 0.1% for general health screening with ultrasonography to 0.42% among patients evaluated for nonendocrinologic symptoms to 4.3% among patients who have a previous diagnosis of cancer. In addition to source of data (autopsy versus clinical series) and reasons for imaging (cancer work-up, nonendocrinologic symptoms, and general health screening), the prevalence of clinically inapparent adrenal masses varies with age. The prevalence of clinically inapparent adrenal masses detected at autopsy is less than 1% for patients younger than 30 years of age and increases to 7% in patients 70 years of age or older. Many of these lesions detected at autopsy are very small. More patients with clinically inapparent adrenal masses are women. This probably reflects the sex distribution of the population undergoing imaging procedures. Autopsy studies or general health examinations show no evidence of difference in prevalence between men and women. There is insufficient information to determine whether the prevalence of clinically inapparent adrenal masses differs by the initial diagnostic test. Causes of Clinically Inapparent Adrenal Masses Clinically inapparent adrenal masses can be benign or malignant. These include adenomas, pheochromocytomas, myelolipomas, ganglioneuromas, adrenal cysts, hematomas, adrenal cortical carcinomas, metastases from other cancers, and other rare entities. The distributions of the pathologic origins of clinically inapparent adrenal masses vary with several clinically important factors, including cancer history and mass size. Three fourths of clinically inapparent adrenal masses among patients with cancer are metastatic lesions. In contrast, two thirds of clinically inapparent adrenal masses in populations with no history of cancer are benign tumors. Prevalence of primary adrenal cortical carcinoma is clearly related to the size of the tumor. Adrenal cortical carcinoma accounts for 2% of tumors that are 4 cm or less, 6% of tumors that are 4.1 to 6 cm, and 25% of tumors that are greater than 6 cm. Among unselected patients and those with nonendocrinologic symptoms, clinically inapparent adrenal masses are most often nonfunctioning tumors (approximately 70%). Approximately 5% to 10% of patients being evaluated for nonendocrinologic symptoms have subclinical hypercortisolism (sometimes called subclinical Cushing syndrome). The percentage of patients with subclinical hypercortisolism depends on the testing methods and cortisol levels achieved after dexamethasone suppression. The distribution of clinically inapparent adrenal masses derived from surgical series will overestimate the prevalence of adrenal cortical carcinoma, since suspicion of adrenal cortical carcinoma is an indication for surgery. Moreover, the reported frequency of adrenal cortical carcinomas is derived from highly selected patient populations and does not reflect the prevalence rates seen in population-based studies. The age and sex of the patient do not seem to help predict the presence of adrenal cortical carcinoma. Distribution estimates from autopsy studies are not biased by surgical indications but may not reflect the risk for adrenal cortical carcinoma among the subset of people undergoing abdominal imaging studies. A precise estimate of the risk for adrenal cortical carcinoma that could guide clinical decision making may not be possible. Almost all the reported large studies used imaging equipment that is now considered obsolete. The use of contemporary equipment may increase the prevalence of detected clinically inapparent adrenal masses and enhance our ability to differentiate adrenal cortical carcinomas from adenomas. In addition, the literature comprises mainly small, retrospective studies with variable definitions of clinically inapparent adrenal masses, which cause variation in the relative proportions of adrenal pathologic classifications. Natural History of Clinically Inapparent Adrenal Masses The observed natural history of clinically inapparent adrenal masses varies, depending on the composition of the study sample and the size and pathologic classification of the adrenal mass. Patients with or without a previous cancer diagnosis found to have adrenal gland metastatic lesions will have a clinical course defined by the stage, grade, and site of the primary tumor. Usually, large clinically inapparent adrenal masses (>6 cm) are treated surgically. Approximately 25% of masses greater than 6 cm in diameter are adrenal cortical carcinomas, and these patients have poor clinical outcomes. Most studies report less than 50% 5-year overall survival for adrenal cortical carcinoma, and several report less than 50% 2-year overall survival. Inconclusive evidence suggests that adrenalectomy at stage 1 or 2 may improve the survival rate. Follow-up of patients with nonfunctioning adrenal masses suggests that 5% to 25% of masses increase in size by at least 1 cm. The threshold for clinically significant