Incidentally, You Have a Tumor on Your Adrenals

Abstract & Commentary

By Allan J. Wilke, MD, MA, Chair, Department of Integrative Medicine, Ross University School of Medicine, Commonwealth of Dominica. Dr. Wilke has no financial relationship to this field of study.

Synopsis: Most adrenal masses found inadvertently as part of an investigation for another illness are benign. The work-up for an adrenal incidentaloma is presented.

Source: Ng VW, et al. Evaluation of functional and malignant adrenal incidentalomas. Arch Intern Med 2010;170:2017-2020.

The term "adrenal incidentaloma" first appeared in the medical literature in 1982.1 Since then, there has been considerable discussion as to the work-up of these coincidentally discovered masses. The current article describes the review that a tertiary endocrine center in Hong Kong undertook to study the clinical characteristics of their patients with adrenal incidentalomas (AIs). They retrospectively reviewed all of their cases from 2000 to 2007, which involved 139 ethnically Chinese patients, 53 men and 86 women, with an average age of 57 years. They gathered the usual demographic data and also looked for signs and symptoms related to hormonal hypersecretion, such as hypertension or diabetes mellitus, or malignant adrenal neoplasm. They followed a protocol for the work-up of these masses. Any mass that was initially detected by ultrasound was confirmed by computed tomography (CT) or magnetic resonance imaging. The hormonal evaluations included an overnight dexamethasone suppression test, 24-hour urine catecholamine collection, and, if the patient was hypertensive, the ratio of plasma aldosterone to plasma renin. If any of these tests were positive, they performed more selective follow-up studies. Patients determined to have benign nonfunctional incidentalomas were reevaluated every 6-12 months with laboratory and radiologic evaluations.

At baseline, the patients did not differ in terms of age, presence of hypertension or diabetes mellitus, or size of the lesions (median size, 2.5 cm; range, 0.8-19.8 cm). One hundred thirteen patients (82%) had benign lesions, 15 (11%) had malignant lesions, and the remaining 11 were uncategorized. Of the benign adenomas, 52 were functional with 27 excreting cortisol, 12 aldosterone, 12 catecholamines, and one that excreted a combination of cortisol and aldosterone. Only five of 27 patients with cortisol-excreting tumors had signs or symptoms of Cushing's disease. Only five of 12 patients with excess catecholamine excretion had hypertension and only six were symptomatic. Of the 15 malignant lesions, six were primary adrenal carcinomas (four nonfunctional, two secreting cortisol), eight adrenal metastases, and one adrenal lymphoma. Four of the six patients with primary adrenal carcinoma died, three related to their illness. Two patients had stage I disease and had been tumor-free for at least 5 years after adrenalectomy.

Commentary

AIs are common. Recent prospective studies in Sweden2 and Italy3 estimate a prevalence of 4.5%. This is similar to the 3% rate of adrenal tumors noted on autopsy of people older than 50 years. The prevalence increases with age, reaching 7% in people older than age 70.4

This study has weaknesses. Foremost are its retrospective design and setting in a tertiary endocrine center in Hong Kong, whose clientele was entirely ethnically Chinese.

The primary care physician presented with the patient with an AI has two questions that must be answered: Is the tumor benign or malignant? Is the tumor functional? Tumors that are malignant or functional should be removed. A recent review recommends the following:5

1. Biochemical testing for pheochromocytoma with plasma or urinary catecholamine measurements,

2. Biochemical testing for hyperaldosteronism in hypertensive patients,

3. Biochemical testing for hypercortisolism in patients with glucose intolerance, weight gain, and unexplained osteopenia,

4. Annual or biennial imaging and biochemical reevaluation for benign lesions, and

5. Repeat evaluation for growth after 3-12 months, with subsequent testing intervals based on the rate of growth, for more indeterminate tumors.

The determination of benign vs malignant tumors is more difficult. There are features on CT (Hounsfield units < 10, contrast washout > 50%, and size < 3 cm) that favor benignity. Lack of functioning does not, however, as was demonstrated in the current study. Intuitively, percutaneous adrenal biopsy would provide the answer. However, a recent review from a U.S. tertiary care center would suggest otherwise.6 Of 30 biopsies performed for isolated adrenal incidentalomas that were radiographically suspicious, only five were malignant. The NIH consensus statement recommends surgical removal of lesions > 6 cm and close follow-up of those between 4 cm and 6 cm.

Some physicians (and, perhaps, their patients) might ask, "Is this trip necessary?" The authors of this review would answer, "Yes," and would cite primary aldosteronism as the most common cause of secondary hypertension and the improvement their patients with subclinical Cushing's syndrome and hypertension, diabetes, or obesity had with successful surgical treatment and weight reduction. They also cite the lethality of silent pheochromocytomas, especially during surgery or percutaneous biopsy. Operative mortality for adrenalectomy is low (2%). Of course, if the adrenal mass should prove to be a metastasis from a known or unknown primary cancer, there is no benefit to adrenalectomy. As always, a frank discussion between you and your patient, discussing what lies at the end of the work-up and weighing the risks and benefits of adrenalectomy, is paramount.

References

1. Geelhoed GW, Druy EM. Management of the adrenal "incidentaloma." Surgery 1982;92:866-874.

2. Hammarstedt L, et al. Adrenal lesion frequency. Acta Radiol 2010;51:1149-1156.

3. Bovio S, et al. Prevalence of adrenal incidentaloma in a contemporary computerized tomography series. J Endocrinol Invest 2006;29:298-302.

4. NIH state-of-the-science statement on management of the clinically inapparent adrenal mass ("incidentaloma"). NIH Consens State Sci Statements 2002;19:1-25.

5. Nieman LK. Approach to the patient with an adrenal incidentaloma. J Clin Endocrinol Metab 2010;95: 4106-4113.

6. Mazzaglia PJ, Monchik JM. Limited value of adrenal biopsy in the evaluation of adrenal neoplasm. Arch Surg 2009;144:465-470.