Clinical Information

Approximately 80 million computerized tomography (CT) scans are performed in the United States every year. Adrenal tumors are found incidentally in about 5% of patients undergoing abdominal CT. Most of these tumors will be benign, but a small fraction are adrenal cortical carcinomas (ACC), a cancer with high mortality and frequent recurrence. Even for localized disease, the 5-year survival rates do not exceed 65%, while distant spread is associated with a greater than 90% mortality rate. Early diagnosis of a malignant adrenal mass is therefore imperative to assure timely and appropriate therapy.

Unfortunately, CT imaging alone is very limited in its ability to distinguish benign from malignant adrenal tumors since only very small and hypodense lesions can be easily dismissed as benign. The sizeable group of patients with larger or denser tumors ends up with an arduous workup that frequently includes additional imaging studies, hormonal testing, and biopsy. However, even the latter has both a high diagnostic false-positive and false-negative rate, and ultimately the tumor is often resected, sometimes unnecessarily. On the other hand, the delays due to the diagnostic work might compromise optimal care for those tumors that prove malignant.

In addition, patients who are believed to probably not have adrenal cancer after their workup, and those who opt out of surgery, often still require long-term follow up with regular re-imaging and repeated hormone testing, with resultant radiation exposure and high healthcare costs.

This adrenal mass panel is a noninvasive and more accurate test to diagnose malignant adrenal tumors, via urinary steroid profiling. It differentiates ACC, a rare and lethal tumor, from benign adrenocortical adenomas (ACA), including those that overproduce corticosteroids, or mineral steroids, or sex steroids, or those that are hormonally inactive. The test utilizes both clinical and laboratory data. The clinical parameters are age at diagnosis and sex of the patient, the size of the tumor by CT scanning and its CT density in Hounsfield units, whether it was detected incidentally or not, and whether there is evidence of hormone overproduction. All of this data are readily available for almost all patients with an adrenal mass and are used by an algorithm to calculate the pretest probability of having ACC. The steroid profile testing is then performed, and the results are added into the risk calculation algorithm to generate an integrated probability. The final result will provide the referring physicians a highly accurate probability for ACC and will thereby facilitate the optimal choice of further investigation, if any, based on an informed discussion between doctor and patient. In addition, it allows, albeit with lesser accuracy, the detection of malignant adrenal tumors that are not ACCs.

Finally, standalone steroid profiles can be performed for the purpose of offering the diagnosis of complex assessment of steroidal disorders, disease monitoring of patients with ACC, and for novel investigations, such as biopharma studies.

Understanding the Adrenal Glands:

The human body has 2 adrenal glands, one above each kidney. Adrenal glands influence many processes and functions of the body, mainly through production of 3 types of steroid hormones:

-Mineralocorticoids (eg, aldosterone, which helps control blood pressure)

-Glucocorticoids (eg, cortisol, which is important for metabolism, immune response, and stress)

-Sex steroids (eg, DHEAS, a precursor of testosterone and estradiol)

These steroids are all synthesized from cholesterol via enzymes in the adrenal glands. In benign ACA, near-normal levels of precursor and bioactive steroids are produced. By contrast, ACC frequently shows abnormal patterns of steroid production. By measuring 25 different steroid metabolites, even subtle abnormalities can be detected. This is the basis for the assessment capability of profiling 25 steroids. In addition, catecholamines-the "flight or fight hormones"-are also synthesized in a different portion of the adrenal glands. This portion is not examined in the ACC panel.

Epidemiology of Adrenal Tumors:

Adrenal masses are found in 1% to 5% of the adult population. The prevalence increases with age, to around 10% in 70-year-old patients.

Although the majority of these tumors are benign, around 30% of adrenal tumors (>4cm) are malignant (half are represented by ACC), and the survival rate for these patients is very poor unless detected early.