Abstract

The paper by Arlt et al. (1) on detecting malignancy in adrenocortical tumors illustrates well the benefits of cooperation between centers and of a systematic approach to classifying data, in this case on urinary steroid profiles. We have long used urine steroid profiling as a means of detecting steroid secretion by adrenocortical tumors (2), but definitive guidance on its accuracy in differentiating malignancy has previously been limited to small patient numbers or a limited set of steroid markers.

Histological classification systems have already served this field well. They continue to evolve (3) and are undoubtedly the best indicator currently available of malignant potential, but there is room to improve differentiation of adrenocortical adenoma from nodular hyperplasia (4).

We wish to offer some pointers on how these approaches could develop further. First, it is important to apply very clear criteria for identifying adrenal neoplasms: Arlt et al. describe their classification as being based on histology and presence of metastases, but only 36/147 cases were given a Weiss score, so it was not possible to judge the performance of their steroid profile findings against this gold standard. In the absence of histology, there are two potential confusing elements: (a) some adrenocortical adenomas might represent dominant nodules in nodular hyperplasia that can remain undetected because of the limited resolution of imaging for sub-centimeter lesions; and (b) not all non-metastatic lesions are necessarily benign, but they could not be diagnosed unless they were evaluated histologically. It would be useful to see the outcome of steroid metabolomic analysis by Arlt et al. applied only to those defined histologically. Second, the greatest need lies in determining the prognosis of those with adrenocortical carcinomas (ACC) on histology that do not have secondaries at presentation. Arlt et al. report no difference of steroid metabolome between those with and without secondaries.

Continuing surveillance of ACC patients initially without secondaries may enable histological and steroid pointers to become recognized. Third, although a large set (32) of steroid metabolites was considered, some reported markers of ACC (e.g., Pregnene-3α,16α,20α-triol, ref. 5) were not included. It has been our experience that close examination of profiles obtained unselectively by full scan gas chromatography-mass spectrometry (GC-MS) often reveals new and unexpected markers of ACC and these can prove crucial for detection of relapse. A system akin to the Weiss system of histological scoring, based on number of steroid markers abnormally increased, may also prove to be more accurate and easier for referral laboratories to apply. What is already clear is that if surgical removal of a mass in the adrenal cortex is contemplated, determining presence or absence of markers in a urine steroid profile should be part of the work up.

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Published: Letter to J Clin Endocrinol Metab. (2012) published online Feb 9th.