Study of urine steroid profiles by gas chromatography-mass spectrometry in patients with adrenocortical cancer in the course of treatment

Background: Adrenocortical carcinoma (ACC) is a rare and aggressive disease. There are only few studies evaluating the diagnostic value of gas chromatography-mass spectrometry (GC-MS) for detection of ACC recurrence after surgery. It is necessary to conduct an in-depth study to search for the most informative markers of the disease relapse.

Aim: To study urine steroid metabolism by GC-MS during treatment to identify early signs of metastatic disease and relapse.

Materials and methods: Thirty nine (39) ACC patients were examined before and after surgery, in the early postoperative period (< 1 year) and late postoperative period (at 2 to 5 years). Ten (10) patients were disease-free at less than 1 year after surgery. Twenty nine (29) patients had metastases in lungs and other organs: 14, within 1 year after surgery, and 15, at 2 to 5 years. The control group included 25 patients with nonfunctioning adrenocortical adenomas (NAA) without malignant characteristics at histological examination. Urine steroid profiles were assessed with a gas chromatograph-mass spectrometer Shimadzu GCMS-QP2020.

Results: As assessed by GC-MS, 16 major ACC biomarkers were found before surgery, including etiocholanolone, dehydroepiandrosterone (DHEA) and its metabolites, pregnanediol, pregnanetriol, 5-ene-pregnenes, and tetrahydro-11-deoxycortisol (THS). Their urine excretion was increased compared to that in the patients with NAA (р < 0.002). A non-classic 5-ene-pregnene, 3β,16,20-pregnenetriol (3β,16,20-dP3), was identified, with its urine excretion of > 500 mcg/day that was typical for ACC patients. After surgery, decreased urinary excretion of THS (р < 0.0001) and 3β,16,20-dP3 (р < 0.0001), increased 3α,16,20-dP3/3β,16,20-dP3 ratio (р = 0.003), compared to those before surgery, were indicative of the absence of any metastases. No difference of urine THS excretion and 3α,16,20-dP3/3e,16,20-dP3 ratio from the corresponding values before surgery (p > 0.05) is a sign of metastatic diseases in the ACC patients at less than 1 year after the surgery, of the disease relapse at 2 to 5 years, and of the disease relapse after chemotherapy. In addition, in the ACC patients with metastatic disease within 1 year after surgery, increased progestogen urine excretion was found. Urine excretion of DHEA and its metabolites in the patients with the disease relapse after chemotherapy was not different from those in the ACC patients before surgery (p > 0.05).

Conclusion: Determination of urine excretion of THS, DHEA and its metabolites, etiocholanolone, 5-ene-pregnenes, 3β,16,20-dP3, and 3α,16,20-dP3/3β,16,20-dP3 ratio by GC-MS is of utmost importance in the monitoring of treatment for ACC and early diagnosis of the disease progression.