Recurrent Hepatocellular Carcinoma in a Male Affected By 21-Hydroxylase Deficiency: A Role for  Hypertestosteronemia?

Presentation Number: SAT 363
Date of Presentation: April 1st, 2017

Antonio Mancini*1, Sebastiano Raimondo1, Carmine Bruno2, Giulio Olivieri1, Edoardo Vergani2, Giuseppe Macis2, Laura Riccardi2, Francesca romana Ponziani2 and Maurizio Pompili2
1Catholic University of the Sacred Heart, Rome, Italy, 2Catholic University of the Sacred Heart


Background: Hepatocellular carcinoma (HCC) is one of the most common fatal cancers in the world. A possible role among ethiologic factors is attributed to androgens. Hepatocytes exhibit androgen receptors and a cell proliferation stimulus is exerted by testosterone (T) or dihydro-T. This association is present even after adjustment for the presence of HBV, HCV, cirrhosis, alcohol consumption and smoke.

Case report: A 35-ys man, affected by adrenal hyperplasia due to 21-hydroxylase deficiency, diagnosed at age of 10 ys for anticipated adrenarche and microorchidism, came to our observation for a clinical control. His sister was also affected by the same syndrome, diagnosed by genetic studies. He had not been previously treated with suppressive or replacement therapy, resulting a chronic exposure to high T levels.

The patient showed an elevated 17-OH-Progesterone (P): basal 9.1, after ACTH 22 ng/ml (electro-chemiluminesce method or ECLIA, nomal range 0.2-0.8); T levels were 15.9 ng/ml (ECLIA, n.r. 2.5-8.4). At abdomen Magnetic Resonance Imaging, performed for adrenal investigation, a 18 mm large nodular lesion was discovered in the liver, together with increased serum α-fetoprotein level. Computed Tomography and Contrast Enhanced Ultrasound suggested increased arterial vascularity of the lesion; on the basis of needle biopsy assessment (showing an hyperplastic-adenomatous lesion with focal inflammatory infiltration and biliary metaplasia of hepatocytes) and of the high cancerous risk, he underwent surgical removal of the lesion. Histological findings showed HCC with moderate differentiation (G1/G2). We showed an unexpected lowering of T levels. One year later recurrence of HCC, localized in a different liver segment, was diasgnosed and treated by percutaneous radiofrequency ablation. Two other HCC recurrences were detected during the subsequent follow up and were treated with the same technique. Every HCC recurrence was accompanied by elevation of T, but also SHBG; therefore we hypothesized a facilitating effect of chronic androgen elevation, but also a possible production of SHBG by tumor itself.

Conclusion: The prevalence of HCC in adrenal hyperplasia is not well described in literature; our report suggests the need for screening of liver lesions in males affected by this syndrome; the role of T in inducing or facilitating the neoplasia and the possible involvement of SHBG secretion remain to be established.


Nothing to Disclose: AM, SR, CB, GO, EV, GM, LR, FRP, MP