Quantitative Proteomic of Rat Livers Shows a Major Reprogramming of Mitochondrial Enzymes in Food-Restriction and Increased Stress Hallmarks in Ad Libitum Feeding

Abstract

Introduction: In the pediatric age group, the incidence of theadrenocortical cancer (ACC) is 0.2%. The effective treatment issurgical resection. The only medical option is mitotane but it hasnegative effects on steroidogenesis. The difficulty in the managementof mitotane therapy is discussed in this case. Case report:An 1110/12 years-old boy was referred with A 5 cm diameter solidhypoecoicmass observed by sonography in the left surrenalregion. The physical examination was all normal at presentation.His pubertal stage was Tanner grade 3. His clinical findings werenormal. In the adrenal hormone profile, DHEA, androstenedion,total testesterone (TT) elevated while the others (11-deoxycortisole,17-OH progesterone, cortizole) were normal. His plasmarenin activity and aldesterone were normal. Analysis of 24-h urinespecimen revealed high cortisole levels. The case was diagnosed asgrade 3 ACC and treated via surgical resection. Postoperativelychemotherapy, mitotane and hydrocortisone treatments werestarted. In the first month of the treatment hormonal profile wasall normal but TT levels started to increase (O1500 ng/dl) atsecond month. In the follow-up, height growth stopped andbilateral gynecomasty developed. Magnetic resonance imaging andpozitron emission tomography scans and scrotal US were negativefor recurrance or metastases at 6 months. The clinic was diagnosedas hypergonadotropic hypogonadism (HH) due to mitotanetreatment. The follow-up of the case is continuing. Discussion:Mitotane treatment leads to HH via reducing the gonadalsteroidogenesis. Additionally, treatment increases the levels ofsex-hormone binding globuline and decreases the activity of 5-alfareductase that results with high levels of testesteron. In our case thetestosterone levels were high but free androgen index was normal.The high levels of testesterone can be the result of metastase,recurrance or mitotane treatment adverse effect. This is astruggling problem in the management of mitotane therapy.</p