Endocrine Abstracts

Introduction: Adrenocortical carcinoma (ACC) is a rare and aggressive tumor. Mitotane has been the mainstay adjuvant therapy of ACC. The study aimed to describe patients diagnosed with precocious puberty (PP) and other endocrinological disorders during mitotane treatment.

Material and methods: This retrospective study enrolled four children with ACC treated with mitotane complicated by PP. The patients were diagnosed at Children’s Memorial Health Institute (CMHI) in Warsaw, Poland. We analyzed clinical manifestations, radiological, histopathological findings, and hormonal results.

Results: The median age at the diagnosis of ACC was 1.5 years (range 0.75 – 7.5 years). The first symptoms of ACC were the appearance of pubic hair and clitoromegaly (in two patients). Children underwent adrenalectomy, and histopathological examination confirmed the diagnosis of ACC. In one patient, a metastatic lesion occurred in the contralateral adrenal gland. All patients were treated with mitotane and, in two children, accompanied by other chemotherapy regimens. The median time from surgery to the initiation of mitotane therapy was 26 days. During mitotane treatment, PP was confirmed based on symptoms, hormonal and imaging tests. The median time from the therapy initiation to the first manifestations of PP was 4 months. In one patient, incomplete peripheral PP was followed by central PP, and gonadotropin-releasing hormone analog (triptorelin) treatment was introduced and continued for 2.5 years. Additionally, due to mitotane-induced adrenal insufficiency, patients required a supraphysiological dose of hydrocortisone (HC), and in one patient, mineralocorticoid (MC) replacement with fludrocortisone was necessary. In two patients, hypothyroidism was diagnosed, and levothyroxine treatment was introduced. Patients presented with neurological adverse events related to mitotane therapy. The following manifestations were observed in our study group: dysarthria, unsteady gait, muscular hypotonia, decreased tendon reflexes, and tremors of limbs.

Conclusions: The side effects of using mitotane should be recognized quickly and adequately treated. In prepubertal children, PP could be a complication of therapy. The need to use supraphysiological doses of HC, sometimes with MC, should be pointed up. Some patients require levothyroxine replacement therapy. In addition to endocrinological side effects, the neurotoxicity of mitotane is a significant clinical problem.