Mitotane treatment in patients with metastatic testicular Leydig cell tutor associated with severe androgen excess

Vasileios Chortis, Nicholas J. Johal, Irina Bancos, Matthew Evans, Kassiani Skordilis, Peter Guest, Michael H. Cullen, Emilio Porfiri, Wiebke Arlt

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Mitotane (o,p'DDD) is established in the adjuvant and advanced stage treatment of adrenocortical carcinoma and counteracts both tumour growth and tumour-related steroid production. Both the adrenal glands and the gonads are steroidogenically active organs and share a common embryogenic origin. Here we describe the effects of mitotane in two patients with metastatic Leydig cell tumour (LCT) of the testes and associated severe androgen excess (serum testosterone 93 and 88 nmol/l, respectively; male reference range 7-27 nmol/L). Both men suffered from severe restlessness, insomnia and irritability, which they described as intolerable and disrupting normal life activities. Urinary steroid profiling by gas chromatography-mass spectrometry (GC-MS) confirmed excess androgen production and revealed concurrent overproduction of glucocorticoids and glucocorticoid precursors, which under physiological conditions are produced only by the adrenal glands but not by the gonads. In a palliative approach, they were commenced on mitotane, which achieved swift control of the hormone excess and the debilitating clinical symptoms, restoring normal quality of life. GC-MS demonstrated normalization of steroid production and decreased 5-reductase activity, resulting in decreased androgen activation, and imaging demonstrated disease stabilization for 4-10 months. In conclusion, mitotane can be highly effective in controlling steroid excess in metastatic LCTs, with anti-tumour activity in some cases.

Original languageEnglish
JournalEuropean Journal of Endocrinology
Early online date12 Jan 2018
Publication statusE-pub ahead of print - 12 Jan 2018


  • Journal Article
  • mitotane
  • metastatic Leydig cell tumour
  • androgen excess
  • SOAT1
  • mass spectrometry


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