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Endocrine Abstracts (2015) 37 EP1145 | DOI: 10.1530/endoabs.37.EP1145

1Centre for Endocrinology, Diabetes and Metabolism, University of Birmingham, Birmingham, UK; 2University Hospital Birmingham, Birmingham, UK.


Introduction: Testicular leydig cell tumours (LCTs) are rare stromal tumors often associated with androgen excess. Metastatic malignant LCTs typically show resistance to radiotherapy and cytotoxic chemotherapy, calling for alternative management options. Here we describe our experience with treatment of two patients with metastatic LCTs with the adrenolytic drug Mitotane.

Patients/methods: Case 1: A 51-year-old patient presented with a 6 month history of restlessness, aggressiveness, insomnia, facial plethora and increasing body hair growth, 15 years after successful orchidectomy for malignant LCT. Imaging by computed tomography revealed disseminated metastatic deposits. Biochemical work-up revealed severe androgen excess as the cause of his signs and symptoms, with a plasma testosterone of 93 nmol/l and a 20-fold rise in urinary excretion of active androgen metabolites (androsterone and etiocholanolone), as well as high urinary cortisol. Case 2: A 65-year-old patient presented with disseminated disease 3 years after orchidectomy for LCT. This was also associated with steroid hormone excess, including high testosterone (104 nmol/l) and oestradiol. Both patients were commenced on palliative chemotherapy with mitotane.

Results: In both cases, introduction of mitotane led to prompt control of the underlying hormonal excess, with a precipitous decrease in circulating testosterone and oestradiol levels, diminution of the excretion rate of all urinary androgen metabolites and substantial inhibition of the conversion of testosterone to dihydrotestosterone, as demonstrated by serial urine steroid profiling by gas chromatography/mass spectrometry. Clinically, this resulted in a rapid alleviation of the debilitating clinical symptomatology of hyperandrogenism. Radiologically, stabilisation of the rapidly progressive disease was documented on follow-up imaging for 6 months in case 1, while partial response was noted in case 2.

Conclusions: Mitotane can be an effective treatment option for patients with functional metastatic LCTs, offering prompt palliation of the distressing symptoms of hormone excess and, in some cases, disease stabilisation.

Disclosure: This work was supported by the European Union under the 7th Framework Program (FP7/2007–2013, grant agreement 259735, ENSAT-CANCER, to Wiebke Arlt), the WellcomeTrust (Clinical Research Training Fellowship WT101671AIA, to Vasileios Chortis).

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