E-Poster Presentation ESA-SRB-ANZBMS 2021

When tissue is the issue: A case of adrenocortical cancer, neurofibromatosis type 1 and gender affirming hormone therapy (#365)

Jessica Bindra 1 2 3 , Prishila Fookerah 1 2 , Sue-Lynn Lau 1 2 3
  1. Department of Endocrinology, Blacktown Hospital, Sydney, NSW, Australia
  2. School of Medicine, Western Sydney University, Sydney, NSW, Australia
  3. Faculty of Medicine and Health, University of Sydney, Sydney, NSW, Australia

Background: Adrenocortical cancer (ACC) is a rare malignancy which occurs more frequently in females.1 Neurofibromatosis type 1 (NF1) has a clear link with a number of endocrine tumours, including reports of nine patients with ACC.2 Normal adrenal glands express oestrogen and progesterone receptors but the role of reproductive hormones on ACC tumorigenesis is unclear. While the development of benign and malignant tumours with gender-affirming hormone therapy (GAHT) in male-to-female (MtF) transgender individuals has been described3, the effect of GAHT on NF1 and ACC remains unknown.

Case: We present the case of JS, who was diagnosed with NF1 at birth. At age 10, CT abdomen to investigate a hydrocele revealed an incidental 13cm right-sided retroperitoneal mass. A paravertebral paraganglioma was suspected but no excess catecholamine secretion was demonstrated. Post-resection, histopathology confirmed extra-adrenal ACC, based on high Ki67 of 50%, vascular invasion and ultrastructural features consistent with steroid-secreting cells. CT/FDG-PET demonstrated no primary adrenal or metastatic lesions. The following year, surveillance imaging revealed a 30mm right adrenal mass and 15mm left lower lobe lung lesion, treated with right adrenalectomy, pulmonary lesion resection and adjuvant chemotherapy.  Surveillance CT the next year showed an 8mm left upper lobe lung lesion, treated with resection and adjuvant mitotane. There was no further recurrence. At age 23, JS disclosed gender dysphoria and a desire for MtF transition. Archived adrenal tissue was assessed for oestrogen receptor expression and showed focal areas of moderate immunopositivity in <10% of tumour cells. After discussion of the potential risks of cancer recurrence and benefits of GAHT, JS opted to commence GAHT.

Conclusion: This is the tenth report raising a possible link between NF1 and ACC. Recognition of individuals on GAHT with higher baseline tumour or malignancy risk is crucial and clinicians should consider increased frequency of cancer screening in these individuals. 

  1. Else T, Kim AC, Sabolch A, et al. Adrenocortical carcinoma. Endocrine Reviews. 2014;35(2): 282–326.
  2. Menon RK, Ferrau F, Kurzawinski TR, et al. Adrenal cancer in neurofibromatosis type 1: case report and DNA analysis. Endocrinology, Diabetes & Metabolism Case Reports. 2014;2014:140074.
  3. McFarlane T, Zajac JD, Cheung AS. Gender-affirming hormone therapy and the risk of sex hormone-dependent tumours in transgender individuals-A systematic review. Clin Endocrinol (Oxf). 2018 Dec;89(6):700-711.