Poster Presentation ESA-SRB-ANZBMS 2024 in conjunction with ENSA

Aggressive ACTH adenoma: a triple a cortisol powered battery (#610)

Amy McCormick 1 , Scott McNeil 1 , Shoshana Sztal-Mazer 1 2
  1. Department of Endocrinology, Alfred Health , Melbourne, Victoria, Australia
  2. Department of Public Health and Preventative Medicine, Monash University , Melbourne, Victoria , Australia

Background:

Aggressive adrenocorticotropin hormone (ACTH) secreting pituitary tumours are rare, complicated by no uniform diagnostic criteria making the true prevalence unclear(1,2,3). Management of aggressive pituitary tumours is challenging, with increased resistance to conventional therapy and higher recurrence rates(4). Evidence based treatment guidelines for refractory tumours is limited, however, novel emerging therapies are being studied(2,5). This case report describes a recurrent, non-crookes cell corticotroph pituitary neuroendocrine tumour (PitNET) exhibiting radiological invasiveness and an increasing Ki-67 index, despite multiple transsphenoidal surgeries (TSS).

Case presentation:

A 36-year-old female was diagnosed with an aggressive ACTH secreting PitNET when she represented with classical cushingoid symptoms, new-onset headache and this time, a cranial nerve 6 palsy on the background of 2 previous TSS for the same; requiring a third resection. After the previous TSS the macroadenoma reoccurred 13- and 11-months respectively, with each recurrence presenting with clinical and biochemical features of Cushing’s Syndrome, and radiological invasion into the cavernous sinus (Figure 1&2). Post third TSS, diplopia and biochemistry normalised (morning cortisol 118nmol/L). Over 3-years, histopathology demonstrated an increasing Ki-67 index from <2% to 10% and increased cellular pleomorphism without histological features of Crooke’s tumour. Given the aggressive nature of the tumour, osilodrostat in conjunction with temozolomide and radiotherapy was considered, however, post multi-disciplinary discussions, stereotactic radiosurgery was decided upon. 5-months post radiosurgery the pituitary lesion remains stable, and biochemistry normalised.

Conclusion:

This case highlights an aggressive non-crookes cell corticotroph PitNET, requiring 3 TSS in 39-months. This case emphasises the importance of monitoring histopathological markers, e.g. Ki-67 index, in PitNETs as an indicator for potential recurrence, transformation to pituitary carcinomas and treatment response. There are many potential treatment options with emerging evidence for aggressive pituitary tumours, however, increased research is required to optimise treatment guidelines tailored to specific tumour characteristics, reduce recurrence risk and improve clinical outcomes.66a75f307a213-Figure+1&2.png

  1. 1. Raverot G, Burman P, McCormack A, Heaney A, Petersenn S, Popovic V, et al. European Society of Endocrinology Clinical Practice Guidelines for the management of aggressive pituitary tumours and carcinomas. Eur J Endocrinol. 2018;178(1):G1-g24.
  2. 2.Yamamoto M, Nakao T, Ogawa W, Fukuoka H. Aggressive Cushing's Disease: Molecular Pathology and Its Therapeutic Approach. Front Endocrinol (Lausanne). 2021;12:650791.
  3. 3.Burman P, Casar-Borota O, Perez-Rivas LG, Dekkers OM. Aggressive Pituitary Tumors and Pituitary Carcinomas: From Pathology to Treatment. J Clin Endocrinol Metab. 2023 Jun 16;108(7):1585-1601. doi: 10.1210/clinem/dgad098. Erratum in: J Clin Endocrinol Metab. 2023 Sep 18;108(10):e1163. doi: 10.1210/clinem/dgad222. PMID: 36856733; PMCID: PMC10271233.
  4. 4.Nakano-Tateno T, Lau KJ, Wang J, McMahon C, Kawakami Y, Tateno T, et al. Multimodal Non-Surgical Treatments of Aggressive Pituitary Tumors. Front Endocrinol (Lausanne). 2021;12:624686.
  5. 5.Cooper O, Bonert V, Liu NA, Mamelak AN. Treatment of Aggressive Pituitary Adenomas: A Case-Based Narrative Review. Front Endocrinol (Lausanne). 2021;12:725014.