Endocrine Abstracts

Background: Rapid progression of corticotroph tumours can occur after bilateral adrenalectomy for treatment of Cushing’s disease. There are currently no guidelines to assist with management of aggressive cases of Nelson’s syndrome, particularly after surgery and radiotherapy.

Clinical case: A 53 year old woman presented with classic clinical features of hypercortisolism. Initial investigations showed a markedly elevated 24 hour urine cortisol level of 2426 nmol/day (<250), unsuppressed cortisol after 1mg dexamethasone and ACTH 22.6 pmol/l (0-12). High dose dexamethasone and CRH tests confirmed a pituitary cause of ACTH-dependent Cushing’s syndrome. MRI of the pituitary fossa revealed a pituitary macroadenoma, maximum dimension 14 mm, without compression of the optic chiasm but extension into the right cavernous sinus. Surgical resection of the tumour could not be completed due to an intraoperative complication of internal carotid artery rupture and haemorrhagic stroke. Consequently, the patient opted for radiotherapy, achieving clinical remission after 2 years. Tumour regrowth 3 years later necessitated treatment with further radiosurgery (2200 cGy). Laparoscopic bilateral adrenalectomy was eventually performed after 2 years due to further relapse. Postoperative ACTH level was 195pmol/l (0-12). 15 months later she was diagnosed with Nelson’s syndrome after significant progression of tumour with a maximum dimension now of 36mm and ACTH level of 2053 pmol/l. Urgent surgical debulking was undertaken via craniotomy. Histopathological evaluation confirmed a pituitary tumour expressing TPIT and ACTH, consistent with a densely granulated corticotroph tumour. Ki67 was elevated around 12-15%. Postoperative ACTH declined to 1190 pmol/l. She completed an 18 month course of temozolamide and capecitabine without progression (ACTH 603 pmol/l). At that point, due to modest tumour growth she received further radiotherapy followed by monthly pasireotide LAR 30mg. ACTH level 9 months after pasireotide is stable at 228 pmol/l, similar to her baseline level before developing Nelson’s syndrome.

Conclusion: We employed a multimodal therapeutic approach including surgery, radiotherapy, temozolamide and pasireotide to successfully manage an aggressive corticotroph tumour. There has been adequate tumour control for up to 3 years since development of Nelson’s syndrome.