Endocrine Abstracts

We report the long-term progress of a 51-year-old female with Lynch syndrome, who presented in 2015 with Cushing’s disease secondary to a constitutional pathogenic MSH2 splice site variant. ¹ Transsphenoidal surgery was followed by gamma knife radiotherapy 6 months later due to persistent hypercortisolism. Radiotherapy resulted in remission, with adrenocorticotrophic hormone (ACTH) deficiency noted 2 years postoperatively. MRI pituitary 3.5 years after surgery showed a small amount of stable residual tissue. By June 2021 she reported increased weight gain. Adrenocorticotrophic hormone was detectable and associated with resumption of adrenal cortisol production. A watchful waiting approach was adopted. Follow-up pituitary MRI in June 2021 was unchanged and 24-hour urinary free cortisol concentrations were normal (121-188 nmol/24 hours, reference range <210 nmol/24 hours). She presented in September 2021 with a left sixth nerve palsy, optic neuropathy and an orbital apex mass. Recurrence of hypercortisolaemia and elevated ACTH were noted. She recommenced a block and replace regime with metyrapone and dexamethasone in November 2021. Further pituitary radiotherapy and/or bilateral adrenalectomy were considered by the multidisciplinary team, but were deemed high risk in the setting of severe hypercortisolaemia-induced comorbidity and frailty. She continued with medical therapy. Her condition progressed with ongoing hypercortisolism and deteriorating vision. Immunotherapy with the PD-1 inhibitor nivolumab was ineffective. Cabergoline was similarly unsuccessful. A 6-month trial of pasireotide titrated to 30 mg monthly did not result in biochemical or tumoral response. Following preoperative optimisation of her physiology she underwent bilateral adrenalectomy with adjunctive radiotherapy. Follow-up MRI to monitor for corticotroph tumour progression after bilateral adrenalectomy is awaited. This is a rare case of an aggressive pituitary neuroendocrine tumour resistant to multi-modal therapy occurring in an individual with Lynch syndrome.

Reference: 1. PB Loughrey, G Baker, B Herron, S Cooke, D Iacovazzo, JR Lindsay, Korbonits M. Cancer Genetics 256–257 (2021) 36–39.