Case history: Patient 1, a 78 year old male, was diagnosed five years ago with a metastatic NET with octreotide avid disease including ileocolic/right common iliac nodal metastases and a solitary segment VII liver lesion. He elected for watchful waiting and was asymptomatic. Interval imaging showed gradual local disease progression. He was diagnosed with motor neurone disease resulting in unilateral arm weakness. He re-presented four years after diagnosis with progressive weakness rendering him bed bound, peripheral oedema, hypertension, hypokalaemia, hyperglycaemia, Cushingoid facies and new onset hypothyroidism. Patient 2, an 83 year old female, was diagnosed in 1984 with a metastatic pancreatic NET resulting in biliary obstruction, and bone metastases. She underwent gastric and biliary bypass with choledochoduodenostomy; histology showed a low grade pancreatic NET with little mitotic activity. She had no further treatment and was lost to follow up in 2009. In 2018, 34 years following diagnosis, she developed gradual deterioration in health culminating in admission to hospital with increasing shortness of breath and peripheral oedema. On admission she was hypokalaemic, hypocalcaemic and hyperglycaemic.
Investigations: Patient 1: random cortisol 1436 nmol/L, urinary cortisol >1650 nmol/24h, ACTH 359 ng/L, no suppression on LDDST. CT showed enlarged smooth adrenal glands with no associated adrenal mass and progression at the known sites of disease. Patient 2: random cortisol 6363 nmol/L, urinary cortisol >23450 nmol/24h, ACTH 3879 ng/L; no suppression on LDDST. CT revealed bilateral adrenal gland enlargement and progression at the known sites of disease. MRI pituitary showed a normal pituitary gland.
Results and treatment: Patient 1 was commenced on ketoconazole and metyrapone, however the former was stopped due to a fungal lung infection requiring treatment with voriconazole. Cortisol fell on high dose metyrapone and lanreotide and he is now on a block and replace regime with gradual functional recovery. Patient 2 was initially treated with metyrapone, but due to rapid deterioration she was admitted to ITU for an etomidate infusion. Despite a rapid fall in cortisol she continued to decline. Active treatment was withdrawn and the patient was palliated, as per her wishes.
Conclusions: Although Cushings due to ectopic ACTH is often due to small, frequently occult primary NETs, these cases serve as a reminder that it can also develop in advanced previously non-functioning NETs. A high index of suspicion is needed for the early symptoms to try to prevent rapid decline.
08 - 10 Apr 2019
Society for Endocrinology