Endocrine Abstracts

Case history: We report the case of a previously healthy 69-year-old female who was referred to our centre after she presented with rapidly progressive weight-gain, hyperglycaemia, hypokalaemia and hypertension. She had no symptoms suggestive of carcinoid syndrome. On assessment, she had pathognomonic features of Cushing’s syndrome: central weight gain (peripheral wasting) proximal myopathy, leg oedema, skin thinning, bruising and facial puffiness; this appearance being markedly different to 2 months earlier. Her serum potassium was 2.9 mmol/l (3.5–5.3).

Investigations: A cortisol day curve was performed on the day of first assessment. On this, the baseline serum ACTH was elevated at 159 nmol/L (0–46) with a paired baseline cortisol of 1454 nmol/l. The mean of 7 cortisol measurements taken was 1278 nmol/l. A computed tomography (CT) scan of the thorax, abdomen and pelvis was also performed. This showed a right lung 13×8 mm middle lobe nodule, a small 9 mm hilar lymph node, multiple liver lesions and bilaterally enlarged adrenal glands. Magnetic resonance imaging of her pituitary gland was normal. Histological analysis of a liver biopsy sample revealed a well-differentiated metastatic NET with low grade (II) morphology and a Ki-67 index of 10%.

Results and treatment: Ectopic ACTH syndrome(EAS) was diagnosed due to the suggestive clinical features, biochemical and radiological findings. The patient was commenced on metyrapone considering the need for urgent clinical stabilisation and management. Her dose was titrated according to a ‘block and replace’ regimen (with hydrocortisone replacement) due to COVID19 pandemic limitations regarding repeated hospitals visits. The conclusion of our regional NET multi-disciplinary meeting, was that the pathology represented a metastatic lung NET. The patient was commenced on Capecitabine and Temozolomide chemotherapy. Following treatment, the patient demonstrated both clinical and biochemical remission of the Cushing’s syndrome (mean day curve LCMS-MS cortisol 159 nmol/l). A repeat CT scan, 6 months post-treatment, showed stability of the lung and hepatic lesions as well as a reduction in the size of the adrenal glands.

Conclusions and point for discussion: Our case demonstrates a significant clinical and biochemical improvement in a patient with a grade III ACTH-secreting lung neuroendocrine tumour (NET) following metyrapone therapy. There is sparse data on the effectiveness and tolerability of metyrapone therapy in managing ectopic ACTH syndrome (especially secondary to NETs). This case serves to highlight that in tumours unsuitable for surgery, metyrapone provides an effective means to manage EAS.