A 78-year-old man with metastatic ileal neuroendocrine tumour (NET) previously controlled on octreotide LAR 20mg monthly presents with sudden onset flushing, diarrhoea, postural dizziness and syncope. His relevant medical history includes poorly controlled T2DM, diabetic neuropathy and essential hypertension.
Compared to 12 months prior, his chromogranin A (CgA) level was 34,000 µg/L (from 263 µg/L; reference range 27-94) and urine 5-HIAA was 475 µmol/d (from 65 µmol/d; reference range <50). CT abdomen demonstrated progressive, small volume hepatic metastases with mild uptake on GaTate scan. He was changed to lanreotide 120mg monthly which improved his diarrhoea and flushing. Due to deteriorating severe postural hypotension (60 mmHg drop), peptide receptor radionuclide therapy (PRRT) was administered with initial post therapy improvement. Three weeks post PRRT, postural hypotension recurred and he had further syncopal episodes despite improvement in the frequency of flushing and resolution of diarrhoea. Fludrocortisone and midodrine were commenced with minimal effect. Tilt table test demonstrated significant postural drop without reflex tachycardia (baseline BP 200/90, HR 71; 11 mins BP 70/50, HR 86). His heart rate variability was reduced at 4.5% (normal >10%), consistent with autonomic neuropathy. Anti-neuronal antibodies were negative.
Discussion
Our subject’s lack of heart rate variability on deep breathing and postural change is highly suggestive of cardiac autonomic neuropathy (CAN). CAN has been reported in 34.3% of patient with T2DM. Risk factors include poor glycaemic control, disease duration, age related neuronal attrition and elevated baseline blood pressure. However, unlike carcinoid syndrome, diabetic autonomic neuropathy is not accompanied by flushing and diaphoresis. Furthermore, the time-course of postural hypotension was rapidly progressive over one month and coincided with the progression of his NET. This raises the possibility of paraneoplastic neuropathy which involved autoimmune responses to onconeural antigens shared by the cancer and the peripheral or central nervous system.