E-Poster 63rd Endocrine Society of Australia Annual Scientific Meeting 2020

Ectopic insulin-secretion by a large cell neuroendocrine carcinoma of the cervix (#105)

Mawson Wang 1 2 , Quinlan Vasey 1 , Winny Varikatt 3 4 , Mark Mclean 1 2
  1. Department of Endocrinology, Blacktown Hospital , Blacktown, NSW, Australia
  2. Blacktown Clinical School, School of Medicine, Western Sydney University, Sydney, NSW, Australia
  3. Institute of Clinical Pathology and Medical Research, Westmead Hospital, Westmead, NSW, Australia
  4. Westmead Clinical School, University of Sydney, Sydney, NSW, Australia

A 62 year-old postmenopausal female presented with postcoital bleeding, on a background of two vaginal childbirths and tubal ligation. Tumour cells from a cervical biopsy stained positively for p16, CD56 and synaptophysin, consistent with a neuroendocrine tumour. Staging scans confirmed a localised 3x4cm cervical mass without metastases, and a diagnosis of Stage IB2 neuroendocrine cervical carcinoma was made. She completed six cycles of carboplatin/etoposide, followed by radiotherapy and brachytherapy.

At one-year post-diagnosis, the patient presented with symptomatic hypoglycaemia (plasma glucose 1.7mmol/L) in the fasted state and not on antidiabetic treatment. She exhibited sinus tachycardia to 120bpm, diaphoresis and tremor. Symptoms were promptly corrected by glucose administration, fulfilling Whipple's triad. During an episode of hypoglycaemia to 2.2mmol/L, serum c-peptide was 2.33nmol/L [0.26-1.73] and serum insulin 19mIU/L [<9]. Computed tomography demonstrated pulmonary and hepatic metastases, and no pancreatic lesion. Retrospective immunohistochemistry on the cervical biopsy revealed positive insulin staining and negative glucagon staining, confirming the diagnosis of an insulin-secreting neuroendocrine carcinoma (NEC).

Intravenous dextrose and hydrocortisone were insufficient to maintain normoglycaemia. The somatostatin analogue octreotide was commenced at 200mcg SC q8hrly, allowing cessation of intravenous therapy and significantly improved hypoglycaemia. In view of progressing aggressive malignancy a palliative approach was decided, and the patient died on day 20 of admission.

Neuroendocrine neoplasms (NENs) are malignancies that arise from neuroendocrine cells and may produce and secrete peptide hormones1. Non-islet cell tumours secreting insulin are infrequently reported, and comprise 1-2% of insulinomas, most commonly arising in peripancreatic or periduodenal regions, but also in ectopic sites including kidney, liver, ovary and lung2. Positive insulin immunohistochemistry in the tumour, combined with elevated c-peptide and insulin levels suggests that the insulin-secreting tumour was the aetiology for the patient's hypoglycaemia. We are aware of only two previously reported cases of insulin-induced hypoglycaemia originating from a cervical NEN3-4.

 

  1. Rindi G., Klimstra D., Abedi-Ardekani B., et al. A common classification framework for neuroendocrine neoplasms: an International Agency for Research on Cancer (IARC) and World Health Organization (WHO) expert consensus proposal. Modern Pathology. 2018;31(12):1770‐1786.
  2. Ramkumar S., Dhingra A., Jyotsna V., et al. Ectopic insulin secreting neuroendocrine tumor of kidney with recurrent hypoglycemia: a diagnostic dilemma. BMC Endocrine Disorders. 2014; 14:36.
  3. Seckl M., Mulholland P., Bishop A., et al. Hypoglycemia due to an insulin-secreting small-cell carcinoma of the cervix. New England Journal of Medicine. 1999;341(10):733‐736.
  4. Kiang D., Bauer G., Kennedy B. Immunoassayable insulin in carcinoma of the cervix associated with hypoglycemia. Cancer. 1973;31(4):801‐805.