Peptide storm following peptide receptor radionuclide therapy (PRRT) for metastatic neuroendocrine tumour — ASN Events

Peptide storm following peptide receptor radionuclide therapy (PRRT) for metastatic neuroendocrine tumour (#124)

Jessie Teng 1 , Sally Abell 1 , Nirupa Sachithanandan 1 , Michael Hofman 2 , Richard MacIsaac 1
  1. Department of Endocrinology & Diabetes, St Vincent's Health, Melbourne
  2. Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia

A previously-well 69-year-old man was diagnosed with metastatic gastrinoma in 2004, after presenting with melaena, gastric ulceration on gastroscopy and markedly elevated gastrin levels. Imaging studies showed a 3cm calcified pancreatic tail lesion and a 14 × 12cm liver lesion. He underwent extensive surgical resection with normalisation of gastrin levels post-operatively. Histopathology of the hepatic mass confirmed a well-differentiated neuroendocrine tumour with Ki-67 proliferative index of 2% (ENETS Grade 1).

Three years later, intra-abdominal recurrence was diagnosed on imaging and biochemistry.. He also reported new-onset symptomatic hyperinsulinaemic hypoglycaemia (fasting glucose 1.7mmol/L; insulin 73mU/L; C-peptide 1.76pmol/L). The patient was intolerant of diazoxide therapy, and subsequently underwent surgery with symptom resolution. Immunohistochemistry of the tumour was positive for gastrin but negative for insulin. Over the ensuing four years, his disease progressed and he developed multiple hepatic, nodal and osseous metastases. Due to the recurrence of symptomatic hypoglycaemia, he was commenced on glucocorticoid and subcutaneous octreotide therapy.

In 2012, he was admitted with a severe hypoglycaemic episode. Despite aggressive management with dextrose infusions, dexamethasone, intramuscular glucagon, diazoxide and nasogastric feeding, his symptomatic hypoglycaemia remained refractory. He then underwent peptide receptor radionuclide therapy with Lutetium-177 octreotate. His second cycle of PRRT was complicated by catastrophic gastrointestinal bleeding and transient worsening of hypoglycaemia likely caused by release of stored peptide hormones within tumour cells.

In total, our patient has now undergone four cycles of PRRT with a decrease in anatomical tumour burden as demonstrated by recent GaTate PET/CT imaging. He remains asymptomatic and his gastrin, insulin and chromogranin levels have reduced significantly.

Discussion points:
 What is the role of GaTate PET-CT imaging modalities for metastatic NETS?
 What is the role of peptide radionuclide receptor therapy (PRRT) in the management of metastatic functional neuroendocrine tumours? What are potential complications of PRRT?

  1. Placzkowski KA, Vella A, Thompson GB, et al. Secular trends in the presentation and management of functioning insulinoma at the Mayo Clinic, 1987-2007. J Clin Endocrinol Metab 2009; 94:1069.
  2. Van Schaik E, van Vliet EI, Feelders RA, et al. Improved control of severe hypoglycemia in patients with malignant insulinomas by peptide receptor radionuclide therapy. J Clin Endocrinol Metab 2011; 96(11):3381-89.
  3. Bernard V, Lombard-Bohas C, Taquet MC, et al. Efficacy of everolimus in patients with metastatic insulinoma and refractory hypoglycaemia. Eur J Endocrinol. 2013 (Epub ahead of print)
  4. Zaknun JJ, Bodei L, Mueller-Brand J, et al. The joint IAEA, EANM, and SNMMI practical guidance on peptide receptor radionuclide therapy (PPRNT) in neuroendocrine tumours. Eur J Nucl Med Mol Imaging 2013; 40:800-16.