Browse

You are looking at 1 - 4 of 4 items for :

  • Clinical Overview x
  • Publication Details x
  • Hypoglycaemia x
Clear All
Open access

Seong Keat Cheah, David Halsall, Peter Barker, John Grant, Abraham Mathews, Shyam Seshadri and Singhan Krishnan

Summary

A frail 79-year-old lady with dementia presented with a 2-year history of frequent falls. Recurrent hypoglycaemic episodes were diagnosed and treated with continuous glucose infusion in multiple hospital admissions. Hypoadrenalism and hypothyroidism were ruled out. Whilst hypoglycaemic (blood glucose 1.6 mmol/L), both plasma C-peptide and proinsulin concentrations, were inappropriately elevated at 4210 pmol/L (174–960) and >200 pmol/L (0–7) respectively with plasma insulin suppressed at 12 pmol/L (0–180). Whilst reported cases of proinsulinoma are typically pancreatic in origin, radiological investigations of the pancreas in this patient did not identify abnormalities. Unexpectedly contrast CT identified a heterogeneously enhancing mass (6.6 cm) at the lower pole of the left kidney consistent with renal cell carcinoma. Non-islet cell tumour-induced hypoglycaemia has been associated with renal malignancy; however, a serum IGF2:IGF1 ratio measured at <10 effectively excludes this diagnosis. Concomitantly on the CT, extensive peripherally enhancing heterogeneous mass lesions in the liver were identified, the largest measuring 12 cm. A palliative approach was taken due to multiple comorbidities. On post-mortem, the kidney lesion was confirmed as clear cell renal carcinoma, whilst the liver lesions were identified as proinsulin-secreting neuroendocrine tumours. In conclusion, the diagnosis of proinsulinoma can be missed if plasma proinsulin concentration is not measured at the time of hypoglycaemia. In this case, the plasma insulin:C-peptide ratio was too high to be accounted for by the faster relative clearance of insulin and was due to proinsulin cross-reactivity in the C-peptide assay. In addition, the concomitant malignancy proved to be a challenging red herring.

Learning points:

  • Even in non-diabetics, hypoglycaemia needs to be excluded in a setting of frequent falls. Insulin- or proinsulin-secreting tumours are potentially curable causes.
  • Whilst investigating spontaneous hypoglycaemia, if plasma insulin concentration is appropriate for the hypoglycaemia, it is prudent to check proinsulin concentrations during the hypoglycaemic episode.
  • Proinsulin cross-reacts variably with C-peptide and insulin assays; the effect is method dependent. In this case, the discrepancy between the insulin and C-peptide concentrations was too great to be accounted for by the faster relative clearance of insulin, raising the suspicion of assay interference. The C-peptide assay in question (Diasorin liaison) has been shown to be 100% cross reactive with proinsulin based on spiking studies with a proinsulin reference preparation.
  • Whilst reported cases of proinsulinoma and 99% of insulinomas are of pancreatic origin, conventional imaging studies (CT, MRI or ultrasound) fail to detect neuroendocrine tumours <1 cm in 50% of cases.
  • The concomitant renal mass identified radiologically proved to be a red herring.
  • In view of the rarity of proinsulinoma, no conclusive association with renal cell carcinoma can be established.
Open access

S A A van den Berg and C G Krol

Summary

We present a patient (87 years, female) who was admitted to the emergency department because of loss of consciousness. Previous medical history included advanced-stage hepatocellular carcinoma and associated weight loss. She was found on the ground in an unresponsive state by her daughter and was determined to be hypoglycaemic. Upon bolus administration of 100 mL intravenous glucose (10%), glucose levels increased to 2.9 mmol/L and the patient regained full consciousness. She was admitted to the hospital for further examination, and treatment and continuous intravenous glucose infusion was initiated. As the patient was known to suffer from advanced-stage hepatocellular carcinoma, tumour-associated hypoglycaemia was suspected. Insulin, c-peptide and IGF1 concentrations were indeed low, cortisol concentration was high and IGF2 and Pro-IGF2 were borderline low and borderline high normal respectively. IGF2:IGF1 ratio was 23, confirming the diagnosis of non-islet cell tumour hypoglycaemia. During the initial phase of treatment, euglycaemia was maintained by continuous variable glucose infusion (5%, varying between 1 and 2 L/24 h), and the patient was advised to eat small snacks throughout the day. After euglycaemia was established and the diagnosis was confirmed, prednisolone was started (30 mg, 1 dd) and glucose infusions were halted. Under prednisolone treatment, glucose levels were slightly increased and no further hypoglycaemic episodes occurred. At her request, no surgery was performed. After 19 days, the patient was discharged to a hospice and died 3 weeks later.

Learning points:

  • Hepatocellular carcinoma may be associated with non-islet cell tumour hypoglycaemia (NICTH).
  • NICTH-induced hypoglycaemia is associated with low insulin and IGF1.
  • Measurement of IGF2 only (without measurement of Pro-IGF2 and IGF1) may be insufficient to prove NICTH.
Open access

Adriana de Sousa Lages, Isabel Paiva, Patrícia Oliveira, Francisco Portela and Francisco Carrilho

Summary

Insulinomas are the most frequent cause of hyperinsulinaemic hypoglycaemia. Although surgical enucleation is the standard treatment, a few other options are available to high-risk patients who are elderly or present with co-morbidities. We present a case report of an 89-year-old female patient who was admitted to the emergency department due to recurrent hypoglycaemia, especially during fasting. Laboratory work-up raised the suspicion of hyperinsulinaemic hypoglycaemia, and abdominal CT scan revealed a 12 mm nodular hypervascular lesion of the pancreatic body suggestive of neuroendocrine tumour. The patient was not considered a suitable candidate for surgery, and medical therapy with diazoxide was poorly tolerated. Endoscopic ultrasound-guided ethanol ablation therapy was performed and a total of 0.6 mL of 95% ethanol was injected into the lesion by a transgastric approach; no complications were reported after the procedure. At 5 months of follow-up, no episodes of hypoglycaemia were reported, no diazoxide therapy was necessary, and revaluation abdominal CT scan revealed a pancreatic nodular lesion with a size involution of about half of its original volume. The patient is regularly followed-up at the endocrinology clinic and shows a significant improvement in her wellbeing and quality of life.

Learning points:

  • Insulinomas are the most frequent cause of hyperinsulinaemic hypoglycaemia.
  • Surgical enucleation is the standard treatment with a few other options available to high-risk patients.
  • Endoscopic ultrasound-guided ethanol ablation therapy is one feasible option in high-risk patients with satisfactory clinical outcomes, significant positive impact on quality of life and low complication rates related to the procedure.
Open access

G K Dimitriadis, K Gopalakrishnan, R Rao, D K Grammatopoulos, H S Randeva, M O Weickert and N Murthy

Summary

We report the case of a 70-year-old previously healthy female who presented acutely to the Accident and Emergency department with left-sided vasomotor symptoms including reduced muscle tone, weakness upon walking and slurred speech. Physical examination confirmed hemiparesis with VIIth nerve palsy and profound hepatomegaly. A random glucose was low at 1.7 mmol/l, which upon correction resolved her symptoms. In hindsight, the patient recalled having had similar episodes periodically over the past 3 months to which she did not give much attention. While hospitalized, she continued having episodes of symptomatic hypoglycaemia during most nights, requiring treatment with i.v. dextrose and/or glucagon. Blood tests including insulin and C-peptide were invariably suppressed, in correlation with low glucose. A Synacthen stimulation test was normal (Cort (0′) 390 nmol/l, Cort (30′) 773 nmol/l). A computed tomography scan showed multiple lobulated masses in the abdomen, liver and pelvis. An ultrasound guided biopsy of one of the pelvic masses was performed. Immunohistochemistry supported the diagnosis of a gastrointestinal stromal tumour (GIST) positive for CD34 and CD117. A diagnosis of a non islet cell tumour hypoglycaemia (NICTH) secondary to an IGF2 secreting GIST was confirmed with further biochemical investigations (IGF2=96.5 nmol/l; IGF2:IGF1 ratio 18.9, ULN <10). Treatment with growth hormone resolved the patient's hypoglycaemic symptoms and subsequent targeted therapy with Imatinib was successful in controlling disease progression over an 8-year observation period.

Learning points

  • NICTH can be a rare complication of GISTs that may manifest with severe hypoglycaemia and neuroglucopenic symptoms.
  • NICTH can masquerade as other pathologies thus causing diagnostic confusion.
  • Histological confirmation of GIST induced NICTH and exclusion of other conditions causing hypoglycaemia is essential.
  • Mutational analysis of GISTs should be carried out in all cases as it guides treatment decision.
  • Tailored management of hypoglycaemia, in this case using growth hormone and targeted cyto-reductive therapy, minimizes the risk of possible life-threatening complications.