’80 year old woman was found collapsed at home with bradycardia and hypothermia



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  • ’80 year old woman was found collapsed at home with bradycardia and hypothermia.
  • A blood glucose concentration of 2.0 mmol/L was recorded using a near-patient testing device.
  • Discuss the differential diagnosis and laboratory investigation of the case’
  • Prepared by Dr Gwen Wark, Consultant Clinical Scientist, SAS Peptide laboratory

Demonstrating hypoglycaemia

Demonstrating hypoglycaemia

  • Even if glycolytic inhibitors in tubes, they do not work straightway and there will still be a loss of glucose.
  • May also be ‘pseudohypoglycaemia’ if delayed sample separation, samples are old and if leukocytosis, thrombocytosis or erythrocytosis is present.

Hypoglycaemia - definition

  • Arbitrary – point at which symptoms occur varies between individuals
  • Not possible to state a single plasma glucose concentration that categorically defines hypoglycaemia
  • Therefore variation in glucose cut offs used

Hypoglycaemia - definition

  • Need to be clear which sample types are being used i.e. plasma vs whole blood or arterial vs venous etc as glucose levels different
  • Symptoms start to appear when venous plasma glucose < 3 mmol/L
  • This is the cut off used in the Endocrine Society Clinical Practice Guideline which is increasing being adopted in UK

Investigation of hypoglycaemia

  • Demonstrate Whipple’s triad
  • Elucidate the cause
    • samples taken during the hypoglycaemic episode before treatment
  • (Anti arrhythmia)
  • (Antibiotic)
  • (Anti microbial)
  • (Anti malarial)
  • (NSAID)

Causes of hypoglycaemia

  • Commonest cause is drugs
    • Insulin, insulin secretagogues (sulphonylurea), alcohol etc
  • Can occur sepsis and critical illness including renal cardiac and liver failure
  • Occurs rarely in cortisol deficiency
  • Endogenous hyperinsulinism and non islet cell tumours are rare

Investigation of hypoglycaemia -history and physical examination

  • Drugs
  • (?patient diabetic or has access to medication via diabetic relative)
  • e.g. samples for ethanol, insulin, C-peptide, oral hypoglycaemic agent screens (sulphonylurea commonest cause as oral agent)
  • Organ failure (renal, hepatic, cardiac)

Investigation of hypoglycaemia -history and physical examination

  • Endocrine deficiency
    • Cortisol, GH and pituitary hormone profile requested – in this case thyroid function tests should definitely be done
  • Infection
  • Starvation
  • (Unlikely at this age that there is an IEM)

Laboratory Investigations so far….

  • Laboratory glucose
  • U&E
  • LFT’s
  • Endocrine profile
  • BNP, Troponin
  • Insulin
  • C-Peptide
  • Oral hypoglycaemic agents
  • CRP, FBC, blood cultures

Insulin assay issues

  • The previous algorithm is for an insulin assay that detects proinsulin (investigation of proinsulinomas) and synthetic analogues (exogenous insulin administration).
  • Some insulin assays do not detect these so procedures need to be in place to ensure these can be tested for.

Other investigations

  • Insulin antibodies and insulin receptor antibodies – rare cause of hypoglycaemia but assays are available.
  • - Insulin antibodies can affect insulin assays and often cause elevated results. However low insulin results can occur depending on the insulin assay.
  • Pattern of results expected to see in different causes of hypoglycaemia shown on next slide
  • The cut-offs for insulin, C-peptide, proinsulin and -hydroxybutyrate are assay dependent

Comments on essay responses

  • Most candidates indicated the need to confirm the near patient testing (NPT) device glucose analysis with a laboratory glucose measurement.
  • Fewer candidates reflected on potential issues with the NPT glucose result e.g. peripheral perfusion - hypotension, assay range, whole blood vs plasma glucose differences in results etc

Comments on essay responses

  • Few candidates reflected on the likelihood that treatment would have been started to raise the glucose level before appropriate samples were collected for the investigation of hypoglycaemia.
  • Limited mention of Whipples triad.
  • It may be necessary to provoke symptoms by performing a diagnostic fast (or a mixed meal test – not an OGTT) if the low NPT glucose is to be investigated further as it may be artifactual.

Comments on essay responses

  • Essay responses reflected a variation in the glucose cut-offs used to define hypoglycaemia.
  • This is to be expected as the definition of hypoglycaemia is arbitrary.

Comments on essay responses

  • Often emphasis on investigation of rarer causes of hypoglycaemia e.g. insulinoma or non-islet cell tumour
  • Some very clear and systematic approaches to investigation and for the interpretation of results was provided.
  • However none suggested that the cut-offs that they mentioned would be assay dependent.

Comments on essay responses

  • Only a few candidates reflected on cross-reactivity issues with insulin assays:
  • e.g. proinsulin so that cases of proinsulinoma are not missed
  • e.g. synthetic insulin analogues. Cases of exogenous insulin administration can be missed with some insulin assays as assays vary in their cross-reactivity for these preparations.

Comments on essay responses

  • Essays tended to focus on the investigation of the low blood glucose due to the NPT result.
  • Only some of the essays mentioned any causes or investigation of bradycardia (e.g. TSH, cortisol, K+, digoxin, amiodarone etc) or hypothermia since this glucose result could be artifactual.

Structure

  • Demonstration of hypoglycaemia
  • Definition of hypoglycaemia
  • Mention BRIEFLY potentially differences between POCT and laboratory
  • Causes of hypoglycaemia - tables
  • Laboratory investigation of causes including limitations – tables, algorithms
  • Investigation of bradycardia and hypothermia if glucose result is artifactual


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