Adult spontaneous hypoglycaemia: preface

Adult spontaneous hypoglycaemia: preface

Hypoglycaemia in adults has many causes; however, in clinical practice it usually occurs in patients with diabetes over-treated with insulin or oral hypoglycaemic drugs. Although uncommon, it is important to recognise spontaneous (non-diabetic) hypoglycaemia and its aetiology because preventative or curative therapy is often available.

Spontaneous hypoglycaemia is not a diagnosis but a manifestation of underlying disease. Investigation of hypoglycaemia and suspected hypoglycaemia involves a high index of suspicion, confirmation or exclusion of hypoglycaemia and elucidation of the cause after confirmed hypoglycaemia.

The investigation of hypoglycaemia and suspected hypoglycaemia, however, is fraught with avoidable potential pitfalls (1-4):

  • Failure to recognise subacute neuroglycopaenia as a clinical manifestation of spontaneous hypoglycaemia.
  • Failure to recognise that neuroglycopaenic symptoms may be non-specific. Acute and subacute neuroglycopaenia may only be confidently confirmed when Whipple’s triad is fulfilled; namely neuroglycopaenic symptoms, a low blood glucose and symptoms relieved by raising blood glucose to or above normal.
  • Failure to confirm or refute hypoglycaemia during symptoms.
  • Mislabelling healthy individuals as “hypoglycaemic” resulting in the “worried well syndrome”.
  • Inappropriate use of obsolete investigations, such as the prolonged oral glucose tolerance test.
  • Failure to provide hypoglycaemic samples in which to measure pancreatic hormones, counter-regulatory hormones and non-glucose substrates.
  • Measurement of pancreatic hormones, counter-regulatory hormones and non-glucose substrates in non-hypoglycaemic samples.
  • Failure to recognise assay limitations, in particular immunoassays.
  • Failure to exclude factitious hypoglycaemia, autoimmune hypoglycaemia and non-insulinoma pancreatogenous hypoglycemia syndrome before diagnosing insulinoma.


All authors have provided up-to-date and informative reviews which will be of interest to our readers. I thank Vincent Marks for asking me to co-author his account of forensic hypoglycaemia—a privilege. Prof. Marks has indicated that this will be his last academic publication but maybe we can persuade him otherwise.

Funding: None.


Provenance and Peer Review: This article was commissioned by editorial office, Journal of Laboratory and Precision Medicine for the series “Adult Spontaneous Hypoglycaemia”. The article did not undergo external peer review.

Conflicts of Interest: The author has completed the ICMJE uniform disclosure form (available at The series “Adult Spontaneous Hypoglycaemia” was commissioned by the editorial office without any funding or sponsorship. RG served as the unpaid Guest Editor of the series and serves as an unpaid Associate Editor-in-Chief of Journal of Laboratory and Precision Medicine.

Ethical Statement: The author is accountable for all aspects of this work in ensuring that questions related to the accuracy or integrity of any part of this work are appropriately investigated and resolved.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See:


  1. Cryer PE, Axelrod L, Grossman AB, et al. Evaluation and management of adult hypoglycemic disorders: an Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab 2009;94:709-28. [Crossref] [PubMed]
  2. Gama R, Teale JD, Marks V. Best practice No 173: clinical and laboratory investigation of adult spontaneous hypoglycaemia. J Clin Pathol 2003;56:641-6. [Crossref] [PubMed]
  3. Griffiths MJ, Gama R. Adult spontaneous hypoglycaemia. Hosp Med 2005;66:277-83. [PubMed]
  4. Yager J, Young RT. Sounding board: non-hypoglycaemia is an epidemic condition. N Engl J Med 1974;291:907-8. [Crossref] [PubMed]
Rousseau Gama

Rousseau Gama1,2

1School of Medicine and Clinical Practice,University of Wolverhampton, Wolverhampton, UK;
2Black Country Pathology Services, Royal Wolverhampton Hospitals NHS Trust, Wolverhampton, UK.

Received: 12 August 2021; Accepted: 25 August 2021; Published: 30 October 2021.

doi: 10.21037/jlpm-2021-03

doi: 10.21037/jlpm-2021-03
Cite this article as: Gama R. Adult spontaneous hypoglycaemia: preface. J Lab Precis Med 2021;6:25.

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