Last reviewed: 8 Nov 2021
Last updated: 28 Jul 2020



History and exam

Key diagnostic factors

  • diaphoresis
  • anxiety
  • tremor
  • hunger
  • generalized tingling
  • nausea
  • palpitations
  • confusion
  • irritability
  • blurred vision
  • drowsiness

Other diagnostic factors

  • unexplained weight gain
  • unexplained weight loss
  • hyperpigmentation
  • hypotension
  • short stature

Risk factors

  • middle age
  • female sex
  • ethanol consumption
  • bariatric surgery
  • liver failure
  • renal failure
  • intense exercise
  • fibromas
  • sarcomas
  • fibrosarcomas
  • insulinoma
  • adrenal insufficiency
  • growth hormone deficiency
  • hypopituitarism
  • sepsis
  • glycogen storage diseases
  • anorexia nervosa
  • malnutrition
  • exogenous insulin
  • ackee fruit ingestion
  • haloperidol exposure
  • quinine exposure
  • fluoroquinolone exposure
  • sulfonylurea exposure
  • disopyramide exposure
  • beta-adrenergic-blocking agent exposure
  • salicylate exposure
  • tramadol exposure
  • proton pump inhibitor exposure

Diagnostic investigations

1st investigations to order

  • serum glucose
  • liver function testing
  • renal function testing
  • serum insulin
  • serum C-peptide
  • serum beta-hydroxybutyrate
  • serum sulfonylurea
  • thyroid-stimulating hormone levels
  • serum cortisol

Investigations to consider

  • 48 to 72 hour fast under observation
  • oral glucose tolerance test
  • serum insulin-like growth factor (IGF)-II
  • serum adrenocorticotropic hormone
  • serum human growth factor (HGH)
  • insulin suppression test
  • serum proinsulin
  • CT scan abdomen and pelvis with and without intravenous contrast
  • transabdominal ultrasound
  • endoscopic ultrasound
  • nuclear imaging with octreotide scan

Treatment algorithm



Udaya Kabadi, MD

Professor of Medicine

University of Iowa

Des Moines Internal Medicine Residency Training Program

Staff Endocrinologist

Veterans Affairs Medical Center

Des Moines



UK is an author of a number of references cited in this topic.


Professor Udaya Kabadi would like to gratefully acknowledge Dr Steven Kunkel, a previous contributor to this topic.


SK declares that he has no competing interests.

Peer reviewers

David J. Leehey, MD

Section Chief

Renal and Hypertension

Professor of Medicine

Division of Nephrology

Department of Medicine

Loyola University School of Medicine and Edward Hines Jr VA Medical Center




DJL declares that he has no competing interests.

Shehzad Basaria, MD

Assistant Professor

Johns Hopkins University School of Medicine




SB declares that he has no competing interests.

David Hopkins, FRCP

Clinical Director/Clinical Lead for Diabetic Medicine

King’s College Hospital NHS Foundation Trust



DH declares that he has no competing interests.

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