Last reviewed: July 2020
Last updated: July  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
More 1st investigations to order

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
More investigations to consider

Treatment algorithm


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.

Peer reviewersVIEW ALL

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.

Assistant Professor

Johns Hopkins University School of Medicine




SB declares that he has no competing interests.

Clinical Director/Clinical Lead for Diabetic Medicine

King’s College Hospital NHS Foundation Trust



DH declares that he has no competing interests.

Use of this content is subject to our disclaimer