- F John Service, MD, PhD
F John Service, MD, PhD
- Emeritus Professor of Medicine
- Mayo Clinic College of Medicine
- Adrian Vella, MD
Adrian Vella, MD
- Professor of Medicine
- Mayo Clinic
Factitious (or factitial) hypoglycemia occurs secondary to the surreptitious use of insulin or insulin secretagogues (sulfonylureas, meglitinides). The term factitious (or factitial) hypoglycemia has been used in medical parlance to imply covert human activity. The consideration of such a possibility often changes the patient-clinician relationship, leading the clinician to feel deceived and the patient to feel mistrusted. However, the pejorative connotation with which factitious illness has been encumbered requires softening because some patients with factitious disease suffer through no fault of their own.
The clinical features, diagnosis, and treatment of factitious hypoglycemia will be reviewed here. Other causes of hypoglycemia are discussed elsewhere. (See "Hypoglycemia in adults: Clinical manifestations, definition, and causes" and "Insulinoma".)
ETIOLOGY OF FACTITIOUS HYPOGLYCEMIA
Factitious hypoglycemia results from the use of insulin or insulin secretagogues (sulfonylurea, meglitinides) but not from metformin or other insulin-sensitizing antidiabetic drugs [1-3].
Ingestion of an oral insulin secretagogue — The first reported case of factitious hypoglycemia related to a sulfonylurea was due to the surreptitious self-administration of chlorpropamide by a patient without diabetes . Inappropriate manipulation of hypoglycemic tablets by a patient with diabetes is another cause of factitious hypoglycemia.
In addition to patients who knowingly take insulin secretagogue drugs, there are patients who, by taking a prescribed medication in good faith, have hypoglycemia because a sulfonylurea was mistakenly dispensed . In most instances, confusion in dispensing the drug arose because of similarity in spelling between the intended medication and the sulfonylurea. The most common errors in early reports were the substitutions of Diabinese for Diamox [6,7] and of Tolinase for Tolectin .
- Hirshberg B, Skarulis MC, Pucino F, et al. Repaglinide-induced factitious hypoglycemia. J Clin Endocrinol Metab 2001; 86:475.
- Marks V, Teale JD. Hypoglycemia: factitious and felonious. Endocrinol Metab Clin North Am 1999; 28:579.
- Waickus CM, de Bustros A, Shakil A. Recognizing factitious hypoglycemia in the family practice setting. J Am Board Fam Pract 1999; 12:133.
- DUNCAN GG, JENSON W, EBERLY RJ. Factitious hypoglycemia due to chlorpropamide. Report of a case, with clinical similarity to an islet cell tumor of the pancreas. JAMA 1961; 175:904.
- Klonoff DC, Barrett BJ, Nolte MS, et al. Hypoglycemia following inadvertent and factitious sulfonylurea overdosages. Diabetes Care 1995; 18:563.
- Aderka D, Pinkhas J. Inadvertently induced hypoglycemia. JAMA 1978; 240:1140.
- Hooper PL, Tello RJ, Burstein PJ, Abrams RS. Pseudoinsulinoma--the Diamox-Diabinese switch. N Engl J Med 1990; 323:488.
- Ahlquist DA, Nelson RL, Callaway CW. Pseudoinsulinoma syndrome from inadvertent tolazamide ingestion. Ann Intern Med 1980; 93:281.
- Kao SL, Chan CL, Tan B, et al. An unusual outbreak of hypoglycemia. N Engl J Med 2009; 360:734.
- Giurgea I, Ulinski T, Touati G, et al. Factitious hyperinsulinism leading to pancreatectomy: severe forms of Munchausen syndrome by proxy. Pediatrics 2005; 116:e145.
- Given BD, Ostrega DM, Polonsky KS, et al. Hypoglycemia due to surreptitious injection of insulin. Identification of insulin species by high-performance liquid chromatography. Diabetes Care 1991; 14:544.
- Roberge RJ, Martin TG, Delbridge TR. Intentional massive insulin overdose: recognition and management. Ann Emerg Med 1993; 22:228.
- Kaminer Y, Robbins DR. Insulin misuse: a review of an overlooked psychiatric problem. Psychosomatics 1989; 30:19.
- Service FJ, Moore GL. Factitial and autoimmune hypoglycemia. In: Hypoglycemic Disorders: Pathogenesis, Diagnosis, and Treatment, GK Hall Medical Publishers, 1983. p.129.
- Murray BJ. Hypoglycemia secondary to factitious hyperinsulinism. Postgrad Med 1981; 69:237, 240.
- Roberts I, Cohen H, Reeves WG. Characterisation of antibodies to insulin to help diagnose factitious hypoglycaemia. Br Med J (Clin Res Ed) 1985; 290:1391.
- Ensberg M, Gossain VV, Rovner DR. Factitious hypoglycemia. Clues to identifying an elusive disorder. Postgrad Med 1986; 79:79.
- Grunberger G, Weiner JL, Silverman R, et al. Factitious hypoglycemia due to surreptitious administration of insulin. Diagnosis, treatment, and long-term follow-up. Ann Intern Med 1988; 108:252.
- Bhatnagar D. Diagnosis of factitious hypoglycaemia. Br J Hosp Med 1988; 40:140.
- Dimitriadis G, Raptis S, Zoupas C, Schizas N. The validity of C-peptide measurement in the diagnosis of factitious hypoglycemia. Acta Diabetol Lat 1980; 17:67.
- Miccoli R, Marchetti P, Giampietro O, et al. Factitious hypoglycemia in an insulin-dependent woman in the eighth week of gestation. Gynecol Obstet Invest 1986; 21:52.
- Toth EL. Factitious hypoglycemia and the multiple personality disorder. Ann Intern Med 1990; 112:76.
- Tattersall R, Gregory R, Selby C, et al. Course of brittle diabetes: 12 year follow up. BMJ 1991; 302:1240.
- Schade DS, Drumm DA, Eaton RP, Sterling WA. Factitious brittle diabetes mellitus. Am J Med 1985; 78:777.
- Schade DS, Burge MR. Brittle diabetes: etiology and treatment. Adv Endocrinol Metab 1995; 6:289.
- GITTLER RD, ZUCKER G, EISINGER R, STOLLER N. Amelioration of diabetes mellitus by an insulinoma. N Engl J Med 1958; 258:932.
- Braithwaite SS, Eatherton JK, Ellos WJ, et al. The ethics of surreptitious diagnostics for factitious hypoglycemia. J Clin Ethics 1990; 1:116.
- Klein RF, Seino S, Sanz N, et al. High performance liquid chromatography used to distinguish the autoimmune hypoglycemia syndrome from factitious hypoglycemia. J Clin Endocrinol Metab 1985; 61:571.
- Perros P, Henderson AK, Carter DC, Toft AD. Lesson of the week. Are spontaneous hypoglycaemia, raised plasma insulin and C peptide concentrations, and abnormal pancreatic images enough to diagnose insulinoma? BMJ 1997; 314:496.
- Neal JM, Han W. Insulin immunoassays in the detection of insulin analogues in factitious hypoglycemia. Endocr Pract 2008; 14:1006.
- Moriyama M, Hayashi N, Ohyabu C, et al. Performance evaluation and cross-reactivity from insulin analogs with the ARCHITECT insulin assay. Clin Chem 2006; 52:1423.
- Owen WE, Roberts WL. Cross-reactivity of three recombinant insulin analogs with five commercial insulin immunoassays. Clin Chem 2004; 50:257.
- Bowsher RR, Lynch RA, Brown-Augsburger P, et al. Sensitive RIA for the specific determination of insulin lispro. Clin Chem 1999; 45:104.
- Andersen L, Jørgensen PN, Jensen LB, Walsh D. A new insulin immunoassay specific for the rapid-acting insulin analog, insulin aspart, suitable for bioavailability, bioequivalence, and pharmacokinetic studies. Clin Biochem 2000; 33:627.
- Walfish PG, Feig DS, Bauman WA. Factitious hyperinsulinemic hypoglycemia: confirmation of the diagnosis by a species-specific insulin radioimmunoassay. J Endocrinol Invest 1987; 10:601.
- Hoizey G, Lamiable D, Trenque T, et al. Identification and quantification of 8 sulfonylureas with clinical toxicology interest by liquid chromatography-ion-trap tandem mass spectrometry and library searching. Clin Chem 2005; 51:1666.
- Wang M, Miksa IR. Multi-component plasma quantitation of anti-hyperglycemic pharmaceutical compounds using liquid chromatography-tandem mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci 2007; 856:318.
- Paroni R, Comuzzi B, Arcelloni C, et al. Comparison of capillary electrophoresis with HPLC for diagnosis of factitious hypoglycemia. Clin Chem 2000; 46:1773.
- Malli D, Gikas E, Vavagiannis A, et al. Determination of nateglinide in human plasma by high-performance liquid chromatography with pre-column derivatization using a coumarin-type fluorescent reagent. Anal Chim Acta 2007; 599:143.
- Service FJ, McMahon MM, O'Brien PC, Ballard DJ. Functioning insulinoma--incidence, recurrence, and long-term survival of patients: a 60-year study. Mayo Clin Proc 1991; 66:711.
- Pfützner A, Löbig M, Fortunato A, Forst T. Evaluation of a new fully automated one-step C-peptide chemiluminescence assay (LIAISON C-Peptid). Clin Lab 2003; 49:227.
- Rubenstein AH, Block MB, Starr J, et al. Proinsulin and C-peptide in blood. Diabetes 1972; 21:661.
- Biliotti GC, Vestrini G, Tonelli P, et al. Factitious hypoglycemia: an unusual clinical picture within Von Münchausen's syndrome. Ital J Surg Sci 1983; 13:41.
- Service FJ, Rubenstein A, Horwitz DL. C-peptide analysis in diagnosis of factitial hypoglycemia in an insulin-dependent diabetic. Mayo Clin Proc 1975; 50:697.
- Seino S, Fu ZZ, Marks W, et al. Characterization of circulating insulin in insulin autoimmune syndrome. J Clin Endocrinol Metab 1986; 62:64.
- Schernthaner G. Immunogenicity and allergenic potential of animal and human insulins. Diabetes Care 1993; 16 Suppl 3:155.
- Fasano CJ, O'Malley G, Dominici P, et al. Comparison of octreotide and standard therapy versus standard therapy alone for the treatment of sulfonylurea-induced hypoglycemia. Ann Emerg Med 2008; 51:400.
- ETIOLOGY OF FACTITIOUS HYPOGLYCEMIA
- Ingestion of an oral insulin secretagogue
- Administration of insulin
- CLINICAL CHARACTERISTICS
- Laboratory tests
- Interpretation of tests
- - Insulin secretagogues
- - Exogenous insulin
- Insulin measurements
- Insulin secretagogue measurements
- C-peptide measurements
- Anti-insulin antibodies
- Long term
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