Factitious Hypoglycemia


Article Author:
Dana Awad


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Marium Ilahi


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Hajira Basit
Phillip Hynes
Tehmina Warsi


Updated:
5/25/2019 4:46:10 PM

Introduction

Factitious hypoglycemia is the intentional attempt to induce low blood glucose levels, and it remains one of the diagnostic challenges that face endocrinologists during their practice, and usually leads to costly, unnecessary investigations to rule out other causes of hypoglycemia.[1]

Etiology

Factitious hypoglycemia results from exogenous self-administration of insulin or insulin secretagogues medications (e.g., sulfonylureas, meglitinides). Note that insulin-sensitizing drugs like metformin, do not cause hypoglycemia.[1]

Epidemiology

There are numerous factitious hypoglycemia cases reported in the literature in both diabetic and non-diabetic individuals. It was shown to be more common in women with diabetes, especially during the third and fourth decades of life.[2][3]

Pathophysiology

Insulin synthesis occurs in the beta cells of the pancreas as proinsulin, which is then processed and cleaved into insulin, and C peptide held together by disulfide bonds and excreted into the circulation. Insulin will be then rapidly removed by the liver, whereas C peptide remains in the circulation for a more extended period till the kidneys clear it and the insulin to C peptide ratio in healthy individuals will be less than one. Some proinsulin molecules would also get excreted in the blood without processing, and this is still detectable in the plasma.[4]

History and Physical

Patients with factitious hypoglycemia usually present with non-specific symptoms of hypoglycemia, which include: tremors, sweating, dizziness, irritability, hunger, weakness, altered mental status, seizures, or coma. However, those with a history of recurrent hypoglycemia may have less severe symptoms that are hard to recognize.

Taking a good history remains a crucial step in evaluating hypoglycemic patients. Factitious hypoglycemia should be a potential diagnosis in the differential for patients who work in the medical profession, who are in close contact with diabetic individuals, and those with underlying psychiatric disorders like major depressive disorder and history of suicide attempts. It is also essential to review the patient's current medication list, including any herbal preparations, as some herbals may be contaminated with sulfonylureas. It should also be suspected in diabetic individuals who despite repeated adjustments of their insulin or oral hypoglycemic doses, continue to present with recurrent episodes of hypoglycemia.

Physical examination is usually nonspecific. Vital signs may show tachycardia and hypothermia, and diaphoresis can be present on skin examination. In some patients, careful skin inspection for insulin needle marks can help direct towards possible factitious disorders in those who are not on prescribed insulin.[5][6][7]

Evaluation

Fulfillment of the Whipple triad is necessary before establishing any diagnosis of a hypoglycemic disorder. The triad consists of[8]:

  1. The presence of hypoglycemic signs and symptoms
  2. Low blood glucose levels lower than 70 mg/dl
  3. Resolution of symptoms after glucose administration and correction of hypoglycemia

After confirming that a hypoglycemic disorder is present, and after excluding other potential causes, the following laboratory tests should be sent during hypoglycemia when the blood glucose level is less than 70mg/dl, and these include plasma insulin, C peptide, proinsulin, and insulin secretagogues blood levels.

Synthetic insulin usually lacks C peptide, so in factitious hypoglycemia secondary to exogenous insulin administration, plasma insulin will show elevated, but there will be suppression of C peptide and proinsulin, and insulin to C peptide ratio will be greater than one. On the other hand, insulinomas and insulin secretagogues like sulfonylureas, stimulate endogenous insulin production; as a result, plasma insulin, C peptide, and proinsulin levels will be all elevated. Note that levels may be within normal limits, but still relatively high for someone with hypoglycemia.[1][2][9]

The only way to differentiate between insulinoma and insulin secretagogues induced hypoglycemia is by detecting the drug, e.g., sulfonylurea, in the blood or urine.[10][11]

Treatment / Management

The first step in the treatment of factitious hypoglycemia is restoring normal blood glucose levels to relieve hypoglycemic symptoms. When the patient is not in the hospital setting, oral glucose and glucagon injections can be administered initially. When a patient is at the hospital, IV glucose should be started, and in comatose patients, hydrocortisone also needs to be added.[12] Close monitoring of serum glucose is then required, and usually, patients would need to be on continuous IV glucose infusions till the drug effect wears off, which may take one to two days.[13] Bolus glucose administration should be avoided in sulfonylurea-induced hypoglycemia as this may lead to more stimulation of insulin by the circulating drug in the blood.

If sulfonylurea-induced hypoglycemia persists despite IV glucose infusion, additional therapy may be warranted. Octreotide, a somatostatin analog that can inhibit beta cells of the pancreas, is a suggestion for the first-line treatment of sulfonylurea overdose in combination with dextrose infusion. It can be administered intravenously or subcutaneously.[14] Some literature data historically suggested the use of diazoxide, which is an oral anti-hypertensive drug that antagonizes the effect of sulfonylurea on the beta cells of the pancreas and inhibits the release of insulin. However, it has then fallen out of favor after the introduction of octreotide.[15]

Long term treatment is best achieved by collaboration with a psychiatrist, and psychotherapy remains the treatment of choice in such patients. Studies have shown that antidepressants and antipsychotics were not beneficial for factitious disorder. Many patients, however, would not agree to be seen by a psychiatrist even when they acknowledge the diagnosis.[2]

Differential Diagnosis

Differential diagnosis of hypoglycemia includes but is not limited to the following:

  • Alcohol intake
  • Hormonal deficiency, e.g., cortisol
  • Non-islet cell tumors
  • Insulinoma
  • Insulin autoimmune hypoglycemia
  • Accidental or factitious hypoglycemia

Other acute, secondary causes of hypoglycemia should also be a consideration, especially in people with known diabetes mellitus, such as infection, sepsis, and transient ischemic attacks. These disorders require exclusion before starting the extensive hypoglycemia work up.[16]

Prognosis

The prognosis of factitious disorder is generally poor, and patients are unlikely to recover, especially when identified late in the disease course.[17] In one study that followed ten patients for many years after the diagnosis of factitious hypoglycemia, two out of the ten patients committed suicide.[2]

Complications

Factitious disorder is a psychiatric disorder in the first place that has a poor outcome, and many patients would continue to harm themselves till they get a permanent medical injury. Patients with factitious hypoglycemia may get complications of acute hypoglycemia if they suffer delays in access to healthcare, and blood sugar is not corrected immediately; these include cardiac arrhythmias, seizures, strokes, coma, and eventually death.[18]

Deterrence and Patient Education

Patients usually tend to underestimate the consequences of low blood sugar, and many individuals may self-inject insulin or take other blood sugar lowering drugs to get the symptoms of hypoglycemia and get individual attention and sympathy. If you feel that a close friend or family member is at risk of such behavior, especially if they have access to insulin or other diabetes medications, it is highly relevant to educate them and help them address their concerns with their primary care provider, before they develop significant complications of hypoglycemia.

Pearls and Other Issues

Autoimmune insulin hypoglycemia is a rare disease, in which patients would be still continuously present with hypoglycemia and elevated endogenous plasma insulin. It can be differentiated from insulinoma and factitious hypoglycemia by detecting insulin autoantibodies in the blood.[10]

Enhancing Healthcare Team Outcomes

Communication between healthcare providers can help in early detection of factitious hypoglycemia in patients who present with recurrent unexplained hypoglycemic episodes, as early recognition is associated with a better prognosis and can save a lot of time and effort.

In diabetic patients who are already on insulin, diagnosis of factitious hypoglycemia can be challenging. In this situation, Patients can be admitted under observation for a few days in a monitored setting, with insulin administration and glucose checks performed by medical staff.

Factitious hypoglycemia requires an interprofessional team approach, including physicians, specialists, specialty-trained nurses, mental health professionals, and pharmacists, all collaborating across disciplines to achieve optimal patient results. [Level V]


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Factitious Hypoglycemia - Questions

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A 65-year-old male with a past medical history of poorly controlled type 2 diabetes mellitus, hypertension, and hyperlipidemia, presented to the emergency department with complaints of dizziness, nausea, sweating, and palpitations. He did not lose consciousness. His BP was 130/85 mmHg, HR 110/minute, RR 16/minute, and T 36.9 C. He is alert and oriented to person, but not time or place. He is accompanied by his wife who says he is at his baseline mental status. His home medications include lisinopril, atorvastatin, metformin, glimepiride, insulin glargine, and a sliding scale of lispro. Blood tests revealed glucose of 45 mg/dL, high blood insulin level, and undetected C peptide. His hypoglycemia was corrected, and his symptoms improved. The wife states that two days ago, he was telling her that he wants to die and she thinks he has been in a very bad mood recently. Which of the following is the most likely cause of his hypoglycemia?



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Factitious Hypoglycemia - References

References

Murray BJ, Hypoglycemia secondary to factitious hyperinsulinism. Postgraduate medicine. 1981 Feb;     [PubMed]
Grunberger G,Weiner JL,Silverman R,Taylor S,Gorden P, Factitious hypoglycemia due to surreptitious administration of insulin. Diagnosis, treatment, and long-term follow-up. Annals of internal medicine. 1988 Feb;     [PubMed]
Bhatnagar D, Diagnosis of factitious hypoglycaemia. British journal of hospital medicine. 1988 Aug;     [PubMed]
Tattersall R,Gregory R,Selby C,Kerr D,Heller S, Course of brittle diabetes: 12 year follow up. BMJ (Clinical research ed.). 1991 May 25;     [PubMed]
Schade DS,Drumm DA,Eaton RP,Sterling WA, Factitious brittle diabetes mellitus. The American journal of medicine. 1985 May;     [PubMed]
Schade DS,Burge MR, Brittle diabetes: etiology and treatment. Advances in endocrinology and metabolism. 1995;     [PubMed]
Cryer PE,Axelrod L,Grossman AB,Heller SR,Montori VM,Seaquist ER,Service FJ, Evaluation and management of adult hypoglycemic disorders: an Endocrine Society Clinical Practice Guideline. The Journal of clinical endocrinology and metabolism. 2009 Mar;     [PubMed]
Biliotti GC,Vestrini G,Tonelli P,Salvietti A,Fucini C, Factitious hypoglycemia: an unusual clinical picture within Von Münchausen's syndrome. The Italian journal of surgical sciences. 1983;     [PubMed]
Klein RF,Seino S,Sanz N,Nolte MS,Vinik AI,Karam JH, High performance liquid chromatography used to distinguish the autoimmune hypoglycemia syndrome from factitious hypoglycemia. The Journal of clinical endocrinology and metabolism. 1985 Sep;     [PubMed]
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 (Clinical research ed.). 1997 Feb 15;     [PubMed]
Marks V,Teale JD, Hypoglycemia: factitious and felonious. Endocrinology and metabolism clinics of North America. 1999 Sep;     [PubMed]
Marks V,Teale JD, Drug-induced hypoglycemia. Endocrinology and metabolism clinics of North America. 1999 Sep;     [PubMed]
Boyle PJ,Justice K,Krentz AJ,Nagy RJ,Schade DS, Octreotide reverses hyperinsulinemia and prevents hypoglycemia induced by sulfonylurea overdoses. The Journal of clinical endocrinology and metabolism. 1993 Mar;     [PubMed]
Altszuler N,Moraru E,Hampshire J, On the mechanism of diazoxide-induced hyperglycemia. Diabetes. 1977 Oct;     [PubMed]
Otto C,Richter WO, [Hypoglycemia. Symptoms, differential diagnosis, therapy]. Fortschritte der Medizin. 1997 Feb 28;     [PubMed]
Huffman JC,Stern TA, The diagnosis and treatment of Munchausen's syndrome. General hospital psychiatry. 2003 Sep-Oct;     [PubMed]
Goto A,Arah OA,Goto M,Terauchi Y,Noda M, Severe hypoglycaemia and cardiovascular disease: systematic review and meta-analysis with bias analysis. BMJ (Clinical research ed.). 2013 Jul 29;     [PubMed]
Fu Z,Gilbert ER,Liu D, Regulation of insulin synthesis and secretion and pancreatic Beta-cell dysfunction in diabetes. Current diabetes reviews. 2013 Jan 1;     [PubMed]

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