Continuing Education Activity

Factitious hypoglycemia is the intentional attempt to induce low blood glucose levels and remains one of the diagnostic challenges that face endocrinologists during their practice. To achieve good outcomes, the diagnosis and management of factitious hypoglycemia must be defined. This activity outlines the evaluation, management, and complications of factitious hypoglycemia and highlights the interprofessional team's role in improving care for patients with this condition.

Objectives:

• Identify the etiology of factitious hypoglycemia.
• Describe the appropriate evaluation of factitious hypoglycemia.
• Outline treatment and management options available for factitious hypoglycemia.
• Discuss interprofessional team strategies for improving care coordination and communication to advance factitious hypoglycemia and improve outcomes.

Introduction

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

When insulin is self-injected, laboratory studies will show high plasma insulin levels in combination with low plasma C-peptide levels during the hypoglycemic episode. With sulfonylurea consumption, the clinical picture may mimic an insulinoma with high plasma levels of both C-peptide and insulin; a positive drug screen can render the diagnosis.

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

Factitious hypoglycemia is more common in women with diabetes, especially during the third and fourth decades of life.[2][3]

Pathophysiology

Insulin synthesis occurs in the β-cells of the pancreas. Preproinsulin secreted from β-cells is cleaved into proinsulin, which is then converted into insulin and C peptide.[4] Insulin and c peptide are stored in secretory granules and will be released in the event of hyperglycemia. The liver will rapidly remove the circulating insulin, whereas C peptide remains in the circulation for a more extended period of time until cleared renally. The insulin to C peptide ratio in healthy individuals is usually less than one. A small quantity of proinsulin is also secreted into blood circulation without processing, which is 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 a 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 hypoglycemia episodes.

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 uncover possible factitious disorders in those who are not 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, including 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 treating 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 antihypertensive 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. However, many patients 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 considered, 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. Many individuals may self-inject insulin or take other blood sugar lowering drugs to produce hypoglycemia symptoms 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 still be 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 the nursing staff and frequent reporting to the interprofessional team. The team must work collaboratively to educate the patient and family to create the best environment to achieve optimal results.

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 5]