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.
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.
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.
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.
Fulfillment of the Whipple triad is necessary before establishing any diagnosis of a hypoglycemic disorder. The triad consists of:
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.
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. 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. 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. 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.
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.
Differential diagnosis of hypoglycemia includes but is not limited to the following:
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.
The prognosis of factitious disorder is generally poor, and patients are unlikely to recover, especially when identified late in the disease course. In one study that followed ten patients for many years after the diagnosis of factitious hypoglycemia, two out of the ten patients committed suicide.
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.
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.
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.
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 together to educate the patient and family to create the best environment for 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 V]
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