Insulin autoimmune syndrome

Last updated

Insulin autoimmune syndrome (IAS), a rare cause of reversible autoimmune hypoglycemia also known as Hirata's disease, [1] was first described by Hirata in Japan in 1970. [2]

Contents

Signs and symptoms

Affected patients are usually adults, experiencing multiple episodes of spontaneous hypoglycemia with neuroglycopenic symptoms. [3]

Causes

The cause of IAS is not clearly understood. However, interaction of disulfide bond in the insulin molecule with sulfhydryl group drugs such as methimazole, carbimazole, captopril, isoniazid, hydralazine, imipenem, and also with lipoic acid has been suggested. [4] [5] [6] Drug-induced autoimmunization is evidenced by insulin autoantibodies appearing a few weeks after the intake of drug containing the sulfhydryl group. Additionally, IAS has a significant genetic predisposition as its association with specific HLA class has been observed [ citation needed ].

Pathophysiology

Following a meal, glucose concentration in the bloodstream rises, providing a stimulus for insulin secretion. Autoantibodies bind to these insulin molecules, rendering them unable to exert their effects. The resultant hyperglycemia promotes further insulin release. As glucose concentration eventually falls, insulin secretion also subsides, and the total insulin level decreases. Now insulin molecules spontaneously dissociate from the autoantibodies, giving rise to a raised free insulin level inappropriate for the glucose concentration, causing hypoglycemia. [7] [8]

Diagnosis

Usual presenting features are multiple episodes of spontaneous hypoglycemia and appearance of insulin autoantibodies without prior history of administration of exogenous insulin. [9] The insulin level is significantly high, usually up to 100 mIU/L, C-peptide level is markedly elevated, and insulin antibodies are positive.[ citation needed ]

Treatment

The best known treatment is recommending frequent, small meals and to avoid simple sugars. Sulfhydryl group-containing drugs should be avoided and steroids can be used in resistant cases. [10] [11]

Related Research Articles

<span class="mw-page-title-main">Hypoglycemia</span> Health condition

Hypoglycemia, also called low blood sugar, is a fall in blood sugar to levels below normal, typically below 70 mg/dL (3.9 mmol/L). Whipple's triad is used to properly identify hypoglycemic episodes. It is defined as blood glucose below 70 mg/dL (3.9 mmol/L), symptoms associated with hypoglycemia, and resolution of symptoms when blood sugar returns to normal. Hypoglycemia may result in headache, tiredness, clumsiness, trouble talking, confusion, fast heart rate, sweating, shakiness, nervousness, hunger, loss of consciousness, seizures, or death. Symptoms typically come on quickly.

<span class="mw-page-title-main">Sulfonylurea</span> Class of organic compounds used in medicine and agriculture

Sulfonylureas or sulphonylureas are a class of organic compounds used in medicine and agriculture. The functional group consists of a sulfonyl group (-S(=O)2) with its sulphur atom bonded to nitrogen atom of a ureylene group (N,N-dehydrourea, a urea derivative). The side chains R1 and R2 distinguish various sulfonylureas.

<span class="mw-page-title-main">Insulinoma</span> Medical condition

An insulinoma is a tumour of the pancreas that is derived from beta cells and secretes insulin. It is a rare form of a neuroendocrine tumour. Most insulinomas are benign in that they grow exclusively at their origin within the pancreas, but a minority metastasize. Insulinomas are one of the functional pancreatic neuroendocrine tumour (PNET) group. In the Medical Subject Headings classification, insulinoma is the only subtype of "islet cell adenoma".

Hyperinsulinemic hypoglycemia describes the condition and effects of low blood glucose caused by excessive insulin. Hypoglycemia due to excess insulin is the most common type of serious hypoglycemia. It can be due to endogenous or injected insulin.

<span class="mw-page-title-main">Hyperinsulinism</span> Medical condition

Hyperinsulinism refers to an above normal level of insulin in the blood of a person or animal. Normal insulin secretion and blood levels are closely related to the level of glucose in the blood, so that a given level of insulin can be normal for one blood glucose level but low or high for another. Hyperinsulinism can be associated with several types of medical problems, which can be roughly divided into two broad and largely non-overlapping categories: those tending toward reduced sensitivity to insulin and high blood glucose levels (hyperglycemia), and those tending toward excessive insulin secretion and low glucose levels (hypoglycemia).

Neuroglycopenia is a shortage of glucose (glycopenia) in the brain, usually due to hypoglycemia. Glycopenia affects the function of neurons, and alters brain function and behavior. Prolonged or recurrent neuroglycopenia can result in loss of consciousness, damage to the brain, and eventual death.

<span class="mw-page-title-main">Hyperinsulinemia</span> Abnormal increase in insulin in the bloodstream relative to glucose

Hyperinsulinemia is a condition in which there are excess levels of insulin circulating in the blood relative to the level of glucose. While it is often mistaken for diabetes or hyperglycaemia, hyperinsulinemia can result from a variety of metabolic diseases and conditions, as well as non-nutritive sugars in the diet. While hyperinsulinemia is often seen in people with early stage type 2 diabetes mellitus, it is not the cause of the condition and is only one symptom of the disease. Type 1 diabetes only occurs when pancreatic beta-cell function is impaired. Hyperinsulinemia can be seen in a variety of conditions including diabetes mellitus type 2, in neonates and in drug-induced hyperinsulinemia. It can also occur in congenital hyperinsulinism, including nesidioblastosis.

Evans syndrome is an autoimmune disease in which an individual's immune system attacks their own red blood cells and platelets, the syndrome can include immune neutropenia. These immune cytopenias may occur simultaneously or sequentially.

<span class="mw-page-title-main">Reactive hypoglycemia</span> Medical condition

Reactive hypoglycemia, postprandial hypoglycemia, or sugar crash is a term describing recurrent episodes of symptomatic hypoglycemia occurring within four hours after a high carbohydrate meal in people with and without diabetes. The term is not necessarily a diagnosis since it requires an evaluation to determine the cause of the hypoglycemia.

<span class="mw-page-title-main">Type 1 diabetes</span> Form of diabetes mellitus

Type 1 diabetes (T1D), formerly known as juvenile diabetes, is an autoimmune disease that originates when cells that make insulin are destroyed by the immune system. Insulin is a hormone required for the cells to use blood sugar for energy and it helps regulate glucose levels in the bloodstream. Before treatment this results in high blood sugar levels in the body. The common symptoms of this elevated blood sugar are frequent urination, increased thirst, increased hunger, weight loss, and other serious complications. Additional symptoms may include blurry vision, tiredness, and slow wound healing. Symptoms typically develop over a short period of time, often a matter of weeks.

Rabson–Mendenhall syndrome is a rare autosomal recessive disorder characterized by severe insulin resistance. The disorder is caused by mutations in the insulin receptor gene. Symptoms include growth abnormalities of the head, face and nails, along with the development of acanthosis nigricans. Treatment involves controlling blood glucose levels by using insulin and incorporating a strategically planned, controlled diet. Also, direct actions against other symptoms may be taken This syndrome usually affects children and has a prognosis of 1–2 years.

Autoimmune hypophysitis is defined as inflammation of the pituitary gland due to autoimmunity.

<span class="mw-page-title-main">Minimed Paradigm</span> Insulin pumps

MiniMed Paradigm is a series of insulin pumps manufactured by Medtronic for patients with diabetes mellitus. The pump operates with a single AAA battery and uses a piston-plunger pump to infuse a programmed amount of insulin into the patient through a length of tubing. The Paradigm uses a one-way wireless radio frequency link to receive blood sugar measurements from select glucose meters. The Paradigm RT series adds the ability to receive data from a mated continuous blood-glucose monitor. Although the pump can use these measurements to assist in calculating a dose of insulin, no actual change in insulin delivery occurs without manual user-intervention.

Complications of diabetes mellitus include problems that develop rapidly (acute) or over time (chronic) and may affect many organ systems. The complications of diabetes can dramatically impair quality of life and cause long-lasting disability. Overall, complications are far less common and less severe in people with well-controlled blood sugar levels. Some non-modifiable risk factors such as age at diabetes onset, type of diabetes, gender and genetics may influence risk. Other health problems compound the chronic complications of diabetes such as smoking, obesity, high blood pressure, elevated cholesterol levels, and lack of regular exercise. Complications of diabetes are a strong risk factor for severe COVID-19 illness.

<span class="mw-page-title-main">Insulin degludec</span> Ultralong-acting basal insulin analogue

Insulin degludec (INN/USAN) is an ultralong-acting basal insulin analogue that was developed by Novo Nordisk under the brand name Tresiba. It is administered via subcutaneous injection once daily to help control the blood sugar level of those with diabetes. It has a duration of action that lasts up to 42 hours, making it a once-daily basal insulin, that is one that provides a base insulin level, as opposed to the fast- and short-acting bolus insulins.

Antithyroid autoantibodies (or simply antithyroid antibodies) are autoantibodies targeted against one or more components on the thyroid. The most clinically relevant anti-thyroid autoantibodies are anti-thyroid peroxidase antibodies (anti-TPO antibodies, TPOAb), thyrotropin receptor antibodies (TRAb) and thyroglobulin antibodies (TgAb). TRAb's are subdivided into activating, blocking and neutral antibodies, depending on their effect on the TSH receptor. Anti-sodium/iodide (Anti–Na+/I−) symporter antibodies are a more recent discovery and their clinical relevance is still unknown. Graves' disease and Hashimoto's thyroiditis are commonly associated with the presence of anti-thyroid autoantibodies. Although there is overlap, anti-TPO antibodies are most commonly associated with Hashimoto's thyroiditis and activating TRAb's are most commonly associated with Graves' disease. Thyroid microsomal antibodies were a group of anti-thyroid antibodies; they were renamed after the identification of their target antigen (TPO).

<span class="mw-page-title-main">Donohue syndrome</span> Medical condition

Donohue syndrome is an extremely rare and severe genetic disorder. Leprechaunism derives its name from the hallmark elvish features exhibited by the affected individuals. The disease is caused by a mutation in the INSR gene, which contains the genetic information for the formation of insulin receptors. As a result, affected individuals have either a decreased number of insulin receptors, or insulin receptor with greatly impaired functionality. The lack and impairment of insulin receptor functionality leads to an inability to regulate blood glucose levels through severe insulin resistance. This will ultimately lead to affected development of tissues and organs throughout the body. In addition to the physical abnormalities, leprechaunism is also characterized by endocrine system abnormalities that can lead to conditions such as hyperglycemia, hypoglycemia, hyperinsulemia, and the enlargement of certain sex organs such as the penis in males, and the clitoris in females.

Ketosis-prone diabetes (KPD) is an intermediate form of diabetes that has some characteristics of type 1 and some of type 2 diabetes. Type 1 diabetes involves autoimmune destruction of pancreatic beta cells which create insulin. This occurs earlier in a person's life, leading to patients being insulin dependent, and the lack of natural insulin makes patients prone to a condition called diabetic ketoacidosis (DKA). Type 2 diabetes is different in that it is usually caused by insulin resistance in the body in older patients leading to beta cell burnout over time, and is not prone to DKA. KPD is a condition that involves DKA like type 1, but occurs later in life and can regain beta cell function like type 2 diabetes. However, it is distinct from latent autoimmune diabetes of adults (LADA), a form of type 1 sometimes referred to as type 1.5 that does not occur with DKA. There are also distinctions to be made between KPD and LADA as patients who exhibit KPD symptoms can regain beta cell function similar to type 2 diabetics whereas LADA will not exhibit this reclamation of beta cell function.

<span class="mw-page-title-main">HAIR-AN syndrome</span> Medical condition

The HAIR-AN syndrome is a rare subtype of polycystic ovary syndrome (PCOS) characterized by hyperandrogenism (HA), insulin resistance (IR) and acanthosis nigricans (AN). The symptoms of the HAIR-AN syndrome are largely due to severe insulin resistance, which can be secondary to blocking antibodies against the insulin receptor or genetically absent/reduced insulin receptor number/function. Insulin resistance leads to hyperinsulinemia which, in turn, leads to an excess production of androgen hormones by the ovaries. High levels of androgen hormones (hyperandrogenism) in females causes excessive hair growth, acne and irregular menstruation. Patients with both underlying mechanisms of insulin resistance may have more severe hyperandrogenism. Insulin resistance is also associated with diabetes, heart disease and excessive darkening of the skin

References

  1. ↑ Alves, Cresio; Constança, Julia; De León, Diva D.; Snider, Kara; Stanley, Charles (2013). "A novel atypical presentation of insulin autoimmune syndrome (Hirata's disease) in a child". Journal of Pediatric Endocrinology and Metabolism. 26 (11–12): 1163–1166. doi:10.1515/jpem-2013-0215. PMC   4361817 . PMID   23843578.
  2. ↑ Y., Hirata (1970). "Insulin autoimmunity in a case of spontaneous hypoglycemia". J Jpn Diabet Soc. 13: 312–319.
  3. ↑ JB, Redmon; FQ, Nuttall (1999). "Autoimmune hypoglycemia". Endocrinol Metab Clin North Am. 28 (3): 603–618. doi:10.1016/S0889-8529(05)70090-6. PMID   10500933.
  4. ↑ T, Yamada; J, Imai; Y, Ishigaki; Y, Hinokio; Y, Oka; H, Katagiri (2007). "Possible relevance of HLA-DRB1*0403 haplotype in insulin autoimmune syndrome induced by alpha-lipoic acid, used as a dietary supplement". Diabetes Care. 30 (12): 131. doi: 10.2337/dc07-1636 . PMID   18042740.
  5. ↑ Y, Uchigata; Y, Hirata; Y, Iwamoto (2009). "Drug-induced insulin autoimmune syndrome". Diabetes Res Clin Pract. 83 (1): 19–20. doi:10.1016/j.diabres.2008.10.015. PMID   19070385.
  6. ↑ BC, Lupsa; AY, Chong; EK, Cochran; MA, Soos; RK, Semple; P, Gorden (2009). "Autoimmune forms of hypoglycemia". Medicine (Baltimore). 88 (3): 141–153. doi: 10.1097/MD.0b013e3181a5b42e . PMID   19440117. S2CID   34429211.
  7. ↑ JB, Redmon; FQ, Nuttall (1999). "Autoimmune hypoglycemia". Endocrinol Metab Clin North Am. 28 (3): 603–618. doi:10.1016/S0889-8529(05)70090-6. PMID   10500933.
  8. ↑ V, Pant; B, Bhandari; S, Baral; SR, Bajracharya (7 February 2019). "Insulin autoimmune syndrome as a cause of recurrent hypoglycemia in a carbimazole user: a case report from Nepal". International Medical Case Reports Journal. 2019 (12): 29–32. doi: 10.2147/IMCRJ.S190908 . PMC   6369838 . PMID   30799961.
  9. ↑ Y., Uchigata (1999). "Insulin autoimmune syndrome (IAS, Hirata disease)". Ann Med Interne (Paris). 150 (3): 245–253. PMID   10445096.
  10. ↑ AA, Ismail (2016). "The insulin autoimmune syndrome (IAS) as a cause of hypoglycaemia: an update on the pathophysiology, biochemical investigations and diagnosis". Clin Chem Lab Med. 54 (11): 1715–1724. doi: 10.1515/cclm-2015-1255 . PMID   27071154. S2CID   33482503.
  11. ↑ V, Pant; B, Bhandari; S, Baral; SR, Bajracharya (7 February 2019). "Insulin autoimmune syndrome as a cause of recurrent hypoglycemia in a carbimazole user: a case report from Nepal". International Medical Case Reports Journal. 2019 (12): 29–32. doi: 10.2147/IMCRJ.S190908 . PMC   6369838 . PMID   30799961.
This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.