Thiamine deficiency (beriberi)

From Wikipedia, the free encyclopedia

Thiamine deficiency
Other names	Beriberi, vitamin B1 deficiency, thiamine-deficiency syndrome
A person with beriberi during the early twentieth century in South-East Asia
Specialty	Neurology, cardiology, pediatrics
Symptoms	Wet: Fast heart rate, shortness of breath, leg swelling Dry: Numbness, confusion, trouble moving the legs, pain
Types	Wet, dry, gastrointestinal
Causes	Not enough thiamine
Risk factors	Diet of mostly white rice; alcoholism, dialysis, chronic diarrhea, diuretics
Prevention	Food fortification
Treatment	Thiamine supplementation
Frequency	Rare (US)

Thiamine deficiency is a medical condition of low levels of thiamine (vitamin B1). A severe and chronic form is known as beriberi. There are two main types in adults: wet beriberi, and dry beriberi. Wet beriberi affects the cardiovascular system resulting in a fast heart rate, shortness of breath, and leg swelling. Dry beriberi affects the nervous system resulting in numbness of the hands and feet, confusion, trouble moving the legs, and pain. A form with loss of appetite and constipation may also occur. Another type, acute beriberi, is found mostly in babies and presents with loss of appetite, vomiting, lactic acidosis, changes in heart rate, and enlargement of the heart.

Risk factors include a diet of mostly white rice, as well as alcoholism, dialysis, chronic diarrhea, and taking high doses of diuretics. Rarely it may be due to a genetic condition which results in difficulties absorbing thiamine found in food. Wernicke encephalopathy and Korsakoff syndrome are forms of dry beriberi. Diagnosis is based on symptoms, low levels of thiamine in the urine, high blood lactate, and improvement with treatment.

Treatment is by thiamine supplementation, either by mouth or by injection. With treatment symptoms generally resolve in a couple of weeks. The disease may be prevented at the population level through the fortification of food.

Thiamine deficiency is rare in the United States. It remains relatively common in sub-Saharan Africa. Outbreaks have been seen in refugee camps. Thiamine deficiency has been described for thousands of years in Asia and became more common in the late 1800s with the increased processing of rice.

Signs and symptoms

Beriberi

Symptoms of beriberi include weight loss, emotional disturbances, impaired sensory perception, weakness and pain in the limbs, and periods of irregular heart rate. Edema (swelling of bodily tissues) is common. It may increase the amount of lactic acid and pyruvic acid within the blood. In advanced cases, the disease may cause high-output cardiac failure and death. 

Symptoms may occur concurrently with those of Wernicke's encephalopathy, a primarily neurological thiamine-deficiency related condition.

Beriberi is divided into four categories as follows. The first three are historical and the fourth, gastrointestinal beriberi, was recognized in 2004:

• Dry beriberi specially affects the peripheral nervous system.
• Wet beriberi specially affects the cardiovascular system and other bodily systems.
• Infantile beriberi affects the babies of malnourished mothers.
• Gastrointestinal beriberi affects the digestive system and other bodily systems.

Dry beriberi

Dry beriberi causes wasting and partial paralysis resulting from damaged peripheral nerves. It is also referred to as endemic neuritis. It is characterized by:

• Difficulty in walking
• Tingling or loss of sensation (numbness) in hands and feet
• Loss of tendon reflexes
• Loss of muscle function or paralysis of the lower legs
• Mental confusion/speech difficulties
• Pain
• Involuntary eye movements (nystagmus)
• Vomiting

A selective impairment of the large proprioceptive sensory fibers without motor impairment can occur and present as a prominent sensory ataxia, which is a loss of balance and coordination due to loss of the proprioceptive inputs from the periphery and loss of position sense.

Brain disease

Wernicke's encephalopathy (WE), Korsakoff's syndrome (alcohol amnestic disorder), Wernicke–Korsakoff syndrome are forms of dry beriberi.

Wernicke's encephalopathy is the most frequently encountered manifestation of thiamine deficiency in Western society, though it may also occur in patients with impaired nutrition from other causes, such as gastrointestinal disease, those with HIV/AIDS, and with the injudicious administration of parenteral glucose or hyperalimentation without adequate B-vitamin supplementation. This is a striking neuro-psychiatric disorder characterized by paralysis of eye movements, abnormal stance and gait, and markedly deranged mental function.

Korsakoff's syndrome is, in general, considered to occur with deterioration of brain function in patients initially diagnosed with WE. This is an amnestic-confabulatory syndrome characterized by retrograde and anterograde amnesia, impairment of conceptual functions, and decreased spontaneity and initiative.

Alcoholics may have thiamine deficiency because of the following:

• Inadequate nutritional intake: Alcoholics tend to intake less than the recommended amount of thiamine.
• Decreased uptake of thiamine from the GI tract: Active transport of thiamine into enterocytes is disturbed during acute alcohol exposure.
• Liver thiamine stores are reduced due to hepatic steatosis or fibrosis.
• Impaired thiamine utilization: Magnesium, which is required for the binding of thiamine to thiamine-using enzymes within the cell, is also deficient due to chronic alcohol consumption. The inefficient utilization of any thiamine that does reach the cells will further exacerbate the thiamine deficiency.
• Ethanol per se inhibits thiamine transport in the gastrointestinal system and blocks phosphorylation of thiamine to its cofactor form (ThDP).

Following improved nutrition and the removal of alcohol consumption, some impairments linked with thiamine deficiency are reversed, in particular poor brain functionality, although in more severe cases, Wernicke–Korsakoff syndrome leaves permanent damage.

Wet beriberi

Wet beriberi affects the heart and circulatory system. It is sometimes fatal, as it causes a combination of heart failure and weakening of the capillary walls, which causes the peripheral tissues to become edematous. Wet beriberi is characterized by:

• Increased heart rate
• Vasodilation leading to decreased systemic vascular resistance, and high output heart failure
• Elevated jugular venous pressure
• Dyspnea (shortness of breath) on exertion
• Paroxysmal nocturnal dyspnea
• Peripheral edema (swelling of lower legs)
• Dilated cardiomyopathy

Gastrointestinal beriberi

Gastrointestinal beriberi causes abdominal pain. Gastrointestinal beriberi is characterized by:

• Abdominal pain
• Nausea
• Vomiting
• Lactic acidosis

Infants

Infantile beriberi usually occurs between two and six months of age in children whose mothers have inadequate thiamine intake. It may present as either wet or dry beriberi.

In the acute form, the baby develops dyspnea and cyanosis and soon dies of heart failure. These symptoms may be described in infantile beriberi:

• Hoarseness, where the child makes moves to moan but emits no sound or just faint moans caused by nerve paralysis
• Weight loss, becoming thinner and then marasmic as the disease progresses
• Vomiting
• Diarrhea
• Pale skin
• Edema
• Ill temper
• Alterations of the cardiovascular system, especially tachycardia (rapid heart rate)
• Convulsions occasionally observed in the terminal stages

Cause

Beriberi may also be caused by shortcomings other than inadequate intake: diseases or operations on the digestive tract, alcoholism, dialysis, genetic deficiencies, etc. All these causes mainly affect the central nervous system, and provoke the development of what is known as Wernicke's disease or Wernicke's encephalopathy. 

Wernicke's disease is one of the most prevalent neurological or neuropsychiatric diseases. In autopsy series, features of Wernicke lesions are observed in approximately 2% of general cases. Medical record research shows that about 85% had not been diagnosed, although only 19% would be asymptomatic. In children, only 58% were diagnosed. In alcohol abusers, autopsy series showed neurological damages at rates of 12.5% or more. Mortality caused by Wernicke's disease reaches 17% of diseases, which means 3.4/1000 or about 25 million contemporaries. The number of people with Wernicke's disease may be even higher, considering that early stages may have dysfunctions prior to the production of observable lesions at necropsy. In addition, uncounted numbers of people can experience fetal damage and subsequent diseases.

Genetics

Genetic diseases of thiamine transport are rare but serious. Thiamine responsive megaloblastic anemia (TRMA) with diabetes mellitus and sensorineural deafness is an autosomal recessive disorder caused by mutations in the gene SLC19A2, a high affinity thiamine transporter. TRMA patients do not show signs of systemic thiamine deficiency, suggesting redundancy in the thiamine transport system. This has led to the discovery of a second high-affinity thiamine transporter, SLC19A3. Leigh disease (subacute necrotising encephalomyelopathy) is an inherited disorder that affects mostly infants in the first years of life and is invariably fatal. Pathological similarities between Leigh disease and WE led to the hypothesis that the cause was a defect in thiamine metabolism. One of the most consistent findings has been an abnormality of the activation of the pyruvate dehydrogenase complex.

Mutations in the SLC19A3 gene have been linked to biotin-thiamine responsive basal ganglia disease which is treated with pharmacological doses of thiamine and biotin, another B vitamin. 

Other disorders in which a putative role for thiamine has been implicated include subacute necrotising encephalomyelopathy, opsoclonic cerebellopathy (a paraneoplastic syndrome), and Nigerian seasonal ataxia. In addition, several inherited disorders of ThDP-dependent enzymes have been reported, which may respond to thiamine treatment.

Pathophysiology

Thiamine in the human body has a half-life of 18 days and is quickly exhausted, particularly when metabolic demands exceed intake. A derivative of thiamine, thiamine pyrophosphate (TPP), is a cofactor involved in the citric acid cycle, as well as connecting the breakdown of sugars with the citric acid cycle. The citric acid cycle is a central metabolic pathway involved in the regulation of carbohydrate, lipid, and amino acid metabolism, and its disruption due to thiamine deficiency inhibits the production of many molecules including the neurotransmitters glutamic acid and GABA. Additionally thiamine may also be directly involved in neuromodulation.

Diagnosis

Oxidation of thiamine derivatives to fluorescent thiochromes by potassium ferricyanide under alkaline conditions

 

A positive diagnosis test for thiamine deficiency can be ascertained by measuring the activity of the enzyme transketolase in erythrocytes (Erythrocyte Transketolase Activation Assay). Thiamine, as well as its phosphate derivatives, can also be detected directly in whole blood, tissues, foods, animal feed, and pharmaceutical preparations following the conversion of thiamine to fluorescent thiochrome derivatives (Thiochrome Assay) and separation by high-performance liquid chromatography (HPLC). In recent reports, a number of Capillary Electrophoresis (CE) techniques and in-capillary enzyme reaction methods have emerged as potential alternative techniques for the determination and monitoring of thiamine in samples. The normal thiamine concentration in EDTA-blood is about 20-100 µg/l.

Treatment

Many people with beriberi can be treated with thiamine alone. Given thiamine intravenously (and later orally), rapid and dramatic recovery can occur within hours. In situations where concentrated thiamine supplements are unavailable, feeding the person with a thiamine-rich diet (e.g. whole grain brown bread) will lead to recovery, though at a much slower rate.

Following thiamine treatment, rapid improvement occurs, in general, within 24 hours. Improvements of peripheral neuropathy may require several months of thiamine treatment.

Epidemiology

Historically, beriberi was associated with a diet including much polished rice (white rice); when the relationship between polishing rice and the disease was discovered, it became possible to prevent and treat the deficiency condition, for example with inexpensive rice bran. Beriberi caused by inadequate nutritional intake is rare today in developed countries because of quality of food and the fact that many foods are fortified with vitamins. No reliable statistics are given for beriberi in developed countries in the 19th century or earlier; neither are statistics available before the last century in countries in extreme poverty.

Beriberi is a recurrent nutritional disease in detention houses, even in this century. In 1999, an outbreak of beriberi occurred in a detention center in Taiwan. High rates of illness and death in overcrowded Haitian jails were traced in 2007 to the traditional practice of washing rice before cooking. In the Ivory Coast, among a group of prisoners with heavy punishment, 64% were affected by beriberi. Before beginning treatment, prisoners exhibited symptoms of dry or wet beriberi with neurological signs (tingling: 41%), cardiovascular signs (dyspnoea: 42%, thoracic pain: 35%), and edemas of the lower limbs (51%). With treatment the rate of healing was about 97%.

Populations under extreme stress may be at higher risk for beriberi. Displaced populations, such as refugees from war, are susceptible to micronutritional deficiency, including beriberi. The severe nutritional deprivation caused by famine also can cause beriberis, although symptoms may be overlooked in clinical assessment or masked by other famine-related problems. An extreme weight-loss diet can, rarely, induce a famine-like state and the accompanying beriberi.

History

Earliest written descriptions of thiamine deficiency are from Ancient China in the context of chinese medicine. One of the earliest is by Ge Hong in his book Zhou hou bei ji fang (Emergency Formulas to Keep up Your Sleeve) written sometime during 3rd century. Hong called the illness by the name jiao qi, which can be intepreted as "foot qi". He described the symptoms to include swelling, weakness and numbness of the feet. He also acknowledged that the illness could be deadly, and claimed that it could be cured by eating certain foods like fermented soybeans in wine. Better known examples of early descriptions of "foot qi" are by Chao Yuanfang (who lived during 550–630) in his book Zhu bing yuan hou lun (Sources and Symptoms of All Diseases) and by Sun Simiao (581–682) in his book Bei ji qian jin yao fang (Essential Emergency Formulas Worth a Thousand in Gold).

In the late 19th century, beriberi was studied by Takaki Kanehiro, a British-trained Japanese medical doctor of the Imperial Japanese Navy. Beriberi was a serious problem in the Japanese navy: Sailors fell ill an average of four times a year in the period 1878 to 1881, and 35% were cases of beriberi. In 1883, Takaki learned of a very high incidence of beriberi among cadets on a training mission from Japan to Hawaii, via New Zealand and South America. The voyage lasted more than nine months and resulted in 169 cases of sickness and 25 deaths on a ship of 376 men. With the support of the Japanese Navy, he conducted an experiment in which another ship was deployed on the same route, except that its crew was fed a diet of meat, fish, barley, rice, and beans. At the end of the voyage, this crew had only 14 cases of beriberi and no deaths. This convinced Takaki and the Japanese Navy that diet was the cause. In 1884, Takaki observed that beriberi was common among low-ranking crew who were often provided free rice and thus ate little else, but not among crews of Western navies, nor among Japanese officers who consumed a more varied diet. 

In 1897, Christiaan Eijkman, a Dutch physician and pathologist, demonstrated that beriberi is caused by poor diet, and discovered that feeding unpolished rice (instead of the polished variety) to chickens helped to prevent beriberi. The following year, Sir Frederick Hopkins postulated that some foods contained "accessory factors"—in addition to proteins, carbohydrates, fats, and salt—that were necessary for the functions of the human body. In 1901, Gerrit Grijns, a Dutch physician and assistant to Christiaan Eijkman in the Netherlands, correctly interpreted beriberi as a deficiency syndrome, and between 1910 and 1913, Edward Bright Vedder established that an extract of rice bran is a treatment for beriberi. In 1929, Eijkman and Hopkins were awarded the Nobel Prize for Physiology or Medicine for their discoveries.

Etymology

Although according to the Oxford English Dictionary, the term "beriberi" comes from a Sinhalese phrase meaning "weak, weak" or "I cannot, I cannot", the word being duplicated for emphasis, the origin of the phrase is questionable. It has also been suggested to come from Hindi, Arabic and few other languages, with many meanings like "weakness", "sailor" and even "sheep". Such suggested origins were listed by Heinrich Botho Scheube among others. Edward Vedder wrote in his book Beriberi (1913) that "it is impossible to definitely trace the origin of the word beriberi". Word berbere was used in writing at least as early as 1568 by Diogo do Couto, when he described the deficiency in India.

"Kakke", which is a Japanese synonym for thiamine deficiency, comes from the way "jiao qi" is pronounced in Japanese. "Jiao qi" is an old word used in Chinese medicine to describe thiamine deficiency. "Kakke" is supposed to have entered in the Japanese language sometime between the 6th and 8th centuries.

Other animals

Poultry

As most feedstuffs used in poultry diets contain enough quantities of vitamins to meet the requirements in this species, deficiencies in this vitamin do not occur with commercial diets. This was, at least, the opinion in the 1960s.

Mature chickens show signs 3 weeks after being fed a deficient diet. In young chicks, it can appear before 2 weeks of age.

Onset is sudden in young chicks. There is anorexia and an unsteady gait. Later on, there are locomotor signs, beginning with an apparent paralysis of the flexor of the toes. The characteristic position is called "stargazing", meaning a chick "sitting on its hocks and the head in opisthotonos".

Response to administration of the vitamin is rather quick, occurring a few hours later.

Differential diagnosis include riboflavin deficiency and avian encephalomyelitis. In riboflavin deficiency, the "curled toes" is a characteristic symptom. Muscle tremor is typical of avian encephalomyelitis. A therapeutic diagnosis can be tried by supplementing thiamine only in the affected bird. If the animals do not respond in a few hours, thiamine deficiency can be excluded.

Ruminants

Polioencephalomalacia (PEM) is the most common thiamine deficiency disorder in young ruminant and nonruminant animals. Symptoms of PEM include a profuse, but transient, diarrhea, listlessness, circling movements, star gazing or opisthotonus (head drawn back over neck), and muscle tremors. The most common cause is high-carbohydrate feeds, leading to the overgrowth of thiaminase-producing bacteria, but dietary ingestion of thiaminase (e.g., in bracken fern), or inhibition of thiamine absorption by high sulfur intake are also possible. Another cause of PEM is Clostridium sporogenes or Bacillus aneurinolyticus infection. These bacteria produce thiaminases that will cause an acute thiamine deficiency in the affected animal.

Snakes

Snakes that consume a diet largely composed of goldfish and feeder minnows are susceptible to developing thiamine deficiency. This is often a problem observed in captivity when keeping garter and ribbon snakes that are fed a goldfish-exclusive diet, as these fish contain thiaminase, an enzyme that breaks down thiamine.

Wild birds and fish

Thiamine deficiency has been identified as the cause of a paralytic disease affecting wild birds in the Baltic Sea area dating back to 1982. In this condition, there is difficulty in keeping the wings folded along the side of the body when resting, loss of the ability to fly and voice, with eventual paralysis of the wings and legs and death. It affects primarily 0.5–1 kg sized birds such as the herring gull (Larus argentatus), common starling (Sturnus vulgaris) and common eider (Somateria mollissima). Researches noted, "Because the investigated species occupy a wide range of ecological niches and positions in the food web, we are open to the possibility that other animal classes may suffer from thiamine deficiency as well."

In the counties of Blekinge and Skåne (south-most Sweden), mass deaths of several bird species, especially the European herring gull, have been observed since the early 2000s. More recently, species of other classes seems to be affected. High mortality of salmon (Salmo salar) in the river Mörrumsån is reported, and mammals such as the Eurasian Elk (Alces alces) have died in unusually high numbers. Lack of thiamine is the common denominator where analysis is done. In April 2012, the County Administrative Board of Blekinge found the situation so alarming that they asked the Swedish government to set up a closer investigation.

Endocrine system

From Wikipedia, the free encyclopedia

Endocrine system
Main glands of the endocrine system. Note that the thymus is no longer considered part of the endocrine system, as it does not produce hormones.
Details
Identifiers
Latin	Systema endocrinum
MeSH	D004703
FMA	t6uk5iii8iu67i6i6ii78ii8 9584, t6uk5iii8iu67i6i6ii78ii8

The endocrine system is a chemical messenger system comprising feedback loops of hormones released by internal glands of an organism directly into the circulatory system, regulating distant target organs. In humans, the major endocrine glands are the thyroid gland and the adrenal glands. In vertebrates, the hypothalamus is the neural control center for all endocrine systems. The study of the endocrine system and its disorders is known as endocrinology. Endocrinology is a branch of internal medicine.

A number of glands that signal each other in sequence are usually referred to as an axis, for example, the hypothalamic-pituitary-adrenal axis. In addition to the specialized endocrine organs mentioned above, many other organs that are part of other body systems, inluding bone, kidney, liver, heart and gonads, have secondary endocrine functions. For example, the kidney secretes endocrine hormones such as erythropoietin and renin. Hormones can consist of either amino acid complexes, steroids, eicosanoids, leukotrienes, or prostaglandins.

The endocrine system can be contrasted to both exocrine glands, which secrete hormones to the outside of the body using ducts and paracrine signalling between cells over a relatively short distance. Endocrince glands have no ducts, are vascular and commonly have intracellular vacuoles or granules that store their hormones. In contrast, exocrine glands, such as salivary glands, sweat glands, and glands within the gastrointestinal tract, tend to be much less vascular and have ducts or a hollow lumen.

The word endocrine derives via New Latin from the Greek words ἔνδον, endon, "inside, within," and "crine" from the κρίνω, krīnō, "to separate, distinguish".

Structure

Major endocrine systems

The human endocrine system consists of several systems that operate via feedback loops. Several important feedback systems are mediated via the hypothalamus and pituitary.

• TRH – TSH – T3/T4
• GnRH – LH/FSH – sex hormones
• CRH – ACTH – cortisol
• Renin – angiotensin – aldosterone
• leptin vs. insulin

Glands

Endocrine glands are glands of the endocrine system that secrete their products, hormones, directly into interstitial spaces and then absorbed into blood rather than through a duct. The major glands of the endocrine system include the pineal gland, pituitary gland, pancreas, ovaries, testes, thyroid gland, parathyroid gland, hypothalamus and adrenal glands. The hypothalamus and pituitary gland are neuroendocrine organs.

Cells

There are many types of cells that comprise the endocrine system and these cells typically make up larger tissues and organs that function within and outside of the endocrine system.

• Hypothalamus

• Anterior Pituitary Gland

• Pineal Gland

• Posterior Pituitary Gland

• Thyroid Gland
  • Follicular cells of the thyroid gland produce and secrete T₃ and T₄ in response to elevated levels of TRH, produced by the hypothalamus, and subsequent elevated levels of TSH, produced by the anterior pituitary gland, which further regulates the metabolic activity and rate of all cells, including cell growth and tissue differentiation.

• Parathyroid Gland
  • Epithelial cells of the parathyroid glands are richly supplied with blood from the inferior and superior thyroid arteries and secrete parathyroid hormone (PTH). PTH acts on bone, the kidneys, and the GI tract to increase calcium reabsorption and phosphate excretion. In addition, PTH stimulates the conversion of Vitamin D to its most active variant, 1,25-dihydroxyvitamin D₃, which further stimulates calcium absorption in the GI tract.

• Adrenal Glands
  • Adrenal Cortex
  • Adrenal Medulla

• Pancreas
  • Alpha Cells
  • Beta Cells
  • Delta Cells
  • F Cells

• Ovaries
  • Granulosa Cells
• Testis
  • Leydig Cells

Function

Hormones

A hormone is any of a class of signaling molecules produced by glands in multicellular organisms that are transported by the circulatory system to target distant organs to regulate physiology and behaviour. Hormones have diverse chemical structures, mainly of 3 classes: eicosanoids, steroids, and amino acid/protein derivatives (amines, peptides, and proteins). The glands that secrete hormones comprise the endocrine system. The term hormone is sometimes extended to include chemicals produced by cells that affect the same cell (autocrine or intracrine signalling) or nearby cells (paracrine signalling). 

Hormones are used to communicate between organs and tissues for physiological regulation and behavioral activities, such as digestion, metabolism, respiration, tissue function, sensory perception, sleep, excretion, lactation, stress, growth and development, movement, reproduction, and mood.

Hormones affect distant cells by binding to specific receptor proteins in the target cell resulting in a change in cell function. This may lead to cell type-specific responses that include rapid changes to the activity of existing proteins, or slower changes in the expression of target genes. Amino acid–based hormones (amines and peptide or protein hormones) are water-soluble and act on the surface of target cells via signal transduction pathways; steroid hormones, being lipid-soluble, move through the plasma membranes of target cells to act within their nuclei.

Cell signalling

The typical mode of cell signalling in the endocrine system is endocrine signaling, that is, using the circulatory system to reach distant target organs. However, there are also other modes, i.e., paracrine, autocrine, and neuroendocrine signaling. Purely neurocrine signaling between neurons, on the other hand, belongs completely to the nervous system.

Autocrine

Autocrine signaling is a form of signaling in which a cell secretes a hormone or chemical messenger (called the autocrine agent) that binds to autocrine receptors on the same cell, leading to changes in the cells.

Paracrine

Some endocrinologists and clinicians include the paracrine system as part of the endocrine system, but there is not consensus. Paracrines are slower acting, targeting cells in the same tissue or organ. An example of this is somatostatin which is released by some pancreatic cells and targets other pancreatic cells.

Juxtacrine

Juxtacrine signaling is a type of intercellular communication that is transmitted via oligosaccharide, lipid, or protein components of a cell membrane, and may affect either the emitting cell or the immediately adjacent cells.

It occurs between adjacent cells that possess broad patches of closely opposed plasma membrane linked by transmembrane channels known as connexons. The gap between the cells can usually be between only 2 and 4 nm.

Clinical significance

Disease

Disability-adjusted life year for endocrine disorders per 100,000 inhabitants in 2002.

  no data

  less than 80

  80–160

  160–240

  240–320

  320–400

  400–480

  480–560

  560–640

  640–720

  720–800

  800–1000

  more than 1000

Diseases of the endocrine system are common, including conditions such as diabetes mellitus, thyroid disease, and obesity. Endocrine disease is characterized by misregulated hormone release (a productive pituitary adenoma), inappropriate response to signaling (hypothyroidism), lack of a gland (diabetes mellitus type 1, diminished erythropoiesis in chronic renal failure), or structural enlargement in a critical site such as the thyroid (toxic multinodular goitre). Hypofunction of endocrine glands can occur as a result of loss of reserve, hyposecretion, agenesis, atrophy, or active destruction. Hyperfunction can occur as a result of hypersecretion, loss of suppression, hyperplastic or neoplastic change, or hyperstimulation. 

Endocrinopathies are classified as primary, secondary, or tertiary. Primary endocrine disease inhibits the action of downstream glands. Secondary endocrine disease is indicative of a problem with the pituitary gland. Tertiary endocrine disease is associated with dysfunction of the hypothalamus and its releasing hormones.

As the thyroid, and hormones have been implicated in signaling distant tissues to proliferate, for example, the estrogen receptor has been shown to be involved in certain breast cancers. Endocrine, paracrine, and autocrine signaling have all been implicated in proliferation, one of the required steps of oncogenesis.

Other common diseases that result from endocrine dysfunction include Addison's disease, Cushing's disease and Graves' disease. Cushing's disease and Addison's disease are pathologies involving the dysfunction of the adrenal gland. Dysfunction in the adrenal gland could be due to primary or secondary factors and can result in hypercortisolism or hypocortisolism . Cushing's disease is characterized by the hypersecretion of the adrenocorticotropic hormone (ACTH) due to a pituitary adenoma that ultimately causes endogenous hypercortisolism by stimulating the adrenal glands. Some clinical signs of Cushing's disease include obesity, moon face, and hirsutism. Addison's disease is an endocrine disease that results from hypocortisolism caused by adrenal gland insufficiency. Adrenal insufficiency is significant because it is correlated with decreased ability to maintain blood pressure and blood sugar, a defect that can prove to be fatal.

Graves' disease involves the hyperactivity of the thyroid gland which produces the T3 and T4 hormones. Graves' disease effects range from excess sweating, fatigue, heat intolerance and high blood pressure to swelling of the eyes that causes redness, puffiness and in rare cases reduced or double vision.

Other animals

A neuroendocrine system has been observed in all animals with a nervous system and all vertebrates have an hypothalamus-pituitary axis. All vertebrates have a thyroid, which in amphibians is also crucial for transformation of larvae into adult form. All vertebrates have adrenal gland tissue, with mammals unique in having it organized into layers. All vertebrates have some form of a renin–angiotensin axis, and all tetrapods have aldosterone as a primary mineralocorticoid.

Additional images

• 

  Female endocrine system.
  
• 

  Male endocrine system
  

Endocrinology

From Wikipedia, the free encyclopedia

Endocrinology

Illustration depicting the primary endocrine organs of a female
System	Endocrine
Significant diseases	Diabetes, Thyroid disease, Androgen excess
Significant tests	Thyroid function tests, Blood sugar levels
Specialist	Endocrinologist
Glossary	Glossary of medicine

Endocrinology (from endocrine + -ology) is a branch of biology and medicine dealing with the endocrine system, its diseases, and its specific secretions known as hormones. It is also concerned with the integration of developmental events proliferation, growth, and differentiation, and the psychological or behavioral activities of metabolism, growth and development, tissue function, sleep, digestion, respiration, excretion, mood, stress, lactation, movement, reproduction, and sensory perception caused by hormones. Specializations include behavioral endocrinology and comparative endocrinology.

The endocrine system consists of several glands, all in different parts of the body, that secrete hormones directly into the blood rather than into a duct system. Hormones have many different functions and modes of action; one hormone may have several effects on different target organs, and, conversely, one target organ may be affected by more than one hormone.

The endocrine system

Endocrinology is the study of the endocrine system in the human body. This is a system of glands which secrete hormones. Hormones are chemicals which affect the actions of different organ systems in the body. Examples include thyroid hormone, growth hormone, and insulin. The endocrine system involves a number of feedback mechanisms, so that often one hormone (such as thyroid stimulating hormone) will control the action or release of another secondary hormone (such as thyroid hormone). If there is too much of the secondary hormone, it may provide negative feedback to the primary hormone, maintaining homeostasis. 

In the original 1902 definition by Bayliss and Starling (see below), they specified that, to be classified as a hormone, a chemical must be produced by an organ, be released (in small amounts) into the blood, and be transported by the blood to a distant organ to exert its specific function. This definition holds for most "classical" hormones, but there are also paracrine mechanisms (chemical communication between cells within a tissue or organ), autocrine signals (a chemical that acts on the same cell), and intracrine signals (a chemical that acts within the same cell). A neuroendocrine signal is a "classical" hormone that is released into the blood by a neurosecretory neuron (see article on neuroendocrinology).

Hormones

Griffin and Ojeda identify three different classes of hormones based on their chemical composition.

Amines

Norepinephrine

 

Triiodothyronine

 

Examples of amine hormones

Amines, such as norepinephrine, epinephrine, and dopamine (catecholamines), are derived from single amino acids, in this case tyrosine. Thyroid hormones such as 3,5,3’-triiodothyronine (T3) and 3,5,3’,5’-tetraiodothyronine (thyroxine, T4) make up a subset of this class because they derive from the combination of two iodinated tyrosine amino acid residues.

Peptide and protein

Peptide hormones and protein hormones consist of three (in the case of thyrotropin-releasing hormone) to more than 200 (in the case of follicle-stimulating hormone) amino acid residues and can have a molecular mass as large as 31,000 grams per mole. All hormones secreted by the pituitary gland are peptide hormones, as are leptin from adipocytes, ghrelin from the stomach, and insulin from the pancreas.

Steroid

Cortisol

 

Vitamin D₃

 

Examples of steroid hormones

Steroid hormones are converted from their parent compound, cholesterol. Mammalian steroid hormones can be grouped into five groups by the receptors to which they bind: glucocorticoids, mineralocorticoids, androgens, estrogens, and progestogens. Some forms of vitamin D, such as calcitriol, are steroid-like and bind to homologous receptors, but lack the characteristic fused ring structure of true steroids.

As a profession

Endocrinologist

Names	Doctor, Medical specialist
Occupation type	Specialty
Activity sectors	Medicine
Specialty	endocrinology
Description
Education required	Doctor of Medicine (M.D.) Doctor of Osteopathic Medicine (D.O.) Bachelor of Medicine, Bachelor of Surgery (M.B.B.S.)
Fields of employment	Hospitals, Clinics

Although every organ system secretes and responds to hormones (including the brain, lungs, heart, intestine, skin, and the kidney), the clinical specialty of endocrinology focuses primarily on the endocrine organs, meaning the organs whose primary function is hormone secretion. These organs include the pituitary, thyroid, adrenals, ovaries, testes, and pancreas.

An endocrinologist is a physician who specializes in treating disorders of the endocrine system, such as diabetes, hyperthyroidism, and many others.

Work

The medical specialty of endocrinology involves the diagnostic evaluation of a wide variety of symptoms and variations and the long-term management of disorders of deficiency or excess of one or more hormones. 

The diagnosis and treatment of endocrine diseases are guided by laboratory tests to a greater extent than for most specialties. Many diseases are investigated through excitation/stimulation or inhibition/suppression testing. This might involve injection with a stimulating agent to test the function of an endocrine organ. Blood is then sampled to assess the changes of the relevant hormones or metabolites. An endocrinologist needs extensive knowledge of clinical chemistry and biochemistry to understand the uses and limitations of the investigations. 

A second important aspect of the practice of endocrinology is distinguishing human variation from disease. Atypical patterns of physical development and abnormal test results must be assessed as indicative of disease or not. Diagnostic imaging of endocrine organs may reveal incidental findings called incidentalomas, which may or may not represent disease. 

Endocrinology involves caring for the person as well as the disease. Most endocrine disorders are chronic diseases that need lifelong care. Some of the most common endocrine diseases include diabetes mellitus, hypothyroidism and the metabolic syndrome. Care of diabetes, obesity and other chronic diseases necessitates understanding the patient at the personal and social level as well as the molecular, and the physician–patient relationship can be an important therapeutic process. 

Apart from treating patients, many endocrinologists are involved in clinical science and medical research, teaching, and hospital management.

Training

Endocrinologists are specialists of internal medicine or pediatrics. Reproductive endocrinologists deal primarily with problems of fertility and menstrual function—often training first in obstetrics. Most qualify as an internist, pediatrician, or gynecologist for a few years before specializing, depending on the local training system. In the U.S. and Canada, training for board certification in internal medicine, pediatrics, or gynecology after medical school is called residency. Further formal training to subspecialize in adult, pediatric, or reproductive endocrinology is called a fellowship. Typical training for a North American endocrinologist involves 4 years of college, 4 years of medical school, 3 years of residency, and 2 years of fellowship. In the US, adult endocrinologists are board certified by the American Board of Internal Medicine (ABIM) or the American Osteopathic Board of Internal Medicine (AOBIM) in Endocrinology, Diabetes and Metabolism.

Diseases and medicine

Diseases

Endocrinology also involves study of the diseases of the endocrine system. These diseases may relate to too little or too much secretion of a hormone, too little or too much action of a hormone, or problems with receiving the hormone.

Societies and organisations

Because endocrinology encompasses so many conditions and diseases, there are many organizations that provide education to patients and the public. The Hormone Foundation is the public education affiliate of The Endocrine Society and provides information on all endocrine-related conditions. Other educational organizations that focus on one or more endocrine-related conditions include the American Diabetes Association, Human Growth Foundation, American Menopause Foundation, Inc., and Thyroid Foundation of America. 

In North America the principal professional organizations of endocrinologists include The Endocrine Society, the American Association of Clinical Endocrinologists, the American Diabetes Association, the Lawson Wilkins Pediatric Endocrine Society, and the American Thyroid Association.

In the United Kingdom, the Society for Endocrinology and the British Society for Paediatric Endocrinology and Diabetes are the main professional organisations. The European Society for Paediatric Endocrinology is the largest international professional association dedicated solely to paediatric endocrinology. There are numerous similar associations around the world.

History

Arnold Berthold is known as a pioneer in endocrinology.

 

The earliest study of endocrinology began in China. The Chinese were isolating sex and pituitary hormones from human urine and using them for medicinal purposes by 200 BC. They used many complex methods, such as sublimation of steroid hormones. Another method specified by Chinese texts—the earliest dating to 1110—specified the use of saponin (from the beans of Gleditsia sinensis) to extract hormones, but gypsum (containing calcium sulfate) was also known to have been used.

Although most of the relevant tissues and endocrine glands had been identified by early anatomists, a more humoral approach to understanding biological function and disease was favoured by the ancient Greek and Roman thinkers such as Aristotle, Hippocrates, Lucretius, Celsus, and Galen, according to Freeman et al., and these theories held sway until the advent of germ theory, physiology, and organ basis of pathology in the 19th century. 

In 1849, Arnold Berthold noted that castrated cockerels did not develop combs and wattles or exhibit overtly male behaviour. He found that replacement of testes back into the abdominal cavity of the same bird or another castrated bird resulted in normal behavioural and morphological development, and he concluded (erroneously) that the testes secreted a substance that "conditioned" the blood that, in turn, acted on the body of the cockerel. In fact, one of two other things could have been true: that the testes modified or activated a constituent of the blood or that the testes removed an inhibitory factor from the blood. It was not proven that the testes released a substance that engenders male characteristics until it was shown that the extract of testes could replace their function in castrated animals. Pure, crystalline testosterone was isolated in 1935.

The Graves' disease was named after Irish doctor Robert James Graves, who described a case of goiter with exophthalmos in 1835. The German Karl Adolph von Basedow also independently reported the same constellation of symptoms in 1840, while earlier reports of the disease were also published by the Italians Giuseppe Flajani and Antonio Giuseppe Testa, in 1802 and 1810 respectively, and by the English physician Caleb Hillier Parry (a friend of Edward Jenner) in the late 18th century. Thomas Addison was first to describe Addison's disease in 1849.

Thomas Addison

 

In 1902 William Bayliss and Ernest Starling performed an experiment in which they observed that acid instilled into the duodenum caused the pancreas to begin secretion, even after they had removed all nervous connections between the two. The same response could be produced by injecting extract of jejunum mucosa into the jugular vein, showing that some factor in the mucosa was responsible. They named this substance "secretin" and coined the term hormone for chemicals that act in this way.

Joseph von Mering and Oskar Minkowski made the observation in 1889 that removing the pancreas surgically led to an increase in blood sugar, followed by a coma and eventual death—symptoms of diabetes mellitus. In 1922, Banting and Best realized that homogenizing the pancreas and injecting the derived extract reversed this condition.

Neurohormones were first identified by Otto Loewi in 1921. He incubated a frog's heart (innervated with its vagus nerve attached) in a saline bath, and left in the solution for some time. The solution was then used to bathe a non-innervated second heart. If the vagus nerve on the first heart was stimulated, negative inotropic (beat amplitude) and chronotropic (beat rate) activity were seen in both hearts. This did not occur in either heart if the vagus nerve was not stimulated. The vagus nerve was adding something to the saline solution. The effect could be blocked using atropine, a known inhibitor to heart vagal nerve stimulation. Clearly, something was being secreted by the vagus nerve and affecting the heart. The "vagusstuff" (as Loewi called it) causing the myotropic (muscle enhancing) effects was later identified to be acetylcholine and norepinephrine. Loewi won the Nobel Prize for his discovery. 

Recent work in endocrinology focuses on the molecular mechanisms responsible for triggering the effects of hormones. The first example of such work being done was in 1962 by Earl Sutherland. Sutherland investigated whether hormones enter cells to evoke action, or stayed outside of cells. He studied norepinephrine, which acts on the liver to convert glycogen into glucose via the activation of the phosphorylase enzyme. He homogenized the liver into a membrane fraction and soluble fraction (phosphorylase is soluble), added norepinephrine to the membrane fraction, extracted its soluble products, and added them to the first soluble fraction. Phosphorylase activated, indicating that norepinephrine's target receptor was on the cell membrane, not located intracellularly. He later identified the compound as cyclic AMP (cAMP) and with his discovery created the concept of second-messenger-mediated pathways. He, like Loewi, won the Nobel Prize for his groundbreaking work in endocrinology.