Syndrome of inappropriate antidiuretic hormone
Encyclopedia
The syndrome of inappropriate antidiuretic hormone hypersecretion (SIADH) is characterized by excessive release of antidiuretic hormone
(ADH or vasopressin) from the posterior pituitary
gland or another source. The result is hyponatremia
and sometimes fluid overload. It is usually found in patients diagnosed with small-cell carcinoma of the lung, pneumonia
, brain tumor
s, head trauma, stroke
s, meningitis
, and encephalitis
.
s is to control the amount of water reabsorbed by kidney nephron
s. ADH acts in the distal portion of the renal tubule (Distal Convoluted Tubule
) as well as on the collecting duct and causes the retention of water, but not solute. Hence, ADH activity effectively dilutes the blood (decreasing the concentrations of solutes such as sodium
).
ADH is secreted to prevent water loss in the kidneys. When water is ingested, it is taken up into the circulation and results in a dilution of the plasma
. This dilution, otherwise described as a reduction in plasma osmolality, is detected by osmoreceptor
s in the hypothalamus
of the brain and these then switch off the release of ADH. The decreasing concentration of ADH effectively inhibits the aquaporin
s in the collecting ducts and distal convoluted tubule
s in the nephron
s of the kidney. Hence, less water is reabsorbed, thereby increasing urine
output, decreasing urine osmolality
, and normalizing blood osmolality.
In SIADH the release of ADH is not inhibited by a reduction in plasma osmolality when the individual ingests water and the osmolality of the plasma drops. As the main solute of plasma is sodium, this hypoosmolar state is usually detected as a low sodium level on laboratory testing. SIADH is therefore primarily a condition that results in the abnormal handling of water loading and not a problem with excessive solute loss. This is why it is usually treated with fluid (in particular water) restriction. Diuretics may also be given to decrease reabsorption of water, but care must be taken not to correct water imbalances too rapidly.
This causes dilutional hyponatremia
and all the consequences associated with that condition: headache
, nausea
, vomiting
, and confusion may ensue. Severe hyponatremia may cause convulsion
s or coma
.
The abnormalities underlying type D syndrome of inappropriate antidiuretic hormone hypersecretion concern individuals where vasopressin release and response are normal but where abnormal renal expression and translocation of aquaporin 2
, or both are found. It has been suggested that this is due to abnormalities in the secretion of secretin
in the brain and that "Secretin as a neurosecretory hormone from the posterior pituitary, therefore, could be the long-sought vasopressin independent mechanism to solve the riddle that has puzzled clinicians and physiologists for decades."
or hypertension
, owing to natriuresis
(the excretion of sodium by the kidneys). The water retention and sodium loss both cause hyponatremia, which is a key feature in SIADH. Hyponatremia and concentrated urine (UOsm >300 mOsm) are seen, as well as no signs of edema or dehydration
. When hyponatremia is severe (sodium <120 mOsm), or acute in onset, symptoms of cerebral edema
become prominent (irritability, confusion, seizures, and coma).
Other findings include-
-No head to head study is currently available to quantify and compare the relative efficacies of V2 vasopressin receptor antagonists with demeclocycline or other treatment options.
Care must be taken when correcting hyponatremia. A rapid rise in the sodium level may cause central pontine myelinolysis
.
Avoid correction by more than 12 mEq/L/day
(including Dr Frederic Bartter
) in two patients with lung cancer
. Criteria were developed by Schwartz and Bartter in 1967 and have remained essentially unchanged since then. The condition is occasionally referred to by the names of the authors of the first report - Schwartz-Bartter syndrome.
Vasopressin
Arginine vasopressin , also known as vasopressin, argipressin or antidiuretic hormone , is a neurohypophysial hormone found in most mammals, including humans. Vasopressin is a peptide hormone that controls the reabsorption of molecules in the tubules of the kidneys by affecting the tissue's...
(ADH or vasopressin) from the posterior pituitary
Posterior pituitary
The posterior pituitary comprises the posterior lobe of the pituitary gland and is part of the endocrine system. Despite its name, the posterior pituitary gland is not a gland, per se; rather, it is largely a collection of axonal projections from the hypothalamus that terminate behind the anterior...
gland or another source. The result is hyponatremia
Hyponatremia
Hyponatremia is an electrolyte disturbance in which the sodium concentration in the serum is lower than normal. In the vast majority of cases, hyponatremia occurs as a result of excess body water diluting the serum sodium and is not due to sodium deficiency. Sodium is the dominant extracellular...
and sometimes fluid overload. It is usually found in patients diagnosed with small-cell carcinoma of the lung, pneumonia
Pneumonia
Pneumonia is an inflammatory condition of the lung—especially affecting the microscopic air sacs —associated with fever, chest symptoms, and a lack of air space on a chest X-ray. Pneumonia is typically caused by an infection but there are a number of other causes...
, brain tumor
Brain tumor
A brain tumor is an intracranial solid neoplasm, a tumor within the brain or the central spinal canal.Brain tumors include all tumors inside the cranium or in the central spinal canal...
s, head trauma, stroke
Stroke
A stroke, previously known medically as a cerebrovascular accident , is the rapidly developing loss of brain function due to disturbance in the blood supply to the brain. This can be due to ischemia caused by blockage , or a hemorrhage...
s, meningitis
Meningitis
Meningitis is inflammation of the protective membranes covering the brain and spinal cord, known collectively as the meninges. The inflammation may be caused by infection with viruses, bacteria, or other microorganisms, and less commonly by certain drugs...
, and encephalitis
Encephalitis
Encephalitis is an acute inflammation of the brain. Encephalitis with meningitis is known as meningoencephalitis. Symptoms include headache, fever, confusion, drowsiness, and fatigue...
.
Pathophysiology
The normal function of ADH on the kidneyKidney
The kidneys, organs with several functions, serve essential regulatory roles in most animals, including vertebrates and some invertebrates. They are essential in the urinary system and also serve homeostatic functions such as the regulation of electrolytes, maintenance of acid–base balance, and...
s is to control the amount of water reabsorbed by kidney nephron
Nephron
The renal tubule is the portion of the nephron containing the tubular fluid filtered through the glomerulus. After passing through the renal tubule, the filtrate continues to the collecting duct system, which is not part of the nephron....
s. ADH acts in the distal portion of the renal tubule (Distal Convoluted Tubule
Distal convoluted tubule
The distal convoluted tubule is a portion of kidney nephron between the loop of Henle and the collecting duct system.- Physiology :It is partly responsible for the regulation of potassium, sodium, calcium, and pH...
) as well as on the collecting duct and causes the retention of water, but not solute. Hence, ADH activity effectively dilutes the blood (decreasing the concentrations of solutes such as sodium
Sodium
Sodium is a chemical element with the symbol Na and atomic number 11. It is a soft, silvery-white, highly reactive metal and is a member of the alkali metals; its only stable isotope is 23Na. It is an abundant element that exists in numerous minerals, most commonly as sodium chloride...
).
ADH is secreted to prevent water loss in the kidneys. When water is ingested, it is taken up into the circulation and results in a dilution of the plasma
Blood plasma
Blood plasma is the straw-colored liquid component of blood in which the blood cells in whole blood are normally suspended. It makes up about 55% of the total blood volume. It is the intravascular fluid part of extracellular fluid...
. This dilution, otherwise described as a reduction in plasma osmolality, is detected by osmoreceptor
Osmoreceptor
An osmoreceptor is a sensory receptor primarily found in the hypothalamus of most homeothermic organisms that detects changes in osmotic pressure. Osmoreceptors can be found in several structures, including the organum vasculosum of the lamina terminalis and the subfornical organ...
s in the hypothalamus
Hypothalamus
The Hypothalamus is a portion of the brain that contains a number of small nuclei with a variety of functions...
of the brain and these then switch off the release of ADH. The decreasing concentration of ADH effectively inhibits the aquaporin
Aquaporin
Aquaporins are proteins embedded in the cell membrane that regulate the flow of water.Aquaporins are integral membrane proteins from a larger family of major intrinsic proteins that form pores in the membrane of biological cells....
s in the collecting ducts and distal convoluted tubule
Distal convoluted tubule
The distal convoluted tubule is a portion of kidney nephron between the loop of Henle and the collecting duct system.- Physiology :It is partly responsible for the regulation of potassium, sodium, calcium, and pH...
s in the nephron
Nephron
The renal tubule is the portion of the nephron containing the tubular fluid filtered through the glomerulus. After passing through the renal tubule, the filtrate continues to the collecting duct system, which is not part of the nephron....
s of the kidney. Hence, less water is reabsorbed, thereby increasing urine
Urine
Urine is a typically sterile liquid by-product of the body that is secreted by the kidneys through a process called urination and excreted through the urethra. Cellular metabolism generates numerous by-products, many rich in nitrogen, that require elimination from the bloodstream...
output, decreasing urine osmolality
Urine osmolality
Urine osmolality is a measure of urine concentration, in which large values indicate concentrated urine and small values indicate diluted urine. In healthy individuals with restricted fluid intake, urine osmolality should be greater than 800mOsm/Kg, while a 24 hour urine osmolality should average...
, and normalizing blood osmolality.
In SIADH the release of ADH is not inhibited by a reduction in plasma osmolality when the individual ingests water and the osmolality of the plasma drops. As the main solute of plasma is sodium, this hypoosmolar state is usually detected as a low sodium level on laboratory testing. SIADH is therefore primarily a condition that results in the abnormal handling of water loading and not a problem with excessive solute loss. This is why it is usually treated with fluid (in particular water) restriction. Diuretics may also be given to decrease reabsorption of water, but care must be taken not to correct water imbalances too rapidly.
This causes dilutional hyponatremia
Hyponatremia
Hyponatremia is an electrolyte disturbance in which the sodium concentration in the serum is lower than normal. In the vast majority of cases, hyponatremia occurs as a result of excess body water diluting the serum sodium and is not due to sodium deficiency. Sodium is the dominant extracellular...
and all the consequences associated with that condition: headache
Headache
A headache or cephalalgia is pain anywhere in the region of the head or neck. It can be a symptom of a number of different conditions of the head and neck. The brain tissue itself is not sensitive to pain because it lacks pain receptors. Rather, the pain is caused by disturbance of the...
, nausea
Nausea
Nausea , is a sensation of unease and discomfort in the upper stomach with an involuntary urge to vomit. It often, but not always, precedes vomiting...
, vomiting
Vomiting
Vomiting is the forceful expulsion of the contents of one's stomach through the mouth and sometimes the nose...
, and confusion may ensue. Severe hyponatremia may cause convulsion
Convulsion
A convulsion is a medical condition where body muscles contract and relax rapidly and repeatedly, resulting in an uncontrolled shaking of the body. Because a convulsion is often a symptom of an epileptic seizure, the term convulsion is sometimes used as a synonym for seizure...
s or coma
Coma
In medicine, a coma is a state of unconsciousness, lasting more than 6 hours in which a person cannot be awakened, fails to respond normally to painful stimuli, light or sound, lacks a normal sleep-wake cycle and does not initiate voluntary actions. A person in a state of coma is described as...
.
The abnormalities underlying type D syndrome of inappropriate antidiuretic hormone hypersecretion concern individuals where vasopressin release and response are normal but where abnormal renal expression and translocation of aquaporin 2
Aquaporin 2
AQP2 is found in the apical cell membranes of the kidney's collecting duct principal cells and in intracellular vesicles located throughout the cell.-Regulation:It is the only aquaporin regulated by vasopressin....
, or both are found. It has been suggested that this is due to abnormalities in the secretion of secretin
Secretin
Secretin is a hormone that controls the secretions into the duodenum, and also separately, water homeostasis throughout the body. It is produced in the S cells of the duodenum in the crypts of Lieberkühn...
in the brain and that "Secretin as a neurosecretory hormone from the posterior pituitary, therefore, could be the long-sought vasopressin independent mechanism to solve the riddle that has puzzled clinicians and physiologists for decades."
Clinical Findings
In general, increased ADH causes water retention and extracellular fluid volume expansion without edemaEdema
Edema or oedema ; both words from the Greek , oídēma "swelling"), formerly known as dropsy or hydropsy, is an abnormal accumulation of fluid beneath the skin or in one or more cavities of the body that produces swelling...
or hypertension
Hypertension
Hypertension or high blood pressure is a cardiac chronic medical condition in which the systemic arterial blood pressure is elevated. What that means is that the heart is having to work harder than it should to pump the blood around the body. Blood pressure involves two measurements, systolic and...
, owing to natriuresis
Natriuresis
Natriuresis is the process of excretion of sodium in the urine via action of the kidneys. Natriuresis is promoted by Brain and Atrial natriuretic peptides, and it is inhibited by chemicals such as aldosterone...
(the excretion of sodium by the kidneys). The water retention and sodium loss both cause hyponatremia, which is a key feature in SIADH. Hyponatremia and concentrated urine (UOsm >300 mOsm) are seen, as well as no signs of edema or dehydration
Dehydration
In physiology and medicine, dehydration is defined as the excessive loss of body fluid. It is literally the removal of water from an object; however, in physiological terms, it entails a deficiency of fluid within an organism...
. When hyponatremia is severe (sodium <120 mOsm), or acute in onset, symptoms of cerebral edema
Cerebral edema
Cerebral edema or cerebral œdema is an excess accumulation of water in the intracellular or extracellular spaces of the brain.-Vasogenic:Due to a breakdown of tight endothelial junctions which make up the blood-brain barrier...
become prominent (irritability, confusion, seizures, and coma).
Diagnosis
Laboratory findings in diagnosis of SIADH include-- HyponatremiaHyponatremiaHyponatremia is an electrolyte disturbance in which the sodium concentration in the serum is lower than normal. In the vast majority of cases, hyponatremia occurs as a result of excess body water diluting the serum sodium and is not due to sodium deficiency. Sodium is the dominant extracellular...
<135 mEq/L, and POsm <270 mOsm/kg.
Other findings include-
- Urine sodium concentration >20 mEq/L (inappropriate natriuresis). Urine sodium concentration may be normal reflecting dietary intake.
- Maintained hypervolemia
- Suppression of renin-angiotensin system
- No equal concentration of atrial natriuretic peptide
- Low blood urea nitrogenBlood urea nitrogenThe blood urea nitrogen test is a measure of the amount of nitrogen in the blood in the form of urea, and a measurement of renal function. Urea is a by- product from metabolism of proteins by the liver and is removed from the blood by the kidneys.-Physiology:The liver produces urea in the urea...
(BUN) - Normal serum creatinineCreatinineCreatinine is a break-down product of creatine phosphate in muscle, and is usually produced at a fairly constant rate by the body...
- Low uric acidUric acidUric acid is a heterocyclic compound of carbon, nitrogen, oxygen, and hydrogen with the formula C5H4N4O3. It forms ions and salts known as urates and acid urates such as ammonium acid urate. Uric acid is created when the body breaks down purine nucleotides. High blood concentrations of uric acid...
- Low albuminAlbuminAlbumin refers generally to any protein that is water soluble, which is moderately soluble in concentrated salt solutions, and experiences heat denaturation. They are commonly found in blood plasma, and are unique to other blood proteins in that they are not glycosylated...
- Normal Acid-Base, K+ balance
- Normal Adrenal, Thyroid function
Causes
Some common causes of SIADH include:- MeningitisMeningitisMeningitis is inflammation of the protective membranes covering the brain and spinal cord, known collectively as the meninges. The inflammation may be caused by infection with viruses, bacteria, or other microorganisms, and less commonly by certain drugs...
- Head injury
- Subarachnoid hemorrhageSubarachnoid hemorrhageA subarachnoid hemorrhage , or subarachnoid haemorrhage in British English, is bleeding into the subarachnoid space—the area between the arachnoid membrane and the pia mater surrounding the brain...
- Subarachnoid hemorrhage
- CancerCancerCancer , known medically as a malignant neoplasm, is a large group of different diseases, all involving unregulated cell growth. In cancer, cells divide and grow uncontrollably, forming malignant tumors, and invade nearby parts of the body. The cancer may also spread to more distant parts of the...
s- Lung cancerLung cancerLung cancer is a disease characterized by uncontrolled cell growth in tissues of the lung. If left untreated, this growth can spread beyond the lung in a process called metastasis into nearby tissue and, eventually, into other parts of the body. Most cancers that start in lung, known as primary...
(especially small-cell lung cancer, as well as other small-cell malignancies of other organs)
- Lung cancer
- InfectionInfectionAn infection is the colonization of a host organism by parasite species. Infecting parasites seek to use the host's resources to reproduce, often resulting in disease...
s- BrainBrainThe brain is the center of the nervous system in all vertebrate and most invertebrate animals—only a few primitive invertebrates such as sponges, jellyfish, sea squirts and starfishes do not have one. It is located in the head, usually close to primary sensory apparatus such as vision, hearing,...
abscessAbscessAn abscess is a collection of pus that has accumulated in a cavity formed by the tissue in which the pus resides due to an infectious process or other foreign materials... - PneumoniaPneumoniaPneumonia is an inflammatory condition of the lung—especially affecting the microscopic air sacs —associated with fever, chest symptoms, and a lack of air space on a chest X-ray. Pneumonia is typically caused by an infection but there are a number of other causes...
- Lung abscessLung abscessLung abscess is necrosis of the pulmonary tissue and formation of cavities containing necrotic debris or fluid caused by microbial infection....
- Brain
- Guillain Barre syndrome
- DrugMedicationA pharmaceutical drug, also referred to as medicine, medication or medicament, can be loosely defined as any chemical substance intended for use in the medical diagnosis, cure, treatment, or prevention of disease.- Classification :...
s- ChlorpropamideChlorpropamideChlorpropamide is a drug in the sulphonylurea class used to treat type 2 diabetes mellitus. It is a long-acting sulphonylurea. It has more side effects than other sulphonylureas and its use is no longer recommended.-Mechanism of action:...
- ClofibrateClofibrateClofibrate is a fibrate. It is a lipid lowering agent used for controlling the high cholesterol and triacylglyceride level in the blood. It increases lipoprotein lipase activity to promote the conversion of VLDL to LDL, and hence reduce the level of VLDL...
- PhenothiazinePhenothiazinePhenothiazine is an organic compound that occurs in various antipsychotic and antihistaminic drugs. It has the formula S2NH. This yellow tricyclic compound is soluble in acetic acid, benzene, and ether. The compound is related to the thiazine-class of heterocyclic compounds...
- CyclophosphamideCyclophosphamideCyclophosphamide , also known as cytophosphane, is a nitrogen mustard alkylating agent, from the oxazophorines group....
- CarbamazepineCarbamazepineCarbamazepine is an anticonvulsant and mood-stabilizing drug used primarily in the treatment of epilepsy and bipolar disorder, as well as trigeminal neuralgia...
- Selective serotonin reuptake inhibitorSelective serotonin reuptake inhibitorSelective serotonin re-uptake inhibitors or serotonin-specific reuptake inhibitor are a class of compounds typically used as antidepressants in the treatment of depression, anxiety disorders, and some personality disorders. The efficacy of SSRIs is disputed...
s (SSRIs, a class of antidepressants) - MethylenedioxymethamphetamineMethylenedioxymethamphetamineMDMA is an entactogenic drug of the phenethylamine and amphetamine class of drugs. In popular culture, MDMA has become widely known as "ecstasy" , usually referring to its street pill form, although this term may also include the presence of possible adulterants...
(MDMA, commonly called Ecstasy. SIADH due to taking ecstasy was cited as a factor in the death of Leah BettsLeah BettsLeah Sarah Betts was a schoolgirl from Latchingdon in Essex, England, United Kingdom. She is notable for the extensive media coverage and moral panic that followed her death several days after her 18th birthday. On 11 November, she took an Ecstasy tablet, and then drank approximately 7 litres of...
) - OxytocinOxytocinOxytocin is a mammalian hormone that acts primarily as a neuromodulator in the brain.Oxytocin is best known for its roles in sexual reproduction, in particular during and after childbirth...
- VincristineVincristineVincristine , formally known as leurocristine, sometimes abbreviated "VCR", is a vinca alkaloid from the Catharanthus roseus , formerly Vinca rosea and hence its name. It is a mitotic inhibitor, and is used in cancer chemotherapy.-Mechanism:Tubulin is a structural protein that polymerizes to...
morphine,amitriptaline
- Chlorpropamide
- HypothyroidismHypothyroidismHypothyroidism is a condition in which the thyroid gland does not make enough thyroid hormone.Iodine deficiency is the most common cause of hypothyroidism worldwide but it can be caused by other causes such as several conditions of the thyroid gland or, less commonly, the pituitary gland or...
- sarcoidosisSarcoidosisSarcoidosis , also called sarcoid, Besnier-Boeck disease or Besnier-Boeck-Schaumann disease, is a disease in which abnormal collections of chronic inflammatory cells form as nodules in multiple organs. The cause of sarcoidosis is unknown...
Management
Management of SIADH includes:- Treating underlying causes when possible.
- Long-term fluid restriction of 1,200–1,800 mL/day to increase serum sodium.
- Intravenous salineSaline (medicine)In medicine, saline is a general term referring to a sterile solution of sodium chloride in water but is only sterile when it is to be placed intravenously, otherwise, a saline solution is a salt water solution...
- For very symptomatic patients (severe confusion, convulsions, or coma) hypertonic saline (3-5%) 200-300 ml IV in 3-4 h should be given. - Drugs
- DemeclocyclineDemeclocyclineDemeclocycline is a tetracycline antibiotic.It is derived from a strain of Streptomyces aureofaciens.-In infections:...
can be used in chronic situations when fluid restrictions are difficult to maintain; demeclocycline is the most potent inhibitor of Vasopressin (ADH/AVP) action. However, demeclocycline has a 2-3 delay in onset with extensive side effect profile, including but not limited to new onset Nephrogenic Diabetes InsipidusNephrogenic diabetes insipidusNephrogenic diabetes insipidus is a form of diabetes insipidus due primarily to pathology of the kidney. This is in contrast to central/neurogenic diabetes insipidus, which is caused by insufficient levels of antidiuretic hormone /Argenine Vasopressin...
(70%), skin photosensitivity, and nephrotoxicity. - Urea: oral daily ingestion has shown favorable long-term results with protective effects in myelinosisCentral pontine myelinolysisCentral pontine myelinolysis is neurological disease caused by severe damage of the myelin sheath of nerve cells in the brainstem, more precisely in the area termed the pons, predominately of iatrogenic etiology...
and brain damage. Limitations noted to be undesirable taste and is contraindicated in patients with cirrhosis to avoid initiation or potentiation of hepatic encephalopathyHepatic encephalopathyHepatic encephalopathy is the occurrence of confusion, altered level of consciousness and coma as a result of liver failure. In the advanced stages it is called hepatic coma or coma hepaticum...
. - ConivaptanConivaptanConivaptan is a non-peptide inhibitor of antidiuretic hormone . It was approved in 2004 for hyponatremia caused by syndrome of inappropriate antidiuretic hormone , and there is some evidence it may be effective in heart failure...
- an antagonist of both V1A and V2 vasopressin receptors. Its indications are "treatment of euvolemic hyponatremia (e.g. the syndrome of inappropriate secretion of antidiuretic hormone, or in the setting of hypothyroidism, adrenal insufficiency, pulmonary disorders, etc.) in hospitalized patients.". Conivaptan, however, is only available as a parenteral preparation. - TolvaptanTolvaptanTolvaptan , also known as OPC-41061, is a selective, competitive vasopressin receptor 2 antagonist used to treat hyponatremia associated with congestive heart failure, cirrhosis, and the syndrome of inappropriate antidiuretic hormone . Tolvaptan was approved by the U.S...
- an antagonist of the V2 vasopressin receptor. A randomized controlled trial showed tolvaptan is able to raise serum sodium in patients with euvolemic or hypervolemic hyponatremia with euvolemic or hypervolemic hyponatremia in 2 different tests. Combined analysis of the 2 trials showed an improvement in hyponatremia in both the short term (primary sodium change in average AUC: 3.62+/- 2.68 and 4.35 +/-2.87) and long term with long term maintenance (primary sodium change in average AUC: 6.22 +/- 4.22 and 6.20 +/- 4.92), at 4 days and 30 days, respectively. Tolvaptan’s side effect profile is minimal. Discontinuation of the Tolvaptan showed return of hyponatremia to control values at their respective time frames.
- Demeclocycline
-No head to head study is currently available to quantify and compare the relative efficacies of V2 vasopressin receptor antagonists with demeclocycline or other treatment options.
Care must be taken when correcting hyponatremia. A rapid rise in the sodium level may cause central pontine myelinolysis
Central pontine myelinolysis
Central pontine myelinolysis is neurological disease caused by severe damage of the myelin sheath of nerve cells in the brainstem, more precisely in the area termed the pons, predominately of iatrogenic etiology...
.
Avoid correction by more than 12 mEq/L/day
History
The condition was first described by researchers from Boston, Massachusetts and Bethesda, MarylandBethesda, Maryland
Bethesda is a census designated place in southern Montgomery County, Maryland, United States, just northwest of Washington, D.C. It takes its name from a local church, the Bethesda Meeting House , which in turn took its name from Jerusalem's Pool of Bethesda...
(including Dr Frederic Bartter
Frederic Bartter
Frederic Crosby Bartter was an American endocrinologist best known for his work on hormones affecting the kidney and his discovery of syndrome of inappropriate antidiuretic hormone and Bartter syndrome...
) in two patients with lung cancer
Lung cancer
Lung cancer is a disease characterized by uncontrolled cell growth in tissues of the lung. If left untreated, this growth can spread beyond the lung in a process called metastasis into nearby tissue and, eventually, into other parts of the body. Most cancers that start in lung, known as primary...
. Criteria were developed by Schwartz and Bartter in 1967 and have remained essentially unchanged since then. The condition is occasionally referred to by the names of the authors of the first report - Schwartz-Bartter syndrome.