- What is Hypernatremia
- Hypernatremia causes
- Hypernatremia signs and symptoms
- Hypernatremia complications
- Hypernatremia diagnosis
- Hypernatremia treatment
What is Hypernatremia
Hypernatremia is defined as a serum sodium concentration greater than 145 mEq/L 1. Hypernatremia implies a deficit of total body water relative to total body sodium caused by water intake being less than water losses. A major symptom of hypernatremia is thirst; other clinical manifestations are primarily neurologic (due to an osmotic shift of water out of brain cells), including confusion, neuromuscular excitability, seizures, and coma 2. Hypernatremia is primarily seen in infants and the elderly population 3. Infants receiving inadequate water replacement in the setting of gastroenteritis or ineffective breastfeeding are common scenarios. Premature infants are at higher risk due to their relatively small mass to surface area and their dependency on the caretaker to administer fluids. Patients with neurologic impairment also are at risk due to lack of communication of the thirst response to the caregiver. Hypernatremia can occur in the hospital setting due to hypertonic fluid infusions, especially when combined with the patient’s inability for water intake.
Hypernatremia diagnosis requires measurement of serum sodium and sometimes other laboratory tests. Hypernatremia treatment is usually controlled water replacement. When the response to treatment is poor, testing (e.g., monitored water deprivation or administration of vasopressin or antidiuretic hormone [ADH]) is directed at detecting causes other than decreased water intake.
Sodium is the dominant cation in extracellular fluid (ECF) and necessary for the maintenance of intravascular volume and extracellular fluid (ECF) volume 3. The human body maintains sodium and water homeostasis by concentrating the urine secondary to the action of antidiuretic hormone (ADH) and increased fluid intake by powerful thirst response. Changes in the extracellular fluid (ECF) volume provide feedback to maintain total sodium content by increasing or decreasing sodium excretion in the urine. Sodium excretion also involves regulatory mechanisms such as the renin-angiotensin-aldosterone systems. When serum sodium increases, the plasma osmolality increases and triggers an increase in thirst response and antidiuretic hormone (ADH) secretion, leading to renal water conservation and concentrated urine. These mechanisms to protect against developing hypernatremia are impaired in certain vulnerable populations and conditions with vasopressin [antidiuretic hormone (ADH)] deficiency or unresponsiveness at the renal tubular level.
Hypernatremia key facts
- Hypernatremia is usually caused by limited access to water or an impaired thirst mechanism, and less commonly by diabetes insipidus.
- Manifestations include confusion, neuromuscular excitability, hyperreflexia, seizures, and coma.
- Patients who do not respond to simple rehydration or in whom there is no obvious cause may need assessment of urine volume and osmolality, particularly after water deprivation.
- Replace intravascular volume and free water orally or intravenously at a rate dictated by how acutely (< 24 hour) or chronically (> 24 hour) the hypernatremia has developed, while watching other serum electrolyte levels (especially potassium and bicarbonate) as well.
How is fluid regulated in the body?
A person’s body regulates fluid by balancing liquid intake and removing extra fluid. Thirst usually controls a person’s rate of liquid intake, while urination removes most fluid, although people also lose fluid through sweating, breathing, or diarrhea. The hormone vasopressin, also called antidiuretic hormone (ADH), controls the fluid removal rate through urination. The hypothalamus, a small gland located at the base of the brain, produces vasopressin [antidiuretic hormone (ADH)]. The nearby pituitary gland stores the vasopressin and releases it into the bloodstream when the body has a low fluid level. Vasopressin signals the kidneys to absorb less fluid from the bloodstream, resulting in less urine. When the body has extra fluid, the pituitary gland releases smaller amounts of vasopressin, and sometimes none, so the kidneys remove more fluid from the bloodstream and produce more urine.
The basic mechanisms of hypernatremia are water deficit and solute excess. Hypernatremia reflects a deficit of total body water relative to total body sodium content. Total body water loss relative to solute loss is the most common reason for developing hypernatremia 3. Because total body sodium content is reflected by extracellular fluid (ECF) volume status, hypernatremia must be considered along with status of the extracellular fluid volume:
Note that the extracellular fluid volume is not the same as effective plasma volume. For example, decreased effective plasma volume may occur with decreased extracellular fluid volume (as with diuretic use or hemorrhagic shock), but it may also occur with an increased extracellular fluid volume (eg, in heart failure, hypoalbuminemia, or capillary leak syndrome).
Hypernatremia usually is associated with hypovolemia, which can occur in conditions that cause combined water and solute loss, where water loss is greater than sodium loss, or free water loss 3. Combined loss can be seen in extra-renal conditions such as gastroenteritis, vomiting, prolonged suction, burns, and excessive sweating. Renal loss can be seen in chronic kidney disease, diabetes mellitus, post-obstructive diuresis, and with the use of osmotic diuretics. Free water loss is seen in central or nephrogenic diabetes insipidus and also in conditions with an increased insensible loss. Central diabetes insipidus is due to inadequate production of antidiuretic hormone (ADH), structural abnormalities, or acquired by autosomal dominant or recessive pattern. Nephrogenic diabetes insipidus is due to tubular unresponsiveness to the action of antidiuretic hormone (ADH) and can be inherited in an X-linked pattern or secondary to a number of medications. Rarely, hypernatremia with inadequate fluid intake can be seen in breastfed babies, child or elder abuse, and in patients with an impaired thirst response. Excess sodium usually is iatrogenic and seen in the hospital setting but also can be associated with improper formula mixing, excess sodium bicarbonate ingestion, hyperaldosteronism, and seawater drowning 4.
Hypernatremia usually involves an impaired thirst mechanism or limited access to water, either as contributing factors or primary causes. The severity of the underlying disorder that results in an inability to drink in response to thirst and the effects of hyperosmolality on the brain are thought to be responsible for a high mortality rate in hospitalized adults with hypernatremia. There are several common causes of hypernatremia.
Hypernatremia associated with hypovolemia occurs with sodium loss accompanied by a relatively greater loss of water from the body. Common extrarenal causes include most of those that cause hyponatremia and volume depletion. Either hypernatremia or hyponatremia can occur with severe volume loss, depending on the relative amounts of sodium and water lost and the amount of water ingested before presentation.
Renal causes of hypernatremia and volume depletion include therapy with diuretics. Loop diuretics inhibit sodium reabsorption in the concentrating portion of the nephrons and can increase water clearance. Osmotic diuresis can also impair renal concentrating capacity because of a hypertonic substance present in the tubular lumen of the distal nephron. Glycerol, mannitol, and occasionally urea can cause osmotic diuresis resulting in hypernatremia.
The most common cause of hypernatremia due to osmotic diuresis is hyperglycemia in patients with diabetes. Because glucose does not penetrate cells in the absence of insulin, hyperglycemia further dehydrates the ICF compartment. The degree of hyperosmolality in hyperglycemia may be obscured by the lowering of serum sodium resulting from movement of water out of cells into the ECF (translational hyponatremia). Patients with renal disease can also be predisposed to hypernatremia when their kidneys are unable to maximally concentrate urine.
Hypernatremia with euvolemia is a decrease in TBW with near-normal total body sodium (pure water deficit). Extrarenal causes of water loss, such as excessive sweating, result in some sodium loss, but because sweat is hypotonic, hypernatremia can result before significant hypovolemia. A deficit of almost purely water also occurs in central diabetes insipidus and nephrogenic diabetes insipidus.
Essential hypernatremia (primary hypodipsia) occasionally occurs in children with brain damage and in chronically ill elderly adults. It is characterized by an impaired thirst mechanism (eg, caused by lesions of the brain’s thirst center). Altered osmotic trigger for vasopressin release is another possible cause of euvolemic hypernatremia; some lesions cause both an impaired thirst mechanism and an altered osmotic trigger. The nonosmotic release of vasopressin appears intact, and these patients are generally euvolemic.
Hypernatremia in rare cases is associated with volume overload. In this case, hypernatremia results from a grossly elevated sodium intake associated with limited access to water. One example is the excessive administration of hypertonic sodium bicarbonate during treatment of lactic acidosis. Hypernatremia can also be caused by the administration of hypertonic saline or incorrectly formulated hyperalimentation.
Hypernatremia in the elderly
Hypernatremia is common among the elderly, particularly postoperative patients and those receiving tube feedings or parenteral nutrition. Other contributing factors may include the following:
- Dependence on others to obtain water
- Impaired thirst mechanism
- Impaired renal concentrating capacity due to diuretics, impaired vasopressin release, or nephron loss accompanying aging or other renal disease.
- Impaired angiotensin II production, which may contribute directly to the impaired thirst mechanism.
Diabetes insipidus hypernatremia
Diabetes insipidus is a rare condition that causes frequent urination (passing a lot of clear urine) and excessive thirst. Diabetes insipidus occurs when a person’s kidneys pass an abnormally large volume of urine that is insipid—dilute and odorless. In most people, the kidneys pass about 1 to 2 quarts of urine a day. In people with diabetes insipidus, the kidneys can pass 3 to 20 quarts of urine a day. As a result, a person with diabetes insipidus may feel the need to drink large amounts of liquids even if you’ve had something to drink. Diabetes insipidus may be caused by problems with your pituitary gland (central diabetes insipidus) and/or your kidneys (nephrogenic diabetes insipidus).
Diabetes insipidus is not related to diabetes mellitus (type 1 and type 2 diabetes), although both conditions cause frequent urination and constant thirst. Diabetes mellitus causes high blood glucose, or blood sugar, resulting from the body’s inability to use blood glucose for energy. People with diabetes insipidus have normal blood glucose levels; however, their kidneys cannot balance fluid in the body.
Diabetes insipidus occurs when your body can’t properly balance the body’s fluid levels.
A hormone called anti-diuretic hormone (ADH), or vasopressin, helps control how fast or slow fluids are excreted. ADH is made in a part of the brain called the hypothalamus and stored in the pituitary gland, a small gland found in the base of the brain.
If you have diabetes insipidus, your body can’t properly balance fluid levels. The cause varies depending on the type of diabetes insipidus you have:
The types of diabetes insipidus include:
- Central diabetes insipidus
- Nephrogenic diabetes insipidus
- Dipsogenic diabetes insipidus
- Gestational diabetes insipidus
Each type of diabetes insipidus has a different cause.
Signs and symptoms of diabetes insipidus include:
- Extreme thirst
- Producing large amounts of diluted urine
- Frequent need to get up to urinate during the night
- Preference for cold drinks
If your condition is serious, urine output can be as much as 20 quarts (about 19 liters) a day if you’re drinking a lot of fluids. A healthy adult typically urinates an average of 1 or 2 quarts (about 1 to 2 liters) a day.
An infant or young child with diabetes insipidus may have the following signs and symptoms:
- Heavy, wet diapers
- Trouble sleeping
- Delayed growth
- Weight loss
Diabetes insipidus can cause an imbalance in electrolytes — minerals in your blood, such as sodium and potassium, that maintain the fluid balance in your body. Symptoms of an electrolyte imbalance may include:
- Loss of appetite
- Muscle cramps
There’s no cure for diabetes insipidus. But treatments can relieve your thirst and decrease your urine output.
Central Diabetes Insipidus
Central diabetes insipidus happens when damage to a person’s hypothalamus or pituitary gland causes disruptions in the normal production, storage, and release of vasopressin [antidiuretic hormone (ADH)]. The posterior lobe of the pituitary is the primary site of vasopressin [antidiuretic hormone (ADH)] storage and release, but vasopressin is synthesized within the hypothalamus. Newly synthesized hormone can still be released into the circulation as long as the hypothalamic nuclei and part of the neurohypophyseal tract are intact. Only about 10% of neurosecretory neurons must remain intact to avoid central diabetes insipidus. The pathology of central diabetes insipidus thus always involves the supraoptic and paraventricular nuclei of the hypothalamus or a major portion of the pituitary stalk. The disruption of vasopressin [antidiuretic hormone (ADH)] causes the kidneys to remove too much fluid from the body, leading to an increase in urination. Damage to the hypothalamus or pituitary gland can result from the following:
- a tumor
- head injury
Central diabetes insipidus can also result from an inherited defect in the gene that produces vasopressin, although this cause is rare. In some cases, the cause is unknown.
Central diabetes insipidus may be:
- Complete (absence of vasopressin)
- Partial (insufficient amounts of vasopressin)
Central diabetes insipidus may be:
- Primary, in which there is a marked decrease in the hypothalamic nuclei of the neurohypophyseal system
- Secondary (acquired)
- Hormonal drugs, eg, desmopressin
- Nonhormonal drugs, eg, diuretics
Central diabetes insipidus can be treated with hormone replacement and treatment of any correctable cause. In the absence of appropriate management, permanent renal damage can result.
Restricting salt intake may also help because it reduces urine output by reducing solute load.
Nephrogenic Diabetes Insipidus
Nephrogenic diabetes insipidus occurs when the kidneys do not respond normally to vasopressin and continue to remove too much fluid from a person’s bloodstream. Nephrogenic diabetes insipidus can result from inherited gene changes, or mutations, that prevent the kidneys from responding to vasopressin. Other causes of nephrogenic diabetes insipidus include:
- chronic kidney disease
- certain medications, particularly lithium
- low potassium levels in the blood
- high calcium levels in the blood
- blockage of the urinary tract
The causes of nephrogenic diabetes insipidus can also be unknown.
Dipsogenic Diabetes Insipidus
A defect in the thirst mechanism, located in a person’s hypothalamus, causes dipsogenic diabetes insipidus. This defect results in an abnormal increase in thirst and liquid intake that suppresses vasopressin secretion and increases urine output. The same events and conditions that damage the hypothalamus or pituitary—surgery, infection, inflammation, a tumor, head injury—can also damage the thirst mechanism. Certain medications or mental health problems may predispose a person to dipsogenic diabetes insipidus.
Gestational Diabetes Insipidus
Gestational diabetes insipidus occurs only during pregnancy. In some cases, an enzyme made by the placenta—a temporary organ joining mother and baby—breaks down the mother’s vasopressin. In other cases, pregnant women produce more prostaglandin, a hormone-like chemical that reduces kidney sensitivity to vasopressin. Most pregnant women who develop gestational diabetes insipidus have a mild case that does not cause noticeable symptoms. Gestational diabetes insipidus usually goes away after the mother delivers the baby; however, it may return if the mother becomes pregnant again.
Diabetes insipidus diagnosis
Your doctor has several ways to check for diabetes insipidus and to find the cause:
- Analysis of urine samples
- Blood tests to see how your pituitary gland is working
- Water deprivation test. While being monitored by a doctor and health care team, you’ll be asked to stop drinking fluids for several hours. To prevent dehydration while fluids are restricted, ADH allows your kidneys to decrease the amount of fluid lost in the urine. While fluids are being withheld, your doctor will measure changes in your body weight, urine output, and the concentration of your urine and blood. Your doctor may also measure blood levels of ADH or give you synthetic ADH during this test. This will determine if your body is producing enough ADH and if your kidneys can respond as expected to ADH.
- You also might have an imaging test of your head (an MRI) to check for problems with your pituitary gland. Your doctor also may order genetic tests.
- Genetic screening. If others in your family have had problems with excess urination, your doctor may suggest genetic screening.
Hypernatremia signs and symptoms
Symptoms and signs of hypernatremia are secondary to central nervous system dysfunction and are seen when serum sodium rises rapidly or is greater than 160 meq/L. Children present with irritability and agitation, which can progress to lethargy, somnolence, and coma. Other symptoms include increased thirst response in alert patients and high-pitched cry in infants. The skin can feel doughy or velvety due to intracellular water loss. Other findings include increased tone with brisk reflexes and myoclonus. It is important to remember that the degree of dehydration can be underestimated in children with hypernatremia due to a shift of water from the intracellular space to the extravascular space. The most serious complication of hypernatremia is brain hemorrhage, including subarachnoid or subdural hemorrhage due to rupture of bridging veins and dural sinus thrombosis. Hypernatremia is associated with a mortality rate as high as 15% to 20%.
The major symptom of hypernatremia is thirst. The absence of thirst in conscious patients with hypernatremia suggests an impaired thirst mechanism. Patients with difficulty communicating or ambulating may be unable to express thirst or obtain access to water. Sometimes patients with difficulty communicating express thirst by becoming agitated.
The major signs of hypernatremia result from CNS dysfunction due to brain cell shrinkage. Confusion, neuromuscular excitability, hyperreflexia, seizures, or coma may result. Cerebrovascular damage with subcortical or subarachnoid hemorrhage and venous thromboses have been described in children who died of severe hypernatremia.
In chronic hypernatremia, osmotically active substances are generated in CNS cells (idiogenic osmoles) and increase intracellular osmolality. Therefore, the degree of brain cell dehydration and resultant CNS symptoms are less severe in chronic than in acute hypernatremia.
When hypernatremia occurs with abnormal total body sodium, the typical symptoms of volume depletion or volume overload are present. Patients with renal concentrating defects typically excrete a large volume of hypotonic urine. When losses are extrarenal, the route of water loss is often evident (eg, vomiting, diarrhea, excessive sweating), and the urinary sodium concentration is low.
The main complication of hypernatremia is dehydration if fluid loss is greater than liquid intake. Signs of dehydration include:
- dry skin
Severe dehydration can lead to seizures, permanent brain damage, and even death.
Usually, people can prevent dehydration by increasing the amount of liquids they drink. People should seek immediate care if they experience symptoms of more severe dehydration, such as
The diagnosis of hypernatremia is clinical and by measuring serum sodium. In patients who do not respond to simple rehydration or in whom hypernatremia recurs despite adequate access to water, further diagnostic testing is warranted. Determination of the underlying disorder requires assessment of urine volume and osmolality, particularly after water deprivation.
In patients with increased urine output, a water deprivation test is occasionally used to differentiate among several polyuric states, such as central diabetes insipidus and nephrogenic diabetes insipidus.
The cause of hypernatremia usually is evident based on the history and physical exam. Plasma volume, plasma osmolality, urine volume, concentrating ability, and osmolality can help to further differentiate between renal and extrarenal causes. In diabetes insipidus, the urine is inappropriately diluted with normal urine volume and urine osmolality less than the serum osmolality. When diabetes insipidus is suspected, a water deprivation test may be performed with administration of desmopressin. In central diabetes insipidus, desmopressin administration demonstrates an increase in urine osmolality, while in the nephrogenic variety, there is no response to desmopressin. In extrarenal causes, the body tries to conserve fluids with appropriately low urine volume, high specific gravity, and urine osmolality greater than serum osmolality.
Proper management of hypernatremia involves identifying the underlying condition and correcting the hypertonicity. Replacement of both intravascular volume and free water is the main goal of treatment. Oral hydration is effective in conscious patients without significant gastrointestinal dysfunction. In severe hypernatremia or in patients unable to drink because of continued vomiting or mental status changes, IV hydration is preferred. Hypernatremia that has occurred within the last 24 hours should be corrected over the next 24 hours. However, hypernatremia that is chronic or of unknown duration should be corrected over 48 h, and the serum osmolality should be lowered at a rate of no faster than 0.5 mOsm/L/h to avoid cerebral edema caused by excess brain solute.
In patients with severe dehydration or shock, the initial step is fluid resuscitation with isotonic fluids before free water correction. Hypernatremia is corrected by calculating the free water deficit using one of the following formulas 5.
- 0.6 (1-145/current sodium) x body weight
- 4ml x body weight x (desired change in serum sodium meq/L)
It is important to remember that rapid correction of hypernatremia can lead to cerebral edema because water moves from the serum into the brain cells. The goal is to decrease the serum sodium by not more than 12 meq in a 24-hour period. Close serial monitoring of serum sodium every 2 to 4 hours is essential during the acute phase of correction. Seizures occurring during correction of hypernatremia is a sign of cerebral edema due to rapid shifts in osmolality, and the administration of hypotonic fluids should be halted. The estimated free water deficit should be corrected over 48 to 72 hours with a decrease in serum sodium not exceeding 0.5 meq per hour. Patients should be carefully monitored for the rate of correction, urine output, and ongoing loss. In cases of sodium intoxication, the free water requirement may be too large and cause volume overload, requiring the use of loop diuretics and, at times, peritoneal dialysis to remove excess sodium. Older children and adults with central diabetes insipidus may need desmopressin, which is available in intranasal and oral forms. Water intoxication and hyponatremia are adverse effects seen with the use of desmopressin.
In patients with hypernatremia and ECF volume overload (excess total body sodium content), the free water deficit can be replaced with 5% D/W (5% dextrose water), which can be supplemented with a loop diuretic. However, too-rapid infusion of 5% D/W may cause glucosuria, thereby increasing salt-free water excretion and hypertonicity, especially in patients with diabetes mellitus. Other electrolytes, including serum potassium, should be monitored and should be replaced as needed.
In patients with hypernatremia and euvolemia, free water can be replaced using either 5% D/W (5% dextrose water) or 0.45% saline.
In patients with hypernatremia and hypovolemia, particularly in patients with diabetes with nonketotic hyperglycemic coma, 0.45% saline can be given as an alternative to a combination of 0.9% normal saline and 5% D/W (5% dextrose water) to replenish sodium and free water. Alternatively, ECF volume and free water can be replaced separately, using the formula given previously to estimate the free water deficit. When severe acidosis (pH <7.10) is present, sodium bicarbonate solution can be added to 5% D/W (5% dextrose water) or 0.45% saline, as long as the final solution remains hypotonic.
Diabetes insipidus treatment
The primary treatment for diabetes insipidus involves drinking enough liquid to prevent dehydration. A health care provider may refer a person with diabetes insipidus to a nephrologist—a doctor who specializes in treating kidney problems—or to an endocrinologist—a doctor who specializes in treating disorders of the hormone-producing glands. Treatment for frequent urination or constant thirst depends on the patient’s type of diabetes insipidus:
- Central diabetes insipidus. A synthetic, or man-made, hormone called desmopressin (DDAVP, Minirin, others) treats central diabetes insipidus. Desmopressin replaces the missing anti-diuretic hormone (ADH) and decreases urination. Desmopressin comes as an injection, a nasal spray, or a pill. Most people still make some ADH, though the amount can vary day to day. So, the amount of desmopressin you need also may vary. Taking more desmopressin than you need can cause water retention and potentially serious low-sodium levels in the blood. This treatment helps a patient manage symptoms of central diabetes insipidus; however, it does not cure the disease. Other medications may also be prescribed, such as indomethacin (Indocin, Tivorbex) and chlorpropamide. These drugs can make ADH more available in the body.
- Nephrogenic diabetes insipidus. In some cases, nephrogenic diabetes insipidus goes away after treatment of the cause. For example, switching medications or taking steps to balance the amount of calcium or potassium in the patient’s body may resolve the problem. Medications for nephrogenic diabetes insipidus include diuretics, either alone or combined with aspirin or ibuprofen. Health care providers commonly prescribe diuretics to help patients’ kidneys remove fluid from the body. Paradoxically, in people with nephrogenic diabetes insipidus, a class of diuretics called thiazides reduces urine production and helps patients’ kidneys concentrate urine. Although hydrochlorothiazide is a type of drug that usually increases urine output (diuretic), in some people it can reduce urine output for people with nephrogenic diabetes insipidus. Aspirin or ibuprofen also helps reduce urine volume.
- Dipsogenic diabetes insipidus. Researchers have not yet found an effective treatment for dipsogenic diabetes insipidus. People can try sucking on ice chips or sour candies to moisten their mouths and increase saliva flow, which may reduce the desire to drink. For a person who wakes multiple times at night to urinate because of dipsogenic diabetes insipidus, taking a small dose of desmopressin at bedtime may help. Initially, the health care provider will monitor the patient’s blood sodium levels to prevent hyponatremia, or low sodium levels in the blood.
- Gestational diabetes insipidus. A health care provider can prescribe desmopressin for women with gestational diabetes insipidus. An expecting mother’s placenta does not destroy desmopressin as it does vasopressin. Most women will not need treatment after delivery.
Most people with diabetes insipidus can prevent serious problems and live a normal life if they follow the health care provider’s recommendations and keep their symptoms under control.References
- Hypernatremia. Clin J Am Soc Nephrol. 2019 Mar 7; 14(3): 432–434. doi: 10.2215/CJN.12141018. Epub 2019 Feb 6. https://cjasn.asnjournals.org/content/14/3/432.long
- Hypernatremia. https://www.merckmanuals.com/professional/endocrine-and-metabolic-disorders/electrolyte-disorders/hypernatremia?query=hypernatremia
- Naganathan S, Al-Dhahir MA. Hypernatremia. [Updated 2019 Feb 17]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2019 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK441960
- Imai N, Shibagaki Y. The prevalence of dysnatremia in the elderly patients without CKD. Am J Emerg Med. 2019 Mar;37(3):499-501
- Baldeweg SE, Ball S, Brooke A, Gleeson HK, Levy MJ, Prentice M, Wass J., Society for Endocrinology Clinical Committee. SOCIETY FOR ENDOCRINOLOGY CLINICAL GUIDANCE: Inpatient management of cranial diabetes insipidus. Endocr Connect. 2018 Jul;7(7):G8-G11