The history, physical exam, and laboratory testing are required to determine the underlying cause of hyponatremia. A blood test demonstrating a serum sodium less than 135 mmol/L is diagnostic for hyponatremia. The history and physical exam are necessary to help determine if the patient is hypovolemic, euvolemic, or hypervolemic, which has important implications in determining the underlying cause. An assessment is also made to determine if the patient is experiencing symptoms from their hyponatremia. These include assessments of alertness, concentration, and orientation.

False hyponatremia, also known as spurious, pseudo, hypertonic, or artifactual hyponatremia is when the lab tests read low sodium levels but there is no hypotonicity. In hypertonic hyponatremia, resorption of water by molecules such as glucose (hyperglycemia or diabetes) or mannitol (hypertonic infusion) occurs. In isotonic hyponatremia a measurement error due to high blood triglyceride level (most common) or paraproteinemia occurs. It occurs when using techniques that measure the amount of sodium in a specified volume of serum/plasma, or that dilute the sample before analysis.

Diagnosis is based on clinical and laboratory findings of low serum osmolality and low serum sodium.

Urinalysis reveals a highly concentrated urine with a high fractional excretion of sodium (high sodium urine content compared to the serum sodium).

A suspected diagnosis is based on a serum sodium under 138. A confirmed diagnosis has seven elements: 1) a decreased effective serum osmolality - <275 mOsm/kg of water; 2) urinary sodium concentration high - over 40 mEq/L with adequate dietary salt intake; 3) no recent diuretic usage; 4) no signs of ECF volume depletion or excess; 5) no signs of decreased arterial blood volume - cirrhosis, nehprosis, or congestive heart failure; 6) normal adrenal and thyroid function; and 7) no evidence of hyperglycemia (diabetes mellitus), hypertriglyceridemia, or hyperproteinia (myeloma).

There are nine supplemental features: 1) a low BUN; 2) a low uric acid; 3) a normal creatinine; 4) failure to correct hyponatremia with IV normal saline; 5) successful correction of hyponatremia with fluid restriction; 6) a fractional sodium excretion >1%; 7) a fractional urea excretion >55%; 8) an abnormal water load test; and 9) an elevated plasma AVP.

Prevention of EAH focuses on reducing fluid consumption to avoid fluid retention before, during, and after exercise.

Antidiuretic hormone (ADH) is released from the posterior pituitary for a number of physiologic reasons. The majority of people with hyponatremia, other than those with excessive water intake (polydipsia) or renal salt wasting, will have elevated ADH as the cause of their hyponatremia. However, not every person with hyponatremia and elevated ADH has SIADH. One approach to a diagnosis is to divide ADH release into appropriate (not SIADH) or inappropriate (SIADH).

Appropriate ADH release can be a result of hypovolemia, a so-called osmotic trigger of ADH release. This may be true hypovolemia, as a result of dehydration with fluid losses replaced by free water. It can also be perceived hypovolemia, as in the conditions of congestive heart failure (CHF) and cirrhosis in which the kidneys perceive a lack of intravascular volume. The hyponatremia caused by appropriate ADH release (from the kidneys' perspective) in both CHF and cirrhosis have been shown to be an independent poor prognostic indicator of mortality.

Appropriate ADH release can also be a result of non-osmotic triggers. Symptoms such as nausea/vomiting and pain are significant causes of ADH release. The combination of osmotic and non-osmotic triggers of ADH release can adequately explain the hyponatremia in the majority of people who are hospitalized with acute illness and are found to have mild to moderate hyponatremia. SIADH is less common than appropriate release of ADH. While it should be considered in a differential, other causes should be considered as well.

Cerebral salt wasting syndrome (CSWS) also presents with hyponatremia, there are signs of dehydration for which reason the management is diametrically opposed to SIADH. Importantly CSWS can be associated with subarachnoid hemorrhage (SAH) which may require fluid supplementation rather than restriction to prevent brain damage.

Most cases of hyponatremia in children are caused by appropriate secretion of antidiuretic hormone rather than SIADH or another cause.

EAH is categorized by having a blood serum or plasma sodium level below normal, which is less than 135 mmol/l. Asymptomatic EAH is not normally detected unless the athlete has had a sodium blood serum or plasma test. Hyponatremic encephalopathy may be detect using brain imaging studies and pulmonary edema may be confirmed by x-ray.

Various investigations aid the diagnosis.

- ACTH (cosyntropin) stimulation test

- Cortisol level (to assess the level of glucocorticoids)

- Fasting blood sugar

- Serum potassium (to assess the level of mineralocorticoids)

- Serum sodium

Adrenal crisis is triggered by physiological stress (such as trauma). Activities that have an elevated risk of trauma are best avoided. Treatment must be given within two hours of trauma and consequently it is advisable to carry injectable hydrocortisone in remote areas.

While CSWS usually appears within the first week after brain injury and spontaneously resolves in 2–4 weeks, it can sometimes last for months or years. In contrast to the use of fluid restriction to treat SIADH, CSWS is treated by replacing the urinary losses of water and sodium with hydration and sodium replacement. The mineralocorticoid medication fludrocortisone can also improve the low sodium level.

Excessive sodium and fluid intake:

- IV therapy containing sodium

- As a Transfusion reaction to a rapid blood transfusion.

- High intake of sodium

Sodium and water retention:

- Heart failure

- Liver cirrhosis

- Nephrotic syndrome

- Corticosteroid therapy

- Hyperaldosteronism

- Low protein intake

Fluid shift into the intravascular space:

- Fluid remobilization after burn treatment

- Administration of hypertonic fluids, e.g. mannitol or hypertonic saline solution

- Administration of plasma proteins, such as albumin

As with all cases of hyponatremia, extreme caution must be taken to avoid the fatal consequences of rapidly correcting electrolytes (e.g. Central pontine myelinolysis, edema). Special considerations with the treatment of potomania are needed. Because this could be a chronic condition, low sodium may be normal for the patient, so an especially careful correction is warranted. It is also very important to note that due to the normal kidney function, and lack of other intrinsic or toxic cause of the electrolyte disturbance, restoration of dietary solutes will correct the electrolytes to normal serum levels. This again must be done with caution.

CSWS is usually caused by brain injury/trauma or cerebral lesion, tumor, or hematoma. CSWS is a diagnosis of exclusion and may be difficult to distinguish from the syndrome of inappropriate antidiuretic hormone (SIADH), which develops under similar circumstances and also presents with hyponatremia. The main clinical difference is that of total fluid status of the patient: CSWS leads to a relative or overt low blood volume whereas SIADH is consistent with a normal or high blood volume. If blood-sodium levels increase when fluids are restricted, SIADH is more likely.

Hypervolemia, or fluid overload, is the medical condition where there is too much fluid in the blood. The opposite condition is hypovolemia, which is too little fluid volume in the blood. Fluid volume excess in the intravascular compartment occurs due to an increase in total body sodium content and a consequent increase in extracellular body water. The mechanism usually stems from compromised regulatory mechanisms for sodium handling as seen in congestive heart failure (CHF), kidney failure, and liver failure. It may also be caused by excessive intake of sodium from foods, intravenous (IV) solutions and blood transfusions, medications, or diagnostic contrast dyes. Treatment typically includes administration of diuretics and limit the intake of water, fluids, sodium, and salt.

The normal human kidney, through suppression of anti-diuretic hormone, is normally able to excrete vast amounts of dilute urine. Thus a normal adult can drink up to 20 liters per day of water without becoming hyponatremic. However, the intake of solutes is also necessary to excrete free water. Under normal circumstances, this is clinically irrelevant. In the lack of proper solute intake, the amount of free water excretion can be severely limited. Without adequate solute intake, the normal functioning electrolyte gradient that pulls water into urine will be effectively destroyed.

Briefly, to excrete free water from urine, the urine flow (which is solute clearance + free water clearance) will equal the rate of solute excretion divided by the urine osmolality. With a diet of only solute poor beer, only about 200-300 mOSM (normal 750 mOSM to greater than 900 mOSM) of solute will be excreted per day, capping the amount of free water excretion at four liters. Any intake above 4 liters would lead to a dilution of the serum sodium concentration and thus hyponatremia.

Any vomiting or GI absorptive problems due to alcohol intoxication can also compound the effect of potomania due to additional electrolyte and acid-base disturbances.

Dogs with infected with the whipworm "Trichuris trichiura" can exhibit low sodium and high potassium values, as is seen in hypoadrenocorticism; however, their ACTH values are normal.

Breeds that began in the Pacific Rim, among them Akitas and Shiba Inus, tend to have higher potassium values in laboratory test, and elevated levels are not abnormal. Dogs who do not have hypoadrenocorticism have normal values on ACTH tests.

Along with obtaining a complete medical history, a series of biochemical tests are required in order to arrive at an accurate diagnosis that verifies the presence of the illness. In addition, imaging of the kidneys (for structure and presence of two kidneys) is sometimes carried out, and/or a biopsy of the kidneys. The first test will be a urinalysis to test for high levels of proteins, as a healthy subject excretes an insignificant amount of protein in their urine. The test will involve a 24-hour bedside urinary total protein estimation. The urine sample is tested for proteinuria (>3.5 g per 1.73 m per 24 hours). It is also examined for urinary casts, which are more a feature of active nephritis. Next a blood screen, comprehensive metabolic panel (CMP) will look for hypoalbuminemia: albumin levels of ≤2.5 g/dL (normal=3.5-5 g/dL). Then a Creatinine Clearance C test will evaluate renal function particularly the glomerular filtration capacity. Creatinine formation is a result of the breakdown of muscular tissue, it is transported in the blood and eliminated in urine. Measuring the concentration of organic compounds in both liquids evaluates the capacity of the glomeruli to filter blood. Electrolytes and urea levels may also be analysed at the same time as creatinine (EUC test) in order to evaluate renal function.

A lipid profile will also be carried out as high levels of cholesterol (hypercholesterolemia), specifically elevated LDL, usually with concomitantly elevated VLDL, is indicative of nephrotic syndrome.

A kidney biopsy may also be used as a more specific and invasive test method. A study of a sample’s anatomical pathology may then allow the identification of the type of glomerulonephritis involved. However, this procedure is usually reserved for adults as the majority of children suffer from minimum change disease that has a remission rate of 95% with corticosteroids. A biopsy is usually only indicated for children that are "corticosteroid resistant" as the majority suffer from focal and segmental glomeruloesclerosis.

Further investigations are indicated if the cause is not clear including analysis of auto-immune markers (ANA, ASOT, C3, cryoglobulins, serum electrophoresis), or ultrasound of the whole abdomen.

It can be diagnosed clinically in the appropriate context, but may be difficult to confirm radiologically using conventional imaging techniques. Changes are more prominent on MRI than on CT, but often take days or weeks after acute symptom onset to develop. Imaging by MRI typically demonstrates areas of hyperintensity on T2-weighted images.

The best diagnostic tool to confirm adrenal insufficiency is the ACTH stimulation test; however, if a patient is suspected to be suffering from an acute adrenal crisis, immediate treatment with IV corticosteroids is imperative and should not be delayed for any testing, as the patient's health can deteriorate rapidly and result in death without replacing the corticosteroids.

Dexamethasone should be used as the corticosteroid if the plan is to do the ACTH stimulation test at a later time as it is the only corticosteroid that will not affect the test results.

If not performed during crisis, then labs to be run should include: random cortisol, serum ACTH, aldosterone, renin, potassium and sodium. A CT of the adrenal glands can be used to check for structural abnormalities of the adrenal glands. An MRI of the pituitary can be used to check for structural abnormalities of the pituitary. However, in order to check the functionality of the Hypothalamic Pituitary Adrenal (HPA) Axis the entire axis must be tested by way of ACTH stimulation test, CRH stimulation test and perhaps an Insulin Tolerance Test (ITT). In order to check for Addison’s Disease, the auto-immune type of primary adrenal insufficiency, labs should be drawn to check 21-hydroxylase autoantibodies.

The treatment of nephrotic syndrome can be symptomatic or can directly address the injuries caused to the kidney.

In suspected cases of Addison's disease, demonstration of low adrenal hormone levels even after appropriate stimulation (called the ACTH stimulation test or synacthen test) with synthetic pituitary ACTH hormone tetracosactide is needed for the diagnosis. Two tests are performed, the short and the long test. It should be noted that dexamethasone does not cross-react with the assay and can be administered concomitantly during testing.

The short test compares blood cortisol levels before and after 250 micrograms of tetracosactide (intramuscular or intravenous) is given. If, one hour later, plasma cortisol exceeds 170 nmol/l and has risen by at least 330 nmol/l to at least 690 nmol/l, adrenal failure is excluded. If the short test is abnormal, the long test is used to differentiate between primary adrenal insufficiency and secondary adrenocortical insufficiency.

The long test uses 1 mg tetracosactide (intramuscular). Blood is taken 1, 4, 8, and 24 hr later. Normal plasma cortisol level should reach 1000 nmol/l by 4 hr. In primary Addison's disease, the cortisol level is reduced at all stages, whereas in secondary corticoadrenal insufficiency, a delayed but normal response is seen.

Other tests may be performed to distinguish between various causes of hypoadrenalism, including renin and adrenocorticotropic hormone levels, as well as medical imaging - usually in the form of ultrasound, computed tomography or magnetic resonance imaging.

Adrenoleukodystrophy, and the milder form, adrenomyeloneuropathy, cause adrenal insufficiency combined with neurological symptoms. These diseases are estimated to be the cause of adrenal insufficiency in about 35% of male patients with idiopathic Addison’s disease, and should be considered in the differential diagnosis of any male with adrenal insufficiency. Diagnosis is made by a blood test to detect very long chain fatty acids.

Common investigations include blood urea nitrogen (BUN) and electrolytes, liver function tests, urinalysis, and thyroid function tests. Hematological investigations include hematocrit levels, which are usually raised in HG. An ultrasound scan may be needed to know gestational status and to exclude molar or partial molar pregnancy.

Routine laboratory investigations may show:

- Hypercalcemia

- Hypoglycemia, low blood sugar (worse in children due to loss of glucocorticoid's glucogenic effects)

- Hyponatremia (low blood sodium levels), due to loss of production of the hormone aldosterone, to the kidney's inability to excrete free water in the absence of sufficient cortisol, and also the effect of corticotropin-releasing hormone to stimulate secretion of ADH.

- Hyperkalemia (raised blood potassium levels), due to loss of production of the hormone aldosterone.

- Eosinophilia and lymphocytosis (increased number of eosinophils or lymphocytes, two types of white blood cells)

- Metabolic acidosis (increased blood acidity), also is due to loss of the hormone aldosterone because sodium reabsorption in the distal tubule is linked with acid/hydrogen ion (H) secretion. Absent or insufficient levels of aldosterone stimulation of the renal distal tubule leads to sodium wasting in the urine and H retention in the serum.

Growth hormone deficiency is almost certain if all other pituitary tests are also abnormal, and insulin-like growth factor 1 (IGF-1) levels are decreased. If this is not the case, IGF-1 levels are poorly predictive of the presence of GH deficiency; stimulation testing with the insulin tolerance test is then required. This is performed by administering insulin to lower the blood sugar to a level below 2.2 mmol/l. Once this occurs, growth hormone levels are measured. If they are low despite the stimulatory effect of the low blood sugars, growth hormone deficiency is confirmed. The test is not without risks, especially in those prone to seizures or are known to have heart disease, and causes the unpleasant symptoms of hypoglycemia. Alternative tests (such as the growth hormone releasing hormone stimulation test) are less useful, although a stimulation test with arginine may be used for diagnosis, especially in situations where an insulin tolerance test is thought to be too dangerous. If GH deficiency is suspected, and all other pituitary hormones are normal, two different stimulation tests are needed for confirmation.

If morning cortisol levels are over 500 nmol/l, ACTH deficiency is unlikely, whereas a level less than 100 is indicative. Levels between 100-500 require a stimulation test. This, too, is done with the insulin tolerance test. A cortisol level above 500 after achieving a low blood sugar rules out ACTH deficiency, while lower levels confirm the diagnosis. A similar stimulation test using corticotropin-releasing hormone (CRH) is not sensitive enough for the purposes of the investigation. If the insulin tolerance test yields an abnormal result, a further test measuring the response of the adrenal glands to synthetic ACTH (the ACTH stimulation test) can be performed to confirm the diagnosis. Stimulation testing with metyrapone is an alternative. Some suggest that an ACTH stimulation test is sufficient as first-line investigation, and that an insulin tolerance test is only needed if the ACTH test is equivocal. The insulin tolerance test is discouraged in children. None of the tests for ACTH deficiency are perfect, and further tests after a period of time may be needed if initial results are not conclusive.

Symptoms of diabetes insipidus should prompt a formal fluid deprivation test to assess the body's response to dehydration, which normally causes concentration of the urine and increasing osmolarity of the blood. If these parameters are unchanged, desmopressin (an ADH analogue) is administered. If the urine then becomes concentrated and the blood osmolarity falls, there is a lack of ADH due to lack of pituitary function ("cranial diabetes insipidus"). In contrast, there is no change if the kidneys are unresponsive to ADH due to a different problem ("nephrogenic diabetes insipidus").

To minimise the risk of this condition developing from its most common cause, overly rapid reversal of hyponatremia, the hyponatremia should be corrected at a rate not exceeding 10 mmol/L/24 h or 0.5 mEq/L/h; or 18 m/Eq/L/48hrs; thus avoiding demyelination. No large clinical trials have been performed to examine the efficacy of therapeutic re-lowering of serum sodium, or other interventions sometimes advocated such as steroids or plasma exchange.

Alcoholic patients should receive vitamin supplementation and a formal evaluation of their nutritional status.

Once osmotic demyelination has begun, there is no cure or specific treatment. Care is mainly supportive. Alcoholics are usually given vitamins to correct for other deficiencies. The favourable factors contributing to the good outcome in CPM without hyponatremia were: concurrent treatment of all electrolyte disturbances, early Intensive Care Unit involvement at the advent of respiratory complications, early introduction of feeding including thiamine supplements with close monitoring of the electrolyte changes and input.

Research has led to improved outcomes. Animal studies suggest that inositol reduces the severity of osmotic demyelination syndrome if given before attempting to correct chronic hyponatraemia. Further study is required before using inositol in humans for this purpose.