Syndrome of inappropriate antidiuretic hormone secretion: Clinical sciences

Syndrome of inappropriate antidiuretic hormone secretion, or SIADH for short, is when too much antidiuretic hormone, also called ADH, or arginine vasopressin, is secreted.

Normally, ADH is secreted when there’s too little water and too much sodium in the body, and it works by increasing water reabsorption in the renal tubule, restoring the water-sodium balance.

However, with SIADH, there’s increased ADH secretion in the absence of fluid depletion, and this causes excessive water reabsorption, diluting the blood to the point of euvolemic hyponatremia.

SIADH most often occurs as a secondary response to another condition, and is commonly seen in patients with pulmonary disease like pneumonia or lung cancer, as well as central nervous system disorders, like meningitis and head trauma.

Now, if your patient presents with chief concerns suggesting SIADH, you should first perform an ABCDE assessment to determine if they are unstable or stable.

If the patient is unstable, stabilize the airway, breathing, and circulation. Next, obtain IV access and put your patient on continuous vital sign monitoring, including blood pressure, heart rate, and pulse oximetry.

Don’t forget to monitor the patient’s urine output closely! Finally, if needed, provide supplemental oxygen.Now, here’s a high-yield fact!

Unstable patients often have severe symptoms like seizures or even respiratory arrest! In severe hyponatremia, sodium levels can fall below 125 milliequivalents per liter, and the hyponatremia is frequently acute, meaning it developed within a 24- to 48-hour period.

Symptomatic hyponatremia indicates the presence of cerebral edema, so if your patient presents with severe symptoms, obtain a serum sodium level to confirm hyponatremia, and administer intravenous 3% hypertonic saline to treat the cerebral edema and correct serum sodium.

Make sure not to give 0.9% isotonic saline, because this can dilute the serum sodium even more! Also, keep in mind that, in patients with severe hyponatremia, raising the serum sodium too rapidly can lead to osmotic demyelination syndrome, a potentially fatal condition associated with lasting neurologic dysfunction!

This is why, generally speaking, the goal is to correct the serum sodium concentration by raising no more than 4 to 6 milliequivalents per liter in a 24-hour period.Now, let’s go back to the ABCDE assessment and look at stable patients.

In this case, obtain a focused history and physical examination and order a basic metabolic panel or BMP.History findings typically include headache, nausea, vomiting, and confusion.

But bear in mind that the vast majority of patients with SIADH can be asymptomatic! Now, patients with SIADHare often elderly and may have a history of pulmonary conditions, like pneumonia or small cell lung cancer; as well as central nervous system conditions, such as meningitis, CNS tumors, or traumatic brain injury.

They might also report use of medications like NSAIDs, antidepressants, or antipsychotics. Alright, now, let’s move on to physical exam findings.

These patients usually have normal blood pressure and heart rate, and appear well hydrated, with moist mucous membranes and normal skin turgor.

Signs of hypervolemia, like ascites and edema, are absent. Finally, labs reveal a sodium level lower than 135 milliequivalents per liter, as well as a normal BUN and creatinine.

If your patient has this spectrum of findings, you should suspect SIADH and check plasma osmolality.If the plasma osmolality is greater than 280 milliosmoles per kilogram, then you should consider alternative diagnoses, such as pseudohyponatremia caused by hyperlipidemia or hyperproteinemia.

Let’s take a look at when the plasma osmolality is lower than 280 milliosmoles per kilogram. If the plasma osmolality is lower than 280 milliosmoles per kilogram, order a urine sodium and urine osmolality.

If urine sodium is lower than 20 milliequivalents or millimoles, per liter, regardless of urine osmolality, you should consider alternative diagnoses, such as primary polydipsia, which is when water ingestion is so high that the urine is extremely over diluted.

But, if the urine sodium is greater than 20 milliequivalents per liter and urine osmolality is greater than 100 milliosmoles per kilogram, you can diagnose SIADH.Now here’s a clinical pearl!

Before confirming the diagnosis of SIADH, also make sure to rule out other conditions that can cause euvolemic hyponatremia.

So check a TSH and cortisol level to assess for hypothyroidism and glucocorticoid insufficiency, respectively! If you find that other cause, initiating hormone replacement therapy can help normalize sodium levels.

On the flip side, euvolemic hyponatremia can also be caused by thiazide diuretics, which can cause sodium and potassium depletion, reduced ability to excrete free water, and inhibition of the sodium-chloride transporter.

If your patient has thiazide-induced hyponatremia, discontinue the thiazide, and proceed with sodium and potassium repletion and oral fluid restriction.Ok, now, once you’ve diagnosed SIADH, your next step is to assess the clinical and biochemical severity of hyponatremia.Keep in mind that the most important determinant of symptom severity is the acuity of onset, not the serum sodium level.

In fact, acute onset, meaning within the previous 24 to 48 hours, typically causes more severe symptoms; while other factors, like coexisting brain injury, also impact symptom severity in hyponatremic patients.Patients with mild clinical manifestations usually have a slightly decreased serum sodium level, typically between 130 and 135 milliequivalents per liter, and they may have a gradual onset of mild symptoms, or even be asymptomatic.On the other hand, patients with moderately severe SIADH usually have a lower serum sodium level, often between 125 and 129 milliequivalents per liter.

Additionally, with acute onset hyponatremia, individuals are more likely to have moderate symptoms, like headache, confusion, nausea, vomiting, or an unstable gait.

Finally, patients with severe SIADH usually have a sodium level below 125 milliequivalents per liter. They also typically present with acute onset of severe symptoms, such as seizures or respiratory arrest.

Your next step is to provide management! Regardless of the severity of SIADH, first-line management includes fluid restriction, treatment of the underlying cause, and discontinuation of any offending medications.

In mild forms, this is often enough to resolve symptoms and hyponatremia. Additionally, in moderate or severe forms, or if hyponatremia persists after 24 to 48 hours of fluid restriction, consider medical management options.

For mild persistent cases, salt tablets can be used; while in moderate or severe cases, medical options include 3% hypertonic saline, which should be started alongside fluid restriction; vasopressin receptor antagonists, also known as “vaptans”, which work by increasing water excretion; urea, which increases water excretion and decreases sodium excretion; and demeclocycline, which decreases urine concentration, despite high ADH levels.And here’s one last clinical pearl!

Rarely, a genetic mutation can cause continuous activation of the V2 vasopressin receptor, which mimics the effects of ADH and leads to increased water reabsorption by the kidneys, despite low serum levels of ADH.

This condition is called nephrogenic syndrome of inappropriate antidiuresis, or NSIAD for short. You should suspect NSIAD in any patient who meets the clinical criteria for SIADH, but has no apparent underlying condition that could explain it.

Treatment of NSIAD includes fluid restriction and oral urea administration.Alright, as a quick recap… If you suspect SIADH, first you should check plasma osmolality.

If it’s lower than 280 milliosmoles per kilogram, check urine sodium and osmolality. If urine sodium is greater than 20 milliequivalents per liter and urine osmolality is greater than 100 milliosmoles per kilogram, you can diagnose SIADH.

Depending on clinical and biochemical severity, SIADH can be mild, moderate, or severe. First-line management of all forms of SIADH includes fluid restriction, treatment of the underlying cause, and discontinuation of any offending medications.

However, in moderate or severe forms or if hyponatremia persists after 24 to 48 hours of fluid restriction, consider additional medical management options, such as salt tablets, 3% hypertonic saline, vaptans, urea, or demeclocycline.

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