Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH)
Etiology
Hereditary Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH)
Mechanism
Mutation in the Gene for the Renal V2 Receptor (“Nephrogenic Syndrome of Inappropriate Antidiuresis”)
Most Patients Have a Mutation Which Locks the V2 Receptor in the Open Position, Making it Unresponsive to Vasopressin Antagonists (Clin Endocrinol-Oxf, 2016) [MEDLINE]
SIADH Occurs More Commonly in Small Cell Lung Cancer than Ectopic Atrial Natriuretic Peptide (ANP) Secretion
Ectopic Atrial Natriuretic Peptide (ANP) Secretion May Also Exacerbate SIADH-Related Hyponatremia by Inducing Sodium Excretion into a Concentrated Urine without Extracellular Volume Expansion
Similar to Other Etiologies of Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH), Hyponatremia in These Conditions is Due to Antidiuretic Hormone-Induced Water Retention and Urinary Sodium Loss
However, it is Not Certain if the Sodium Losses are Due to an Antidiuretic Hormone-Induced Expansion in the Extracellular Volume or Whether They are Due to Cerebral Salt-Wasting with a Secondary Release of Antidiuretic Hormone in Response to Decreased Extracellular Volume
Due to This Uncertainty, Therapy of This Group of Etiologies Typically Involves the Use of Hypertonic (3%) Saline, Rather than Fluid Restriction or Isotonic Saline
Hyponatremia in SAH is Usually Due to SIADH, But Cerebral Salt Wasting May Instead Be Etiologic (J Am Soc Nephrol, 2008) [MEDLINE] (see Cerebral Salt Wasting)
Since SIADH and Cerebral Salt Wasting are Similar, the Main Differentiating Feature is Clinical Hypovolemia Despite a Urine Sodium Which is Not Low, Which Supports the Diagnosis of Cerebral Salt Wasting Instead
Associated with Surgical Procedures (Including Ones as Noninvasive as Cardiac Catheterization, etc) (Am J Kidney Dis, 2002) [MEDLINE]
May Occur as a Late Complication of Transsphenoidal Pituitary Surgery (Occurs in 21-35% of Cases (J Clin Endocrinol Metab, 1994) [MEDLINE] (J Clin Endocrinol Metab, 1995) [MEDLINE]
Mechanism Likely Involves Predominantly SIADH (Due to Antidiuretic Hormone Release from the injured Posterior Pituitary Gland), Although Relative Cortisol Deficiency May Contribute to a Lesser Extent
Hyponatremia is the Most Severe ob the 6th-7th Postoperative Day
The Occurrence of Delayed Hyponatremia is Likely a Subset of the Classic Triphasic Cycle (Initial Polyuria, Followed by Transient SIADH, and Then, Either Recovery or a Third Phase of Permanent Central Diabetes Insipidus)
Physiology
Surgery is Commonly Associated with Antidiuretic Hormone Secretion (Likely Mediated by Pain Afferents) (Ann Surg, 1985) [MEDLINE] (Kidney Int, 1986) [MEDLINE] (Clin Nephrol, 1998) [MEDLINE]
Most Associated with High-Dose Intravenous Use (30-50 mg/kg used to treat malignancy or 6 g/m2 as given in the STAMP protocol in preparation for bone marrow rescue)
Although less common, hyponatremia can also occur with the lower doses (10-15 mg/kg) that are given as pulse therapy in autoimmune diseases such as lupus nephritis
Exacerbated by the Fact that These Patients Also Receive Intravenous Fluid Loading to Prevent the Complication of Hemorrhagic Cystitis
Pharmacology
Stimulation of Vasopressin Release
Chemotherapy-Induced Nausea May Contribute Since Nausea is a Potent Stimulus to Antidiuretic Hormone Release
Management
The fall in the plasma sodium concentration in this setting can be minimized by using isotonic saline rather than free water to maintain a high urine output
Potentiation of Peripheral Activity of Vasopressin
Chlorpropamide Stimulates Vasopressin Release and Increases Concentrating Ability Both by Increasing Sodium Chloride Reabsorption in the Loop of Henle (Enhancing the Efficiency of Countercurrent Exchange) and by Augmenting Collecting Tubule Water Permeability (the Latter Effect Mediated by an Increased Number of Antidiuretic Hormone Receptors in the Collecting Tubule Cells)
Known Association Between SSRI Use and SIADH (Psychosomatics, 2014) [MEDLINE] (Arch Gerontol Geriatr, 2014) [MEDLINE] (Br J Clin Pharmacol, 2017)[MEDLINE]
Risk of Developing Severe Hyponatremia Requiring Hospitalization is Greatest in the First Few Weeks After Initiating the SSRI
Low Serum Osmolality was Present in the Described Cases (with Vasopressin Use in the Treatment of Septic Shock), Suggesting Either Hypovolemia or an SIADH-Type Mechanism (J Intensive Care Med, 2015) [MEDLINE]
Idiopathic Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH)
Epidemiology
Has Been Described, Predominantly in Older Patients (Ann Intern Med, 1983) [MEDLINE] (Am J Kidney Dis, 1999) [MEDLINE] (J Am Geriatr Soc, 2001) [MEDLINE]
Importantly, Occult Malignancy Needs to Be Ruled Out
Physiology
Background
Antidiuretic Hormone (ADH, Also Known as Arginine Vasopressin) Secretion Results in a Concentrated Urine and, Consequently, a Decreased Urine Volume
The Higher the Plasma ADH, the More Concentrated the Urine
Syndrome of Inappropriate Secretion of Antidiuretic Hormone Secretion (SIADH) is a Disorder Characterized by Impaired Water Excretion Due to an Inability to Suppress the Secretion of Antidiuretic Hormone (ADH)
If Water Intake Exceeds the Decreased Urine Output, Water Retention Will Result in the Development of Hyponatremia
In Most Patients with SIADH, the Ingestion of Water Does Not Adequately Suppress Antidiuretic Hormone Secretion
Consequently, the Urine is Concentrated with Associated Water Retention
Water Retention Increases Total Body Water, Which Results in a Dilutional Decrease in the Plasma Sodium Concentration
The Increase in Total Body Water Transiently Expands the Extracellular Fluid Volume, Triggering Increased Urinary Sodium Excretion
This Returns the Extracellular Fluid Volume Back Toward Normal and Further Decreases the Plasma Sodium Concentration, Exacerbating the Hyponatremia
Clinical Features of Syndrome of Inappropriate Secretion of Antidiuretic Hormone Secretion (SIADH)
Hyponatremia
Hypoosmolality
Increased Urine Sodium (>20 mEq/L and Usually >40 mEq/L)
High Urine Osmolality (>100 mosmol/kg)
Other Features
Normal Serum Potassium Concentration
Absence of Acid-Base Disturbance
Low Serum Uric Acid Concentration (Frequently)
Due to the Phenomenon of “Desalination”, Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH) Can Occur Even if the Only Fluid Given is Isotonic/Normal Saline
In Patients with Postoperative Hyponatremia Due to Surgery-Associated Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH), Isotonic Intravenous Fluid Administration Results in Volume Expansion, Resulting in Increased Urinary Sodium Excretion
With High Antidiuretic Hormone Levels, Sodium Excretion in a Concentrated Urine Results in a Further Decrease in the Serum Sodium (“Desalination”) (Ann Intern Med, 1997) [MEDLINE]
Patterns of Antidiuretic Hormone Secretion
General Comments
In Normal Patients, Plasma Antidiuretic Hormone Levels are Very Low when the Plasma Osmolality is <280 mOsmol/kg, Permitting the Excretion of Ingested Water
As the Plasma Osmolality Increases Above 280 mOsmol/kg, Antidiuretic Hormone Levels Increase Progressively
Various Patterns of Antidiuretic Hormone Secretion in Patient Populations with the Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH)
Type A: elevated antidiuretic hormone unresponsive to osmotic deviations
Antidiuretic Hormone are Typically Above Levels Required for Maximum Antidiuresis
Antidiuretic Hormone Levels Above the Physiologic Range Suggest Ectopic Antidiuretic Hormone Production (Due to Lung Cancer, etc)
Urine Osmolality is Typically Very High
Type B: abnormally low threshold for antidiuretic hormone release (threshold below the level of plasma osmolality at which plasma antidiuretic hormone becomes detectable in normal patients) and a linear increase in plasma antidiuretic hormone in response to a increasing plasma osmolality
Typically, These Patients are Defined as Having a “Reset Osmostat
In These Patients, the Plasma Sodium Will Not Continue to Decrease without Therapy, Since Antidiuretic Hormone Will Be Suppressed When the Plasma Osmolality Decrease Below the Reset Osmolality Threshold
Type C: antidiuretic hormone levels within the physiologic range and neither suppressed by decreased plasma osmolality nor stimulated by increasing plasma osmolality
This Pattern May Occur in Patients with Ectopic Antidiuretic Hormone Production
Type D: antidiuretic hormone levels vary appropriately with the plasma osmolality, but the urine remains concentrated even if antidiuretic hormone release is suppressed
May Occur Due to Germ Cell Mutation in Which the Vasopressin V2 Receptor is Constitutively Activated
May Occur Due to Production of an Antidiuretic Substance Other than Immunoreactive Arginine Vasopressin and a Postreceptor Defect in Trafficking of Aquaporin-2 Water Channels (Which Mediate Antidiuretic Hormone-Induced Antidiuresis)
Type E: decrease in plasma antidiuretic hormone as the serum sodium concentration increase during the infusion of hypertonic saline
Due to Altered Baroreceptor Signaling Despite Normovolemia, Such that a Minor Decrease in Blood Pressure or Blood Volume Results in a Large Increase in Antidiuretic Hormone Secretion
Similarly, a Minor Increase in Blood Pressure or Blood Volume During Saline Infusion Results in a Large Decrease in Antidiuretic Hormone Secretion
Determinants of Urine Output
In Addition to the Effect of Antidiuretic Hormone, Two Other Determinants of Urine Output Occur in Patients with Patients with the Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH)
Rate of Solute Excretion
In Normal Patients, the Urine Output is Primarily Determined by Water Intake
Increased Water Intake Results in a Decrease in Plasma Osmolality, Sensed by Hypothalamic Osmoreceptors (Which Regulate Both Antidiuretic Hormone Release and Thirst)
Antidiuretic Hormone Secretion is Then Decreased, Resulting in Decreased Collecting Tubule Permeability to Water
Net Effect is the Rapid Excretion of Excess Water in Dilute Urine
In SIADH, an Increase in Water Intake Does Not Produce an Increase in Water Excretion Because Antidiuretic Hormone Secretion is Relatively Fixed
Because the Urine Osmolality Cannot Be Reduced, the Urien Output Will Be Determined by the Rate of excretion of Solutes (Sodium Salts, Potassium Salts, and Urea)
This Strategy to Use Ingested Solutes (Such as Oral Urea) with a High Salt/High Protein Diet Will Increase Water Excretion, Raising the Serum Sodium Toward Toward Normal
Partial Escape from the Effect of Antidiuretic Hormone
Animal Studies Using the Administration of Both Antidiuretic Hormone and Water Suggest that There is an Initial Phase of Water Retention and Hyponatremia, Followed by Partial Escape from the Antidiuresis
Due to This Escape, Despite High Antidiuretic Hormone Levels, Urine Osmolality May Decrease, Resulting in Increased Water Excretion (Matching Water Intake) and the Plasma Sodium Tends to Stabilize
The Escape is Likely Mediated by Decreased Aquaporin-2 Expression (the Antidiuretic Hormone-Sensitive Water Channel in the Renal Collecting Tubule)
In the Presence of Hyperproteinemia/Hypertriglyceridemia (with Expansion of Nonaqueous Component of the Serum), Pseudohyponatremia May Be Seen with This Assay Method
Sodium-Selective Electrode Assay of Sodium
Measures Sodium Activity in Serum Water: this assay gives the true, physiologically relevant sodium concentration as it measures sodium activity in serum water alone
Indirect Potentiometry: current assay used in many hospital laboratories
Normal Minimum Urine Osmolality is 40-100 mOsmol/kg
Diagnostic Strategies to Differentiate Cerebral Salt Wasting from Syndrome of Inappropriate Antidiuretic Hormone Secretion (see Cerebral Salt Wasting)
Cerebral Salt Wasting and Syndrome of Inappropriate Antidiuretic Hormone Secretion Share the Following Clinical Features (see Cerebral Salt Wasting)
Hyponatremia with Increased Antidiuretic Hormone Release and Inappropriately Increased Urine Osmolality
Hyponatremia Would Normally Inhibit Antidiuretic Hormone Release
The Increased ADH Release is an Appropriate Response in Cerebral Salt Wasting, But is an Inappropriate Response in SIADH
Increased Urine Sodium (Usually >40 mEq/L)
In Cerebral Salt Wasting, This is Due to Renal Salt Wasting
In SIADH, This is Due to Volume Expansion
Decreased Serum Uric Acid Due to Decreased Urinary Uric Acid Excretion
In Cerebral Salt Wasting, This is Likely Due to Brain Natriuretic Peptide (BNP)
In SIADH, This is Likely Due to Volume Expansion and a Direct Effect of Antidiuretic Hormone on the V1 Receptor (Am J Kidney Dis, 1992) [MEDLINE]
Cerebral Salt Wasting from Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH) are Distinguished by the Following Clinical Features (see Cerebral Salt Wasting)
In Cerebral Salt Wasting, Clinical Hypovolemia is Present
In SIADH, Extracellular Fluid Volume is Normal-Slightly Increased
Clinical Manifestations
General Comments
Schwartz and Bartter Criteria for the Diagnosis of the Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH) (Am J Med, 1957) [MEDLINE] (Am J Med, 1967) [MEDLINE]
Criteria were Developed in 1967
Criteria
Hyponatremia with Corresponding Hypo-Osmolality of Plasma and Extracellular fluid
Continued Renal Excretion of Sodium
Urine Less than Maximally Dilute
Urinary Osmolality Greater than Appropriate Considering the Plasma Osmolality
Absence of Clinical Volume Depletion
Absence of Other Causes of Hyponatremia
Normal Renal and Adrenal Function
Correction of Hyponatremia by Fluid Restriction
Cardiovascular Manifestations
Euvolemia/Modest Hypervolemia
This Distinguishes SIADH from Cerebral Salt Wasting, Where the Patient is Typically Hypovolemic (see Cerebral Salt Wasting)
Demeclocycline Inhibits the Renal Action of Antidiuretic Hormone
Demeclocycline Interferes with Intracellular Adenylyl Cyclase Activation After Antidiuretic Hormone Binds to Renal Vasopressin V2 Receptors
Administration
Oral Dose: 300 mg PO BID
Fluid Restriction
Clinical Use
Fluid Restriction is the Most Commonly Used First-Line Therapy for Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH)
Fluid Restriction is the Most Commonly Used Treatment for SIADH (Used in 48% of Cases) (Am J Med, 2016) [MEDLINE]
Clinical Efficacy
Fluid Restriction to 50-60% of the Daily Requirement (Approximately <800 mL/Day) May be Required to Achieve Negative Water Balance (NEJM, 2000) [MEDLINE]
However, This Level of Fluid Restriction is Difficult for Most Patients to Maintain
Practically, Most Patients are Able to Tolerate a Fluid Restriction Between 1000-1200 mL/Day
Effectiveness of Fluid Restriction is Predicted by Urine/Plasma Electrolyte Ratio (Urine Na + Urine K/ Serum Na) <0.5 (Am J Med Sci, 2000) [MEDLINE]
Urine/Plasma Electrolyte Ratio >1.0 Suggests that Fluid Restriction Will Not Be Effective
Fluid Restriction Typically Results in a Median Increase in the Serum Sodium of Approximately 2 mEq/L in the First 24 hrs of Therapy (Am J Med, 2016) [MEDLINE]
In a Small Trial (n = 46) in Patients with Chronic Asymptomatic SIADH, Fluid Restriction of <1L/day Resulted in an Increase in Serum Sodium by 3 mEq/L at 3 Days with Minimal Subsequent Additional Improvement (J Clin Endocrinol Metab, 2020) [MEDLINE]
Contraindications
Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH) in the Setting of Subarachnoid Hemorrhage (SAH) (see Subarachnoid Hemorrhage)
In This Clinical Setting, Fluid Restriction May Cause Undesirable Hypovolemia and Hypotension, Which May Impair Cerebral Perfusion and Exacerbate Cerebral Vasospasm (and Worsen Cerebral Infarction) (Clin Neurol Neurosurg, 1990) [MEDLINE]
Approximate Hypertonic Saline Infusion Rate = Desired Rate of Correction Per Hour (ex: 1 mEq/L/hr) x Lean Body Weight (in kg)
Rationale
If the Serum Sodium Concentration is to Be Increased, the Sodium Concentration of the Fluid Administered Must Exceed the Sodium Concentration of the Urine, Not Simply the Sodium Concentration of the Plasma (Am J Med, 1986) [MEDLINE]
Sodium and Water Excretion in the Urine are Regulated Independently
Sodium Excretion in the Urine is Regulated by Aldosterone and Atrial Natriuretic Peptide
Water Excretion in the Urine is Regulated by Antidiuretic Hormone (Arginine Vasopressin)
Urine Volume is Normally Regulated by Antidiuretic Hormone (Arginine Vasopressin) in Response to Changes in Water Intake
When Antidiuretic Hormone Does Not Respond to Changes in Water Intake, as Occurs in Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH), the Urine Osmolality is Relatively Fixed and the Urine Volume Varies with Changes in Solute Excretion
Increasing Urine Solute Excretion by Giving Salt or Urea Will Increase the Urine Volume and Raise the Serum Sodium
Indications
Life-Threatening Hyponatremia
Loop Diuretics
Clinical Effectiveness
In Addition to Other Measures, Loop Diuretics May Be Effective in the Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH) if the Urine/Serum Cation Ratio is >1.0
Furosemide Inhibits Sodium chloride Reabsorption in the Thick Ascending Limb of the Loop of Henle, Resulting in Interference with the Countercurrent Mechanism and Inducing Renal Antidiuretic Hormone Resistance and Excretion of Water
May Be Useful (and is Well-Tolerated) as an Alternative to Oral Sodium Chloride Tablets and Diuretics (Nephrol Dial Transplant, 2014) [MEDLINE] (Kidney Int, 2015) [MEDLINE] (Clin J Am Soc Nephrol, 2018) [MEDLINE]
Administration
Oral Dose: 15g BID
Potassium Replacement (When Required for Hypokalemia) (see Potassium Chloride)
Pharmacology
Potassium is as Osmotically Active as Potassium and Replacing Potassium in the Setting of Hypokalemia Will Increase Serum Osmolality (Am J Kidney Dis, 2010) [MEDLINE]
Potassium Movement Intracellularly Increases the Serum Sodium by the Following Mechanisms
Intracellular Movement of Potassium Will Result in an Exchange of Sodium into the Extracellular Fluid (to Maintain Intracellular Electroneutrality)
Intracellular Movement of Potassium Will Result in an Exchange of Hydrogen Ions into the Extracellular Fluid
Hydrogen Ions are Buffered by Extracellular Bicarbonate (and Plasma Proteins), Creating Carbon Dioxide and Water (Bicarbonate is Replaced by Chloride Which was Administered with the Potassium)
Intracellular Movement of Potassium Drags Drags Chloride into the Cells, Increasing the Intracellular Osmolality, Which Results in Free Water Movement into Cells
Intracellular Movement of Potassium Increases the Intracellular Osmolality, Which Results in Free Water Movement into Cells
The SALT-1 Trial/SALT-2 Trials Comparing Tolvaptan to Placebo in Patients with Chronic Hyponatremia (None with Clinically Apparent Neurologic Symptoms at Baseline; Almost All Patients Had Na ≥120 mEq/L) Demonstrated a Benefit in Mental Status in Patients with Na 120-129 mEq/L, But Not in Patients with Na 130-134 mEq/L (NEJM, 2006) [MEDLINE]
Avoid Use of the Following
Normal Saline (see Normal Saline): sodium will generally worsen the hyponatremia in Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH)
In Patients with Postoperative Hyponatremia Due to Surgery-Associated Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH), Isotonic Intravenous Fluid Administration Results in Volume Expansion, Resulting in Increased Urinary Sodium Excretion
With High Antidiuretic Hormone Levels, Sodium Excretion in a Concentrated Urine Results in a Further Decrease in the Serum Sodium (“Desalination”) (Ann Intern Med, 1997) [MEDLINE]
Therapy of Syndrome of Inappropriate Antidiuretic Hormone Secretion in the Setting Subarachnoid Hemorrhage (SAH) (see Subarachnoid Hemorrhage)
Avoid Fluid Restriction
Since Patients with Subarachnoid Hemorrhage are Susceptible to Cerebral Vasospasm and Infarction, Fluid Restriction is Contraindicated, as it May Cause Hypotension and Exacerbate the Prior Complications (Clin Neurol Neurosurg, 1990) [MEDLINE]
Syndrome of inappropriate secretion of antidiuretic hormone (SIADH) in malignant disease. J Intern Med. 1995;238(2):97 [MEDLINE]
Elevated arginine vasopressin levels in squamous cell cancer of the head and neck. Laryngoscope. 1996;106(3 Pt 1):317 [MEDLINE]
Syndrome of inappropriate antidiuretic hormone secretion associated with head neck cancers: review of the literature. Ann Otol Rhinol Laryngol. 1997;106(10 Pt 1):878 [MEDLINE]
A prospective study of patients with lung cancer and hyponatremia of malignancy. Am J Respir Crit Care Med. 1997;156(5):1669 [MEDLINE]
Acute hyponatremia in the perioperative period: insights into its pathophysiology and recommendations for management. Clin Nephrol. 1998;50(6):352 [MEDLINE]
Hyponatremia with venlafaxine. Ann Pharmacother. 1998 Jan;32(1):49-51. doi: 10.1345/aph.17117 [MEDLINE]
The syndrome of inappropriate antidiuretic hormone secretion of unknown origin. Am J Kidney Dis. 1999;33(1):161 [MEDLINE]
Hyponatremia. N Engl J Med. 2000;342(21):1581 [MEDLINE]
Adverse events during use of intranasal desmopressin acetate for haemophilia A and von Willebrand disease: a case report and review of 40 patients. Haemophilia. 2000;6(1):11 [MEDLINE]
Chronic idiopathic hyponatremia in older people due to syndrome of inappropriate antidiuretic hormone secretion (SIADH) possibly related to aging. J Am Geriatr Soc. 2001 Jun;49(6):788-92 [MEDLINE]
Hyponatremia as a complication of cardiac catheterization: a prospective study. Am J Kidney Dis. 2002;40(5):940 [MEDLINE]
A review of drug-induced hyponatremia. Am J Kidney Dis. 2008 Jul;52(1):144-53. doi: 10.1053/j.ajkd.2008.03.004 [MEDLINE]
Molecular mechanisms of antidiuretic effect of oxytocin. J Am Soc Nephrol. 2008;19(2):225 [MEDLINE]
Clinical practice guideline on diagnosis and treatment of hyponatraemia. Neprhol Dial Transplant 2014; 29 Suppl 2:i1 [MEDLINE]
Severe hyponatremia in older patients at admission in an internal medicine department. Arch Gerontol Geriatr. Nov-Dec 2014;59(3):642-7. doi: 10.1016/j.archger.2014.08.002 [MEDLINE]
Antidepressants and the risk of hyponatremia: a class-by-class review of literature. Psychosomatics. Nov-Dec 2014;55(6):536-47. doi: 10.1016/j.psym.2014.01.010 [MEDLINE]
Hyponatremia is a predictor for poor outcome in Guillain-Barré syndrome. Neurol Res. 2015 Apr;37(4):347-51. doi: 10.1179/1743132814Y.0000000455 [MEDLINE]
Nephrogenic syndrome of inappropriate antidiuresis secondary to an activating mutation in the arginine vasopressin receptor AVPR2. Clin Endocrinol (Oxf). 2016;85(2):306 [MEDLINE]
J Syndrome of Inappropriate Secretion of Antidiuretic Hormone Preceding Guillain-Barré Syndrome. Clin Diagn Res. 2017 Sep;11(9):OD16-OD17. doi: 10.7860/JCDR/2017/30445.10662 [MEDLINE]
Medication-induced SIADH: distribution and characterization according to medication class. Br J Clin Pharmacol. 2017 Aug;83(8):1801-1807. doi: 10.1111/bcp.13256 [MEDLINE]
Hyponatremia induced by antiepileptic drugs in patients with epilepsy. Expert Opin Drug Saf. 2017 Jan;16(1):77-87. doi: 10.1080/14740338.2017.1248399 [MEDLINE]
Associations of proton pump inhibitors and hospitalization due to hyponatremia: A population-based case-control study. Eur J Intern Med. 2019 Jan;59:65-69. doi: 10.1016/j.ejim.2018.08.012 [MEDLINE]
Syndrome of Inappropriate Secretion of Antidiuretic Hormone Caused by Very Short-term Use of Proton Pump Inhibitor. Keio J Med. 2021 Mar 25;70(1):19-23. doi: 10.2302/kjm.2020-0008-CR [MEDLINE]
Unusual Neurological Manifestation of Proton Pump Inhibitor: A Case Report of Acute Disseminated Encephalomyelitis and Severe Hyponatremia After Brief Use of Proton Pump Inhibitor. Cureus. 2021 Jun; 13(6): e15571 [MEDLINE]
Diagnosis
Diagnosing and Treating the Syndrome of Inappropriate Antidiuretic Hormone Secretion. Am J Med. 2016;129(5):537.e9 [MEDLINE]
Clinical
A syndrome of renal sodium loss and hyponatremia probably resulting from inappropriate secretion of antidiuretic hormone. Am J Med. 1957 Oct;23(4):529-42. doi: 10.1016/0002-9343(57)90224-3 [MEDLINE]
The syndrome of inappropriate secretion of antidiuretic hormone. Am J Med 1967; 42: 790-806 [MEDLINE]
Cerebral salt wasting versus SIADH: what difference? J Am Soc Nephrol. 2008;19(2):194 [MEDLINE]
Treatment
New approach to disturbances in the plasma sodium concentration. Am J Med. 1986;81(6):1033 [MEDLINE]
Hyponatremia responsive to fludrocortisone acetate in elderly patients after head injury. Ann Intern Med. 1987;106(2):187 [MEDLINE]
Effect of fludrocortisone acetate in patients with subarachnoid hemorrhage. Stroke. 1989;20(9):1156 [MEDLINE]
The effects of treating hypertension following aneurysmal subarachnoid hemorrhage. Clin Neurol Neurosurg. 1990;92(2):111 [MEDLINE]
Fludrocortisone therapy in cerebral salt wasting. Pediatrics. 2006;118(6):e1904 [MEDLINE]
Performance characteristics of a sliding-scale hypertonic saline infusion protocol for the treatment of acute neurologic hyponatremia. Neurocrit Care. 2009;11(2):228 [MEDLINE]
Clinical practice guideline on diagnosis and treatment of hyponatraemia. Neprhol Dial Transplant 2014; 29 Suppl 2:i1 [MEDLINE]
Diagnosing and Treating the Syndrome of Inappropriate Antidiuretic Hormone Secretion. Am J Med. 2016;129(5):537.e9 [MEDLINE]
Fluid Restriction Therapy for Chronic SIAD; Results of a Prospective Randomized Controlled Trial. J Clin Endocrinol Metab. 2020;105(12) [MEDLINE]
