SIADH

General

Definition: Euvolemic hyponatremia, with inappropriate urine concentration, low urine volume, and natriuresis, with the exclusion of hypocortisolaemia and hypothyroidism.

Reason as to why there is weight gain in SIADH (as a differentiating factor vs CSW) but it is known as a Euvolemic state: Patients with SIADH can experience mild weight gain due to increased total body water, but the fluid is spread throughout the body such that clinical features of fluid overload (Oedema) are absent, upholding the term “euvolemic hyponatremia

Aetiology

Category	Causes
Central nervous system disorders	Head injury, Meningitis, Encephalitis, Brain tumour, Brain abscess, Cerebral hemorrhage/thrombosis, Guillain-Barre syndrome, Acute intermittent porphyria
Tumours	Carcinoma (especially lung), Lymphoma, Leukaemia, Thymoma, Sarcoma, Mesothelioma
Respiratory Causes	Pneumonia, Tuberculosis, Severe Asthma, Pneumothorax, Positive-pressure ventilation, Emphysema
Drugs	Carbamazepine, Clofibrate, Chlorpropamide, Thiazides, Phenothiazines, MAO inhibitors, Cytotoxics, Desmopressin, Vasopressin, Oxytocin, Selective serotonin reuptake inhibitors, PPIs

Diagnostic criteria

Hyponatremia

Inappropriate concentrated urine:

Low effective serum osmolality < 275mOsm/
High ratio of urine: serum osmolality: 1.5-2.5:1
BUN <10
High urinary sodium

No evidence of renal or adrenal dysfunction

No hypotension
No hyperkalemia

Pathophysiology

Release of ADH in the absence of physiological osmotic stimulation

Rise in ADH for 4 days

Extracellular volume high

Low K

S&S

100% symptomatic if Na <125

Paradoxical thirst

Further testing

NOT COMMONLY DONE

Measure ADH levels in Urine and serum

Rarely needed, since if urine osmolality >100 is sufficient to indicate excessive ADH
ADH is only detectable in SIADH, other causes of hyponatremia does not produce high enough ADH to be detectable

Water-load test

Patient asked to consume a water load of 20ml/kg (max 1.5L)
Positive for SIADH if pt cannot pee out 65% of fluid in 4hrs or 80% in 5hrs
Do not do if

Starting serum Na is <124mEq/L or
Patient has symptoms of hyponatremia

Treatment


flowchart LR
    A["Severe Hyponatremia<br/>([Na+] &lt; 125 mEq/L)"] --> B{Duration}
    B -- "&lt; 48 hours" --> C["Aggressive<br/>Treatment<br/>(see text)"]
    B -- "&ge; 48 hours<br/>or unknown" --> D{Symptoms}
    D -- "none" --> E["Routine<br/>Treatment<br/>(see text)"]
    D -- "moderate or nonspecific<br/>(H/A, lethargy)" --> F["Intermediate<br/>Treatment<br/>(see text)"]
    D -- "severe<br/>(coma, seizures)" --> C
    G["Mild to Moderate<br/>Hyponatremia<br/>([Na+] = 125-135 mEq/L)"] --> H{Any symptoms?}
    H -- "no<br/>(asymptomatic)" --> E
    H -- "yes" --> F

    %% Styling for blocks
    style C fill:#b3d6ee,stroke:#000,stroke-width:1px
    style E fill:#b3d6ee,stroke:#000,stroke-width:1px
    style F fill:#b3d6ee,stroke:#000,stroke-width:1px
    style G fill:#fff,stroke:#000,stroke-width:1px
    style A fill:#fff,stroke:#000,stroke-width:1px

    %% Style for diamonds (decisions) - use fill for red
    classDef diamond fill:#FF0000,stroke:#000,stroke-width:1.5px
    class B,D,H diamond

    %% Set all font color to black
    classDef allNodes color:#000;
    class A,B,C,D,E,F,G,H allNodes

Aggressive treatment

3%NS: 1ml/kg/hr

Furosemide 20mg IV

Accelerates Na rise and prevents volume overload (due to release of ANF —> urinary dumping of extra Na)

Check Na 2 Hrly and adjust 3% NS rate

Check K and replace it

If has signs of osmotic demyelination syndrome:

Stop treatment
Lower Na with DDAVP

Intermediate treatment

NS 125ml/hr

Furosemide 20mg IV

Consider conivaptan (Vaprisol®): a nonpeptide antagonist of V1A & V2 vasopressin receptors.

Check Na 4hrsly and adjust NS rate

Routine treatment

Fluid restriction according to table (ENSURE NOT CSW)

Can be impractical in SAH patients
Adult

Solute ratio*	Recommended fluid intake
>1	<500 ml/d
1	500-700 ml/d
<1	<1 L/d

*Solute ratio define as

\frac{\text{urinary } [\text{Na}] + \text{urinary } [\text{K}]}{\text{plasma } [\text{Na}]}

Predictors of likely failure of fluid restriction

Urine osmolality is greater than 500 mOsm/kg H₂O

The sum of urine sodium (Na⁺) and potassium (K⁺) concentrations exceeds serum sodium concentration

24-hour urine volume is less than 1500 mL/day

Serum sodium concentration increases by less than 2 mmol/L/day with 1L/day fluid restriction over 24–48 hours

If the patient has been concentrating urine, fluid restriction cannot work

Paeds: 1L/m2/day

Encourage dietary salt and protein

For refractory cases use

Demeclocycline

Tetracycline antagonises effects of ADH
Can cause nephrotoxicicity
300-600mg PO BD

Conivaptan

A nonpeptide antagonist of V1A & V2 vasopressin receptors.
20mg IV over 24 hrs for 3 days

DO not use lithium as not effective and many side effects

DDx

Although it can be difficult to evaluate volume status clinically, particularly when endeavouring to separate mild hypovolemia from eunatremia, cerebral salt wasting is usually characterised by profound natriuresis, diuresis, and marked volume depletion

Parameter	CSW	SIADH
Plasma volume	↓ (< 35 ml/kg)	↑ or WNL
Salt balance	negative	variable
Signs & symptoms of dehydration	present	absent
Weight	↓	↑ or no Δ
PCWP	↓ (< 8 mm Hg)	↑ or WNL
CVP	↓ (< 6 mm Hg)	↑ or WNL
Orthostatic hypotension	+	±
Hematocrit	↑	↓ or no Δ
Serum osmolality	↑ or WNL†	↓
Ratio of serum BUN]:[creatinine]	↑	WNL
Serum [protein]	↑	WNL
Urinary [Na+]	↑↑	↑
Serum [K+]	↑ or no Δ	↓ or no Δ
Serum [uric acid]	WNL	↓

Abbreviations: ↓ = decreased, ↑ = increased, ↑↑ = significantly increased, WNL = within normal limits, no Δ = no change, []= concentration, + = present, ± = may or may not be present

† in reality, serum osmolality is usually ↓ in CSW

There is no idea why SIADH has high urinary Na

The presence of elevated plasma BNP concentrations could not be regarded as a reliable predictor of either blood volume status or the development of hyponatremia