SYNDROME OF INNAPROPRIATE ADH SECRETION (SIADH)

Syndrome of Innapropriate ADH Secretion (SIADH)

Pathophysiology

Antidiuretic hormone (ADH) is secreted by the posterior pituitary gland (neurohypophysis) and acts on the kidneys to induce water retention primarily at the level of the collecting ducts. SIADH results from innapropriate ADH secretion resulting in innapropriate retention of ingested/infused water. It is important to note that although water excretion is impaired, salt handling is NORMAL. i.e. The body attempts to get rid of the excess water by dumping sodium in the urine.

Signs and Symptoms

headache, nausea / vomiting, muscle cramps, restlessness, lethargy, confusion, decreased reflexes, seizure, coma, death

- these signs and symptoms are secondary to hyponatremia and are not specific for SIADH

Diagnosis

- clinically euvolemic (e.g. assess postural BP and pulse, JVP, mucus membranes and skin turgor)

- serum hypoosmolarity (serum osm <280 mOsm/kg)

- hyponatremia (serum sodium <135 mmol/L, but usually only investigate if <130)

- urine sodium >20 mmol/L

- urine osmolarity > serum osmolarity

****The diagnosis of SIADH cannot be made if the patient is on diuretics or if renal, thyroid or adrenal function is abnormal

NOTE: It is possible for a patient to be hypovolemic and have SIADH. In this setting, urine sodium may be <20 mmol/L and urine osmolarity <200 mOsm/kg. Once the patient is rehydrated, the picture of SIADH will develop. Hence, urine lytes may need to be followed serially in hypovolemic patients at risk of having SIADH.

Investigations

CBC, electrolytes, urea, creatinine, glucose, serum Osm, urine Osm and lytes

Consider: TSH, random cortisol, LFTs, chest x-ray, CT head

Causes

- CNS disturbance: stroke, subarachnoid hemorrhage, infection (meningitis / encephalitis), trauma, psychosis

- Tumor (ectopic production of ADH): small cell lung cancer most commonly, more rarely other types of lung cancers, pancreatic cancer, colon adenocarcinoma, olfactory neuroblastoma, lymphoma, leukemia

- Drugs: carbamazepine, cyclophosphamide, vincristine, ecstasy (MDMA), neuroleptics, TCAs, SSRIs, MAOIs, NSAIDs

- Major surgery: abdominal, thoracic, transphenoidal surgery (after pituitary surgery, SIADH may occur on its own or as a transient event as part of a “triphasic response” i.e. early post-op period of diabetes insipidus followed by SIADH followed by diabetes insipidus)

- Pulmonary disease: pneumonia (bacterial, TB, Aspergillosis), bronchiectasis, occasionally with asthma, atelectasis, pneumothorax, acute respiratory failure

- Hormone administration: vasopressin, dDAVP, oxytocin

- AIDS

- Other: nausea (potent stimulus for ADH secretion), pain, severe stress (these 3 factors may explain some of the etiologies of SIADH above e.g. surgery)

- Idiopathic

***In the setting of CNS disturbances, especially subarachnoid hemorrhage, SIADH must be differentiated from cerebral salt wasting (see separate topic for review)

Treatment

***CORRECT SLOWLY because of risk of central pontine myelinolysis***

The maximum correction rate should be a rise of serum sodium no greater than 0.5 mmol/L/h or 8 mmol/L/day. In patients with severe symptoms, can increase the initial rate to 1 mmol/L./h for 2-3 hours and then decrease to above rate (especially if the drop in sodium was acute rather than chronic)

1. Water restriction (0.8-1.5L/day) is usually sufficient on its own

2. High salt, high protein diet

3. Consider a loop diuretic e.g. lasix 20 mg IV (impairs renal responsiveness to ADH, excrete more water than sodium)

4. Salt infusion is only required if hyponatremia persists despite the above methods. Nephrology or Internal medicine should be consulted if administration of hypertonic saline is required.

NOTE: In order to correct hyponatremia, the osmolality of the fluid given must exceed the osmolality of the urine

e.g. A patient with SIADH has a urine osmolality = 600 mmol/L and is given 1L of 0.9% normal saline. There are 150 mEq of Na and Cl in normal saline and, therefore the Osm of normal saline = 300 mEq/L. Given that salt handling is NORMAL in SIADH, all the NaCl will be excreted but in only 500 ml (i.e. the urine osm = 600 and therefore 300 mEq of NaCl will be excreted in 500 ml = 600 mEq/L). Giving normal saline, therefore, will actually make the hyponatremia WORSE by increasing fluid volume another 500ml! The serum concentration of sodium may transiently rise but then it will fall.

If the same patient is given 1L of 3% saline, which contains 513 mEq of Na and Cl (Osm=1026), all the NaCl will be excreted but in a LARGER volume. i.e. 1024 mEq / 600 mEq/L = 1700 ml. A net loss of 700 ml of water will occur.

***see hyponatremia notes for calculation of rate and rise in Na with saline infusion

5. MONITOR serum lytes frequently to ensure that the serum sodium level is being corrected and that the rate of rise is less than 8 mmol/L/day. e.g. q6h initially then BID then OD

6. Treat underlying condition if possible

References:

UpToDate

NEJM 342:1585 '00

Last update: 2002-03-03

Reviewed by:

Neurological Medicine Pocketbook

http://www.uwo.ca/cns/resident

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