Definition: Common hyponatremic d/o caused by non-osmotic release of vasopressin or ADH from the posterior pituitary or an ectopic source. It is a diagnosis of exclusion.
Causes:
Neuropsychiatric d/o: head trauma, stroke, SAH, hydrocephalus, tumor, encephalitis, GBS, MS, DT, ALS, hydrocephalus, psychosis, peripheral neuropathy, meningitis, acute psychosis, brain abscess.
Pulmonary: TB, lung abscess, bacterial pneumonia, aspergillosis, bronchiectasis, lung CA (SCLC), IPPV, PTx
Malignancies: Bronchogenic CA, pancreatic, duodenal, ovarian, bladder, ureter, prostatic, RCC, adenoca. of colon, thymoma, osteosarcoma, malignant lymphoma, leukemia, mesothelioma, bronchial adenoma, carcinoid, Ewing's sarcoma, gangliocytoma
Metabolic: acute intermittent porphyria, hypothyroidism
Drugs:
Vasopressin or desmopressin, TCA, MAO-I, SSRIs, antipsychotics (thiothexene, thioridazine, fluphenazine, haloperidol, trifluoperazine), carbamazepine, oxcarbazepine
Narcotics
Chemotherapeutic agents: cyclophosphamide, vincristine
Carbamazepine, MDMA, ecstasy, clofibrate, chlorpropamide, tolbutamide, NSAIDs, somatostatin
Others: Post-op, pain, stress, AIDS, pregnancy (reset osmostat), hypokalemia
HIV
It is a diagnosis of exclusion. Get a CXR always in a smoker, wt. loss with suspicion of SIADH, may reveal a lung mass.
Subtypes of SIADH: Based on the pattern of AVP secretion.
Erratic autonomous AVP secretion (ectopic production)
Normal regulation of AVP release around a lower osmolality set point or reset osmostat (cachexia, malnutrition)
Normal AVP response to hypertonicity with failure to suppress completely at low osmolality (incomplete pituitary stalk section)
Normal AVP secretion with increased sensitivity to it actions or secretion of some other antidiuretic factor.
Patients with nephrogenic syndrome of inappropriate diuresis have clinical and lab features consistent with SIADH but undetectable levels of AVP. It is hypothesized that this d/o is due to gain of function mutations in the V2 receptor.
Clincial features:
Hypo-osmotic Hyponatremia
Euvolemia
Osm(plasma) <280 mosm/kg
Osm(urine) >100 mosm/kg (is high due to high AVP levels). Expect Uosm > Posm.
No cardiac, renal or liver dz, normal thyroid, adrenal function
UNa: >40 mEq/L, BUN <10 mg/dL, Sr. Uric: <4 mg/dL.
Normal Sr. K+ and acid-base balance.
**A high BUN r/o SIADH**
Tx:
Acute: Free water restriction (<750 mL). If sx hyponatremia (seizures), give rapid correction with hypertonic saline, at a rate of correction of Na+ is 1 - 2 mEq/L/hr x 3 - 4 hours, if patient is symptomatic. Correction must be acute, but no more than 12 mEq/L in 24 hrs. 3% saline has 513 mEq of Na+ in a liter of the solution.
Overtly aggressive correction of hyponatremia (>20 mEq/L per day) can lead to central pontine myelinolysis (CPM)
Avoid rapid correction of serum sodium. Goal of correction is 6-8 mEq/24 hours with a rate not to exceed 1 mEq/L/hour.
F/up with 3% at 30 - 40 mL/hr +/- furosemide.
Chronic: Fluid restriction, high-salt diet. Consider furosemide, demeclocycline 300 mg bid-qid (may induce diabetes insipidus and play a role in chronic therapy). Avoid demeclocycline in the setting of liver disease as death from liver failure can occur.
"Appropriate" ADH secretion occurs with a fall in effective circulating volume. ADH is released in response to slight increases in tonicity of the ECFV. Because the sodium concentration is the main determinant of tonicity, changes in the sodium concentration are the main determinant of ADH secretion. In these conditions, thirst and water retention is stimulated, protecting volume status at the cost of osmolar status. ADH increases the permeability of the renal collecting tubule to water and allows water to flow down its concentration gradient to be reabsorbed into the hypertonic medullary interstitium. ECFV tonicity is decreased. Changes of only a few mOsm/L will stimulate hypothalamic osmoreceptors and lead to ADH release. The urine osmolality may be as high as 1200 mOsm/L when ADH is present, and as low as 50 mOsm/L when ADH is absent. Volume depletion, however, may cause ADH release even if the sodium concentration is normal or if hyponatremia is present.
Cerebral salt-wasting (CSW):
CSW is characterized by hyponatremia and extracellular fluid depletion due to inappropriate sodium wasting in the urine. CSW is associated with extracellular fluid depletion. As a result, hypotension, decreased skin turgor, and/or an elevated hematocrit may be observed.
CSW has also been reported in patients with SAH, carcinomatous or infectious meningitis, encephalitis, poliomyelitis, and central nervous system tumors, as well as following CNS surgery.
Pathophysiology:
Sympathetic nervous system promotes sodium, uric acid, and water reabsorption in the proximal tubule, as well as renin release. Impaired sympathetic neural input could explain the reductions in proximal sodium and urate reabsorption and the impaired release of renin and aldosterone. The failure of serum aldosterone to rise in response to volume depletion would explain the absence of potassium wasting despite the increase in distal sodium delivery.
The second theory is that a circulating factor that impairs renal tubular sodium reabsorption is released in patients with brain injury. The primary candidate is brain natriuretic peptide (BNP), which decreases sodium reabsorption and inhibits renin release. BNP may also decrease autonomic outflow via effects at the level of the brainstem.
Lab/Dxtic:
In the setting of CNS disease, patients with CSW meet the traditional laboratory criteria for SIADH but clearly have decreased extracellular volume due to excessive urinary sodium excretion. By comparison, SIADH is associated with a slightly increased or normal extracellular volume.
Hyponatremia (less than 135 meq/L) with a low plasma osmolality - hypo-osmotic hyponatremia.
An inappropriately elevated urine osmolality, > 100 mosmol/kg and usually above 300 mosmol/kg)
UNa: > 40 meq/L. Urine sodium concentration should be markedly elevated in CSW, whereas it is variable in SIADH.
A low serum uric acid concentration due to urate wasting in the urine
Clinical evidence of hypovolemia is crucial, since all of these laboratory findings are also seen in SIADH.
Hypotension, decreased skin turgor, elevated hematocrit, possibly increased BUN/serum creatinine ratio is seen in CSW.
Serum protein concentration suggest dehydration and argue against the presence of SIADH. Evaluating the response to isotonic saline is also important in distinguishing between CSW and SIADH
An elevated serum potassium level during hyponatremia is incompatible with SIADH and suggests CSW
Restoration of euvolemia in CSW should remove the stimulus to ADH release, resulting in a dilute urine and correction of the hyponatremia.
In contrast, isotonic saline often worsens the hyponatremia in SIADH as the salt is excreted and some of the water is retained
The distinction does not make a difference; regardless of volume status, hyponatremia complicating intracranial disease should be treated with hypertonic saline.