Sindrome of Inappropriate Antidiuretic Hormone Secretion

         SIADH - syndrome in which Hyponatremia & hypo-osmolarity are results from prolonged secretion or/and action of ADH despite of increased plasma volume.
ADH is produced by the pituitary gland.  ADH stimulates the kidneys to conserve water. SIADH causes the body to retain too much water. As a result, the concentration of sodium decreases in the bloodstream, which is called Hyponatremia. ADH facilitates the reabsorption of water from the tubular fluid in the collecting duct, also it causes arteriolar vasoconstriction and rise in arterial BP.

 Arginine vasopressin (AVP) - natural ADH in humans.

     There are 2 major stimuli for AVP secretion:

1. hyperosmolarity (sensed by osmoreceptors in the hypothalamus, which "feel" ECF osmolarity changes )
2. depletion of effective circulating volume (sensed by baroreceptors in the carotid sinus, aortic arch & left atrium, they respond to changes in effective circulating volume ).

Usually, AVP stops when plasma osmolarity drops bellow 275.

            SIADH:

1. hyponatremia
2. elevated urine osmolarity >100
3. decreased serum osmolarity < 280

You need to find these findings in the setting of normal cardiac,  renal, adrenal, hepatic, thyroid functions, absence of diuretic therapy and any other cause, that may stimulate ADH secretion, such as pain, hypotension, nausea, stress.

      SIADH can be divided into 4 categories:

1. drug induced (bromocriptine, carbachol, clofibrate, haloperidol, halothane, thiopental, MAOIs)
2. pulmonary disease (asthma, cystic fibrosis, sarcoidosis, tuberculosis,  pneumothorax, acute respiratory failure)
3. neoplasia (lung carcinoma & mesothelioma, carcinoma of the duodenum, pancreas & colon, carcinoma of the cervix, prostate, brain tumors, Ewing sarcoma, leukemia, thymoma, lymphoma).
4. NS disorder (acute psychosis, epilepsy, head trauma, schizophrenia, subdural hematoma, delirium tremens and so on)

Treatment:

1. tolvaptan - 15 mg once daily (up to 60 mg)
2. conivaptan - 20 mg loading dose, followed by boluses or infusion but no more than 4 days
3. furosemid