What is the most common symptom of SIADH fluid retention?

Clinical Presentation

The hyponatremia of SIADH is usually asymptomatic.

Symptoms occur most often when the sodium level is less than 120 mEq/L or when a drop in sodium develops rapidly.

Signs and symptoms include nausea, cramps, lethargy, disorientation, agitation, seizures, and coma.

Etiology

Excess ADH leads to retention of free water by the kidney, resulting in expansion of the intravascular space and hyponatremia.

There is no clear unifying cause or pathophysiology.

Most patients appear to have disordered regulation ADH in response to hypo‐osmolality.

CAUSES OF SIADH

SIADH is associated with a great number of illnesses and most often presents as a coincidental biochemical manifestation of the causative disease. The most common causes of SIADH are summarized in Table 21-3. The origin of SIADH is clinically divided into four categories: malignant, pulmonary, pharmacologic, and neurologic causes.

Bartter and Schwartz first described SIADH in association with bronchogenic lung carcinoma. In small cell carcinoma of the lung, SIADH is relatively common, occasionally occurring as the presenting abnormality that prompts a search for the tumor.99 Most neoplasms have been reported to cause SIADH, and the association between malignant disease and SIADH is so strong that a patient presenting with SIADH, general malaise, and unexplained weight loss should be considered to have an underlying malignancy until proven otherwise.

SIADH is commonly associated with intracranial diseases, particularly traumatic brain injury,65-67 in which almost all cases resolve spontaneously with recovery from brain injury. More than 50% of patients with subarachnoid hemorrhage develop hyponatremia in the first week following the bleed, and 70% of these events are due to SIADH.100 SIADH also commonly occurs after hypophysectomy and after surgery for primary brain tumor.

Many drugs are important clinical causes of hyponatremia. The selective serotonin reuptake inhibitors [SSRIs] are thought to cause SIADH by direct stimulation of AVP secretion by serotonin.101 SIADH usually occurs in the first few weeks after SSRIs are introduced, particularly in elderly patients.102 It has been estimated that 12% of hospitalized patients on SSRI therapy develop SIADH.103 Psychotropic medications such as phenothiazines, haloperidol, and tricyclic antidepressants all cause SIADH. Many patients who have conditions treated with psychotropic drugs also have abnormal thirst; if these patients develop drug-induced SIADH, they can develop very significant hyponatremia. For instance, up to 20% of patients with chronic schizophrenia have psychogenic polydipsia, and excess fluid intake can precipitate severe hyponatremia. MDMA [“Ecstasy”] is thought to stimulate both AVP release and thirst as a result of hyperthermia, and this has been implicated in the development of cases of life-threatening hyponatremia.104

SIADH must be distinguished from exercise-associated hyponatremia [EAH],105 in which the electrolyte profile mimics SIADH. The pathophysiology is different, however. EAH occurs in athletes who ingest excessive hypotonic fluid during exercise, with resultant dilutional hyponatremia. Women, marathon runners racing for longer than 4 hours, and athletes of low body mass index are at greatest risk.106 Although some athletes with EAH fail to suppress AVP, EAH probably should be considered to be distinct from SIADH.

5.6 The Syndrome of Inappropriate Antidiuretic Hormone Secretion [SIADH]

The syndrome of inappropriate antidiuretic hormone secretion [SIADH, also known as Schwartz–Bartter syndrome] is due to excessive and inappropriate release of antidiuretic hormone [ADH]. Usually reduction of plasma osmolality causes reduction of ADH secretion, but in SIADH reduced plasma osmolality does not inhibit ADH release from the pituitary gland, causing water overload. The main clinical features of SIADH include:

Hyponatremia [plasma sodium20 mmol/L]

No edema.

Various causes of SIADH are listed in Table 5.1.

Table 5.1. Causes of SIADH*

Type of DiseaseSpecific Disease/CommentsPulmonary diseasesPneumonia, pneumothorax, acute respiratory failure, bronchial asthma, atelectasis, tuberculosis.NeurologicalMeningitis, encephalitis, stroke, brain tumor infection.MalignanciesLung cancer especially small cell carcinoma, head and neck cancer, pancreatic cancer.HereditaryTwo genetic variants, one affecting renal vasopressin receptor and another affecting osmolality sensing in hypothalamus have been reported.Hormone therapyUse of desmopressin or oxytocin can cause SIADH.DrugsCyclophosphamide, carbamazepine, valproic acid, amitriptyline, SSRI, monoamine oxidase inhibitors and certain chemotherapeutic agents may also cause SIADH.

19.2.3.5 Epidemiology of SIADH

SIADH is one of the most common causes of hyponatremia in the hospital setting and frequently leads to severe hyponatremia [plasma Na