Syndrome of inappropriate antidiuretic hormone secretion (SIADH) can be primary or secondary to various etiologies ranging from drugs to tumors. It is characterized primarily by hyponatremia and low serum osmolality. The syndrome is caused by the inappropriate synthesis of the antidiuretic hormone (ADH) in patients with normal plasma volume levels [1]. Risk factors for SIADH include advanced age as aging is associated with elevated levels of ADH and atrial natriuretic peptide (ANP), and increased susceptibility to osmotic stimulation [2] [3]. In addition, the elderly may be on several medications which can cause SIADH. Postoperative patients, patients with head injury or those on mechanical ventilation, as well as individuals with tumors secreting ADH, are other groups who are at high risk of developing SIADH. Factors like stress, low blood pressure, severe pain, and general anesthesia can also predispose to SIADH.

Clinical presentation of SIADH depends on the severity and rate of hyponatremia development. Slowly progressive hyponatremia is usually asymptomatic while manifestations in acute, rapidly progressing hyponatremia include confusion, tremors, ataxia, myoclonus, asterixis, abnormal reflexes, dysarthria, seizures, coma. Neurological features appear as intracranial pressure increases and cerebral edema develops. Chronic moderate hyponatremia is associated with a poor reaction time, cognitive dysfunction, and ataxia with frequent falls [4] [5].

• Pneumonia

  Tolvaptan was also associated with reduced costs and increased QALYs in the SCLC and pneumonia subpopulations. [ncbi.nlm.nih.gov]

  Four patients were diagnosed with pneumonia in the emergency room, and 13 were diagnosed during admission. [analesdepediatria.org]

  See also Hyponatraemia Malignancy Carcinoma, especially Lung Pancreas Lymphoma (non-Hodgkin) Respiratory disorders Pneumonia Tuberculosis Lung abscess Neurological disorders Head injury Subdural haematoma Cerebral infarction Subarachnoid haemorrhage Encephalitis [rcpa.edu.au]

  Examples of treating the underlying cause Pneumonia – antibiotics Carbamazepine – consider switching to alternative anti-epileptic i.e. sodium valproate Hypothyroidism – levothyroxine replacement References 1. [geekymedics.com]

• Dyspnea

  History may also provide information about a head injury, drug abuse, long-standing pain, neurological symptoms, and features of lung tumors or pathology such as dyspnea, chronic cough, and hemoptysis. [symptoma.com]

• Nausea

  A 70-year-old female patient had nausea and collapsed. Although euvolemic, pathological laboratory findings showed hyponatremia and hypoosmolality, and cerebral magnetic resonance imaging showed hypertrophic pachymeningitis. [ncbi.nlm.nih.gov]

• Vomiting

  Four days later she developed vomiting with serum sodium 119 mEq/L. Fluid restriction, which the woman had not performed, was reinstituted and she was discharged on day 17. [ncbi.nlm.nih.gov]

  Early symptoms may be mild and include cramping, nausea, and vomiting. In severe cases, SIADH can cause confusion, seizures, and coma. Treatment usually begins with limiting fluid intake to prevent further buildup. [healthline.com]

• Loss of Appetite

  Severe cases may involve these symptoms: irritability and restlessness loss of appetite cramps nausea and vomiting muscle weakness confusion hallucinations personality changes seizures stupor coma Your doctor will ask for your complete medical history [healthline.com]

  The onset of symptoms may be acute or chronic, with sudden or gradual loss of appetite, nausea and vomiting, sleepiness, confusion and disorientation, and ultimately seizures, coma, and death. [britannica.com]

• Hypertension

  Diclofenac 75 mg qd for osteoarthritic pain and lisinopril 10 mg qd for hypertension was begun in 1990. [ncbi.nlm.nih.gov]

  […] and Hypertension, University of Colorado Health Sciences Center, Denver (T.B.). [doi.org]

• Muscle Weakness

  A 66-year-old woman, diagnosed with Parkinson disease, developed asthenia, anorexia, weight loss, lethargy and feeling of muscle weakness, and severe hyponatremia, with diagnostic criteria for SIADH, after exposure to amantadine. [ncbi.nlm.nih.gov]

  GBS can result in muscle weakness, pain, and even temporary paralysis of the facial, chest, and leg muscles. Paralysis of the chest muscles can lead to breathing problems.) [chop.edu]

  Severe cases may involve these symptoms: irritability and restlessness loss of appetite cramps nausea and vomiting muscle weakness confusion hallucinations personality changes seizures stupor coma Your doctor will ask for your complete medical history [healthline.com]

  Anorexia Nausea Muscle aches Generalized muscle weakness Myoclonus Decreased reflexes Ataxia Pathological reflexes Tremor Asterixis Cheyne-Stokes respiration Dysarthria Lethargy Confusion Delirium Seizures Coma (from brain swelling) Death Causes of SIADH [en.wikipedia.org]

• Fear

  Central nervous system (CNS) responses to fear, pain, psychoses, and acute distress are known to increase the rate of ADH secretion by the posterior pituitary gland. [medical-dictionary.thefreedictionary.com]

  Noncardiogenic pulmonary edema Central pontine myelinolysis is the feared complication of excessive, overly rapid correction of hyponatremia. Spastic quadriparesis Pseudobulbar palsy Cnfusion Coma. [medcaretips.com]

  Sewards, Fear and power-dominance motivation: proposed contributions of peptide hormones present in cerebrospinal fluid and plasma, Neuroscience & Biobehavioral Reviews, 10.1016/S0149-7634(03)00034-4, 27, 3, (247-267), (2003). T. J. Vachharajani, F. [doi.org]

  Noncardiogenic pulmonary edema may develop, especially in marathon runners. [12] CPM is the feared complication of excessive, overly rapid correction of hyponatremia. [emedicine.com]

• Euphoria

  Schwartz-Bartter’s syndrome is clinically described through all clinical manifestations of water intoxication that associates digestive manifestations (anorexia, nausea, vomiting), neuropsychiatric manifestations (euphoria, aggressiveness, mental confusion [medichub.ro]

• Nocturnal Enuresis

  P Eggert and B Kuhn, Antidiuretic hormone regulation in patients with primary nocturnal enuresis., Archives of Disease in Childhood, 10.1136/adc.73.6.508, 73, 6, (508-511), (1995). [doi.org]

• Seizure

  After the dosage was titrated to 6 mg/d, she experienced generalized seizure attacks. [ncbi.nlm.nih.gov]

• Confusion

  Afterwards, she drank 6 litres of water and gradually developed nausea and vomiting, confusion, lethargy, muscle weakness, spasms and cramps, seizure, decreased consciousness level and short-term memory loss. [ncbi.nlm.nih.gov]

  In severe cases, SIADH can cause confusion, seizures, and coma. Treatment usually begins with limiting fluid intake to prevent further buildup. Additional treatment will depend on the cause. Another name for the syndrome is “ectopic ADH secretion.” [healthline.com]

• Headache

  CASE SUMMARY: A 76-year-old white woman who was being treated with lisinopril and metoprolol for hypertension presented with headaches accompanied by nausea and a tingling sensation in her arms. [ncbi.nlm.nih.gov]

  Symptoms and signs include headache, confusion, disorientation, hostility and other mental aberrations without motor or sensory defects. Reflexes are normal and there is no dehydration or oedema, and no signs of renal, hepatic, or cardiac disease. [whonamedit.com]

• Tremor

  In severe cases, symptoms can include nausea or vomiting, cramps or tremors, irritability, and memory problems The most common treatment for SIADH is limiting how much fluid and water your child has. [elcaminohospital.org]

  Slowly progressive hyponatremia is usually asymptomatic while manifestations in acute, rapidly progressing hyponatremia include confusion, tremors, ataxia, myoclonus, asterixis, abnormal reflexes, dysarthria, seizures, coma. [symptoma.com]

  Symptoms, in more severe cases of SIADH, may include: Nausea or vomiting Cramps or tremors Depressed mood,memory impairment Irritability Personality changes, such as combativeness, confusion, and hallucinations Seizures Stupor or coma The symptoms of [chop.edu]

  Anorexia Nausea Muscle aches Generalized muscle weakness Myoclonus Decreased reflexes Ataxia Pathological reflexes Tremor Asterixis Cheyne-Stokes respiration Dysarthria Lethargy Confusion Delirium Seizures Coma (from brain swelling) Death Causes of SIADH [en.wikipedia.org]

  Prominent physical findings may be seen only in severe or rapid-onset hyponatremia and can include the following: Confusion, disorientation, delirium Generalized muscle weakness, myoclonus, tremor, asterixis, hyporeflexia, ataxia, dysarthria, Cheyne-Stokes [emedicine.com]

• Lethargy

  A 66-year-old woman, diagnosed with Parkinson disease, developed asthenia, anorexia, weight loss, lethargy and feeling of muscle weakness, and severe hyponatremia, with diagnostic criteria for SIADH, after exposure to amantadine. [ncbi.nlm.nih.gov]

  Symptoms of SIADH include: fatigue anorexia headache nausea vomiting muscle cramps worsening mental status, including lethargy, weakness, irritability, agitation, confusion, combativeness, delirium, disorientation, hallucinations and poor balance seizures [cancer.ca]

  Symptoms can be subtle and consist mainly of changes in mental status, including altered personality, lethargy, and confusion. [merckmanuals.com]

The diagnosis of SIADH is based on laboratory findings but patient history can raise suspicion of the condition and its underlying etiology. The onset of the manifestations is an indicator of whether the condition is acute or chronic. History may also provide information about a head injury, drug abuse, long-standing pain, neurological symptoms, and features of lung tumors or pathology such as dyspnea, chronic cough, and hemoptysis. It is essential to elicit whether the patient has consumed excessive fluids (an indicator of psychogenic polydipsia) or has received hypotonic fluids.

Laboratory tests include serum electrolytes, bicarbonate, creatinine, blood urea nitrogen, uric acid, cortisol, and thyroid stimulating hormone (TSH). Once the tests reveal hyponatremia, the urine and plasma osmolality is determined along with urine sodium. SIADH is confirmed using Bartter and Schwartz criteria [6]:

• Hyponatremia with reduced plasma osmolality with values <275 mOsm/kg

• Relatively increased urine osmolality (>100 mOsm/kg)

• Normal plasma volume

• Elevated levels of urine sodium (>20 mEq/L)

• Exclusion of hypothyroidism, hypoadrenalism, cardiac failure, pituitary dysfunction, renal dysfunction, liver disease, and diuretic use.

• No clinical features of dehydration e.g. mucosal dryness, loss of skin turgor, or hypotension

Imaging studies like chest X-ray may show a lung tumor as the underlying cause of SIADH while computed tomography (CT) of the head and magnetic resonance imaging (MRI) of the brain may reveal features of cerebral edema or may detect an underlying brain tumor.

Patients who are already hospitalized may develop SIADH. Diagnosis of the condition in such patients may be challenging especially if they are on diuretics [7]. Fractional excretion of uric acid (FE-UA) is very useful in these patients to diagnose SIADH [8].

• Hypouricemia

  Hypouricemia is the rule in SIADH, whereas hyperuricemia commonly accompanies volume contraction. This report presents an AIDS patient with SIADH and normouricemia secondary to pyrazinamide and ethambutol. [ncbi.nlm.nih.gov]

  Nephron 64 : 189 – 192, 1993 ↵ Beck LH: Hypouricemia in the syndrome of inappropriate secretion of antidiuretic hormone. [cjasn.asnjournals.org]

  Hypouricemia and an elevated FEUA may be seen in either salt-wasting syndromes or SIADH. In SIADH, both typically resolve after correction of hyponatremia but persist in those with salt-wasting syndromes. [medcaretips.com]

  Hypouricemia appears to occur in any volume expanded state and, therefore, lacks both sensitivity and specificity for making the diagnosis of SIADH. [razianesth.freeservers.com]

The most influential variables in our analysis were reduction in hospital length of stay, duration of treatment and long term treatment with tolvaptan in SCLC patients. [ncbi.nlm.nih.gov]

Melanoma is a relatively common cancer and is often associated with a dire prognosis once diagnosed as metastatic. [ncbi.nlm.nih.gov]

[…] according to SIADH etiology. [ncbi.nlm.nih.gov]

Syndrome of inappropriate antidiuretic hormone secretion (SIADH) can be primary or secondary to various etiologies ranging from drugs to tumors. It is characterized primarily by hyponatremia and low serum osmolality. [symptoma.com]

Epidemiology, symptoms, and treatment characteristics of hyponatremic psychiatric inpatients. J Clin Psychopharmacol. 2013; 33(6): 799–805. 6. Padhi R, Panda BN, Jagati S, Patra SC. Hyponatremia in critically ill patients. [jpccr.eu]

In this article, we review the epidemiology and presentation of patients with hyponatremia, the pathophysiologic groups for the disorder with respect to sodium and water balance and the diagnostic measures for determining the correct pathophysiologic [doi.org]

Hyponatremia: a prospective analysis of its epidemiology and the pathogenetic role of vasopressin. Ann Intern Med. 1985;102:164–8. PubMed CrossRef Google Scholar 3. [link.springer.com]

Idiopathic Epidemiology Occurrence in the United States Hyponatremia is the most common electrolyte derangement occurring in hospitalized patients. [emedicine.com]

In this article, we review the epidemiology and presentation of patients with hyponatremia, the pathophysiologic groups for the disorder with respect to sodium and water balance and the diagnostic measures for determining the correct pathophysiologic [doi.org]

The article presents pathophysiology, diagnostics and recommendations of management of this oncological emergency. [ncbi.nlm.nih.gov]

With such widespread use of cisplatin in a diverse range of cancers, prompt recognition is crucial to detect and prevent severe neurological sequelae. [ncbi.nlm.nih.gov]

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