Edit concept Question Editor Create issue ticket

Syndrome of Inappropriate Antidiuretic Hormone Secretion

Adh Syndrome Inappropriate

Syndrome of inappropriate antidiuretic hormone secretion is characterized by excessive secretion of the antidiuretic hormone, dilutional hyponatremia, reduced serum osmolality, relatively increased values of urine osmolality, and elevated levels of urinary sodium in patients with a normal plasma volume. Diagnosis is based on excluding other causes of hyponatremia.


Presentation

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].

Intermittent Fever
  • We experienced a male ASD patient who complained of arthralgia and intermittent fever. Chest radiograph and pleural fluid analysis revealed pleurisy with effusion.[ncbi.nlm.nih.gov]
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]
  • A 58-year-old schizophrenic male who had been drinking at least 4-5 l of pure water every day for 30 years was admitted to a hospital with complaints of nausea, fatigue, and irregular, fluctuating fevers (up to 39 degrees C).[ncbi.nlm.nih.gov]
  • Her medications included desvenlafaxine, and symptoms included nausea, anxiety and confusion.[ncbi.nlm.nih.gov]
  • She had reported generalized weakness for 15 days and nausea and vomiting for 3 days. Findings from laboratory analysis showed severe hyponatremia (sodium, 110 mEq/L).[ncbi.nlm.nih.gov]
  • The most common etiologies were malignancies and medication-induced SIADH, followed by idiopathic SIADH, pulmonary infections, pain and nausea, and central nervous system (CNS) disorders.[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]
  • She suffered from lower abdominal pain, vomiting and irritability since one week. Physical findings showed euvolemia and an altered mental status with severe agitation and slurred speech.[ncbi.nlm.nih.gov]
  • She had reported generalized weakness for 15 days and nausea and vomiting for 3 days. Findings from laboratory analysis showed severe hyponatremia (sodium, 110 mEq/L).[ncbi.nlm.nih.gov]
  • 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]
  • Due to continuing symptoms of hyponatremia including headaches, nausea, vomiting, and paresthesias after reinitiation of fluid restriction and salt tablets, tolvaptan was compounded to continue to titrate at lower doses.[ncbi.nlm.nih.gov]
Loss of Appetite
  • 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]
  • 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]
Seizure
  • After the dosage was titrated to 6 mg/d, she experienced generalized seizure attacks.[ncbi.nlm.nih.gov]
  • Limbic encephalitis (LE) is a rare disorder characterized by cognitive dysfunction with memory disturbance, seizures and psychiatric symptoms.[ncbi.nlm.nih.gov]
  • In the subsequent 2 weeks the patient was readmitted twice for acute hyponatraemia and a tonic-clonic seizure. Laboratory studies revealed severe SIADH. Clinical status and sodium levels improved after treatment.[ncbi.nlm.nih.gov]
  • In the subsequent 2 weeks the patient was readmitted twice for acute hyponatraemia and a tonic-clonic seizure. Laboratory studies revealed severe SIADH. Clinical status and sodium levels improved after treatment.[ncbi.nlm.nih.gov]
  • A 54-year-old woman was seen in the hospital because of severe hyponatremia accompanied by generalized seizures. Her serum sodium concentration was 112 mEq/L, with concomitant serum and urine osmolalities of 235 and 639 mOsm/kg, respectively.[ncbi.nlm.nih.gov]
Confusion
  • A 76-year-old woman was admitted to our department for evaluation of left facial pain, confusion and disorientation.[ncbi.nlm.nih.gov]
  • Her medications included desvenlafaxine, and symptoms included nausea, anxiety and confusion.[ncbi.nlm.nih.gov]
  • 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]
  • Five patients experienced confusion or decreased consciousness. Four patients were diagnosed with NMO and two were diagnosed with recurrent optic neuritis. Magnetic resonance imaging showed 11 of 41 patients (26.8 %) had hypothalamic lesions.[ncbi.nlm.nih.gov]
  • Two days later, the patient became progressively confused and fell. Neurologic examination and computed brain tomography were normal.[ncbi.nlm.nih.gov]
Headache
  • Due to continuing symptoms of hyponatremia including headaches, nausea, vomiting, and paresthesias after reinitiation of fluid restriction and salt tablets, tolvaptan was compounded to continue to titrate at lower doses.[ncbi.nlm.nih.gov]
  • 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]
  • After the development of a severe headache, nausea, diplopia, and attacks of hypertension in the early postoperative period, a computer tomography of the brain was normal.[ncbi.nlm.nih.gov]
  • Two days after the first dose (including cyclophosphamide 500 mg), the patient developed vomiting, drowsiness, and headache. Medication history included sertraline, started in 2005.[ncbi.nlm.nih.gov]
  • When symptoms do occur, they may include any of the following: Nausea and vomiting Headache Problems with balance that may result in falls Mental changes, such as confusion, memory problems, strange behavior Seizures or coma, in severe cases Treatment[medlineplus.gov]
Irritability
  • She suffered from lower abdominal pain, vomiting and irritability since one week. Physical findings showed euvolemia and an altered mental status with severe agitation and slurred speech.[ncbi.nlm.nih.gov]
  • 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]
  • 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]
  • 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]
  • 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]
Neurologic Manifestation
  • In case of severe hyponatraemia with neurological manifestations, the treatment with hypertonic saline solution is instituted.[medichub.ro]
  • Neurologic manifestations Neurologic complications in SIADH occur as a result of the brain's response to changes in osmolality. Hyponatremia and hypo-osmolality lead to acute edema of the brain cells.[emedicine.medscape.com]

Workup

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)

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].

Mediastinal Mass
  • Computed tomography revealed a mediastinal mass. A tentative diagnosis of extrapulmonary cryptococcoma or a tumor was made.[ncbi.nlm.nih.gov]
Glycosuria
  • In addition, she had a generalized reabsorption defect of the proximal tubules, including decreased tubular reabsorption of phosphate, increased fractional excretion of uric acid, glycosuria despite a normal blood glucose level, and panaminoaciduria.[ncbi.nlm.nih.gov]
Hyponatremia
  • Algorithm 1 addresses acute correction of hyponatremia posing as a medical emergency, and is applicable to both severe euvolemic and hypovolemic hyponatremia. The mainstay of this algorithm is the iv use of 3% hypertonic saline solution.[ncbi.nlm.nih.gov]
  • Hyponatremia gradually developed but improved after hypertonic sodium treatment. One month later, severe hyponatremia rapidly recurred. We considered the hyponatremia's cause as SIADH.[ncbi.nlm.nih.gov]
  • BACKGROUND: The syndrome of inappropriate antidiuretic hormone secretion is the most common cause of hyponatremia in clinical practice, but current management of hyponatremia and outcomes in patients with syndrome of inappropriate antidiuretic hormone[ncbi.nlm.nih.gov]
  • Abstract Hyponatremia is prevalent in hospitalized patients and predicts a poor prognosis. The syndrome of inappropriate secretion of antidiuretic hormone (SIADH) is perceived as one of the most frequent causes of hyponatremia.[ncbi.nlm.nih.gov]
  • Clinical presentation of SIADH depends on the severity and rate of hyponatremia development.[symptoma.com]
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]
  • An 83-year-old Japanese woman was admitted to our hospital with severe hyponatremia (sodium, 108 mEq/L [108 mmol/L]), hypokalemia, hypochloridemia, hypocalcemia, hypophosphatemia, and hypouricemia.[ncbi.nlm.nih.gov]
  • 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]
  • 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]
  • Maesaka et al. noted that hypouricemia and an increased FEUrate improve in SIADH, but not in C/RSW after the correction of hyponatremia ( 23, 37, 39 ).[journal.frontiersin.org]

Treatment

  • 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]
  • The mean rate of [Na( )] change (mEq/L/d) was greater for all active therapies than no active treatment.[ncbi.nlm.nih.gov]
  • The sodium and chloride levels decreased continuously during treatment with citalopram; six days after the citalopram was discontinued, sodium and chloride levels returned to normal. We then switched treatment to mirtazapine.[ncbi.nlm.nih.gov]
  • Surgery, chemotherapy, and radiotherapy are the choices of treatment; among these, surgery is an indispensible treatment.[ncbi.nlm.nih.gov]
  • During the long-term treatment, 15 of 18 enrolled patients achieved 6 mo and 10 achieved 12 mo of treatment. The SNa response was maintained during this time with a good tolerance.[ncbi.nlm.nih.gov]

Prognosis

  • Melanoma is a relatively common cancer and is often associated with a dire prognosis once diagnosed as metastatic.[ncbi.nlm.nih.gov]
  • Abstract Hyponatremia is prevalent in hospitalized patients and predicts a poor prognosis. The syndrome of inappropriate secretion of antidiuretic hormone (SIADH) is perceived as one of the most frequent causes of hyponatremia.[ncbi.nlm.nih.gov]
  • Pure small cell neuroendocrine carcinoma of the prostate is a rare entity characterized by a poor prognosis due to early metastatic spread as well as resistance to treatment.[ncbi.nlm.nih.gov]
  • Long-term survival was determined primarily by SIADH etiology rather than hyponatremia severity, with hazard ratios for death of up to 7.31 (95% CI 4.93-10.82, p CONCLUSIONS: Patients with SIADH have different characteristics and a different prognosis[ncbi.nlm.nih.gov]
  • CONCLUSIONS: Two complementary strategies were elaborated to treat SIADH-induced hyponatremia in an attempt to increase awareness of its importance, simplify its therapy, and improve prognosis.[ncbi.nlm.nih.gov]

Etiology

  • […] according to SIADH etiology.[ncbi.nlm.nih.gov]
  • RESULTS: Eleven of the 99 patients without an apparent etiology for SIADH at presentation were found to have an underlying cause on workup.[ncbi.nlm.nih.gov]
  • OBJECTIVE: Tolvaptan, an oral antagonist of the vasopressin V(2) receptor, has been found to improve hyponatremia in patients with mixed etiologies.[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]
  • After multiple alternative etiologies were excluded, drug-induced SIADH due to linezolid use was determined to be the most likely diagnosis.[ncbi.nlm.nih.gov]

Epidemiology

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

Pathophysiology

  • The article presents pathophysiology, diagnostics and recommendations of management of this oncological emergency.[ncbi.nlm.nih.gov]
  • It therefore behooves clinicians treating such patients to have a good understanding of the pathophysiology, the differential diagnosis and the management of these disorders.[ncbi.nlm.nih.gov]
  • This study reviews the pathophysiology of diabetes insipidus and inappropriate ADH secretion after pituitary surgery, and is intended to serve as a guide for their diagnosis, differential diagnosis, treatment, and monitoring. Copyright 2013 SEEN.[ncbi.nlm.nih.gov]
  • Traditional therapies such as fluid restriction, sodium repletion, and diuretics can help correct hyponatremia but do not address the underlying pathophysiology of excess arginine vasopressin secretion.[ncbi.nlm.nih.gov]
  • 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]

Prevention

  • The present case demonstrates the need for a high level of suspicion in order to diagnose this disorder in unexplained syndrome of inappropriate antidiuretic hormone secretion and prevent life-threatening complications.[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]
  • Routine physical and laboratory examinations may prevent silent disease progression.[ncbi.nlm.nih.gov]
  • OBJECTIVE: To determine whether the administration of isotonic saline in patients undergoing spinal fusion surgery prevents the development of hyponatremia, thus masking the detection of syndrome of inappropriate antidiuretic hormone secretion (SIADH)[ncbi.nlm.nih.gov]
  • […] inappropriate antidiuretic hormone secretion (SIADH) who developed profound aquaresis with symptomatic extracellular fluid depletion after initiation of therapy with tolvaptan who was later successfully treated with smaller doses of compounded tolvaptan to prevent[ncbi.nlm.nih.gov]

References

Article

  1. Cuesta M, Thompson CJ. The syndrome of inappropriate antidiuresis (SIAD). Best Pract Res Clin Endocrinol Metab. 2016;30 (2):175-187.
  2. Miller M, Hecker MS, Friedlander DA, Carter JM. Apparent idiopathic hyponatremia in an ambulatory geriatric population. J Am Geriatr Soc.1996;44:404–408.
  3. Miller M. Syndrome of excess antidiuretic hormone release. Crit Care Clin. 2001;17:11–23.
  4. Renneboog B, Musch W, Vandemergel X, Manto MU, Decaux G. Mild chronic hyponatremia is associated with falls, unsteadiness, and attention deficits. Am J Med. 2006;119(1):71.e1-8.
  5. Decaux G. Is asymptomatic hyponatremia really asymptomatic?. Am J Med. 2006;119(7 Suppl 1):S79-82.
  6. Bartter FC, Schwartz WB. The syndrome of inappropriate secretion of antidiuretic hormone. Am J Med. 1967;42(5):790-806.
  7. Pillai BP, Unnikrishnan AG, Pavithran PV. Syndrome of inappropriate antidiuretic hormone secretion: revisiting a classical endocrine disorder. 2011;15(Suppl 3): S208-S215.
  8. Fenske W, Störk S, Koschker AC, et al. Value of fractional uric acid excretion in differential diagnosis of hyponatremic patients on diuretics. J Clin Endocrinol Metab. 2008;93:2991–2997.

Ask Question

5000 Characters left Format the text using: # Heading, **bold**, _italic_. HTML code is not allowed.
By publishing this question you agree to the TOS and Privacy policy.
• Use a precise title for your question.
• Ask a specific question and provide age, sex, symptoms, type and duration of treatment.
• Respect your own and other people's privacy, never post full names or contact information.
• Inappropriate questions will be deleted.
• In urgent cases contact a physician, visit a hospital or call an emergency service!
Last updated: 2019-06-28 09:16