Hyponatremia and the syndrome of inappropriate secretion of antidiuretic hormone associated with the use of selective serotonin reuptake inhibitors: a review of spontaneous reports

OBJECTIVE: To review reported cases of hyponatremia and the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) associated with the use of selective serotonin reuptake inhibitors (SSRIs). DATA SOURCES: A search of MEDLINE for reports of hyponatremia and SIADH associated with the use of fluoxetine, fluvoxamine, paroxetine or sertraline published between January 1980 and May 1995. Unpublished reports of cases were requested from the pharmaceutical industry, the Ontario Medical Association, the Health Protection Branch of Health Canada, the US Food and Drug Administration and the World Health Organization. DATA SELECTION AND EXTRACTION: Spontaneous reports from postmarketing surveillance. DATA SYNTHESIS: A total of 736 cases of hyponatremia [corrected] and SIADH associated with SSRI use were reported. Fluoxetine was involved in 554 (75.3%) of the cases, paroxetine in 91 (12.4%), sertraline in 86 (11.7%) and fluvoxamine in 11 (1.5%). Reports of 30 cases were published. The remaining 706 cases were reported to monitoring bodies and the pharmaceutical industry. According to information in the published reports, the median time to onset of hyponatremia was 13 days (range 3 to 120 days). Most (83%) of the published cases involved patients 65 years of age or more, as compared with 74% of the unpublished cases. CONCLUSION: Elderly people may be at increased risk for hyponatremia associated with SSRI use. Physicians caring for elderly patients should be aware of this potentially serious but reversible adverse effect. Further research is required to determine the incidence of this adverse effect, the relative risk of hyponatremia and SIADH in different age groups and the risk associated with different SSRI drugs.     

Long-term results after scleral buckling surgery in uncomplicated juvenile retinal detachment without proliferative vitreoretinopathy

Hyponatremia is a common complication after subarachnoid hemorrhage (SAH). Although the mechanism of hyponatremia is still controversial, cerebral salt-wasting syndrome (CSNS) is currently regarded as being more responsible than the syndrome of inappropriate secretion of antidiuretic hormone (SIADH). The aim of our study was to assess the plasma volume status of a patient with hyponatremia following subarachnoid hemorrhage. In doing this it may be possible to indirectly differentiate its pathogenesis. Fifty patients with SAH were studied. Twenty patients demonstrated hyponatremia (serum sodium < 135 mEq/L) during day 7 to 13 after subarachnoid hemorrhage. Patients with hyponatremia were categorized on the basis of their daily body weight, and central venous pressure. Group A consisted of patients with hypovolemia (16 patients), with the onset time of hyponatremia being day 7 to 9. Group B included those with hypervolemia (4 patients); hyponatremia was observed during day 10 to 11 and was corrected in all patients within 72 hours after induction of fluid restriction. Our findings suggest that hyponatremia following subarachnoid hemorrhage usually occurs due to CSWS, although SIADH remains as a minor pathogenesis. We conclude that the combination of daily body weight and CVP measurements is a simple and practical method to distinguish promptly SIADH from CSWS.     

A case of prostatic ductal adenocarcinoma with endometrioid features, associated with rectal invasion and multiple liver metastases

A 66-year-old man was admitted with destructive arthropathy, and calcium pyrophosphate dihydrate was demonstrated in the synovial fluid specimen. He was found to have a hyponatremia. The serum sodium concentration was 121 mmol/l, plasma arginine vasopressin (AVP) 6.6 pmol/l, and serum interleukin (IL)-6 96 pg/l. The clinical findings suggest the diagnosis of syndrome of inappropriate secretion of antidiuretic hormone (SIADH). However, destructive arthropathy with increased values of C-reactive protein and IL-6 is the only background of SIADH in this patient. We suggest the possibility that IL-6 produced at inflammatory lesions may have stimulated an excessive release of AVP resulting in the hyponatremia and hypochloremia of SIADH.     

Symptomatic syndrome of inappropriate antidiuretic hormone secretion associated with azithromycin

OBJECTIVE: To report a case of symptomatic syndrome of inappropriate antidiuretic hormone (SIADH) secretion associated with azithromycin and review the literature related to this adverse drug reaction. DATA SOURCES: Review articles identified by a computerized (MEDLINE) (1966-April 1996) and manual (Index Medicus) search. DATA SYNTHESIS: Azithromycin is a well-tolerated broad-spectrum macrolide antibiotic. We report a symptomatic case of SIADH secretion associated with azithromycin. The patient received two doses of azithromycin before the development of sudden mental status changes associated with severe hyponatremia. All other potential causes were ruled out. No previous reports exist in the literature. CONCLUSIONS: Azithromycin may be associated with symptomatic SIADH secretion. Awareness and attention are required if patients develop mental status changes or hyponatremia while receiving azithromycin so that appropriate diagnostic and therapeutic actions can be implemented.     

Syndrome of inappropriate secretion of antidiuretic hormone in nasopharynx carcinoma

The syndrome of inappropriate secretion of antidiuretic hormone (ADH) or SIADH has been reported in various disorders. We report a pediatric patient with nasopharynx carcinoma who may have developed a clinical SIADH with severe hyponatremia and generalized seizure during the administration of intravenous hydration. We propose that the inappropriately high plasma level of ADH led to the inability to excrete sufficient amounts of free water during a hyperhydration protocol with a relatively hypotonic fluid, which resulted in acute hyponatremia and central nervous system involvement. To avoid this complication, intravenous hydration before chemotherapy in children with nasopharynx carcinoma should be performed at a slower infusion rate and with a sodium chloride concentration of more than half isotonic.     

Syndrome of inappropriate antidiuretic hormone associated with vinorelbine therapy

OBJECTIVE: To describe onset of syndrome of inappropriate antidiuretic hormone (SIADH) associated with vinorelbine therapy for advanced breast cancer. CASE SUMMARY: A 50-year-old white woman with a history of advanced breast cancer refractory to other treatment modalities was receiving vinorelbine. Blood chemistries revealed severely depleted sodium and potassium concentrations from a normal baseline within a 7-day period. A recheck of blood chemistries confirmed hyponatremia. The patient was admitted to the hospital and treated for SIADH. After successful treatment, she was given demeclocycline prophylactically and rechallenged with vinorelbine without recurrence of the syndrome. DISCUSSION: SIADH has been reported as a complication of treatment with vinca alkaloids. To our knowledge, this is the first report of this syndrome related to vinorelbine therapy. CONCLUSIONS: Because of its structural similarity to the other vinca alkaloids, vinorelbine is believed to be responsible for SIADH in our patient. Clinicians should be aware of the possibility that vinorelbine may cause SIADH and possibly hypokalemia.     

The syndrome of inappropriate secretion of vasopressin (SIADH) (author's transl)

The syndrome of inappropriate ADH secretion ("SIADH") was first recognized 1935 by Roth et al. and described in detail 1957 by Schwartz et al. The clinical symptoms (hyponatremia, hypertonicity of urine and inability to excrete a water load) are caused by inadequately elevated ADH secretion under a variety of situations and diseases. Some recent work was focused on the pathogenesis of this syndrome and new clinical findings (low plasma levels of uric acid and potassium) as well as special forms ("SIADH" without elevated vasopressin levels in plasma) are thought to be of relevance. New therapeutical recommendations will be discussed.     

Miliary tuberculosis presenting with hyponatremia and thrombocytopenia

A 74-year-old woman with miliary tuberculosis had moderately severe hyponatremia due to inappropriate secretion of antidiuretic hormone (SIADH) and very severe thrombocytopenia without other hematologic abnormalities. She was treated with isoniazid, rifampin, ethambutol, prednisone, vincristine and fluid restriction and recovered completely. The SIADH may have been a response by the posterior pituitary to a decrease in intravascular volume resulting from the extensive pulmonary disease or associated hypoxia, or the tuberculous lung may have released ADH or an ADH-like substance. The thrombocytopenia may have resulted from a direct or indirect toxic effect of infection or, less likely, the tuberculosis may have activated latent idiopathic thrombocytopenic purpura.     

Fluoxetine-induced SIADH: a geriatric occurrence?

After major depression was diagnosed in a 83-year-old woman, fluoxetine was prescribed. Six days later she became delirious and weak, necessitating hospitalization. She was found to have hyponatremia secondary to fluoxetine-induced syndrome of inappropriate antidiuretic hormone secretion (SIADH). Recovery was complete after discontinuation of the medication.     

Intestinal intussusception as an unusual complication of oral anticoagulation therapy

Hyponatremia is a common neuromedical problem seen in survivors of central nervous system injury. The etiology of this hyponatremia is often diagnosed as syndrome of inappropriate diuretic hormone (SIADH). Fluid restriction is usually the first line of treatment. However, this can exacerbate vasospasm and produce resultant ischemia. Cerebral salt wasting is a syndrome of renal sodium loss that may occur commonly after central nervous system injury, yet remains unrecognized. Treatment of cerebral salt wasting consists of hydration and salt replacement. This article uses a case report to discuss the importance of recognition of this syndrome, and treatment concerns are reviewed.     

Neuropsychiatric systemic lupus erythematosus and the syndrome of inappropriate secretion of antidiuretic hormone: a case report with very late onset systemic lupus erythematosus

The syndrome of inappropriate secretion of antidiuretic hormone (SIADH) associated with neuropsychiatric lupus (NP-SLE) is rare. We report a case of SIADH associated with the new onset of SLE in an 88-yr-old female. The unique features of this case include the extreme age of onset of SLE presenting with neuropsychiatric manifestations and positive antiribosomal P antibody titres. Both the NP manifestations of SLE and SIADH were highly correlated with the SLE disease activity. This case illustrates a novel presentation of NP-SLE with SIADH which may develop due to antibody-mediated hypothalamic dysfunction.     

Grand rounds: Acute changes in mental status secondary to selective serotonin reuptake inhibitor-induced hyponatremia.

Hyponatremia represents the most common electrolyte abnormality in hospitalized patients and is of particular concern in hospitalized elderly patients. Multiple studies have identified an association between hyponatremia and selective serotonin reuptake inhibitor (SSRI) therapy. The present report provides as illustration 2 elderly patients identified to develop hyponatremia following initiation of SSRI therapy, which subsequently resolved following discontinuation of the medications. These cases demonstrate the unique position of the rehabilitation psychologist in identifying SSRI-induced hyponatremia as one potential mechanism underlying acute changes in mental status. Diagnostic factors and differential causes of hyponatremia are discussed, and alternative medications for addressing depressive symptomatology in cases of SSRI-induced hyponatremia are provided. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Development of syndrome of inappropriate secretion of antidiuretic hormone during progression of metastatic breast cancer

A patient who developed syndrome of inappropriate secretion of antidiuretic hormone (SIADH) during progression of metastatic breast cancer is described. The classic criteria for SIADH as defined by Bartter and Schwartz were fulfilled and conditions other than malignant disease were excluded as causes of the syndrome. To the knowledge of the authors SIADH has never been reported to develop during the course of malignant disease in a patient with metastatic breast cancer. It should be borne in mind that SIADH may occur in patients with malignant disease and hyponatraemia, even in the absence of small-cell lung cancer, which is the classic tumour type to develop SIADH.     

Eradication project for poliomyelitis and surveillance of acute paralysis

We report three lymphoma patients in whom the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) was observed during the course of lymphoma-associated hemophagocytic syndrome (LAHS). The clinical course was devoid of any known mechanism for SIADH which could be attributable to lymphoma or antineoplastic treatment. Alternatively, high serum levels of interleukin-1 beta and tumor necrosis factor-alpha, which stimulate the secretion of antidiuretic hormone, may have contributed to the development of SIADH in our patients, who were receiving glucocorticoids. In conclusion, LAHS patients should be considered to be at high risk for SIADH.     

The syndrome of inappropriate secretion of antidiuretic hormone: an unusual presentation for childhood craniopharyngioma: report of three cases

OBJECTIVE AND IMPORTANCE: Childhood craniopharyngiomas may present with variable endocrine dysfunctions. However, hyponatremia secondary to the syndrome of inappropriate secretion of antidiuretic hormone has never been reported. We describe three children with craniopharyngioma who presented with hyponatremia. CLINICAL PRESENTATION: Three children had hyponatremia at presentation, two of whom had experienced generalized seizures. Urine sodium levels measured in two patients were abnormally high. Neuroimaging tests, including computed tomography and magnetic resonance imaging, showed a large partially calcified and partially cystic craniopharyngioma in the sellar/suprasellar location. INTERVENTION: Intake of fluids was restricted for each patient, with improvement of hyponatremia, and each patient subsequently underwent a successful tumor resection. Postoperatively, all patients developed panhypopituitarism, including diabetes insipidus, and needed multiple hormonal replacement therapy. CONCLUSION: Endocrine dysfunctions at diagnosis are commonly associated with childhood craniopharyngiomas, but the association of the syndrome of inappropriate secretion of antidiuretic hormone with craniopharyngioma has never been reported. Craniopharyngiomas should be included as a possibility in making the differential diagnosis of the syndrome of inappropriate secretion of antidiuretic hormone in children.     

Force-feeding of infants in North Cameroon. A harmful tradition-- preventive approach

Repeated infant force-feeding is a widespread custom among mothers in the district of Tokombéré in North Cameroon. It is started in neonates and maintained until approximately one year of age, using mostly hot water. The authors describes the complications of this practice, the most severe one being aspiration pneumonia which can cause death. The traditional and cultural aspects of infant force-feeding in this area are discussed. The author believes that these aspects have to be taken into account in any preventive action directed towards the renunciation of this harmful practice.     

Transient exercise-induced water intoxication and rhabdomyolysis

Water loading only rarely results in adverse effects due to the high efficiency of the kidney in excreting free water. However, when renal diluting ability is impaired, such as in inappropriate vasopressin secretion, water intoxication can occur in otherwise normal individuals. We report the case of a 19-year-old man with acute voluntary water intoxication following exercise, which resulted in a transient defect in renal diluting capability. Hyponatremia was further complicated by rhabdomyolysis. We review the literature regarding other cases of hyponatremia following excessive water intake, and discuss the possible association between hyponatremia and rhabdomyolysis. We conclude that monitoring of muscle enzymes is indicated in acute hyponatremia, to allow for timely intervention intended to prevent rhabdomyolysis-associated acute renal failure.     

Pathogenesis of hyponatremia following subarachnoid hemorrhage due to ruptured cerebral aneurysm

BACKGROUND: Hyponatremia following subarachnoid hemorrhage (SAH) occurs due to the inappropriate secretion of antidiuretic hormone (SIADH). However, this condition is also sometimes associated with certain dehydration states. METHODS: To clarify the pathogenesis, daily values of urine volume, water balance, and sodium balance (Na Bal) were correlated with plasma levels of atrial natriuretic peptide (ANP), antidiuretic hormone (ADH), and plasma renin activity (PRA) in 31 cases of SAH. RESULTS: Na Bal was markedly negative on days 2 and 3. Cumulative Na Bal showed continuous negative values until day 10 following SAH. ANP values showed a consistent elevation, while ADH showed only an initial surge. PRA, as the gross indicator of circulatory volume, showed a lack of suppression, indicating no increase in the circulatory volume. CONCLUSION: Hyponatremia following SAH therefore appears to be the result of increased natriuresis, due to the inappropriate elevation of ANP rather than SIADH. In this situation, water restriction should not be recommended, since the circulatory volume is decreased.     

New systems of cardiac mapping or life to the electrophysiologist may become complicated

We report the case of an infant with progressive human immunodeficiency virus (HIV) infection and persistent seronegativity. The child had Pneumocystis carinii pneumonia at 4 months of age and was documented to be HIV-infected by HIV-1 deoxyribonucleic acid (DNA) polymerase chain reaction (PCR), but enzyme-linked immunosorbent assay (ELISA) and Western blot tests for HIV-1 and HIV-2 specific antibodies remained negative until the infant was 10 months old. This case should increase awareness about the possibility of seronegative HIV infection in infants and stress the fact that in questionable cases, even if the screening serology is negative, additional methods of diagnosis (ie, PCR, viral culture, and p24 antigen) should be considered.     

Chlorpropamide-induced hyponatremia

A 29-year-old woman with severe idiopathic diabetes insipidus, while being treated by a combination of chlorpropamide and chlorothiazide, developed the syndrome of inappropriate secretion of ADH (SIADH) following an overdose of chlorpropamide. The syndrome resolved as the serum chlorpropamide level fell. This report demonstrates that a chlorpropamide-induced SIADH can occur in a patient with idiopathic diabetes insipidus, and it appears that the antidiuretic effect of the drug is dose-related.