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A Rare Cause of Hyponatremia: Inappropriate Antidiuretic Hormone Secretion due to Brucella Encephalitis
Abstract
The syndrome of inappropriate antidiuretic hormone secretion (SIADH) is a cause of euvolemic hyponatremia. Neoplasms, infections and some drugs are the most frequent reasons of SIADH. Brucella melitensis is an infectious microorganism that is frequently seen in some regions of our country. It may cause multisystemic disease or nonspecific symptoms. A 44-year-old female patient, who presented with hyponatremia and fever, was diagnosed with SIADH due to brucellosis-related encephalitis and she recovered with treatment of the brucellosis. SIADH due to brucellosis-related encephalitis is a quite rare cause of hyponatremia.
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Hyponatraemia is a common electrolyte disorder associated with significant complications and controversies regarding its optimal management. Clinical practice guidelines and consensus statements have attempted to provide clinicians with evidence-based diagnostic and treatment strategies for hyponatraemia. Recently published guidance documents differ in their methods employed to review the quality of available evidence. Nagler et al. used the Appraisal of Guideline for Research and Evaluation (AGREE II) instrument in a systematic review of guidelines and consensus statements for the diagnosis and management of hyponatraemia. Nagler and colleagues highlighted the variability in methodological rigour applied to guideline development and inconsistencies between publications in relation to management of hyponatraemia (including the recommended rate of correction of a low serum sodium concentration). These differences could cause confusion for practising physicians managing patients with hyponatraemia.
Please see related article: http://www.biomedcentral.com/1741-7015/12/231.
Objective:
Various studies have shown that a number of infectious disease causes syndrome of inappropriate antidiuretic hormone (SIADH). However, the relationship between infectious disease and SIADH is not yet fully known. In this prospective study, we aimed to assess the presence of SIADH in patients with brucellosis.
Patients and methods:
Thirty-five patients with acute brucellosis were retrospectively reviewed. The diagnosis of brucellosis was performed using the Wright test in connection with blood culture. SIADH was defined by euvolemic hyponatremia (serum sodium level lower than 135 mEq/l) with increased urinary sodium excretion (urinary sodium higher than 40 mmol/l).
Results:
Of the 35 patients, 19 (54%) had SIADH; 20 (57%) also had hypouricemia (uric acid level lower than 4 mg/dl). Additionally, all of the studied patients had a high mean urinary sodium excretion rate (mean 132 mmol/l; range 40-224). Most importantly, the hyponatremic patients were more likely to have a lower albumin level (P < 0.01).
Conclusions:
SIADH is a major complication of brucellosis. The presence of SIADH could be a diagnostic tool for diagnosing brucellosis. Further larger randomized studies may confirm these findings.
Brucellosis is a worldwide zoonosis caused by Brucella species. The disease remains a significant economic and public health problem particularly in the Mediterranean countries. Clinical manifestations of brucellosis are variable and often nonspecific, simulating infectious and noninfectious diseases. Osteoarticular involvement is the most common focal complication of brucellosis and morbidity. Mortality rate due to brucellosis is low, mostly secondary to endocarditis and central nerve involvement of disease.
The diagnosis of brucellosis depends on the clinical presentations and laboratory tests. Detection of Brucella species by culture method is sometimes unsuccessful; therefore, serological tests are preferred. These tests are easy to perform, and results can be obtained within a short span of time. Several serologic tests have been developed for the diagnosis of human brucellosis, including the standard agglutination tube (SAT) test, anti-human globulin (Coombs) test, indirect fluorescence antibody (IFA) test, and enzyme-linked immunosorbent assay (ELISA). SAT is the primary test used in many clinical laboratories. IFA and ELISA are simple and reliable for the detection of immunoglobulin classes especially in complicated cases. Polymerase chain reaction (PCR) technique is highly sensitive and specific for the determination of Brucella spp. from peripheral blood and other tissues.
Recent patents are especially based on molecular assays in the diagnosis of brucellosis. However, PCR is still expensive and may not be appropriate for daily practice.
Syndrome of inappropriate secretion of antidiuretic hormone (SIADH) is an extremely rare complication of infectious diseases. A rare case of brucellosis complicated by syndrome of inappropriate secretion of antidiuretic hormone (SIADH) cholestasis and pericardial involvement is reported. A 27-year-old woman was admitted for fever, abdominal pain, and scleral icterus. Her medical history revealed no recent use of diuretic agents. In addition to cholestasis and elevated liver enzymes, euvolemic hyponatremia, hypouricemia, low plasma osmolality, and high urinary osmolality were also detected. Surrenal and thyroid tests were also within normal range. Echocardiography revealed minimal pericardial effusion with normal cardiac functions. The final diagnosis was SIADH due to Brucellosis. Hyponatremia, cholestasis, and pericardial disease were resolved with effective antibrucellar treatment with streptomycine and doxycycline. After completing treatment of brucellosis, there was not any more evidence of cholestasis and pericardial fluid.
Hyponatremia is defined as a serum below 135 mmol/l and is the most frequent electrolytes disorder. The treatment is essential because hyponatremia is associated with increased morbidity and mortality. There are multiple aetiologies associated with this challenging diagnosis. The correct one must be established in order to manage this disorder appropriately. Serum and urine osmolalities, serum sodium concentration and evaluation of extracellular fluid volume are necessary for the diagnosis. The rate of correction of hyponatremia should be closely monitored to avoid cerebral complications. This article reviews the recommended approaches for the diagnosis and treatment of hyponatremia.
Brucellosis in humans is a zoonosis of greatly varied clinical image. It occurs on all inhabited continents. The course of the disease may be acute, sub-acute or chronic. The etiologic factors of brucellosis are small, aerobic Gram-negative rods of the genus Brucella, which currently contains ten species: B. abortus, B. suis, B. ovis, B. melitensis, B. canis, B. neotomae, B. pinnipedialis, B. ceti, B. microti and B. inopinata. In humans, the disease is caused mainly by: B. melitensis as the most pathogenic species, followed by B. suis, whereas B. abortus is considered as the mildest type of brucellosis. The natural reservoir of the germ and the source of infection in humans are infected domestic animals, primarily cattle, sheep, goats, as well as wild animals. Infection in humans occurs by penetration through damaged skin, conjunctiva, and more rarely via the alimentary route by the consumption of infected products. Especially exposed are: veterinarians, veterinary technicians, insemination service employees, zoo technicians, farmers working on multi-herd farms (production cooperatives), e.g. cattlemen, also private farmers, employees of slaughter houses and meat processing enterprises. A basis for diagnosing brucellosis are serologic tests which allow the detection of antibodies occurring in response to infection, performed with the use of the following methods: agglutination test, complement fixation test, Coombs test, 2-mercaptoethanol agglutination test, and Burnet's intradermal allergy test which detects the state of hypersensitivity of the infected organism to Brucella abortus rods.
The syndrome of inappropriate ADH secretion (SIADH), also termed ''syndrome of inappropriate antidiuresis (SIAD)'', is an often unrecognized cause of hypotonic hyponatremia, arising from ectopic release of ADH in lung cancer or as a side effect of various drugs. In SIADH, hyponatremia results from selectively impaired water excretion by the kidney, whereas the external Na+ balance is normally regulated. Despite the increase in total body water, only a slight reduction of urine output and modest edema are usually seen. Renal function and acid-base balance are generally preserved, while subclinical neurological impairment may occasionally become life-threatening, when hyponatremia has an abrupt onset. The major clinical variants of SIADH are reviewed here, with particular emphasis on causes, iatrogenic complications and hospital-acquired hyponatremia. Effective treatment of SIADH is based on water restriction, hypertonic saline plus loop diuretics, or aquaretics. Worsening of hyponatremia may result from parenteral isotonic fluid administration, emphasizing the importance of an early diagnosis and careful follow-up of these patients.
The syndrome of inappropriate antidiuresis (SIAD; formerly the syndrome of inappropriate secretion of antidiuretic hormone) is the most frequent cause of hyponatremia. A strong association exists between mortality and hyponatremia, which reflects the severity of the underlying disease. In SIAD, hyponatremia is associated with normovolaemia but the assessment of extracellular volume can be difficult. Clinical features are mainly neurological and can lead to death but mechanisms of adaptation can limit cerebral oedema. The notion of mild asymptomatic hyponatremia was questioned by the observation of subclinical neurocognitive impairment, a greater risk of falls and fractures. Aetiologies are classified into six groups: neurologic disorders, infections mainly cerebral, meningeal and pulmonary, drugs in particular antidepressants, tumors, genetic causes, and idiopathic. Symptomatic acute hyponatremia is a therapeutic emergency that is not specific of SIAD. When hyponatremia is asymptomatic, fluid restriction with salt intake is generally sufficient but urea can be an alternative. In chronic SIAD, there is currently no recommendation. Fluid restriction is not always feasible; urea has proved its efficacy, its good tolerance and its long-term harmlessness. Vaptans have demonstrated their good tolerance and their efficacy on the correction of hyponatremia from SIAD in studies subgroups, for moderate hyponatremia and asymptomatic patients. In the only study having compared vaptans and urea, efficacy and tolerance were similar. Because of the cost difference between vaptans and urea and while waiting for follow-up studies, urea appears at present as the first-line treatment of hyponatremia in SIAD.
Copyright © 2012 Société nationale française de médecine interne (SNFMI). Published by Elsevier SAS. All rights reserved.
Renal function was assessed in 270 patients with brucellosis. In 58 consecutive patients of this total, plasma and urinary osmolality and urinary sodium excretion as well as adrenal and thyroid functions were measured prospectively. Results of these measurements satisfy criteria for the syndrome of inappropriate secretion of antidiuretic hormone (SIADH). Such inappropriate secretion explains the asymptomatic hyponatraemia observed in our patients. The hyponatraemia together with the usual haematological findings and cellular derangement of the liver may be useful in the differential diagnosis of brucellosis which should be considered as one of the clinical conditions leading to SIADH.
Infection with Brucella spp. continues to pose a human health risk globally despite strides in eradicating the disease from domestic animals. Brucellosis has been an emerging disease since the discovery of Brucella melitensis by Sir David Bruce in 1887. Although many countries have eradicated B. abortus from cattle, in some areas B. melitensis and B. suis have emerged as causes of this infection in cattle, leading to human infections. Currently B. melitensis remains the principal cause of human brucellosis worldwide including India. The recent isolation of distinct strains of Brucella from marine mammals as well as humans is an indicator of an emerging zoonotic disease. Brucellosis in endemic and non-endemic regions remains a diagnostic puzzle due to misleading non-specific manifestations and increasing unusual presentations. Fewer than 10% of human cases of brucellosis may be clinically recognized and treated or reported. Routine serological surveillance is not practiced even in Brucella - endemic countries and we suggest that this should be a part of laboratory testing coupled with a high index of clinical suspicion to improve the level of case detection. The screening of family members of index cases of acute brucellosis in an endemic area should be undertaken to pick up additional unrecognised cases. Rapid and reliable, sensitive and specific, easy to perform and automated detection systems for Brucella spp. are urgently needed to allow early diagnosis and adequate antibiotic therapy in time to decrease morbidity / mortality. The history of travel to endemic countries along with exposure to animals and exotic foods are usually critical to making the clinical diagnosis. Laboratory testing is indispensable for diagnosis. Therefore alertness of clinician and close collaboration with microbiologist are essential even in endemic areas to correctly diagnose and treat this protean human infection. Existing treatment options, largely based on experience gained > 30 years ago, are adequate but not optimal. In our experience, an initial combination therapy with a three drug-regimen followed by a two-drug regimen for at least six weeks and a combination of two drugs with a minimum of six weeks seems warranted to improve outcome in children and adult patients respectively with laboratory monitoring. A safe and effective vaccine in humans is not yet available. Prevention is dependent upon the control of the disease in animal hosts, effective heat treatment of dairy produce and hygienic precautions to prevent occupational exposure. This review compiles the experiences and diagnostic and treatment paradigms currently employed in fighting this disease.