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.     

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.     

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.     

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.     

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.     

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.     

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.     

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.     

Bilateral pneumonia and inappropriate secretion of antidiuretic hormone in a premature infant

A 6-week-old infant born prematurely had severe hyponatremia and other features of the syndrome of inappropriate secretion of antidiuretic hormone (SIADH). This disturbance was believed to be secondary to extensive bilateral pneumonia with collapse of the right upper lobe. Although this association has been recognized in adults, this is the first report of its occurrence in an infant. SIADH must be considered in the differential diagnosis of hyponatremia in association with pneumonia in an infant.     

Thrombocytopenia in HIV infection

Thrombocytopenia commonly occurs in individuals with HIV disease. However, profound thrombocytopenia, occurring in only 1.5% of cases, is relatively rare. The mechanisms of thrombocytopenia appear to be multifactorial: profound thrombocytopenia in HIV disease is related to an immune destruction either by antiplatelet antibodies or by immune complexes. In addition, a defect in platelet production is quite frequent both in immune thrombocytopenia (ITP) and in mild thrombocytopenia. This impaired platelet production may be due to an HIV infection of megakaryocytes that express a functional CD4 molecule. Treatment of HIV-associated thrombocytopenia is quite similar to that of non-HIV ITP. However, zidovudine increases the platelet count without correlation with its antiviral effect. In animal models and HIV patients, this enhancement of platelet count appears to be due to a stimulation of platelet production, the precise mechanism of which remains unknown. Splenectomy is as effective in severe HIV thrombocytopenia as in non-HIV ITP and has no significant adverse effects on HIV disease.     

Brain-stem trigeminal and auditory evoked potentials in multiple sclerosis: physiological insights

Although suramin has long been used to treat human trypanosomiasis, recent clinical trials have tested its efficacy against the acquired immunodeficiency syndrome (AIDS) and various malignancies. Thromobocytopenia was observed in early trials with suramin in AIDS, but has been uncommon in patients treated for solid tumors. Here we describe 5 patients out of a total of 67 (7%) who developed severe thrombocytopenia while receiving suramin as part of a phase II clinical trial for metastatic prostate carcinoma refractory to hormonal therapy. IgG purified from one patient's plasma caused suramin-dependent platelet aggregation. There was also evidence of crossreactivity between suramin and heparin in this system. An immune mechanism, however, could not be documented in the other cases, suggesting that multiple mechanisms may be responsible for severe thrombocytopenia in this patient population.     

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.     

Treatment of head lice

We report two cases with complex partial and secondarily generalized seizures, both on oxcarbazepine and vigabatrin, with additional lamotrigine in one case. Both died in a manner resembling SUDEP, i.e. suddenly, unexpectedly, probably following a seizure with pulmonary oedema at autopsy. Both had SIADH. A number of drugs may cause SIADH, among them carbamazepine and oxcarbazepine. A search for SIADH in patients on carbamazepine and oxcarbazepine, and in cases of sudden death in epilepsy, is recommended.     

Increase in beta-galactosidase activity in a non-isothermal bioreactor utilizing immobilized cells of Kluyveromyces fragilis: fundamentals and applications

Heparin-induced thrombocytopenia is an increasingly common side effect associated with heparin usage. In the more severe manifestation of the syndrome, patients can develop thrombosis; a 10% mortality is associated with heparin induced thrombocytopenia. To date, the therapeutic options for patients with heparin-induced thrombocytopenia are limited. Glycoprotein IIb/IIIa inhibitors have been shown to block platelet aggregation induced by a wide variety of agonists. The ability of antibody and synthetic small molecule inhibitors of glycoprotein IIb/IIIa to block in vitro activation and aggregation of platelets in response to heparin-induced thrombocytopenia positive serum/heparin was examined using flow cytometry, platelet aggregometry, and luminescence aggregometry. Abciximab, YM 337, and SR 121566A were each found to inhibit platelet microparticle formation and P-selectin expression in whole blood, in response to heparin-induced thrombocytopenia positive serum/heparin. In a platelet rich plasma system, the platelet aggregation response was inhibited by all three agents. The IC50 for inhibition of heparin-induced thrombocytopenia positive serum/heparin induced platelet aggregation by SR 121566A was 18 nM, a concentration which was 4 to 8 fold lower than that observed for collagen and arachidonic acid induced aggregation. Adenosine triphosphate release from activated platelets, as measured by luminescence aggregometry, was concentration-dependently inhibited by SR 121566A. These results suggest that glycoprotein Ilb/IIIa inhibitors may be beneficial in the management of heparin-induced thrombocytopenia and warrant further investigation.     

Acute brucella sacroiliitis: clinical features

Chronic fatigue disorders are characterized by a subjectively defined group of symptoms such as chronic fatigue, mental confusion, exertional malaise, weight changes, and/or diffuse multi-joint pains. Significant clinical overlap exists between chronic fatigue disorders and the syndrome of serum inappropriate anti-diuretic hormone (SIADH). Both chronic fatigue disorders and SIADH are characterized by lethargy and mental confusion. Both disorders can be induced or exacerbated by viral illnesses, physical exertion, emotional stress and/or hypotension. Both can be treated with salt loading and glucocorticoids. Therefore, altered water metabolism resulting from inappropriate release and/or response to arginine vasopressin (AVP) is proposed as a pathophysiological basis of certain chronic fatigue disorders. Moreover, these data suggest that salt loading and/or direct inhibition of AVP may be an effective therapeutic approach in individuals with chronic fatigue disorders.     

Transgenic pigs expressing human CD59 and decay-accelerating factor produce an intrinsic barrier to complement-mediated damage

OBJECTIVE: The antenatal and intrapartum management of women with autoimmune thrombocytopenia is controversial. The current approach emphasizes an effort to identify maternal characteristics predictive of severe neonatal thrombocytopenia or to measure fetal platelet counts and perform cesarean section in patients considered to be at risk for neonatal intracranial hemorrhage. In the current study we review our experience with maternal autoimmune thrombocytopenia and neonatal outcome. STUDY DESIGN: Fifty-five pregnancies with autoimmune thrombocytopenia over a 10-year period in three major medical centers in San Diego, California, were evaluated. Maternal characteristics and neonatal outcomes were assessed and compared with those in other recent reports. Data were submitted to Fisher's exact (two-tailed), chi2, and Student t tests, with linear regression performed to analyze the association between variables. RESULTS: Maternal characteristics including platelet count, presence of antiplatelet antibody, antecedent history of autoimmune thrombocytopenia, and corticosteroid therapy were not predictive of severe neonatal thrombocytopenia. Maternal history of splenectomy was significantly correlated with fetal platelet counts <50 x 10(9)/L (odds ratio 5.63; 95% confidence interval 2.2 to 14.3). There were four neonates with severe neonatal thrombocytopenia (8%), and one who was delivered by cesarean section had intracranial hemorrhage. CONCLUSIONS: These findings, combined with others in the literature, confirm that severe neonatal thrombocytopenia is an infrequent complication of maternal autoimmune thrombocytopenia and is not reliably predicted by maternal characteristics. Intracranial hemorrhage is also a rare event and is not related to mode of delivery. Cesarean section should be reserved for obstetric indications only.     

A case of concomitant tuberculosis and sarcoidosis with mycobacterial DNA present in the sarcoid lesion

A 35-year-old Chinese woman initially presented with histologically and bacteriologically confirmed tuberculous lymphadenitis. She was also found to have thrombocytopenia, elevated serum alkaline phosphatase, and bilateral lung infiltrates. After 15 months of antituberculosis treatment, despite resolution of the cervical lymphadenopathy, she started to experience dyspnea. Chest radiograph appearance, thrombocyte count, and liver biochemistry had all deteriorated as well. Histologic findings from tissues obtained via transbronchial biopsy and open lung biopsy were consistent with sarcoidosis but also showed the presence of mycobacterial DNA by the polymerase chain reaction. She subsequently achieved a very good response clinically, radiographically, hematologically, and biochemically with 1-year of corticosteroid treatment for her sarcoidosis, and she remained relapse-free afterwards. The concomitant presence of tuberculosis and sarcoidosis in this patient together with the presence of mycobacterial DNA in the sarcoid lesion reiterate the possibility that mycobacteria or some of its components may be capable of inducing the immune response and the pathologic changes of sarcoidosis.     

Occurrence of papillary carcinoma in a hyperfunctioning thyroid nodule: report of a case and diagnostic considerations

HIV-infected patients commonly experience haematological disturbances including anemia, neutropenia or thrombocytopenia. Bone marrow failure may be caused by HIV itself, or by secondary involvement by opportunistic pathogens and malignancy. The need for multiple concomitant suppressive treatments may increase the risk of cytopenias. Strategy to reduce both anemia and neutropenia as well as to improve the haematological tolerance to myelotoxic agents have been developed by using haematological growth factors. So far, erythropoietin and granulocyte(macrophage) colony-stimulating factors have been successfully used in clinical trials including HIV-patients with either zidovudine-associated anemia or severe HIV or drug-induced neutropenia. However, according to the cost of these palliative approaches, there is a need for more reliable data showing that these growth factors could really have a major impact on the patient's compliance to therapy, reduction of hospitalization and infection rate and improvement of the overall survival.     

Prenatal treatment of alloimmune thrombocytopenia using high-dosage IgG

Alloimmunization of the mother against foetal alloantigens can cause neonatal alloimmune thrombocytopenia (NAITP). The recurrence rate is high (90%). The thrombocytopenia in subsequent children is often more severe. Most feared are intracranial haemorrhages (ICH). Current diagnostics indicate that ICH often occurs in utero or during labour. Postnatal therapy is therefore of limited value. We treated three women who had had earlier newborns with severe NAITP, in 5 subsequent pregnancies with weekly high dose intravenous IgG from week 30-34. Four newborns of two women had no thrombocytopenia at birth. Only in one child was the NAITP as severe as in the previous affected sibling. We conclude that antenatal therapy with weekly high dose intravenous IgG is safe and often effective. In utero transfusions are indicated only in exceptional cases.     

Morphological changes in paraboloid glycogen of the accessory cone of the chick retina by exposure to light (author''s transl)

We studied five patients in whom severe thrombocytopenia developed during intermittent intravenous heparin treatment of arterial and venous thrombosis. Platelet aggregation was demonstrated when heparin (0.5 U per milliliter) was incubated with the patients' citrated platelet-rich plasma or with normal platelet-rich plasma in the presence of the patients' serum. Antiplatelet antibody was not detected in the patient globulin fractions prepared from serum collected within one week after heparin withdrawal by use of the platelet factor 3 availability technic. When the studies were repeated with modifications to detect heparin-dependent antiplatelet antibodies, positive results were obtained in four of five patients. The data suggest that a casual relation, mediated by an immune mechanism, existed between heparin therapy and thrombocytopenia, and that this syndrome may occur more often than has previously.