Syndrome of inappropriate secretion of antidiuretic hormone in patients with lymphoma-associated hemophagocytic syndrome

Summary 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 and tumor necrosis factor-, 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.     

不适当抗利尿激素分泌综合征的临床观察

目的 为了提高对少见疾病的认识和诊断，分析不适当抗利尿激素分泌综合征(SIADH)的临床和生化病理特点。方法 对本院12年来22例患者进行回顾性临床分析，总结了此病的一般性规律。结果 SIADH的病因多种多样，临床表现及体征不具特异性，易被临床医师所忽视。结论 提高对SIADH的认识是及早发现、及早治疗的关键。     

抗利尿激素分泌不适当综合征的不同诊断标准的比较研究

目的分析评价由经典、Smith、美国及欧洲建议的抗利尿激素分泌不适当综合征(SIADH)诊断标准的一致性。方法回顾性分析1990年1月至2010年10月解放军总医院收治依据经典标准诊断为SIADH的60例患者的临床资料,对另外3个标准用κ检验比较其一致性,并进行ROC曲线下面积比较。结果 (1)4个诊断标准在代谢紊乱组分中的比例,只有血浆渗透压差异存在统计学意义(P<0.05)。(2)欧洲与美国、欧洲与Smith、美国与Smith诊断标准两两之间的一致率分别为90%、83.33%、93.33%,Kappa值分别为0.58、0.43、0.8。(3)以经典标准为参照标准,欧洲、美国、Smith标准的Youden指数分别为0.917、0.817、0.75,绘制的ROC曲线下面积分别为0.958、0.908、0.875。结论 4个诊断标准的一致性较好,以经典标准为参照,欧洲标准对SIADH的诊断价值更高。     

Angiotropic B-cell lymphoma with hemophagocytic syndrome associated with syndrome of inappropriate secretion of antidiuretic hormone

 A case of angiotropic B-cell lymphoma associated with hemophagocytic syndrome (HPS) has been reported. In addition to fever, pancytopenia, hepatosplenomegaly, and lack of lymphadenopathy, unique clinical features, such as syndrome of inappropriate secretion of antidiuretic hormone (SIADH) and pulmonary infarction, were manifested. Both soluble interleukin-2 receptor (sIL-2R) and IL-6 were elevated in the patient's sera in addition to an increase of serum lactate dehydrogenase and ferritin. In contrast, tumor necrosis factor-α and interferon-γ were within normal ranges. Serum antibodies against Epstein-Barr virus and cytomegalovirus showed a past infection pattern. An autopsy examination revealed systemic intravascular proliferation of lymphoma cells with a B-cell phenotype, confirming the diagnosis of angiotropic B-cell lymphoma. Moreover, SIADH was suggested to result from the infiltration of tumor cells into the pituitary gland. Triple association of angiotropic B-cell lymphoma, HPS and SIADH is quite rare. Therefore, the present case seems to be helpful for clarifying the mechanism for HPS of non-Hodgkin's lymphoma with B-cell origin. Received: 22 June 1999 / Accepted: 25 February 2000     

提高抗利尿激素分泌异常综合征的诊治水平

抗利尿激素分泌异常综合征(SIADH)以稀释性低钠血症为主要表现,是住院患者等容量性低钠血症最常见的病因.SIADH的传统治疗包括限制液体入量、输注盐溶液及一些调节体液平衡的药物.由于各种原因,常规治疗的疗效欠佳.抗利尿激素受体拮抗剂是一种新型的药物,可以阻断抗利尿激素介导的受体活化,是针对SIADH的病因治疗.     

Syndrome of inappropriate secretion of antidiuretic hormone after endoscopic submucosal dissection for early gastric cancer

We report the first case of syndrome of inappropriate secretion of antidiuretic hormone (SIADH) after endoscopic submucosal dissection (ESD) for early gastric cancer. A 64-year-old man with early gastric cancer was admitted to our hospital for ESD. Baseline laboratory tests showed a serum sodium concentration of 132 mEq l⁻¹. We performed an ESD for the gastric cancer, which was 9 mm in diameter and located in the posterior wall of the mid-gastric body. The patient experienced nausea and lethargy the second day after ESD. His serum sodium level was low (118 mEq l⁻¹), and he fulfilled the criteria for SIADH. Fluid restriction, infusion of normal saline, and administration of diuretics gradually increased his serum sodium level, and his symptoms disappeared. Endoscopists should recognize that SIADH is a potential complication of endoscopic procedures such as ESD, especially among patients with low baseline sodium concentrations.     

A case report of syndrome of inappropriate secretion of antidiuretic hormone with marked edema due to administration of hypertonic saline

A 61-year-old man had hyponatremia (serum Na 112 mmol/L), which was associated with disturbance of consciousness. Therefore, administration of hypertonic saline was commenced. Eventually he was diagnosed with the syndrome of inappropriate secretion of antidiuretic hormone (SIADH). Hypertonic saline was continued for 45 days, and plasma Na concentration rose to 138 mmol/L. At that time we were consulted regarding further administration of hypertonic saline. At the time of the consultation marked edema had developed affecting the whole body. The cardiothoracic ratio was increased and pleural effusion was evident on the chest X-ray. Administration of hypertonic saline was discontinued to prevent further worsening of the edema. Furthermore, water restriction (500 mL/day) was started. Body weight decreased by 4.3 kg in 7 days and the edema was diminished. However, plasma Na concentration decreased to 117 mmol/L. At that stage, we needed to balance the treatment of hyponatremia to the increased extracellular fluid volume (ECF). To normalize the ECF, we carried out ultrafiltration (UF) three times. Resolution of edema by using an extracorporeal UF method allowed the control of plasma Na concentration. In this case increased ECF volume hindered the adjustment of plasma Na concentration. The infusion of hypertonic saline is now used commonly by physicians. It is necessary to consider the potential risks of such treatment.     

Rapid onset of syndrome of inappropriate antidiuretic hormone secretion induced by duloxetine in an elderly type 2 diabetic patient with painful diabetic neuropathy

Diabetic neuropathy is the most common diabetic complication. Duloxetine, a serotonin noradrenaline reuptake inhibitor (SNRI), is widely used for the treatment of diabetic painful neuropathy (DPN) because of the efficacy and safety profile. Syndrome of inappropriate antidiuretic hormone secretion, which is strongly associated duloxetine, is a rare but occasionally life‐threatening adverse effect. Here, we report a case of syndrome of inappropriate antidiuretic hormone secretion that rapidly developed after starting duloxetine in an elderly Japanese female type 2 diabetes mellitus patient. Furthermore, we discuss the possible relationship between the onset of syndrome of inappropriate antidiuretic hormone secretion and the gene polymorphism of cytochrome P450 isoform 1A2 and 2D6, both of which are responsible for duloxetine metabolism.     

Inappropriate secretion of antidiuretic hormone:a rare complication after common bile duct exploration

BACKGROUND:The syndrome of inappropriate secretion of antidiuretic hormone(SIADH)as a dilutional hyponatremia is due to a pathological increase of antidiuretic hormone(ADH).It is characterized by hyponatremia and decreased serum osmolarity as well as an increase in urinary osmolarity.The most common etiological factors of this syndrome include diseases or trauma of the central nervous system and malignant tumor or inflammation of the lung.SIADH following abdominal surgery is rare. METHODS:We report the case...     

支气管肺类癌所致抗利尿激素分泌不适当综合征(附一例报道)

目的为了提高对罕见病例的诊断水平,本文分析了支气管肺类癌致抗利尿激素分泌不适当综合症（ＳＩＡＤＨ）的临床和病理特点。方法讨论一例患者的诊断过程及术中分别抽取进入肿瘤的动、静脉血查ＡＤＨ水平,结果明显高于正常,术后病理诊断为支气管肺非典型类癌,使用多克隆ＡＤＨ抗体对肿瘤组织行免疫组织化学染色阳性。结果支气管肺非典型类癌异位分泌ＡＤＨ导致ＳＩＡＤＨ。结论支气管肺非典型类癌是不同于燕麦细胞癌等的另一种能导致ＳＩＡＤＨ的肺部肿瘤     

Syndrome of inappropriate secretion of antidiuretic hormone associated with multiple sclerosis.

A 63-year-old man who developed episodes of the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) twice in the course of multiple sclerosis (MS) is reported. SIADH in this patient occurred only during the administration of antibiotics (sulbactam/cefoperazone, SBT/CPZ). At autopsy, demyelinating lesions in the optic nerves, cervical and thoracic spinal cord, and areas adjacent to the lateral ventricles were observed. Destruction and loss of neuronal cells were found in the supraoptic nuclei. Lymphocytic infiltration was observed in the area adjacent to the supraoptic nuclei. Destruction and swelling of axons and reactive astrocytic gliosis were observed in the hypothalamus. SIADH associated with MS is rare and the histological findings in such a case have not yet been reported. It is suggested that the development of SIADH in MS may be related to the damage in the supraoptic nuclei of the hypothalamus.     

Renal function in amyotrophic lateral sclerosis patients on long-term treatment with edaravone

Edaravone, a free radical-scavenger, was approved in Japan for the treatment of amyotrophic lateral sclerosis (ALS). However, the effect of the drug on renal function in ALS patients remains unclear. This study aimed to investigate renal function in ALS patients on long-term treatment with edaravone by measuring the serum estimated glomerular filtration rate based on cystatin C (eGFR-CysC).In a retrospective study, the data of ALS patients who were treated with over 10 cycles of intravenous edaravone treatment and were evaluated by eGFR-CysC before and after 10 cycles of treatment between July 2015 and June 2018 were analyzed. Then, the results were compared with those of a control ALS group that had never been treated with edaravone.There were 11 patients with ALS who received over 10 cycles of intravenous edaravone treatment. The mean interval between the first and final eGFR-CysC measurements was 18.7 ± 7.9 months. Three patients (27.3%) had >20 mL/min/1.73 m² decrease in serum eGFR-CysC. However, no patients discontinued edaravone treatment because of renal dysfunction. The average variation rate of eGFR-CysC was not different between the long-term edaravone group (0.29 ± 1.07) and the control group (–0.34 ± 0.40).This retrospective, single-center analysis showed no clinical exacerbation of renal function in ALS patients who received long-term treatment with edaravone.     

Optineurin and amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis is a devastating disease, and thus it is important to identify the causative gene and resolve the mechanism of the disease. We identified optineurin as a causative gene for amyotrophic lateral sclerosis. We found three types of mutations: a homozygous deletion of exon 5, a homozygous Q398X nonsense mutation and a heterozygous E478G missense mutation within its ubiquitin‐binding domain. Optineurin negatively regulates the tumor necrosis factor‐α‐induced activation of nuclear factor kappa B. Nonsense and missense mutations abolished this function. Mutations related to amyotrophic lateral sclerosis also negated the inhibition of interferon regulatory factor‐3. The missense mutation showed a cyotoplasmic distribution different from that of the wild type. There are no specific clinical symptoms related to optineurin. However, severe brain atrophy was detected in patients with homozygous deletion. Neuropathologically, an E478G patient showed transactive response DNA‐binding protein of 43 kDa‐positive neuronal intracytoplasmic inclusions in the spinal and medullary motor neurons. Furthermore, Golgi fragmentation was identified in 73% of this patient's anterior horn cells. In addition, optineurin is colocalized with fused in sarcoma in the basophilic inclusions of amyotrophic lateral sclerosis with fused in sarcoma mutations, and in basophilic inclusion body disease. These findings strongly suggest that optineurin is involved in the pathogenesis of amyotrophic lateral sclerosis. Geriatr Gerontol Int 2013; 13: 528–532.     

Ultrasonographic evaluation of the diaphragm in patients with amyotrophic lateral sclerosis

Real-time diaphragmatic movement was evaluated with ultrasonography in three patients with amyotrophic lateral sclerosis (ALS). The initial complaint of two patients was weakness of the extremities followed by dyspnoea later in the disease course, while the third patient had dyspnoea as the initial symptom. Ultrasonographic analyses revealed that the contractile function of the diaphragm was not maintained during maximum inspiratory effort, with unsatisfactory diaphragmatic excursion and no change in diaphragmatic thickness during respiration, indicating diaphragmatic paralysis. Ultrasonography may be useful for the diagnosis and follow up of diaphragmatic involvement with amyotrophic lateral sclerosis and other motor-neuron diseases.     

Syndrome of inappropriate secretion of thyroid-stimulating hormone in a subject with galactorrhea and menstrual disorder and undergoing infertility treatment: Case report

Rationale:Syndrome of inappropriate secretion of thyroid-stimulating hormone (SITSH) is a rare cause of hyperthyroidism. Thyroid-stimulating hormone (TSH) levels are usually normal or high, and triiodothyronine (FT₃) and free thyroxine (FT₄) levels are usually high in subjects with SITSH.Patient concern:A 37-year-old woman had experienced galactorrhea and menstrual disorder for a couple of years before. She had undergone infertility treatment in 1 year before, hyperthyroidism was detected and she was referred to our institution.Diagnosis:She was suspected of having SITSH and was hospitalized at our institution for further examination. The data on admission were as follows: FT₃, 4.62 pg/mL; FT₄, 1.86 ng/dL; TSH, 2.55 μIU/mL. Although both FT₃ and FT₄ levels were high, TSH levels were not suppressed, which is compatible with SITSH. In addition, in brain contrast-enhanced magnetic resonance imaging, nodular lesions were observed in the pituitary gland with a diameter of approximately 10 mm. In the thyrotropin-releasing hormone load test, TSH did not increase at all, which was also compatible with TSH-secreting pituitary adenoma. In the octreotide load test, the TSH levels were suppressed. Based on these findings, we diagnosed this subject as SITSH.Interventions:Hardy surgery was performed after the final diagnosis. In TSH staining of the resected pituitary adenoma, many TSH-producing cells were observed. These findings further confirmed the diagnosis of pituitary adenoma producing TSH.Outcomes:Approximately 2 months after the operation, TSH, FT₃, and FT₄ levels were normalized. Approximately 3 months after the operation, she became pregnant without any difficulty.Lessons:We should consider the possibility of SITSH in subjects with galactorrhea, menstrual disorders, or infertility. In addition, we should recognize that it is very important to repeatedly examine thyroid function in subjects with galactorrhea, menstrual disorder, or infertility.     

肌萎缩侧索硬化患者体内氧化压力的定量分析

目的检测肌萎缩侧索硬化(ALS)患者尿液中8-异前列腺素F_(2a)(8-iso-PGF_(2a))浓度和LDL体外氧化延迟时间的变化,评价ALS患者体内的氧化压力及抗氧化能力情况。方法根据EL Escorial诊断标准选择ALS患者19例为ALS组,同时选择年龄、影响因素相匹配的健康成年男性19例为对照组。通过铜氧化共轭双烯法检测LDL体外氧化延迟时间,酶联免疫吸附法检测尿液中8-iso-PGF_(2a)浓度。结果与对照组比较,ALS组尿液中8-iso-PGF_(2a)浓度虽有升高趋势[(48.28±4.78)ng/mmol肌酐vs(47.25±2.32)ng/mmol肌酐],但差异无统计学意义(P>0.05),而LDL体外氧化延迟时间明显缩短[(59.32±8.65)min vs(83.16±8.37)min],差异有统计学意义(P<0.01)。结论增高的氧化压力与降低的抗氧化能力在ALS的发病机制中具有一定作用。提示有效的抗氧化治疗可能对控制ALS的发展及改善预后有一定的临床意义。     

Amyotrophic lateral sclerosis associated with the syndrome of inappropriate secretion of antidiuretic hormone.

A 71-year-old female with amyotrophic lateral sclerosis (ALS) developed the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) during respiratory failure due to atrophy of the respiratory muscles. Serum sodium concentration fell to 116 mEq/l and then returned to the normal range after water restriction and respiratory care. This is considered to be the first case report of ALS associated with SIADH.     

Syndrome of inappropriate antidiuretic hormone secretion (SIADH) and enalapril

Abstract. A 69-year-old woman with a history of diabetes and hypertension, was referred to the Hospital of Laredo because of hyponatraemia. She had weakness and slight dyspnoea with no evidence of extracellular fluid volume depletion or oedema. Serum sodium level on admission was 125 mol l^?1, plasma osmolality 270 mosmol kg^?1, simultaneous urine osmolality was 580 mosmol kg^?1 and urine sodium 32.6 mmol l^?1. She had been treated with enalapril (20 mg) daily for 4 months. She was diagnosed with the Syndrome of inappropriate secretion of antidiuretic hormone (SIADH) that was reversed after cessation of treatment with enalapril and reappeared on reintroduction of the drug at the same daily doses.     

Syndrome of inappropriate secretion of antidiuretic hormone associated with strongyloidiasis

We report a case of syndrome of inappropriate secretion of antidiuretic hormone (SIADH) with accompanying severe strongyloidiasis in a 52-year-old male. On admission, he showed drowsiness and emaciation with severe hyponatremia. We gave sodium (saline or salts) in an i.v. drip infusion and orally without improvement. A urinalysis and plasma osmotic pressure test indicated SIADH, therefore, treatment was changed to restrict his sodium intake. The hyponatremia gradually improved initially, but the appetite loss, nausea, and hyponatremia continued. Endoscopy revealed white patches on the stomach wall and histopathological examination revealed infestation of the mucosal epithelium with numerous Strongyloides stercoralis larvae. Ivermectin treatment was then initiated and the abdominal symptoms and hyponatremia gradually resolved. We carefully investigated the underlying cause of the SIADH, such as disease of the central nervous system, lung cancer, and other malignancies, but no abnormality or clear cause could be found. We concluded that the patient developed SIADH secondary to severe S. stercoralis infection.     

Relationship between statins and the risk of amyotrophic lateral sclerosis: A PRISMA-compliant meta-analysis

Objective:Previous studies on overlapping surveillance databases have suggested that statin use was associated with the development of amyotrophic lateral sclerosis (ALS)-like syndrome. However, the association between statin use and ALS incidence has not been clearly elucidated. To further explore this issue, we performed a systemic review and meta-analysis of all available clinical studies on the association between statin use and ALS incidence.Methods:A comprehensive database search on PubMed, Embase, Cochrane Library, and SCOPUS was conducted. We included studies up to January 31, 2020 that fulfilled our inclusion and exclusion criteria. Statin use between the ALS and control groups was collected for the meta-analysis.Results:Three case-control studies and 1 cohort study, that related the risk of ALS to statin use, satisfied the inclusion criteria for the meta-analysis. There was no statistically significant difference in statin use between the ALS and control groups (odds ratio, 0.75 [95% confidence interval, 0.53–1.08]).Conclusion:No definite association was found between statin use and the development of ALS. Further large-scale prospective randomized control studies are necessary to draw definite conclusions.