Syndrome of inappropriate antidiuretic hormone release secondary to central nervous system coccidioidomycosis with vasculitis.

A man in his 60s presented to the clinic due to night sweats and weight loss following pneumonia. He was found to have hyponatraemia due to a syndrome of inappropriate antidiuretic hormone (SIADH). CT of the thorax was concerning for pulmonary nodules. He was ultimately diagnosed with pulmonary coccidioidomycosis (CM) and started on fluconazole 400 mg daily with improvement in symptoms. Due to the report of headaches, head MRI was conducted which suggested central nervous system (CNS) involvement. Cerebrospinal fluid analysis was consistent with CNS CM and head magnetic resonance angiography confirmed the presence of CNS vasculitis. Fluconazole dose was increased to 800 mg daily which the patient continued to tolerate and showed improvement. This report depicts a case of SIADH associated with CNS CM with vasculitis and demonstrates the importance of high clinical suspicion for SIADH secondary to CNS CM in the setting of hyponatraemia and headache.

[SIADH treatment: beyond fluid restriction]. / Traitement du SIADH : au-delà de la restriction hydrique.

Treatment of chronic hyponatremia due to secretion of anti-diuretic hormone (SIADH) is often more complicated than it seems. Although initial treatment with fluid restriction is well established, it has limitations and is often insufficient. These limitations can be overcome by different second-line treatments. In this article, we address the limits of fluid restriction and propose pragmatic management based on the urinary spot.

La prise en charge de l'hyponatrémie chronique due au syndrome de sécrétion inappropriée d'hormone antidiurétique (SIADH) s'avère souvent plus compliquée qu'il n'y paraît. Même si le traitement initial par restriction hydrique est bien établi, celui-ci présente des limitations et est souvent insuffisant. Ces limitations peuvent être surmontées par différents traitements de seconde ligne. Dans cet article, nous explorons les limites de la restriction hydrique et proposons une prise en charge pragmatique basée sur le spot urinaire.

The syndrome of inappropriate antidiuretic hormone associated with nasal and paranasal malignant tumors.

PURPOSE: To investigate the clinical characteristics of the syndrome of inappropriate antidiuretic hormone (SIADH) associated with nasal and paranasal malignant tumors. METHODS: Patients with locally advanced or recurrence/metastatic malignant tumors of the nasal and paranasal sinuses were included. The SIADH was diagnosed according to the diagnostic criteria. The clinical characteristics of SIADH patients were retrospectively analyzed. RESULTS: Six patients (6/188, 3.2%) met the diagnostic criteria of SIADH, including four olfactory neuroblastoma (4/26, 15.4%), one neuroendocrine carcinoma (1/9, 11.1%), and one squamous cell carcinoma (1/63, 1.6%). Five patients (83.3%) had severe hyponatremia; however, the hyponatremia could be improved by fluid restriction or tolvaptan. Three patients' SIADH were recovered during the chemotherapy and the other three were recovered after the surgery. CONCLUSION: The incidence of SIADH associated with nasal and paranasal malignant tumors is relatively more common in olfactory neuroblastoma and neuroendocrine carcinoma. The hyponatremia caused by SIADH may be corrected by fluid restriction or tolvaptan, and the SIADH may be recovered through anti-tumor therapy.

Tolvaptan for Treatment of Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH) in a Child with Corpus Callosum Agenesis.

Syndrome of inappropriate antidiuretic hormone secretion (SIADH) is one of the common causes of euvolemic hyponatremia (serum Na+ < 135 mEq/L) in hospitalized children. It is characterized by increased serum ADH, leading to water retention via its action on V2 receptors in the distal renal tubules. Various conditions such as pain, the postoperative state, drugs, central nervous system infections, tumors, malformations, and pneumonia can predispose a person to SIADH. The conventional treatment of SIADH includes fluid restriction and salt supplementation. Occasionally, this may fail to control hyponatremia, mandating pharmacological therapy. V2-receptor antagonists are an FDA-approved therapy for adults with euvolemic and hypervolemic hyponatremia. However, there is limited experience with their use in the pediatric population. Here, the authors present a girl with corpus callosum agenesis with severe symptomatic hyponatremia due to SIADH who was successfully managed with the V2-receptor antagonist tolvaptan.

Acid base homeostasis and serum bicarbonate concentration in syndrome of inappropriate anti-diuretic hormone secretion (SIADH) with hyponatremia.

The Syndrome of Inappropriate ADH secretion (SIADH) presents with excess ADH release caused by a range of conditions; including pneumonia, brain tumors, certain lung cancers, and diseases of the hypothalamus. It presents with significant reduction in both sodium and chloride concentrations in the blood. However, reports examining the acid base status indicate a normal serum bicarbonate concentration and systemic acid base homeostasis. The mechanisms for the absence of abnormalities in acid base homeostasis remain speculative. This mini review is highlighting the recent advances in renal molecular physiology to provide answers for the maintenance of acid base status and serum bicarbonate in a physiological range.

A retrospective study on tolvaptan prescription in clinical practice in patients with syndrome of inappropriate secretion of antidiuretic hormone (SIADH) using the Japanese claims database.

We aimed to survey the status of tolvaptan administration in routine clinical practice since the approval of a novel indication for treating syndrome of inappropriate secretion of antidiuretic hormone (SIADH) in Japan. Data from a population of 3,152 patients aged ≥18 years and diagnosed with SIADH between July 1, 2020 and June 30, 2021 were extracted from a Japanese database. Tolvaptan was administered to 586 patients while 2,566 patients were followed up without tolvaptan. In the tolvaptan-treated group, the standard initial doses were 3.75 mg and 7.5 mg in 290 (49.5%) and 250 (42.7%) patients, respectively. The dose was increased in 112 (38.6%) and 71 (28.4%) and decreased in 8 (2.8%) and 46 (18.4%) of patients with 3.75 and 7.5 mg initial doses, respectively. Of the total 586 SIADH patients treated with tolvaptan, serum sodium concentrations were analyzed in 60 patients. In both treatment groups of 3.75 and 7.5 mg initial doses, the serum sodium concentration was elevated from the second day of treatment and reached 135 mEq/L on the fourth day, which was maintained for 2 weeks. Rapid correction of hyponatremia (>10 mEq/L increase in serum sodium concentration over 1 day or >18 mEq/L increase over 2 days) occurred in 26.7% patients with a 7.5 mg initial dose (4 of 15 patients) but not in the patients with a 3.75 mg initial dose (n = 16), suggesting that an initial dose of 3.75 mg of tolvaptan may be a better choice for the safe and proper correction of hyponatremia.

[Reset osmostat syndrome - when hyponatremia become «a normal¼: diagnostics, case report].

Reset osmostat syndrome (ROS) is characterized by a change of normal plasma osmolality threshold (decrease or increase), which leads to chronic dysnatremia (hypo- or hypernatremia). We have described a clinical case of ROS and chronic hyponatremia in a patient with chordoid glioma of the III ventricle. It is known that the patient had previously been diagnosed with hyponatremia (131-134 mmol/l). She has not hypothyroidism and hypocorticism. There is normal filtration function of the kidneys was (CKD-EPI 91.7 ml/mi/1,73m2). Urine osmolality and sodium level were studied to exclude of concentration kidney function disorder. During first three days after removal of the tumor of the third ventricle (chordoid glioma, WHO Grade II), the sodium level decreased to 119 mmol/l. Repeated infusions of 200-300 ml hypertonic 3% sodium chloride solution, gluco- and mineralocorticoid therapy was ineffective, increasing plasma sodium levels by 2-3 mmol/l with the return to the initial level during 6-8 hours. Hypopituitary disorders did not develop after surgery. With further observation, the sodium level remained within 126-129 mmol/l for 6 months after surgery. The water load test make exclude the classic syndrome of inappropriate secretion of antidiuretic hormone, and confirmed the diagnosis of RSO. Because of absence of clinical symptoms associated with hyponatremia, no medical correction was required, patient was recommended to clinical follow-up.

Neuromyelitis optica spectrum disorder with herpes simplex viral infection presenting with syndrome of inappropriate antidiuretic hormone: A case report.

RATIONALE: Neuromyelitis optica spectrum disorder (NMOSD) is a demyelinating disease that causes lesions in areas with abundant aquaporin-4 (AQP4) channels, including the hypothalamus. Hypothalamic lesions can disrupt antidiuretic hormone regulation, resulting in hyponatremia due to syndrome of inappropriate antidiuretic hormone (SIADH). Various factors can trigger NMOSD, including viral infections. We report the case of a young female patient who presented with hyponatremia due to SIADH and was found to have bilateral hypothalamic lesions along with positive serum herpes simplex virus immunoglobulin M. PATIENT CONCERNS: An 18-year old female patient presented with fever and nausea that had persisted for 5 days. Three days after hospitalization, the patient complained of blurred vision, hiccups, and excessive daytime sleepiness. DIAGNOSIS: The patient hyponatremia was attributed to SIADH. Magnetic resonance imaging revealed bilateral lesions in the hypothalamus, and serum laboratory tests were positive for herpes simplex virus immunoglobulin M. On the 15th day of admission, the anti-AQP4 antibody test result was positive, leading to the diagnosis of NMOSD. INTERVENTIONS: On the initial suspicion of herpes encephalitis, treatment with acyclovir was initiated. However, upon the confirmation of after anti-AQP4 antibody, the patient was additionally treated with a high-dose intravenous steroid for 5 days. OUTCOMES: The patient fever, nausea, visual disturbances, and other complaints improved within 1 week of initiating steroid treatment. LESSONS: In young patients presenting with hyponatremia and suspected SIADH accompanied by neurological abnormalities, it is crucial to differentiate central nervous system diseases, including NMOSD, which can involve lesions in AQP4-abundant areas, such as the hypothalamus.

Pituitary Apoplexy-associated Cerebral Salt Wasting Syndrome: A Case Report and Literature Review.

PURPOSE: This is a case report of a patient experiencing hyponatremia who was ultimately diagnosed with pituitary apoplexy-associated cerebral salt wasting syndrome (CSWS). METHODS: Laboratory tests, clinical evaluations, and magnetic resonance imaging were performed by specialists. FINDINGS: The patient presented with severe headache, thirst, and polyuria. Results of laboratory tests indicated hyponatremia, decreased plasma osmolality, and elevated urine osmolality. Fluid restriction worsened the situation, and normal saline treatment helped return serum sodium and chloride levels to normal. Pituitary apoplexy-associated CSWS was finally considered. IMPLICATIONS: Pituitary apoplexy is a rare but reasonable etiology for CSWS with hyponatremia. Saline therapy is usually effective.

Syndrome of inappropriate antidiuretic hormone with recurrent giant cabergoline-resistant prolactinoma.

A macro pituitary tumour or giant pituitary tumour is regarded as a rare causal factor in syndrome of inappropriate antidiuretic hormone (SIADH) cases. Previous reports have presented findings showing that blood flow insufficiency related to stress caused by an obstructive mass may lead to inappropriate secretion of arginine vasopressin. On the other hand, prolactin is known to influence water metabolism, and several cases of a macroprolactinoma or giant prolactinoma (PRLoma) in patients with SIADH have been reported. Nevertheless, few studies have examined such a relationship with SIADH and discussion of pathophysiological factors has been limited. The present report provides details of an elderly patient with SIADH in a chronic giant PRLoma. Of note, exacerbation of prolactin level accompanied the occurrence of SIADH. Findings obtained in this case suggest the possibility of development of SIADH in PRLoma cases due to more than only the effect of the mass.

Effect of tolvaptan on hyponatremia in a dog with syndrome of inappropriate secretion of antidiuretic hormone.

A 1-year-old spayed female Miniature Schnauzer had chronic hyponatremia, accompanied by polyuria and polydipsia. Blood tests and urinalysis revealed severe hyponatremia, low plasma osmolality with euvolemia, and increased sodium excretion in urine. Hypothyroidism and hypoadrenocorticism were ruled out as causes. These findings led to the diagnosis of syndrome of inappropriate secretion of antidiuretic hormone (SIADH). Magnetic resonance imaging (MRI) showed dilation of the lateral ventricles, indicating severe hydrocephalus. Tolvaptan, a vasopressin V2 receptor antagonist commonly used in human SIADH, was administered along with water restriction. This treatment resulted in a consistent increase in plasma sodium levels without any adverse effects. This case report represents the first documented evidence of the therapeutic efficacy of tolvaptan in treating SIADH in a dog.

Inappropriate therapy of euvolemic hyponatremia, the most frequent type of hyponatremia in SARS-CoV-2 infection, is associated with increased mortality in COVID-19 patients.

Introduction: Admission hyponatremia, frequent in patients hospitalized for COVID-19, has been associated with increased mortality. However, although euvolemic hyponatremia secondary to the Syndrome of Inappropriate Antidiuresis (SIAD) is the single most common cause of hyponatremia in community-acquired pneumonia (CAP), a thorough and rigorous assessment of the volemia of hyponatremic COVID-19 subjects has yet to be described. We sought to identify factors contributing to mortality and hospital length-of-stay (LOS) in hospitalized COVID-19 patients admitted with hyponatremia, taking volemia into account. Method: Retrospective study of 247 patients admitted with COVID-19 to a tertiary hospital in Madrid, Spain from March 1st through March 30th, 2020, with a glycemia-corrected serum sodium level (SNa) < 135 mmol/L. Variables were collected at admission, at 2nd-3rd day of hospitalization, and ensuing days when hyponatremia persisted. Admission volemia (based on both physical and analytical parameters), therapy, and its adequacy as a function of volemia, were determined. Results: Age: 68 years [56-81]; 39.9% were female. Median admission SNa was 133 mmol/L [131- 134]. Hyponatremia was mild (SNa 131-134 mmol/L) in 188/247 (76%). Volemia was available in 208/247 patients; 57.2% were euvolemic and the rest (42.8%) hypovolemic. Hyponatremia was left untreated in 154/247 (62.3%) patients. Admission therapy was not concordant with volemia in 43/84 (51.2%). In fact, the majority of treated euvolemic patients received incorrect therapy with isotonic saline (37/41, 90.2%), whereas hypovolemics did not (p=0.001). The latter showed higher mortality rates than those receiving adequate or no therapy (36.7% vs. 19% respectively, p=0.023). The administration of isotonic saline to euvolemic hyponatremic subjects was independently associated with an elevation of in-hospital mortality (Odds Ratio: 3.877, 95%; Confidence Interval: 1.25-12.03). Conclusion: Hyponatremia in COVID-19 is predominantly euvolemic. Isotonic saline infusion therapy in euvolemic hyponatremic COVID-19 patients can lead to an increased mortality rate. Thus, an exhaustive and precise volemic assessment of the hyponatremic patient with CAP, particularly when due to COVID-19, is mandatory before instauration of therapy, even when hyponatremia is mild.

DOCK8 deficiency with hypereosinophilia and the syndrome of inappropriate antidiuretic hormone secretion during herpes infection.

BACKGROUND: Hyperimmunoglobulin E syndrome (HIES) due to dedicator of cytokinesis8 (DOCK8) deficiency may present in infancy and childhood with different clinical features involving recurrent infections, allergic dysregulation, and autoimmunity. CASE: In this report, we describe a patient who first presented with severe hypereosinophilia and went on to develop the syndrome of inappropriate antidiuretic hormone secretion (SIADH) in the context of a severe herpes infection. Investigation revealed the presence of underlying DOCK8 deficiency presenting with atypical clinical features. CONCLUSIONS: Distinct inflammatory features associated with infections may be seen in the course of primary immunodeficiency diseases, and early functional and molecular genetic tests will aid the proper management.

Long-term low-dose tolvaptan efficacy and safety in SIADH.

PURPOSE: Tolvaptan, a selective vasopressin V2-receptor antagonist, is approved for the treatment of SIADH-related hyponatremia, but its use is limited. The starting dose is usually 15 mg/day, but recent clinical experience suggests a lower starting dose (<15 mg/day) to reduce the risk of sodium overcorrection. However, long-term low-dose efficacy and safety has not been explored, so far. Aim of our study is to characterize safety and efficacy of long-term SIADH treatment with low-dose Tolvaptan. METHODS: We retrospectively evaluated 11 patients receiving low-dose Tolvaptan (<15 mg/day) for chronic SIADH due to neurological, idiopathic and neoplastic causes. Plasma sodium levels were measured before and 1, 3, 5, 15 and 30 days after starting Tolvaptan and then at 3-month intervals. Anamnestic and clinical data were collected. RESULTS: Mean time spanned 27.3 ± 29.8 months (range 6 months-7 years). Mean plasma sodium levels were within normal range 1, 3 and 6 months after starting Tolvaptan as well as after 1, 2, 3, 5 and 7 years of therapy. Neither osmotic demyelination syndrome nor overcorrection were observed. Plasma sodium levels normalization was associated with beneficial clinical effects. Neurological patients obtained seizures disappearance, improvement in neurological picture and good recovery from rehabilitation. Neoplastic patients were able to start chemotherapy and improved their general condition. Patients did not show hypernatremia during long-term follow-up and reported mild thirst and pollakiuria. CONCLUSIONS: The present study shows that long-term low-dose Tolvaptan is safe and effective in SIADH treatment. No cases of overcorrection were documented and mild side effects were reported.

Associations between neuromyelitis optica spectrum disorder, Sjögren's syndrome, and conditions with electrolyte disturbances.

OBJECTIVE: Electrolyte disorders are among the important conditions negatively affecting the disease course of neuromyelitis optica spectrum disorder (NMOSD). Possible mechanisms may include renal tubular acidosis (RTA) accompanying Sjögren's syndrome (SS), syndrome of inappropriate antidiuretic hormone secretion (SIADH), and central diabetes insipidus (DI). Currently, the overlap profiles between these conditions remain uncertain. METHODS: This cross-sectional study collected data from the nationwide administrative Diagnosis Procedure Combination (DPC) database and evaluated the overlap profiles. RESULTS: Among the 28,285,908 individuals from 1203 DPC-covered hospitals, 8477 had NMOSD, 174108 had SS, 4977 had RTA, 7640 had SIADH, and 24,789 had central DI. Of those with NMOSD, 986 (12%) had SS. The odds ratio (OR) for a diagnosis of NMOSD in those with SS compared with those without was 21 [95% confidence interval (CI), 20-23]. Overlap between NMOSD and SS was seen both in males (OR, 28 [95% CI, 23-33]) and females (OR, 16 [15-17]) and was more prominent in the younger population. Among patients with SS, the prevalence of RTA was lower in patients with NMOSD compared with those without NMOSD. Patients with NMOSD showed a higher prevalence of SIADH (OR, 11 [7.5-17]; p < 0.0001) and DI (OR, 3.7 [2.4-5.3]; p < 0.0001). Comorbid SS in NMOSD was associated with a higher prevalence of DI. CONCLUSIONS: Patients with NMOSD are likely to have SS, SIADH, and central DI. RTA in SS does not facilitate the overlap between NMOSD and SS. SS in NMOSD may predispose patients to DI.

Pearls & Oy-sters: Syndrome of Inappropriate Antidiuretic Hormone Secretion Presenting as Neuromyelitis Optica Spectrum Disorder Flare.

While it was previously believed that neuromyelitis optic spectrum disorder (NMOSD) mostly affected the optic nerves and the spinal cord, it is increasingly recognized that NMOSD can involve any area of the CNS where aquaporin-4 is highly expressed. These other areas can include the hypothalamus and the circumventricular organs that surround the third and fourth ventricles, serving as osmoregulators. The syndrome of inappropriate antidiuretic hormone secretion (SIADH) is one of the most common causes of hyponatremia and has been associated with NMOSD due to these lesions. In this report, we present a case of a patient with known NMOSD, who presented with dizziness, fatigue, and generalized weakness and whose workup revealed hyponatremia in the setting of SIADH and hypothalamic demyelinating lesions. This case illustrates an atypical presentation of NMOSD and the importance of looking for syndromes, such as SIADH. This can guide diagnostic testing, such as getting thin MRI cuts through the hypothalamus and brainstem, as well as advanced management techniques such as immunotherapy.

Relapsing Syndrome of Inappropriate Antidiuretic Hormone Production Responding to Tolvaptan Treatment in a Patient With a Micronodular Formation of the Posterior Pituitary Gland.

The syndrome of inappropriate ADH-secretion (SIADH) is a common cause of low sodium levels with diverse aetiology. Here, we report a case of a 41 years old male patient diagnosed with SIADH and a good response to Tolvaptan therapy. Of interest, as a potential unique cause, magnetic resonance imaging revealed a micronodular structure in the posterior pituitary, while no other common cause of SIADH could be identified. Hence, to the best of our knowledge, this is the first case of a Tolvaptan-responsive SIADH associated with a pituitary micronodular structure.