Plasma atrial natriuretic hormone levels in patients with the syndrome of inappropriate antidiuretic hormone secretion

This study explored whether atrial natriuretic hormone (ANH) might be involved in the escape from salt and water retention that occurs in patients with the syndrome of inappropriate antidiuretic hormone secretion (SIADH). Sixteen patients with low serum Na+ concentrations [123 +/- 1 (+/- SE) mmol/L] were studied. Each patient excreted urine that was hyperosmolar (mean, 391 +/- 4 mosmol/kg) in relation to serum osmolality (mean, 258 +/- 4 mosmol/kg). Sodium excretion (81 +/- 20 mmol/L) also was inappropriate to the low serum Na+ level. The probable causes of SIADH were head trauma (4), pneumonia (5), lung cancer (3), and chlorpropamide therapy (4). In the nontumor patients, plasma and/or urinary vasopressin (AVP) concentrations were in the normal range, but inappropriate for serum osmolality. Urinary AVP values of 50 pg/mL or more (greater than 46 pmol/L) were found in the three tumor patients. The mean plasma ANH concentration was 6-fold higher than that in normal subjects [296 +/- 51 vs. 51 +/- 13 pg/mL (100 +/- 20 vs. 17 +/- 4 pmol/L); P less than 0.01]. Six SIADH patients were studied again after brief (1-3 days) water restriction. Although serum osmolality increased in each, their plasma AVP concentrations decreased very little, and urinary AVP excretion and plasma ANH did not change. These results indicate that plasma ANH levels are markedly increased in patients with SIADH. Their increased ANH secretion may antagonize water retention resulting from the inappropriate AVP secretion.     

Systematic evaluation of 8 arginine vasopressin and neurophysins plasma levels in 10 patients with oat cells carcinoma of the lung (author's transl)]

Plasma AVP level, neurophysins and osmolality have been measured in 10 patients with oat cell carcinoma of the lung but without any biological signs of syndrome of inappropriate secretion of ADH (SIADH), before and 15 mn after an intravenous injection of Ethanol. No statistically significant difference was noted in the AVP, neurophysins and osmolality values between 10 patients with asymptomatic oat cell carcinoma and control population (10 normal volunteers, 12 patients with non neoplasic lung pathology and 10 patients with different lung carcinoma). We concluded that AVP and neurophysins cannot be considered as a good tumoral marker in the detection of oat cell carcinoma of the lung.     

A case of syndrome of inappropriate secretion of antidiuretic hormone (SIADH) with low plasma concentrations of antidiuretic hormone.

A 66-year-old Japanese man presented with persistent hyponatremia without polydipsia and polyuria. Laboratory examination showed serum sodium of 117 mEq/l, plasma osmolality 239 mosm/kg, urine sodium 108 mEq/l, urine osmolality 577 mosm/kg, and normal levels (less than 2.0 pg/ml) of serum antidiuretic hormone (ADH). ADH release was regulated normally with changes in plasma osmolality. No obvious cause for the syndrome of inappropriate secretion of ADH (SIADH) could be detected. However, 20 months later, the patient had bouts of hematuria and was found to have cancer of the urinary bladder. Increased renal sensitivity to ADH was suspected as the underlying mechanism of SIADH.     

Syndrome of inappropriate secretion of antidiuretic hormone and thrombocytopenia caused by cytomegalovirus infection in a young immunocompetent woman

We report the first case of the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) associated with cytomegalovirus (CMV) infection. A 32-year-old woman was admitted to our hospital because of pandysautonomic signs and symptoms. Thrombocytopenia and hyponatremia were present. Serum anti-CMV IgM and IgG antibodies were positive. Despite hyponatremia, urinary osmolality exceeded plasma osmolality and plasma vasopressin levels related to plasma osmolality were high. Restriction of water intake and administration of dimethylchlorotetracycline improved hyponatremia, suggesting this patient had SIADH. In this patient, SIADH may have been caused by acute pandysautonomia that developed following CMV infection.     

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...     

Syndrome of Inappropriate Antidiuretic Hormone Secretion as the Initial Presentation in a Patient with Stage I Small-cell Lung Cancer

A 67-year-old man with a history of esophageal cancer resection was referred to our hospital because of nausea and appetite loss. Laboratory findings showed severe hyponatremia and were compatible with syndrome of inappropriate antidiuretic hormone (SIADH) secretion. Chest computed tomography (CT) revealed a nodule measuring 13 mm in the lower lobe of the right lung. Right thoracotomy was performed, and the histopathological diagnosis was small-cell lung cancer (T1bN0M0; Stage 1b). Although SIADH is frequently associated with small-cell lung cancer, it is extremely rare as the initial clinical feature in stage I small-cell lung cancer.     

Close association of urinary excretion of aquaporin-2 with appropriate and inappropriate arginine vasopressin-dependent antidiuresis in hyponatremia in elderly subjects

The present study was undertaken to determine whether urinary excretion of aquaporin-2 (AQP-2) participates in the involvement of arginine vasopressin (AVP) in hyponatremia less than 130 mmol/L in 33 elderly subjects (> or =65 yr old) during the last 5-yr period. Subjects were separated into euvolemic hyponatremia groups: 13 with hypopituitarism, 8 with syndrome of inappropriate secretion of antidiuretic hormone (SIADH), 8 with mineralocorticoid-responsive hyponatremia of the elderly, and 4 with miscellaneous diseases. Approximately 40% of those with hyponatremia was derived from hypopituitarism, but severe hyponatremia was found in the patients with SIADH and mineralocorticoid-responsive hyponatremia of the elderly. Plasma AVP levels remained relatively high despite hypoosmolality and were tightly linked with exaggerated urinary excretion of AQP-2 and antidiuresis in the 3 groups of patients, except for one miscellaneous one. An acute water load test verified the impairment in water excretion, because the percent excretion of the water load was less than 42% and the minimal urinary osmolality was not sufficiently diluted. Also, plasma AVP and urinary excretion of AQP-2 were not reduced after the water load. The inappropriate secretion of AVP was evident in the patients with SIADH and hypopituitarism, and hydrocortisone replacement normalized urinary excretion of AQP-2 and renal water excretion in those with hypopituitarism. In contrast, the appropriate antidiuresis seemed to compensate loss of body fluid in the patients with mineralocorticoid-responsive hyponatremia of the elderly, who lost circulatory blood volume by 7.3% (mean). Fludrocortisone acetate increased renal sodium handling and body fluid, resulting in the reduction in AVP release and urinary excretion of AQP-2 in mineralocorticoid-responsive hyponatremia of the elderly. These findings indicate that urinary excretion of AQP-2 may be a more sensitive measure of AVP effect on renal collecting duct cells than are plasma AVP levels, and that increased urinary excretion of AQP-2 shows exaggerated AVP-induced antidiuresis in hyponatremic subjects in the elderly. In addition, mineralocorticoid-responsive hyponatremia of the elderly has to be carefully differentiated from SIADH in elderly subjects.     

Syndrome of inappropriate secretion of antidiuretic hormone in brucellosis

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.     

Syndrome of inappropriate antidiuretic hormone secretion disclosing a sinonasal neuroendocrine carcinoma: case report

We report a 74-year-old woman with histologically confirmed neuroendocrine carcinoma of the nasal cavity disclosing a syndrome of inappropriate antidiuretic hormone secretion (SIADH). Since SIADH is a paraneoplastic syndrome commonly associated with small cell lung cancer, an extra-pulmonary localisation of neuroendocrine carcinoma has to be investigated.     

SIADH closely associated with non-functioning pituitary adenoma

We demonstrated severe hyponatremia in a 68 year-old man who had pituitary tumor. He had poor appetite and was disoriented. Tests revealed hyponatremia of 110 mmol/l, and he was admitted to Jichi Medical School Omiya Medical Center to undergo further tests. Physical findings revealed disturbance of consciousness with Japan Coma Scale I-2. There was neither dehydration nor edema. Laboratory data showed a serum sodium level of 112 mmol/l; plasma osmolality, 219 mmol/kg; and urinary osmolality, 555 mmol/kg. Plasma arginine vasopressin (AVP) level was 1.6 pmol/l despite the marked hypoosmolality. Anterior pituitary function was normal. Brain magnetic resonance imaging showed a pituitary tumor of 20 x 18 x 20 mm in size, which pushed the pituitary stalk upward. After the adenomectomy, serum sodium level was kept normal without any treatment. Histology showed basophilic adenoma. These findings indicate that local pituitary tumor may cause exaggerated secretion of AVP, resulting in the syndrome of inappropriate secretion of antidiuretic hormone (SIADH).     

Ewing's sarcoma as a cause of the syndrome of inappropriate secretion of antidiuretic hormone.

A patient with Ewing's sarcoma presented with the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) (1). Plasma values for vasopressin were found to be over four times the normal values expected for the plasma osmolality. At postmortem examination, the arginine vasopressin concentration in the tumor tissue was ten times that of the plasma. These data suggest that Ewing's sarcoma may cause SIADH.     

Imaging of the sella in the syndrome of inappropriate secretion of antidiuretic hormone

Abstract. Objective . The syndrome of inappropriate secretion of antidiuretic hormone (SIADH) results either from ectopic production or inappropriate release of antidiuretic hormone from the neurohypophysis. Although magnetic resonance imaging (MRI) has provided new insights into the morphological changes of the hypophysis in health and disease, no previous studies have evaluated its use in SIADH. The aim of this study was to evaluate the MRI appearance of the neurohypophysis in patients with SIADH. Design . Retrospective case-control study. Setting . Tertiary care teaching hospital. Subjects . We studied retrospectively eight patients with SIADH who had been hospitalized in Boston's Beth Israel between 1984 and 1994 and who had MRI scans including the sella turcica. We also evaluated prospectively the MRIs of the heads of 23 consecutive control patients who had no pituitary pathology and no serum osmolality or electrolyte abnormalities. Interventions . Clinical evaluation as well as sagittal and axial T1-MR images. Main outcome measures . Presence or absence of the high intensity signal of the neurohypophysis. Results . In seven out of eight patients (87.5%) the normal high intensity signal of the neurohypophysis was not present. In one patient (12.5%), two interpreting radiologists disagreed about its presence. The high intensity signal was present in the neurohypophysis of 20 out of 23 controls (87.5%). Conclusions . Our data indicate an association of SIADH with the absence of the normal hyperintense signal of the neurohypophysis, confirming the usefulness of MRI as a tool to visualize ADH processing. These data also raise the possibility that the absence of the high intensity signal may be a useful diagnostic tool in cases of SIADH that are difficult to diagnose clinically. Additional studies to correlate this signal with various forms of SIADH will be needed.     

Vasopressin V2 receptor antagonists

Hyponatremia, whether due to the syndrome of inappropriate antidiuretic hormone secretion (SIADH) or disorders of water retention such as congestive heart failure and cirrhosis, is a very common problem encountered in the care of medical patients. To date, available treatment modalities for disorders of excess arginine vasopressin (AVP) secretion or action have been limited and suboptimal. The recent discovery and development of nonpeptide AVP V(2) receptor antagonists represents a promising new treatment option to directly antagonize the effects of elevated plasma AVP concentrations at the level of the renal collecting ducts. By decreasing the water permeability of renal collecting tubules, excretion of retained water is promoted, thereby normalizing or improving hypo-osmolar hyponatremia. In this review, SIADH and other water retaining disorders are briefly discussed, after which the published preclinical and clinical studies of several nonpeptide AVP V(2) receptor antagonists are summarized. The likely therapeutic indications and potential complications of these compounds are also described.     

Severe hyponatremia caused by syndrome of inappropriate secretion of antidiuretic hormone developed as initial manifestation of human herpesvirus‐6–associated acute limbic encephalitis after unrelated bone marrow transplantation

Severe hyponatremia is a critical electrolyte abnormality in allogeneic stem cell transplantation (allo‐SCT) recipients and >50% of cases of severe hyponatremia are caused by the syndrome of inappropriate secretion of antidiuretic hormone (SIADH). Here, we present a patient with rapidly progressive severe hyponatremia as an initial sign and symptom of human herpesvirus‐6–associated post‐transplantation acute limbic encephalitis (HHV‐6 PALE) after allo‐SCT. A 45‐year‐old woman with acute lymphoblastic leukemia received unrelated bone marrow transplantation from a one locus‐mismatched donor at the DR locus. On day 21, she developed a generalized seizure and loss of consciousness with severe hyponatremia, elevated serum antidiuretic hormone (ADH), and decreased serum osmolality. A high titer of HHV‐6 DNA was detected in cerebrospinal fluid. Treatment with foscarnet sodium and hypertonic saline was started with improvement of neurological condition within several days. Although an elevated serum ADH, low serum osmolality, and high urinary osmolality persisted for 2 months, she had no other recurrent symptoms of encephalitis. Our experience suggests that hyponatremia accompanied by SIADH should be recognized as a prodromal or concomitant manifestation of HHV‐6 PALE, and close monitoring of serum sodium levels in high‐risk patients for HHV‐6 PALE is necessary for immediate diagnosis and treatment initiation.     

Vasopressin V2 receptor antagonists

Hyponatremia due to the syndrome of inappropriate antidiuretic hormone secretion (SIADH) and disorders of water retention such as congestive heart failure and cirrhosis is a common problem encountered in the care of the medical patient. Thus far, available treatment modalities for disorders of excess arginine vasopressin (AVP) secretion or action have been suboptimal. The development of nonpeptide AVP V2 receptor antagonists represents a promising treatment option to directly antagonize the effects of elevated plasma AVP concentrations by increasing the water permeability of renal collecting tubules, thereby promoting excretion of retained water and normalizing hypoosmolar hyponatremia. In this review, SIADH and other water retaining disorders are briefly discussed, after which the published preclinical and clinical studies in the development of several nonpeptide AVP V2 receptor antagonists are summarized. The likely therapeutic indications and potential complications of these compounds, as well as their vascular effects, are also described.     

Herpes zoster ophthalmicus and syndrome of inappropriate antidiuretic hormone secretion

The syndrome of inappropriate antidiuretic hormone (SIADH) secretion is a common consequence of neurologic and pulmonary infections as well as drug intake and many other clinical situations. This report describes SIADH that developed in an elderly woman with single dermatomal herpes varicella zoster ophthalmicus without evidence of varicella zoster encephalitis or dissemination. A 76-year-old woman was admitted to our department for evaluation of left facial pain, confusion and disorientation. Further investigation revealed hyponatremia 112 mEq/L, low serum osmolality, high urine osmolality, normal renal function, normal adrenal and thyroid hormones, and high plasma vasopressin 40 pg/mL. These results indicate that the hyponatremia in this case was due to SIADH and that SIADH was caused by an increased release of vasopressin probably because of the antiviral drug (acyclovir) or infection of varicella zoster virus (VZV) in a single dermatome.     

Syndrome of inappropriate secretion of antidiuretic hormone (SIADH) and adrenal insufficiency induced by rathke's cleft cyst: a case report

We report a case of a seventy-year-old woman with syndrome of inappropriate secretion of antidiuretic hormone (SIADH) and adrenal insufficiency induced by Rathke's cleft cyst. She experienced nausea, vomiting, diarrhea, and headache and disturbance of consciousness induced by hyponatremia at a serum sodium level of 100 mEq/l. In spite of severe hyponatremia, urinary sodium excretion was not suppressed and serum osmolality (270 mOsm/kg) was lower than urine osmolality (304 mOsm/kg), and arginine vasopressin (AVP) remained within normal range. SIADH was diagnosed because she was free from other diseases known to cause hyponatremia such as dehydration, cardiac dysfunction, liver dysfunction, renal dysfunction, hypothyroidism, and adrenal insufficiency. Cranial computed tomographic (CT) scan and cranial magnetic resonance (MR) imaging showed a cystic lesion of approximately 2 cm in diameter in the pituitary gland. These images suggested that the cystic lesion was a Rathke's cleft cyst, which was the cause of SIADH. Water restriction therapy normalized her serum sodium concentration and improved her symptoms. After one year, she suffered from general fatigue, appetite loss, fever, and body weight loss (5 kg/2 months). She had neither hypotension nor hypoglycemia, but her serum sodium level was low and serum cortisol, ACTH, and urine free cortisol were very low. Therefore, secondary adrenal insufficiency was suspected and diagnosed by stimulation tests. After start of hydrocortisone replacement therapy (10 mg/day), her symptoms disappeared. In conclusion, Rathke's cleft cyst should be kept in mind as a potential cause in a patient with SIADH, hypopituitarism, and/or adrenal insufficiency.     

Hypouricemia, inappropriate secretion of antidiuretic hormone, and small cell carcinoma of the lung

The hospital records of 106 patients with small cell carcinoma of the lung were reviewed to determine if hypouricemia accompanied hyponatremia (less than 130 mmole/L) and if coexistent hypouricemia and hyponatremia were predictive of the presence of the syndrome of inappropriate secretion of antidiuretic hormone (SIADH). Thirty-seven patients were excluded because of insufficient data or factors that would affect the uric acid level. Six of eight patients with SIADH had hypouricemia. The coexistence of hypouricemia and hyponatremia predicted SIADH reliably (6/6 patients), but hypouricemia alone had a low predictive value (46%) since it was seen in seven of 61 patients without SIADH.     

Hyponatremia and antidiuresis syndrome

Antidiuretic hormone (ADH), or arginine vasopressin (AVP), is primarily regulated through plasma osmolarity, as well as non-osmotic stimuli including blood volume and stress. Links between water-electrolyte and carbohydrate metabolism have also been recently demonstrated. AVP acts via the intermediary of three types of receptors: V1a, or V1, which exerts vasoconstrictive effects; pituitary gland V1b, or V3, which participates in the secretion of ACTH; and renal V2, which reduces the excretion of pure water by combining with water channels (aquaporin 2). Antidiuresis syndrome is a form of euvolaemic, hypoosmolar hyponatraemia, which is characterised by a negative free water clearance with inappropriate urine osmolality and intracellular hyper-hydration in the absence of renal, adrenal and thyroid insufficiency. Ninety percent of cases of antidiuresis syndrome occur in association with hypersecretion of vasopressin, while vasopressin is undetectable in 10% of cases. Thus the term “antidiuresis syndrome” is more appropriate than the classic name “syndrome of inappropriate ADH secretion” (SIADH). The clinical symptoms, morbidity and mortality of hyponatraemia are related to its severity, as well as to the rapidity of its onset and duration. Even in cases of moderate hyponatraemia that are considered asymptomatic, there is a very high risk of falls due to gait and attention disorders, as well as rhabdomyolysis, which increases the fracture risk. The aetiological diagnosis of hyponatraemia is based on the analysis of calculated or measured plasma osmolality (POsm), as well as blood volume (skin tenting of dehydration, oedema). Hyperglycaemia and hypertriglyceridaemia lead to hyper- and normoosmolar hyponatraemia, respectively. Salt loss of gastrointestinal, renal, cutaneous and sometimes cerebral origin is hypovolaemic, hypoosmolar hyponatraemia (skin tenting), whereas oedema is present with hypervolaemic, hypoosmolar hyponatraemia of heart failure, nephrotic syndrome and cirrhosis. Some endocrinopathies (glucocorticoid deficiency and hypothyroidism) are associated with euvolaemic, hypoosmolar hyponatraemia, which must be distinguished from SIADH. Independent of adrenal insufficiency, isolated hypoaldosteronism can also be accompanied by hypersecretion of vasopressin secondary to hypovolaemia, which responds to mineralocorticoid administration. The causes of SIADH are classic: neoplastic (notably small-cell lung cancer), iatrogenic (particularly psychoactive drugs, chemotherapy), lung and cerebral. Some causes have been recently described: familial hyponatraemia via X-linked recessive disease caused by an activating mutation of the vasopressin 2 receptor; and corticotropin insufficiency related to drug interference between some inhaled glucocorticoids and cytochrome p450 inhibitors, such as the antiretroviral drugs and itraconazole, etc. SIADH in marathon runners exposes them to a risk of hypotonic encephalopathy with fatal cerebral oedema. SIADH treatment is based on water restriction and demeclocycline. V2 receptor antagonists are still not marketed in France. These aquaretics seem effective clinically and biologically, without demonstrated improvement to date of mortality in eu- and hypervolaemic hyponatraemia. Obviously treatment of a corticotropic deficit, even subtle, should not be overlooked, as well as the introduction of fludrocortisone in isolated hypoaldosteronism and discontinuation of iatrogenic drugs.     

Lack of appropriate investigations in making a diagnosis of syndrome of inappropriate antidiuretic hormone

The syndrome of inappropriate antidiuretic hormone (SIADH) is reported as the most common cause of hyponatraemia. This retrospective cross‐sectional study evaluated the diagnosis of SIADH in 110 hospitalised patients in an Australian tertiary hospital with reference to recently published clinical guidelines. Investigation of SIADH was incomplete in all but 20% of cases. Adrenal insufficiency and hypothyroidism were not excluded in a significant number of cases.