demeclocycline and Inappropriate-ADH-Syndrome

Hyponatraemia (HN) is the most common electrolyte balance disorder in clinical practice. Since the 1970s, demeclocycline has been used in some countries to treat chronic HN secondary to syndrome of inappropriate antidiuretic hormone secretion (SIADH). The precise mechanism of action of demeclocycline is unclear, but has been linked to the induction of nephrogenic diabetes insipidus. Furthermore, the safety profile of demeclocycline is variable with an inconsistent time to onset, and a potential for complications. There has been no systematic evaluation of the use of demeclocycline for the treatment of HN secondary to SIADH to date. A systematic literature review was performed to obtain an insight into the clinical safety and efficacy of demeclocycline for this condition.. Embase(™) , MEDLINE(®) , MEDLINE(®) In-Process, and The Cochrane Library were searched on two occasions using MeSH terms combined with free-text terms. References were screened by two independent reviewers. Relevant publications were then extracted by two independent reviewers, with a third reviewer collating and finalising extractions.. The searches returned a total of 705 hits. 632 abstracts were screened after the removal of duplicates. Following screening, 35 full-length publications were reviewed. Of these, 17 were excluded, resulting in 18 studies deemed relevant for data extraction. Two were randomised controlled trials (RCTs), 16 were non-RCTs, and 10 were case reports.. Although most reports suggest that demeclocycline can address serum sodium levels in specific patients with HN, efficacy is variable, and may depend upon the underlying aetiology. Demeclocycline dose adjustments can be complex, and as its use in clinical practice is not well defined, it can differ between healthcare professionals.. There is a lack of clinical and economic evidence supporting the use of demeclocycline for HN secondary to SIADH. Patients receiving demeclocycline for HN secondary to SIADH must be closely monitored.

Topics: Demeclocycline; Humans; Hyponatremia; Inappropriate ADH Syndrome

Hyponatremia is the most frequent electrolyte disorder in hospitalized patients. Acute and severe hyponatremia can be a life-threatening condition, but recent evidence indicates that also mild and chronic hyponatremia is associated with neurological and extra-neurological signs, such as gait disturbances, attention deficits, falls and fracture occurrence, and bone loss. The syndrome of inappropriate ADH secretion (SIADH) is the most frequent cause of hyponatremia. Hyponatremia secondary to SIADH may result for instance from ectopic release of ADH in lung cancer, from diseases affecting the central nervous system, from pneumonia or other pneumopathies or as a side-effect of various drugs In SIADH, hyponatremia results from a pure disorder of water handling by the kidney, whereas external sodium balance is usually well regulated. Despite increased total body water, only minor changes of urine output and modest oedema are usually seen. Neurological impairment may range from subclinical to life-threatening, depending on the degree and mostly on the rate of serum sodium reduction. The management of hyponatremia secondary to SIADH is largely dependent on the symptomatology of the patient. This review briefly summarizes the main aspects related to hyponatremia and then discusses the available treatment options for the management of SIADH, including vaptans, which are vasopressin receptor antagonists targeted for the correction of euvolemic hyponatremia, such as that observed in SIADH.

Topics: Antidiuretic Hormone Receptor Antagonists; Benzazepines; Blood Volume; Body Water; Chemical and Drug Induced Liver Injury; Clinical Trials as Topic; Demeclocycline; Diabetes Insipidus, Nephrogenic; Disease Management; Drug Interactions; Hospitalization; Humans; Hydrocortisone; Hyponatremia; Hypothyroidism; Inappropriate ADH Syndrome; Kidney Tubules, Collecting; Lithium; Multicenter Studies as Topic; Osmolar Concentration; Paraneoplastic Syndromes; Saline Solution, Hypertonic; Tolvaptan

The vaptans are non-peptide arginine-vasopressin-receptor antagonists, that are orally and intravenously active. A few vaptans have undergone sufficient clinical development to be on the market. In the EU only tolvaptan is accepted to treat hyponatremia related to SIADH. The place of this new treatment is compared with water restriction, demeclocyclin, furosemide and urea.

Topics: Anti-Bacterial Agents; Antidiuretic Hormone Receptor Antagonists; Antipsychotic Agents; Benzazepines; Demeclocycline; Hormone Antagonists; Humans; Inappropriate ADH Syndrome; Lithium; Models, Biological; Tolvaptan

Disorders of sodium [Na+] and water metabolism are commonly encountered in the hospital setting due to the wide range of disease states that can disrupt the balanced control of water and solute intake and output. In particular, the prompt identification and appropriate management of abnormally low serum [Na+] is critical if we are to reduce the increased morbidity and mortality that accompany hyponatremia in hospitalized patients. Use of an algorithm that is based primarily on the symptomatology of hyponatremic patients, rather than the serum [Na+] or the chronicity of the hyponatremia, will help to choose the correct initial therapy in hospitalized hyponatremic patients. However, careful monitoring of serum [Na+] responses is required in all cases to adjust therapy appropriately in response to changing clinical conditions. Although this approach will enable efficacious and safe treatment of hyponatremic patients with syndrome of inappropriate antidiuretic hormone secretion (SIADH) at the present time, evolving knowledge of the consequences of chronic hyponatremia will likely alter treatment indications and guidelines in the future.

Topics: Algorithms; Antidiuretic Hormone Receptor Antagonists; Arginine Vasopressin; Consciousness Disorders; Demeclocycline; Disease Management; Diuresis; Extracellular Fluid; HIV Infections; Humans; Hyponatremia; Iatrogenic Disease; Inappropriate ADH Syndrome; Inpatients; Mineralocorticoids; Natriuresis; Neoplasms; Osmolar Concentration; Pneumonia; Saline Solution, Hypertonic

Etiopathogenesis, diagnostics and therapy of hyponatremias are summarized for clinicians. Hyponatremia is the most common electrolyte abnormality. Mild to moderate hyponatremia and severe hyponatremia are found in 15-30% and 1-4% of hospitalized patients, respectively. Pathophysiologically, hyponatremias are classified into two groups: hyponatremia due to non-osmotic hypersecretion of vasopressin (hypovolemic, hypervolemic, euvolemic) and hyponatremia of non-hypervasopressinemic origin (pseudohyponatremia, water intoxication, cerebral salt wasting syndrome). Patients with mild hyponatremia are almost always asymptomatic. Severe hyponatremia is usually associated with central nervous system symptoms and can be life-threatening. Diagnostic evaluation of patients with hyponatremia is directed toward identifying the extracellular fluid volume status, the neurological symptoms and signs, the severity and duration of hyponatremia, the rate at which hyponatremia developed. The first step to determine the probable cause of hyponatremia is the differentiation of the hypervasopressinemic and non-hypervasopressinemic hyponatremias with measurement of plasma osmolality, glucose, lipids and proteins. For further differential diagnosis of hyponatremia, the determination of urine osmolality, the clinical assessment of extracellular fluid volume status and the measurement of urine sodium concentration provide important information. The most important representative of euvolemic hyponatremias is SIADH. The diagnosis of SIADH is based on the exclusion of other hyponatremic conditions; low plasma osmolality (<275 mosmol/kg) and inappropriate urine concentration (urine osmolality >100 mosmol/kg) are of pathognomic value. Acute (<48 hrs) severe hyponatremia (<120 mmol/l) necessitates emergency care with rapid restoration of normal osmotic milieu (1 mmol/l/hr increase rate of serum sodium). Patients with chronic symptomatic hyponatremia have a high risk of osmotic demyelination syndrome in brain if rapid correction of the plasma sodium occurs (maximal rate of correction of serum sodium should be 0.5 mmol/l/hr or less). The conventional treatments for chronic asymptomatic hyponatremia (except hypovolemic patients) include water restriction and/or the use of demeclocycline or lithium or furosemide and salt supplementation. Vasopressin receptor antagonists have opened a new forthcoming therapeutic era. V2 receptor antagonists, such as lixivaptan, tolvaptan, satavaptan and the V2+

Topics: Antidiuretic Hormone Receptor Antagonists; Azepines; Benzamides; Benzazepines; Blood Volume; Brain Diseases; Central Nervous System; Chronic Disease; Demeclocycline; Demyelinating Diseases; Diagnosis, Differential; Diuretics; Extracellular Fluid; Furosemide; Humans; Hyponatremia; Inappropriate ADH Syndrome; Lithium Compounds; Morpholines; Osmolar Concentration; Osmosis; Pyrroles; Severity of Illness Index; Sodium; Spiro Compounds; Time Factors; Tolvaptan; Vasopressins

The etiology, pathophysiology, clinical features, diagnosis, and medical treatment of the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) are reviewed. SIADH is a common cause of hyponatremia in hospitalized patients. Increased concentrations of antidiuretic hormone (ADH) result in retention of free water, increased excretion of sodium, and hyponatremia. Symptoms generally occur only when hyponatremia is severe (less than or equal to 125 meq/L) and may include anorexia, vomiting, and confusion, followed by seizures, coma, and death. SIADH may result from a variety of diseases, as well as from the use of drugs such as chlorpropamide, carbamazepine, diuretics, and some antineoplastic agents. Diagnosis of SIADH is confirmed by demonstration of a high urine osmolality with a low plasma osmolality, in the absence of diuretic use. Immediate treatment of the symptomatic patient with SIADH includes intravenous furosemide and 3% sodium chloride injection to produce a negative free-water balance. If the underlying cause of SIADH cannot be corrected, the treatment of choice for chronic SIADH is fluid restriction. If this is not tolerated by the patient, demeclocycline can be used to induce a negative free-water balance. Urea, lithium, phenytoin, and loop diuretics have been reported to be effective, but there are few data to support their use. Future research into the treatment of SIADH must be directed at developing effective antagonists of ADH. Treatment of SIADH consists of elimination of underlying causes and restriction of fluid intake; if these measures are unsuccessful or poorly tolerated, long-term drug therapy may be indicated.

Topics: Demeclocycline; Drug-Related Side Effects and Adverse Reactions; Humans; Hyponatremia; Inappropriate ADH Syndrome; Lithium; Urea

Topics: Demeclocycline; Humans; Hypothyroidism; Inappropriate ADH Syndrome; Lithium; Neoplasms; Osmolar Concentration; Vasopressins

The syndrome of inappropriate antidiuresis is often undertreated with most patients discharged with persistent hyponatraemia. This study tested the hypothesis that an endocrine input is superior to routine care in correcting hyponatraemia and can improve patient outcomes.. This single-centre prospective-controlled intervention study included inpatients admitted at a UK teaching hospital, with serum sodium ≤ 127 mmol/l, due to syndrome of inappropriate antidiuresis over a 6-month period. The prospective intervention group (18 subjects with mean serum sodium 120.7 mmol/l) received prompt endocrine input, while the historical control group (23 patients with mean serum sodium 124.1 mmol/l) received routine care. The time needed for serum sodium increase ≥ 5 mmol/l was the primary endpoint.. The intervention group achieved serum sodium rise by ≥5 mmol/l in 3.5 vs. 7.1 days in the control group (P = 0.005). In the intervention group, the mean total serum sodium increase was 12 mmol/l with only 5.8 % of patients discharged with serum sodium < 130 vs. 6.3 mmol/l increase (P < 0.001) and 42.1 % of the subjects discharged with serum sodium < 130 mmol/l in the control group (P = 0.012). The mean length of hospital stay in the intervention group (10.9 days) was significantly shorter than in the control group (14.5 days; P = 0.004).The inpatient mortality rate was 5.5 % in intervention arm vs. 17.4 % in control arm, but this difference was not statistically significant.. Since the endocrine input improved time for correction of hyponatraemia and shortened length of hospitalisation, widespread provision of endocrine input should be considered.

Topics: Aged; Aged, 80 and over; Antidiuretic Hormone Receptor Antagonists; Benzazepines; Demeclocycline; Female; Humans; Inappropriate ADH Syndrome; Male; Middle Aged; Prospective Studies; Retrospective Studies; Saline Solution, Hypertonic; Sodium; Tolvaptan; Treatment Outcome

Hyponatraemia is a very common medical condition that is associated with multiple poor clinical outcomes and is often managed suboptimally because of inadequate assessment and investigation. Previously published guidelines for its management are often complex and impractical to follow in a hospital environment, where patients may present to divergent specialists, as well as to generalists.. A group of senior, experienced UK clinicians, met to develop a practical algorithm for the assessment and management of hyponatraemia in a hospital setting. The latest evidence was discussed and reviewed in the light of current clinical practicalities to ensure an up-to-date perspective. An algorithm was largely developed following consensus opinion, followed up with subsequent additions and amendments that were agreed by all authors during several rounds of review.. We present a practical algorithm which includes a breakdown of the best methods to evaluate volume status, simple assessments for the diagnosis of the various causes and a straightforward approach to treatment to minimise complexity and maximise patient safety.. The algorithm we have developed reflects the best available evidence and extensive clinical experience and provides practical, useable guidance to improve patient care.

Topics: Algorithms; Anti-Bacterial Agents; Antidiuretic Hormone Receptor Antagonists; Benzazepines; Demeclocycline; Fluid Therapy; Hospitalization; Humans; Hyponatremia; Inappropriate ADH Syndrome; Practice Guidelines as Topic; Tolvaptan; Water-Electrolyte Imbalance

Topics: Algorithms; Anti-Bacterial Agents; Antidiuretic Hormone Receptor Antagonists; Benzazepines; Demeclocycline; Fluid Therapy; Humans; Hyponatremia; Inappropriate ADH Syndrome

Topics: Algorithms; Anti-Bacterial Agents; Antidiuretic Hormone Receptor Antagonists; Benzazepines; Demeclocycline; Fluid Therapy; Humans; Hyponatremia; Inappropriate ADH Syndrome

Binding of vasopressin to its type 2 receptor in renal collecting ducts induces cAMP signaling, transcription and translocation of aquaporin (AQP)2 water channels to the plasma membrane, and water reabsorption from the prourine. Demeclocycline is currently used to treat hyponatremia in patients with the syndrome of inappropriate antidiuretic hormone secretion (SIADH). Demeclocycline's mechanism of action, which is poorly understood, is studied here. In mouse cortical collecting duct (mpkCCD) cells, which exhibit deamino-8-D-arginine vasopressin (dDAVP)-dependent expression of endogenous AQP2, demeclocycline decreased AQP2 abundance and gene transcription but not its protein stability. Demeclocycline did not affect vasopressin type 2 receptor localization but decreased dDAVP-induced cAMP generation and the abundance of adenylate cyclase 3 and 5/6. The addition of exogenous cAMP partially corrected the demeclocycline effect. As in patients, demeclocycline increased urine volume, decreased urine osmolality, and reverted hyponatremia in an SIADH rat model. AQP2 and adenylate cyclase 5/6 abundances were reduced in the inner medulla but increased in the cortex and outer medulla, in the absence of any sign of toxicity. In conclusion, our in vitro and in vivo data indicate that demeclocycline mainly attenuates hyponatremia in SIADH by reducing adenylate cyclase 5/6 expression and, consequently, cAMP generation, AQP2 gene transcription, and AQP2 abundance in the renal inner medulla, coinciding with a reduced vasopressin escape response in other collecting duct segments.

Topics: Adenylyl Cyclases; Animals; Anti-Bacterial Agents; Aquaporin 2; Cells, Cultured; Cyclic AMP; Deamino Arginine Vasopressin; Demeclocycline; Disease Models, Animal; Hyponatremia; In Vitro Techniques; Inappropriate ADH Syndrome; Kidney Medulla; Male; Mice; Minocycline; Rats; Rats, Wistar; Vasopressins

Treatment strategies for hyponatremia such as hypertonic saline, normal saline with furosemide, urea, fluid restriction and demeclocycline are well established. However, these treatment modalities may themselves be associated with life-threatening complications. An important complication is rapid correction of hyponatremia with its consequent serious neurologic deficits and death. An unrecognized complication is the development of severe hypernatremia as a result of strict fluid restriction and concomitant excessive free water excretion from prolonged outpatient demeclocycline therapy. The authors report a case of a patient with hyponatremia due to the syndrome of inappropriate antidiuretic hormone secretion who developed severe hypernatremia as a result of rigid fluid restriction and demeclocycline therapy.

Topics: Aged; Demeclocycline; Female; Humans; Hypernatremia; Inappropriate ADH Syndrome; Severity of Illness Index; Syndrome; Treatment Outcome

Topics: Amitriptyline; Carbamazepine; Comorbidity; Demeclocycline; Diabetic Neuropathies; Diuretics; Furosemide; Humans; Hyponatremia; Inappropriate ADH Syndrome; Male; Middle Aged; Saline Solution, Hypertonic; Spain; Urea; Vasopressins

We herein describe a rare case of hyponatremia that was aggravated by a burn injury. The patient was also found to have hypothyroidism, followed by SIADH, and finally CSWS, which showed complicated clinical features. A 68-year-old man was admitted for evaluation and treatment of a thermal burn. On admission, the patient was dehydrated, which was evidenced by physical signs. The patient had hyponatremia (serum Na 123 mmol/L) with high excretion of urinary sodium. Plasma AVP levels related to plasma osmolality were high. Plasma levels of renin and aldosterone were low, while the plasma ANP level was normal. However, there was no deficiency of mineralocorticoid or glucocorticoid. After admission, the hyponatremia worsened, and edema with hypoproteinemia developed. The patient was found to have hypothyroidism due to chronic thyroiditis. However, hyponatremia was not completely recovered with replacement of thyroid hormone. The hyponatremia was normalized by administration of DMC. The skin injury was treated with a skin graft. After DMC was discontinued, hyponatremia developed once again. However, this time, there was no inappropriate antidiuresis and the hyponatremia was normalized with the administration of fludrocortisone. These findings revealed that the hyponatremia in this patient may have been primarily due to CSWS. It was most likely exacerbated by hypothyroidism, burn injury, and SIADH caused by the infection. The patient showed physical signs of dehydration and edema. Furthermore, biochemical laboratory data were unable to distinguish between hypovolemia and non-hypovolemia. These complicated features were explained by multiple disorders

Topics: Aged; Anti-Bacterial Agents; Anti-Inflammatory Agents; Burns; Dehydration; Demeclocycline; Fludrocortisone; Humans; Hyponatremia; Hypothyroidism; Inappropriate ADH Syndrome; Male; Sodium

To clarify the characteristics of vasopressin (AVP) secretion in patients with the syndrome of inappropriate antidiuresis (SIAD) related to central nervous system disorders, we examined the response of AVP secretion to osmotic stimulus by hypertonic saline infusion and analyzed the possible causative factors in six patients with SIAD associated with head trauma or cerebral infarction. Hyponatremia developed after head trauma in four patients and cerebral infarction in two patients. In all patients the clinical state and laboratory findings fulfilled the criteria for SIAD, which was supported by either nonsuppressible plasma AVP levels or effectiveness of treatments with water restriction, demeclocycline, nonpeptide V2 AVP antagonist or diphenylhydantoin. Although patterns of plasma AVP response to the osmotic stimulus varied, plasma AVP concentrations neither increased nor decreased to undetectable levels with a rise in plasma osmolality. In one patient, plasma AVP levels responded to increasing plasma osmolality when plasma osmolality normalized; in which the threshold and the sensitivity of osmostat were normal. In two other patients, AVP secretion responded to plasma osmolality after the treatment. The changes in AVP secretion were not due to nonosmotic stimuli for AVP release. In conclusion, this study shows that patients with SIAD and central nervous system disorders may have persistent AVP secretion with a loss of hypotonic suppression such as found in patients with adrenal insufficiency or depletional hyponatremia in central nervous system disorders, indicating that careful evaluation is necessary to determine the relationship between persistent AVP secretion and the pathogenesis of hyponatremic disorders.

Topics: Aged; Arginine Vasopressin; Cerebral Infarction; Craniocerebral Trauma; Demeclocycline; Female; Follow-Up Studies; Hormone Antagonists; Humans; Hyponatremia; Inappropriate ADH Syndrome; Male; Middle Aged; Phenytoin; Saline Solution, Hypertonic; Water Deprivation; Water-Electrolyte Balance

The syndrome of inappropriate secretion of antidiuretic hormone (SIADH) is a common cause of hyponatremia. In this study a case of SIADH caused by head trauma is reported, in which severe hyponatraemia, escorted by life-threatening neurological symptoms was observed that could only be managed by parenteral sodium chloride infusions. Severe hyponatraemia was accompanied by elevated urinary sodium excretion, a characteristic sign of SIADH. After introducing the therapy with demeclocycline, a tetracycline type antibiotic that inhibits the renal action of antidiuretic hormone, serum sodium levels began to rise gradually, and the urinary sodium excretion slowly decreased. These observations show the effectiveness of demeclocycline in the treatment of SIADH.

Topics: Craniocerebral Trauma; Demeclocycline; Female; Humans; Inappropriate ADH Syndrome; Middle Aged

Six patients are with inappropriate secretion of antidiuretic hormone syndrome are reported (two with bacterial acute meningitis, two with bacterial pneumonia, one with oat cell lung carcinoma, other with mediterranean fever boutonneuse) and the clinical manifestations were: mind changes (four cases) nausea-vomiting (two cases) and inappetence (six cases). All patients presented hyponatremia criteria, serum decreased osmolarity, urinary sodium and osmolarity increased, without edemas, renal disease endocrine (hypophysis, thyroids, adrenal) without diuretic treatment. Treatment was, effective water restriction in three patients and hydrochloride of demeclocycline in other three patients.

Topics: Adolescent; Adult; Aged; Anti-Bacterial Agents; Demeclocycline; Diuretics; Female; Humans; Inappropriate ADH Syndrome; Male; Middle Aged

Topics: Acute Disease; Butorphanol; Chronic Disease; Demeclocycline; Drinking Behavior; Furosemide; Humans; Inappropriate ADH Syndrome; Lithium Carbonate; Saline Solution, Hypertonic; Sodium

Chronic syndrome of inappropriate secretion of antidiuretic hormone (chronic SIADH) has been reported in adults after traumatic brain injury (TBI) but few similar cases have been reported in the pediatric population. We present a case of a 14-year-old boy who developed chronic SIADH after TBI in which caloric needs could not be adequately provided, with concomitant fluid restriction as the first line of treatment. Demeclocycline was ultimately used, which allowed for increased fluid liberalization and for provision of adequate calories. This form of therapy should be considered early in a child's course to prevent nutritional decline. Demeclocycline may be used for prolonged periods until the child's clinical condition permits fluid restriction to be effective therapy.

Topics: Adolescent; Brain Injuries; Chronic Disease; Demeclocycline; Energy Intake; Humans; Inappropriate ADH Syndrome; Male

We report a case of phosphate diabetes in a patient with the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) associated with sarcoidosis. Our patient was affected by systemic sarcoidosis and he fits the criteria of Schwartz for the diagnosis of SIADH. He presented with phosphate diabetes which appeared during demeclocycline (DMC) therapy and persisted for about 1 month from the end of DMC. It constitutes the fourth case of phosphate diabetes induced by tetracycline described in the literature and it is the third case of SIADH associated with sarcoidosis.

Topics: Demeclocycline; Humans; Hypophosphatemia, Familial; Inappropriate ADH Syndrome; Male; Middle Aged; Sarcoidosis

To examine a possible role for atrial natriuretic peptide (ANP) in water and sodium metabolism disturbances associated with abnormal vasopressin (AVP) secretion, we measured plasma ANP concentrations in 15 patients with the syndrome of inappropriate antidiuretic hormone secretion (SIADH) and in 17 patients with central diabetes insipidus (DI). The mean plasma ANP concentration (30.2 +/- 10.4 pmol/L) in SIADH patients who had hyponatremia, plasma hypoosmolality, hyperosmolar urinary compared to plasma sodium levels, and increased plasma AVP levels relative to plasma osmolality was significantly higher than that in normal subjects (12.6 +/- 4.9 pmol/L), although there was a considerable individual variation in plasma ANP ranging from normal to clearly elevated levels (15.1-47.0 pmol/L). When hyponatremia was corrected by water restriction or demeclocycline administration, plasma ANP levels decreased significantly and fell into the normal range (12.5 +/- 4.3 pmol/L). DI patients who complained of polyuria and polydipsia and had hypoosmolar urine, normal or elevated plasma sodium concentrations, and decreased plasma AVP levels relative to plasma osmolality, on the other hand, had a significantly lower mean plasma ANP level (7.6 +/- 2.9 pmol/L) than normal subjects. There was, again, a considerable overlap between plasma ANP levels in individual DI patients (4.2-13.9 pmol/L) and those in normal subjects. Treatment with 1-desamino-8-D-arginine vasopressin resulted in a significant increase in the mean plasma ANP level (18.6 +/- 8.0 pmol/L). There were no significant correlations between plasma ANP and AVP levels in either group of patients. The results indicate that ANP secretion is modulated by changes in plasma volume consequent to abnormal AVP secretion, which may have a pathophysiological significance in maintaining volume homeostasis.

Topics: Adolescent; Adult; Aged; Atrial Natriuretic Factor; Blood Volume; Deamino Arginine Vasopressin; Demeclocycline; Diabetes Insipidus; Female; Humans; Inappropriate ADH Syndrome; Male; Middle Aged; Polyuria; Sodium; Vasopressins; Water-Electrolyte Balance

The authors describe a case of subarachnoid hemorrhage with hyponatremia accompanied by elevation of plasma atrial natriuretic peptide (ANP). The early phase of hyponatremia was classified as the syndrome of inappropriate secretion of antidiuretic hormone (ADH) due to subarachnoid hemorrhage. However, in the later phase, hyponatremia and natriuresis were accompanied by suppression of ADH while plasma ANP remained elevated. The patient was effectively treated with demeclocycline and hypertonic saline. The significance of ANP in the pathophysiology of increased natriuresis is discussed.

Topics: Aged; Atrial Natriuretic Factor; Demeclocycline; Female; Humans; Hyponatremia; Inappropriate ADH Syndrome; Intracranial Aneurysm; Natriuresis; Saline Solution, Hypertonic; Subarachnoid Hemorrhage; Vasopressins

Topics: Acute Disease; Demeclocycline; Humans; Inappropriate ADH Syndrome; Male; Middle Aged; Pancreatitis

A 64-year-old male developed symptomatic recurrent syndrome of inappropriate ADH secretion in association with locally advanced squamous cell carcinoma of the tongue. His SIADH was managed successfully with saline infusion, frusemide, and maintenance treatment with demeclocycline.

Topics: Carcinoma, Squamous Cell; Demeclocycline; Humans; Inappropriate ADH Syndrome; Male; Middle Aged; Neoplasm Recurrence, Local; Paraneoplastic Endocrine Syndromes; Tongue Neoplasms

Psychiatric patients presenting with chronic psychogenic polydipsia are often difficult to treat with standard psychiatric interventions. Pharmacologic intervention was attempted in three patients and was successful in one. One patient had a significant and sustained reduction of water intake while on 160 mg of propranolol. One patient did not improve with either propranolol or captopril while a third patient showed no improvement of serum sodium with demeclocycline nor reduction of water intake with propranolol. The potential mechanisms by which these pharmacologic agents might alter thirst in patients with primary polydipsia are discussed.

Topics: Adult; Captopril; Demeclocycline; Drinking Behavior; Humans; Inappropriate ADH Syndrome; Male; Mental Disorders; Middle Aged; Propranolol

Serum sodium concentration increased significantly in eight hyponatremic schizophrenic subjects treated with demeclocycline. The incidence of severe hyponatremic episodes was significantly reduced. The authors argue that mild impairments in urinary dilution contribute to water intoxication in most chronic psychotics who develop this syndrome. Demeclocycline may help these patients.

Topics: Adult; Chronic Disease; Compulsive Behavior; Demeclocycline; Drinking Behavior; Female; Humans; Hyponatremia; Inappropriate ADH Syndrome; Male; Middle Aged; Schizophrenia

Topics: Demeclocycline; Female; Humans; Hypophosphatemia, Familial; Inappropriate ADH Syndrome; Middle Aged

We report the case of a child with a medulloblastoma who developed inappropriate secretion of antidiuretic hormone postoperatively. The etiology of this condition and the related literature are discussed.

Topics: Cerebellar Neoplasms; Child; Demeclocycline; Female; Humans; Inappropriate ADH Syndrome; Medulloblastoma; Postoperative Complications

Topics: Demeclocycline; Diuretics; Humans; Inappropriate ADH Syndrome; Kidney; Urea

Topics: Demeclocycline; Humans; Inappropriate ADH Syndrome; Lithium

Three instances of inappropriate ADH syndrome following craniofacial operations are reported. The cornerstone to diagnosis is careful fluid and electrolyte monitoring. Treatment consists of fluid restrictions in the acute phase and demeclocycline for refractory cases. Seizures should be symptomatically treated. Surgeons involved in the care of craniofacial anomalies must be aware of this syndrome because the symptoms closely mimic those commonly observed following intracranial procedures. If unrecognized, the consequence is potentially lethal.

Topics: Child; Demeclocycline; Face; Female; Humans; Inappropriate ADH Syndrome; Male; Skull; Surgery, Plastic; Water-Electrolyte Imbalance

Topics: Compulsive Behavior; Demeclocycline; Humans; Inappropriate ADH Syndrome; Water Intoxication

The syndrome of hyponatremia in psychiatric patients is described, and cases associated with psychotropic drug treatment are reviewed. The causative role of the drug should be documented by rechallenge or a water loading test. In some instances it is possible to continue psychotropic treatment by restricting fluids or administering demeclocycline.

Topics: Adult; Child; Demeclocycline; Humans; Hyponatremia; Inappropriate ADH Syndrome; Infant; Mental Disorders; Psychotropic Drugs

A case of tuberculous Addison's disease presenting with psychosis, profound hyponatraemia, and detectable plasma antidiuretic hormone is reported. Clinical and biochemical improvement after corticosteroid replacement was followed by relapse with further psychosis and inappropriate antidiuretic hormone secretion: both were promptly reversed by demethylchlortetracycline. The association of psychological symptoms with Addison's disease, the role of anti-diuretic hormone secretion in Addison's disease, and the inter-relationship between Addison's disease, psychosis and anti-diuretic hormone secretion are discussed.

Topics: Addison Disease; Body Weight; Demeclocycline; Fludrocortisone; Humans; Hydrocortisone; Inappropriate ADH Syndrome; Male; Middle Aged; Psychotic Disorders; Vasopressins; Water Intoxication

Two new observations of ISADH following head injury are described. A review of the medical literature is presented. Reports of ISADH after head injury are rare in comparison to the frequent occurrence of hydroelectrolytic disorders in the same situation. Attention is drawn to misleading clinical pictures, suggestive of neurosurgical conditions. Intracranial hematoma is frequently associated with ISADH and should be looked for in patients who fail to respond to therapy.

Topics: Aged; Craniocerebral Trauma; Demeclocycline; Female; Humans; Hyponatremia; Inappropriate ADH Syndrome; Male

Demeclocycline, a competitive inhibitor of antidiuretic hormone at renal tubules, was studied in a patient with the syndrome of psychosis, psychogenic polydipsia, and episodic water intoxication. Under double-blind, placebo-controlled conditions, demeclocycline substantially reduced the severity and frequency of hyponatremic episodes.

Topics: Adult; Demeclocycline; Dose-Response Relationship, Drug; Double-Blind Method; Female; Humans; Hyponatremia; Inappropriate ADH Syndrome; Schizophrenia; Schizophrenic Psychology; Water Intoxication

Topics: Demeclocycline; Humans; Inappropriate ADH Syndrome; Lithium; Water Intoxication

Topics: Bronchopneumonia; Cardiomyopathies; Child; Child, Preschool; Demeclocycline; Diuretics; Female; Humans; Hypokalemia; Hyponatremia; Inappropriate ADH Syndrome; Respiratory Insufficiency

Topics: Aged; Carbamazepine; Demeclocycline; Female; Glucocorticoids; Humans; Inappropriate ADH Syndrome; Lung Diseases; Lung Neoplasms; Male; Phenytoin; Vasopressins

Topics: Aged; Demeclocycline; Humans; Inappropriate ADH Syndrome; Male; Prostatic Neoplasms

Three patients with tuberculous meningitis complicated by hypersecretion of anti-diuretic hormone are described. The recognition of this complication is important in the treatment and prognosis of tuberculous meningitis.

Topics: Adult; Demeclocycline; Female; Humans; Inappropriate ADH Syndrome; Male; Tuberculosis, Meningeal; Unconsciousness; Water-Electrolyte Imbalance

Topics: Demeclocycline; Female; Humans; Hyponatremia; Inappropriate ADH Syndrome; Lung Neoplasms; Middle Aged

Topics: Demeclocycline; Female; Humans; Hyponatremia; Hypothyroidism; Inappropriate ADH Syndrome; Middle Aged; Vasopressins; Water-Electrolyte Imbalance

Known physiologic mechanisms explain the elevated blood ADH levels observed in most patients with the syndrome of inappropriate ADH. Therefore the word "inappropriate" is a misnomer. It implies that the mechanisms that regulate ADH release are not functioning normally--which is not true. The term misleads the physician who, ideally, should determine why a patient has an excessive blood ADH level and initiate appropriate treatment. Patients with ectopic production of ADH and hyponatremia should be so labeled: "Hyponatremia due to ectopic ADH production." The term SIADH, if used at all, should be reserved for the rare patient with CNS injury or disease that causes increased ADH release and in which the hypothalamic center does not respond normally to afferent peripheral stimuli.

Topics: Blood; Demeclocycline; Furosemide; Humans; Hyponatremia; Inappropriate ADH Syndrome; Lithium; Osmolar Concentration; Pressoreceptors; Saline Solution, Hypertonic; Vasopressins

The hypothalamic-neurohypophyseal system functions to maintain plasma osmolality within narrow limits. It also is an important mechanism in maintaining normal body fluid volume. The system exerts its influence via release or inhibition of vasopressin (antidiuretic hormone, ADH) which acts on the kidney to decrease water excretion. Deficiency of ADH is usually due to hypothalamic-neurohypophyseal lesions (central diabetes insipidus) or insensitivity of the kidney to ADH (nephrogenic diabetes insipidus). These patients, if untreated, have the predictable result of dehydration, hyperosmolality, hypovolemia, and eventual death in severe cases. On the other hand, ADH excess of the syndrome of inappropriate ADH secretion due to a variety of causes promotes water retention, hypoosmolality and hyponatremia which, if untreated, may progress to convulsions, coma, and death. It is obviously important to diagnose accurately these pathologic states of hydration. Not only is initiation of treatment in general dependent upon recognition of the disease, but each type of pathologic hydration state has specific treatment which rewards both patient and physician with effective correction of the problem.

Topics: Demeclocycline; Diabetes Insipidus; Humans; Inappropriate ADH Syndrome; Kidney; Pituitary Gland, Posterior; Vasopressins

Topics: Demeclocycline; Heart Failure; Hyponatremia; Inappropriate ADH Syndrome; Lung Neoplasms; Respiratory Tract Infections; Water Deprivation

A patient with a syndrome of inappropriate antidiuretic hormone secretion secondary to an undifferentiated bronchogenic carcinoma with distant metastases was treated with demethylchlortetracycline. Up until recently, treatment of this syndrome was based on water restriction and when the plasma sodium concentration became extremely low, hypertonic saline solution administration. Recently it has been demonstrated that the antibiotic demethylchlortetracycline inhibits the action of the antidiuretic hormone on the renal tubules. The drug has been used successfully in five patients with the syndrome of inappropriate antidiuretic hormone secretion. The administration of 900 mg of demethylchlortetracycline per day for 7 days in our patient produced an increase of free water clearance, diuresis, plasma sodium concentration, and plasma osmolarity. Urinary excretion of sodium and urinary osmolarity declined. Furthermore, the neurological symptoms attributed to hyponatremia improved markedly. The patient lost 6 kg during treatment, probably because of negative water balance induced by demethylchlortetracycline. Even though the administration of demethylchlortetracycline did not produce significant decreases in the glomerular filtration rate or renal blood flow in our patient, it is advisable to control the renal function in individuals treated with this drug since it may on occasion determine renal insufficiency.

Topics: Carcinoma, Bronchogenic; Demeclocycline; Diuresis; Drug Evaluation; Glomerular Filtration Rate; Humans; Inappropriate ADH Syndrome; Lung Neoplasms; Male; Middle Aged; Osmolar Concentration

One the basis of two special typical cases, the authors detail the symptoms and signs and consider the physiopathology of inappropriate secretion of antidiuretic hormone related to vincristine. Urinary ADH was measured in both cases. ADH levels could be studied on ten consecutive occasions during the course of one of the cases (obs. n 1). Eleven similar cases have been found in the literature. ADH was measured in only three of them. Methods of treatment are considered, with particular emphasis on the role of demeclocycline.

Topics: Child; Demeclocycline; Humans; Inappropriate ADH Syndrome; Leukemia, Lymphoid; Vasopressins; Vincristine

Fourteen patients with the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) have been treated with demethylchlortetracycline (demeclocycline) 1200 mg daily. In 12 patients the underlying lesion was malignant. The serum sodium returned to normal (greater than 135 mmol/l) in all patients after a mean of 8.6 days (SD +/- 5.3 days). Blood urea rose significantly from the pretreatment level of 4.2 +/- 2.3 mmol/l to 10.1 +/- 5.1 mmol/l at ten days (P less than 0.001). The average maximum blood urea was 13.4 +/- 6.8 mmol/l. In four patients the urea rose above 20 mmol/l, and in two of these demecyocycline was discontinued because of thie rise. The azotaemia could be attributed to a combination of increased urea producation and a mild specific drug-induced nephrotoxicity. Discontinuation of demeclocycline in six patients led to a fall in serum sodium, in one case precipitously, and return of the urea towards normal levels. Demeclocycline appears therefore to be an effective maintenance treatment of SIADH, and the azotaemia that occurs is reversible and probably dose dependent.

Topics: Adult; Aged; Creatinine; Demeclocycline; Female; Humans; Inappropriate ADH Syndrome; Male; Middle Aged; Sodium; Urea; Uremia

A 72-year-old woman with the syndrome of inappropriate secretion of antidiuretic hormone of unknown cause during more than one year of observation is reported. Plasma vasopressin levels were excessively elevated, even during a water load test. Her serum electrolyte abnormalities and general state were ameliorated after fluid restriction. During treatment with demeclocycline the patient was able to increase fluid without deterioration.

Topics: Aged; Demeclocycline; Electrolytes; Female; Humans; Inappropriate ADH Syndrome; Osmolar Concentration; Vasopressins; Water

Topics: Aged; Demeclocycline; Humans; Inappropriate ADH Syndrome; Male; Middle Aged; Osmolar Concentration; Osmotic Pressure; Sodium; Vasopressins

A sixteen month girl with inappropriate ADH secretion was treated with demethylchlortetracycline. On a dose of 20 mgs/kg/day the disorder resolved completely. Treatment was continued with a maintenance dose of 15 mgs/kg/day. No side effects were observed.

Topics: Demeclocycline; Dose-Response Relationship, Drug; Female; Humans; Inappropriate ADH Syndrome; Infant

Two patients with the syndrome of inappropriate secretion of antidiuretic hormone were studied in a metabolic ward during treatment with 1.2 g demeclocycline daily. In both patients, demeclocycline treatment led to increased renal water excretion with consequent correction of hyponatremia and hypo-osmolality. Three episodes of reversible deterioration in glomerular filtration rate developed in these patients. Each episode was accompanied by clinical evidence of extracellular fluid volume contraction, and on each occasion there was an inappropriate natriuresis with daily urinary sodium excretion remaining above 50 mEq. Although demeclocycline effectively reverses the electrolyte abnormalities of this syndrome, the potentially dangerous side effects that may develop exclude the routine usage of the drug.

Topics: Demeclocycline; Glomerular Filtration Rate; Humans; Inappropriate ADH Syndrome; Kidney; Male; Middle Aged; Natriuresis

A patient with the syndrome of inappropriate antidiuretic hormone release (SIADH) following head injury and meningitis was studied during treatment with demeclocycline, a drug known to produce a reversible nephrogenic diabetes insipidus. No changes were observed during six days of demeclocycline 1200 mg/24 hr but urine output increased significantly, with the production of a dilute urine, when the dose was increased to 2400 mg/24 hr. The patient lost weight, and all biochemical features of the syndrome were rapidly corrected despite an unchanged fluid intake and despite the persistence of high plasma levels of ADH. The rise in serum sodium was accompanied by mild sodium retention, as measured by external balance and exchangeable sodium. A complication of treatment was the development of acute renal failure possibly induced by a nephrotoxic effect of high circulating levels of demeclocyline. On stopping demeclocyline renal function returned to normal and, after some delay, SIADH returned, and was still present 9 months after initial presentation. This confirms earlier reports of the efficacy of demeclocycline in SIADH; but the authors advise caution against increasing the dose above 1200 mg/24 hr.

Topics: Demeclocycline; Humans; Inappropriate ADH Syndrome; Male; Middle Aged; Sodium; Time Factors; Vasopressins