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.

Syndrome of inappropriate antidiuretic hormone secretion secondary to trauma in a dog.

OBJECTIVE: To describe a case of inappropriate antidiuretic hormone (ADH) secretion in a dog secondary to trauma. CASE SUMMARY: A 14-year-old neutered female mixed breed dog presented for evaluation of bite wounds. The dog sustained multiple puncture wounds to the cervical area, stifle, and elbow. Treatment was initiated with isotonic crystalloid fluids, analgesia, broad-spectrum antimicrobials, and gastroprotectants. The dog developed hyponatremia with concurrent serum hypoosmolality and inappropriate urine hyperosmolality and urine sodium secretion, leading to a diagnosis of the syndrome of inappropriate ADH secretion. The hyponatremia improved, and the dog improved clinically and was discharged 3 days after admission. NEW OR UNIQUE INFORMATION PROVIDED: This is the first case description of the syndrome of inappropriate ADH secretion in a dog suffering from trauma. Inappropriate ADH secretion is largely under-recognized in veterinary patients. Increased awareness of this syndrome can lead to initiation of appropriate treatment and improved outcomes.

Syndrome of inappropriate antidiuretic hormone secretion in a dog with a histiocytic sarcoma.

A 7-year-old female neutered Bernese mountain dog was presented in a semi-comatose state. Based on serum hypo-osmolality with inappropriate urine hyper-osmolality and urine sodium excretion, the dog was diagnosed with a syndrome of inappropriate antidiuretic hormone secretion secondary to a histiocytic sarcoma. This report describes the first case of this syndrome in a dog with histiocytic sarcoma.

Syndrome de sécrétion inappropriée d'hormone antidiurétique chez un chien avec un sarcome histiocytaire. Une chienne stérilisée de 7 ans, Bouvier bernois, est présentée dans un état semi-comateux. Basé sur une hypo-osmolalité sérique associée à une hyper-osmolalité urinaire et une excrétion sodique urinaire toutes deux inappropriées, un diagnostic de syndrome de sécrétion inappropriée d'hormone antidiurétique secondaire à un sarcome histiocytaire est posé. Ce cas est le premier cas de ce syndrome chez un chien avec un sarcome histiocytaire.(Traduit par les auteurs).

A Quick Reference on Hyponatremia.

The article focuses on causes of hyponatremia, including hypovolemia, diabetes mellitus and others. Hypovolemia is a major cause of hyponatremia in veterinary medicine. Hypovolemia causes a decrease in effective circulating volume, triggering antidiuretic hormone (ADH) secretion and free water retention, and develops after gastrointestinal losses, renal losses, hemorrhagic shock, hypoadrenocorticism, and other causes of hypovolemia. The article reviews the clinical approach to diagnosing the cause of hyponatremia in critically ill patients, including recognition of the syndrome of inappropriate ADH secretion (SIADH).

Syndrome of Inappropriate Antidiuretic Hormone Secretion in a Mini-Breed Puppy Associated With Aspiration Pneumonia.

A 3-month-old intact male Prague ratter was presented to the emergency service for evaluation of progressive lethargy, weakness, coughing and labour breathing after an episode of resistance to oral deworming. The patient exhibited depression, increased respiratory effort and cyanosis at initial presentation. Results of first diagnostic work-up (complete blood cell count, biochemistry panel and thoracic x-rays) were all consistent with aspiration pneumonia. The puppy was initially treated with balanced isotonic crystalloids, broad spectrum antibiotics, nebulization with thoracic coupage and was transferred to an infant incubator with a sustained FiO2 of 40-50%. Twenty-four hours after ICU admission the patient's condition suffered a worsening and the dog was orthopneic, severely depressed with episodes of intermittent dysphoria and seizuring. New thoracic radiographs and several samples of blood and urine were collected to go further in the diagnostic workup revealing severe hyponatremia, severe plasma hypotonicity, high natriuresis and metabolic acidosis with a worsening of the radiological pulmonary pattern. Based on these new clinical findings a diagnosis of SIADH was established. Emergency treatment with hypertonic 3% saline solution and loop diuretics was started like a sodium supplement and to inhibit water resorption in renal tubules, thus reducing the volume overload. The goal of this treatment was to achieve a progressive and controlled increase of plasma sodium concentration and promoting the excretion of positive body water imbalance. The patient's condition improved clinically over the following days, treatment was progressively discontinued and the dog was discharged 7 days after admission. To the author's knowledge this is the first report of a puppy younger than 12 weeks with respiratory distress developing SIADH associated to aspiration pneumonia.

Syndrome of inappropriate antidiuretic hormone secretion in a cat with a putative Rathke's cleft cyst.

An 11-year-old spayed female domestic shorthair cat was evaluated for anorexia, lethargy and weight loss of 6 days' duration. Bilateral mydriasis, absent menace response, slow-to-absent pupillary light reflexes, bilateral retinal detachment, intermittent horizontal nystagmus, intermittent ventral strabismus and systemic hypertension were present. Biochemical analysis revealed severe hyponatremia, severe hypochloremia and mild hypokalemia. Multifocal central nervous system disease was suspected based on optic, trigeminal sensory (ophthalmic branch), vestibulocochlear and possible oculomotor nerve dysfunction. Thoracic radiographs showed mild cardiomegaly without evidence of congestive heart failure. Ultrasound revealed mild pleural and peritoneal effusion. A cause of the severe hyponatremia was not identified, and it persisted despite fluid therapy. Syndrome of inappropriate antidiuretic hormone secretion (SIADH) was suspected as the cause of hyponatremia. Humane euthanasia was elected owing to continued clinical decline. Serum hyposmolality, urine hyperosmolality, natriuresis and lack of confirmed renal, thyroid and pulmonary disease aided in the presumed diagnosis of SIADH. Post-mortem histopathology of the brain revealed degeneration of the hypothalamus and optic tracts, along with a prominent fluid-filled craniopharyngeal duct (putative Rathke's cleft cyst) separating the pars distalis and the pars intermedius. The hypothalamic degeneration, possibly secondary to a Rathke's cleft cyst, was hypothesized to be the cause of presumptive SIADH in the patient. Although rare in occurrence, Rathke's cleft cyst should be included as a differential diagnosis in dogs and cats with signs of pituitary dysfunction.

Syndrome of inappropriate antidiuretic hormone secretion concurrent with liver disease in a dog.

A 5-year-old female Chihuahua was presented for acute collapse. Laboratory examinations showed markedly elevated levels of hepatobiliary enzymes. Empiric antibiotic therapy for bacterial infection of the liver was ineffective. The clinical signs worsened with the development of hyponatremia with hypoosmolality and elevated urine sodium levels. The dog was suspected of having acute cholangiohepatitis associated with an immune-mediated disease. Subsequently, it was diagnosed with syndrome of inappropriate antidiuretic hormone secretion (SIADH) on the basis of the specific disease criteria. Further tests showed normal function of the adrenal and thyroid glands, and MRI and cerebrospinal fluid (CSF) analysis did not show any intracranial diseases. Immunosuppressive therapy and water restriction resolved the clinical signs and improved the SIADH in this dog. This case indicates that SIADH can occur concurrently with suspected immune-mediated liver disease in dogs.

Syndrome of inappropriate antidiuretic hormone secretion in a cat.

A 3-year-old, spayed female, domestic shorthaired cat was presented for evaluation of liver disease. Following anesthesia, laparoscopy, and medical therapy, the cat developed severe hyponatremia that was unresponsive to fluid therapy. Further evaluation of serum and urine osmolality determined that the cat fulfilled the criteria for syndrome of inappropriate antidiuretic hormone secretion. Treatment with fluid restriction resulted in resolution of the hyponatremia and clinical signs associated with the electrolyte imbalance.

Syndrome of inappropriate antidiuretic hormone secretion associated with congenital hydrocephalus in a dog.

A 13-month-old, male bichon frise was examined for the investigation of intermittent seizures, ataxia, abnormal behavior, polyuria, and polydipsia. At presentation, clinical and neurological examinations were unremarkable with the exception of mild truncal ataxia and a domed skull. Severe hyponatremia and hypoosmolality were identified, and following diagnostic testing a diagnosis of the syndrome of inappropriate antidiuretic hormone secretion (SIADH) was made. Magnetic resonance imaging revealed changes consistent with severe hydrocephalus. Water restriction resulted in increased serum osmolality and a reduction in severity of clinical signs. The current case report documents SIADH associated with hydrocephalus in a dog. Structural brain disease should be excluded before a diagnosis of idiopathic SIADH is made.

Effects of anesthesia, surgery, and intravenous administration of fluids on plasma antidiuretic hormone concentrations in healthy dogs.

OBJECTIVE: To evaluate effects of anesthesia, surgery, and intravenous administration of fluids on plasma concentrations of antidiuretic hormone (ADH), concentration of total solids (TS), PCV, arterial blood pressure (BP), plasma osmolality, and urine output in healthy dogs. ANIMALS: 22 healthy Beagles. PROCEDURE: 11 dogs did not receive fluids, and 11 received 20 ml of lactated Ringer's solution/kg of body weight/h. Plasma ADH adn TS concentrations, PCV, osmolality, and arterial BP were measured before anesthesia (T0) and after administration of preanesthetic agents (T1), induction of anesthesia (T2), and 1 and 2 hours of surgery (T3 and T4, respectively). Urine output was measured at T3 and T4. RESULTS: ADH concentrations increased at T1, T3, and T4, compared with concentrations at T0. Concentration of TS and PCV decreased at all times after administration of preanesthetic drugs. Plasma ADH concentration was less at T3 in dogs that received fluids, compared with those that did not. Blood pressure did not differ between groups, and osmolality did not increase > 1% from To value at any time. At T4, rate of urine production was less in dogs that did not receive fluids, compared with those that did. CONCLUSIONS AND CLINICAL RELEVANCE: Plasma ADH concentration increased and PCV and TS concentration decreased in response to anesthesia and surgery. Intravenous administration of fluids resulted in increased urine output but had no effect on ADH concentration or arterial BP. The causes and effects of increased plasma ADH concentrations may affect efficacious administration of fluids during the perioperative period in dogs.

Effects of an oral vasopressin receptor antagonist (OPC-31260) in a dog with syndrome of inappropriate secretion of antidiuretic hormone.

OBJECTIVE: The syndrome of inappropriate secretion of antidiuretic hormone is a rare disorder in dogs characterised by hypo-osmolality and persistent arginine vasopressin production in the absence of hypovolaemia and/or hypotension. The study describes the efficacy and safety of the nonpeptide selective arginine vasopressin V2 receptor antagonist OPC-31260 in a dog with the naturally occurring syndrome. DESIGN: The detailed case history of a dog with spontaneous syndrome of inappropriate secretion of antidiuretic hormone that received long-term therapy with oral OPC-31260 is presented. Effects of the first dose of OPC-31260 and of a dose administered after a continuous dosing period of 12 days are reported. PROCEDURE: Packed cell volume, plasma sodium, total protein, arginine vasopressin, renin activity, atrial natriuretic peptide, urine specific gravity, urine output, heart rate and body weight were monitored for 2 h before, and for 4 h after, the first dose of OPC-31260. The same parameters plus plasma osmolality and urine osmolality were monitored when an identical dose was administered after 12 days of therapy. RESULTS: Oral administration of OPC-31260 at 3 mg/kg body weight resulted in marked aquaresis with increased urine output and decline in urine specific gravity within 1 h. Corresponding increases in concentrations of plasma sodium, plasma osmolality and plasma renin activity were recorded over a 4 h period. Arginine vasopressin concentration remained inappropriately elevated throughout the study. Results were similar when the trial procedure was repeated after a stabilisation period of 12 days. Long-term therapy with OPC-31260 at a dose of 3 mg/kg body weight orally every 12 h resulted in good control of clinical signs with no deleterious effects detected during a 3-year follow-up period. Despite sustained clinical benefits observed in this case, plasma sodium did not normalise with continued administration of the drug. CONCLUSIONS: Treatment of a dog with naturally occurring syndrome of inappropriate secretion of antidiuretic hormone with OPC-31260 at 3 mg/kg body weight orally every 12 h resulted in marked aquaresis and significant palliation of clinical signs with no discernible side-effects detected over a 3-year period. Thus, OPC-31260 appears to offer a feasible medical alternative to water restriction for treatment of dogs with syndrome of inappropriate secretion of antidiuretic hormone. Higher doses of OPC-31260 may be required to achieve and maintain normal plasma sodium in dogs with this syndrome.

Inappropriate vasopressin secretion in two dogs.

Two dogs with hyponatremia due to inappropriate arginine vasopressin (AVP) secretion are described. Threshold and sensitivity of AVP secretion were investigated by increasing plasma osmolality with hypertonic saline infusion. In one dog, osmoregulation of AVP secretion occurred at normal sensitivity but at a low threshold. The other dog had a relatively high plasma AVP concentration under (resting) hypotonic conditions with an otherwise normal response to increasing plasma tonicity. In the absence of evidence for associated disease, it is suggested that both dogs have an idiopathic form of the syndrome of inappropriate AVP secretion.

An experimental model of syndrome of inappropriate antidiuretic hormone secretion in the rat.

An experimental model of the syndrome of inappropriate antidiuretic hormone secretion (SIADH) was developed using continuous subcutaneous infusions of arginine vasopressin (AVP) or 1-desamino-8-D-arginine vasopressin (DDAVP) in conscious unrestrained rats drinking 5% dextrose solution. Retention of both ingested water and endogenously generated free water from tissue catabolism was the primary determinant of hyponatremia using either AVP or DDAVP infusions. Natriuresis occurred transiently following water expansion but only slightly further lowered plasma [Na+]. Cessation of antidiuretic infusion resulted in free water excretion with correction of plasma [Na+]. Erythrocyte cell volume was significantly increased in hyponatremic animals and intracellular [K+] and [Na+] both decreased equivalently, consistent with dilution of intracellular fluid by retained water. This model of SIADH differs significantly from those previously described, in that escape from the hydroosmotic effect of AVP and DDAVP does not occur in the absence of high urinary flow rates. The observed results using this model suggest that the retained water in SIADH primarily resides intracellularly following isotonic equilibration of extracellular fluid volume.

Inappropriate secretion of antidiuretic hormone in a dog.

Hyponatremia with simultaneous renal sodium loss was associated with the inappropriate secretion of antidiuretic hormone in a dog with heartworm disease. Antidiuresis caused expansion of extracellular fluid volume, which induced renal salt wasting and a negative sodium balance. The combination of water retention, salt wasting, and inactivation of intracellular solute contributes to the decrease in serum sodium concentration. Water intoxication due to hypotonicity of body gluids induced anorexia, depression, weakness, and incoordination.