Long-term hormone replacement treatment in a horse with central diabetes insipidus

This case report describes the clinical presentation, and the diagnostic and therapeutic approaches of a 4-year-old gelding presented with severe polyuria and polydipsia. The horse was diagnosed with central diabetes insipidus. After diagnosis, different therapeutic regimens with intraocular desmopressin acetate (Minirin, Ferring GmbH, Kiel, Germany) (a synthetic arginine vasopressin analog) were tested, but without success. Only the subcutaneous injection of desmopressin acetate (Minirin, Ferring GmbH) led to an increase in urine specific gravity and a decrease in water intake and urine output. Daily subcutaneous treatment with desmopressin acetate (Minirin, Ferring GmbH) was initiated and maintained for at least 5 years. The horse did not develop adverse effects or re-occurrence of the initial complaints. This case report describes successful long-term treatment of central diabetes insipidus in a horse.     

Polyuria and polydipsia. Diagnostic approach and problems associated with patient evaluation.

Primary disorders of water balance (central diabetes insipidus [DI], nephrogenic DI, and psychogenic polydipsia) should always be considered in the differential diagnosis of polyuria and polydipsia. In general, animals with these disorders have only one laboratory abnormality: a low urine specific gravity. In most instances, the more common causes of polyuria and polydipsia (e.g., hyperadrenocorticism, chronic renal failure, pyelonephritis, pyometra) have specific and obvious abnormalities associated with the complete blood cell count, the serum chemistry profile, and urinalysis. In some cases, however, a low urine specific gravity may be the only abnormality associated with these more common findings. The workup for polyuria and polydipsia can be tedious, time-consuming, expensive, confusing, and not without significant patient morbidity, especially in those cases with normal or near-normal blood work. This article focuses on the diagnostic approach and problems associated with diagnostic testing in patients with disorders of water balance.     

Water transport in the kidney and nephrogenic diabetes insipidus

Nephrogenic diabetes insipidus is caused by an inability of the kidney to concentrate urine despite adequate concentration of vasopressin in blood and is characterized by polyuria, polydipsia, and hyposthenuria in the presence of plasma hyperosmolality. Nephrogenic diabetes insipidus is the result of defects in water homeostasis in the kidney. Nephrogenic diabetes insipidus occurs when the kidneys cannot or do not respond to vasopressin. There are 2 categories of nephrogenic diabetes insipidus. Congenital nephrogenic diabetes insipidus is a rare, inherited, irreversible cause of polyuria and polydipsia in humans that is even rarer in animals. Acquired nephrogenic diabetes insipidus is more common and is often secondary to illness or medication that interferes with the action of vasopressin in the renal tubules. Unlike congenital nephrogenic diabetes insipidus, acquired or secondary nephrogenic diabetes insipidus is often reversible with correction of the associated or causative problem.     

The role of vasopressin in dogs with polyuria

Polyuria and polydipsia (PUPD) occur frequently in dogs and may be caused by a variety of endocrine, metabolic, and renal disturbances. The studies described in this PhD Thesis, which was defended in January 2004 in Utrecht, investigated the role of the antidiuretic hormone vasopressin (VP) in the pathogenesis of different forms of canine polyuria. Experiments in healthy dogs demonstrated that the ranges of urine specific gravity and urine osmolality are much larger than previously thought. A water deprivation test is not required in all polyuric dogs, because serial measurements of urine osmolality may already lead to the diagnosis of primary polydipsia, in some cases. In dogs with primary polydipsia a wide variation in VP responses to hypertonic stimulation can be found, including a hyperresponse, a hyporesponse, and a non-linear response. The significance of the VP response to hypertonic saline infusion as the 'gold standard' for a diagnosis of canine polyuria is discussed. In the dog, VP is secreted in a pulsatile fashion with a wide variation in the number of VP pulses, VP pulse duration, and VP pulse amplitude and height. The occurrence of spontaneous VP pulses may severely hamper the interpretation of the curve describing the relationship between plasma osmolality and plasma VP concentration during osmotic stimulation. A radioimmunoassay to measure the VP-dependent water channel aquaporin-2 (AQP2) in urine was developed in dogs. In healthy dogs, urinary AQP2 excretion closely reflects changes in collecting duct exposure to VP. Measurement of urinary AQP2 excretion in polyuric dogs may be helpful to distinguish between central diabetes insipidus, nephrogenic diabetes insipidus, and primary polydipsia.     

Central diabetes insipidus in five cats: clinical presentation, diagnosis and oral desmopressin therapy

Five cases of central diabetes insipidus (CDI) in domestic shorthair cats are described. All cats were under 3 years of age at the onset of clinical signs, and outdoor or outdoor/indoor cats, in which a prior trauma was either present or possible. The history included polydipsia and polyuria, and physical examination abnormalities included urinary bladder distention and dehydration. All cats had hyposthenuria with a urine specific gravity between 1.003 and 1.006. The diagnosis was confirmed by an observed inability to concentrate urine during a water deprivation test or compatible serum osmolality, followed by an increase in urine concentration after desmopressin administration. All cats in this report were treated successfully with oral desmopressin. The dose (25-50 microg q8-12h) and the response to therapy were variable. Oral desmopressin administration may serve as an effective alternative route for cat owners who find the conjunctival or nasal application of the solution an inconvenient mode of therapy.     

Vasopressin response to osmotic stimulation in 18 young dogs with polyuria and polydipsia

Common disorders of water homeostasis leading to polyuria include a variety of endocrine, metabolic, and renal disturbances. After exclusion of most of these conditions, the diagnostic dilemma of differentiating between central diabetes insipidus, primary polydipsia, and nephrogenic diabetes insipidus may remain. Here, we report on 18 young dogs with polyuria that had been present in most cases since the dogs were puppies. The conditions were categorized according to the plasma vasopressin (VP) response to hypertonicity. The VP response to osmotic stimulation was tested by IV infusion of 20% NaCl for 2 hours. The VP response in all dogs was abnormal. Three categories could be distinguished: an exaggerated response (n = 3), a subnormal response (n = 4), and a nonlinear response with high plasma VP concentrations unrelated to increases in plasma osmolality (n = 11). The VP response to hypertonicity did not consistently distinguish among different clinical entities. In the 9 dogs with variations in urine osmolality compatible with primary polydipsia, exaggerated, subnormal, and nonlinear responses were observed. Examination of the present data questions the generally accepted notion that VP measurements during hypertonic saline infusion are the "gold standard" for the diagnostic interpretation of causes of polydipsia and polyuria. Studies of the peripheral reflection in plasma of the pulsatile VP release in healthy and polyuric individuals, with and without osmotic provocation, should be performed.     

Idiopathic neurogenic diabetes insipidus in a cat

SUMMARY A 5-year-old, domestic long-haired cat was presented for examination because of polydipsia, polyuria and inappropriate urination of 3 months' duration. Neurogenic diabetes insipidus was diagnosed, based on hyposthenuria with failure to concentrate urine in response to water deprivation and positive response to antidiuretic hormone administration. Treatment with hydrochlorothiazide or chlorpropamide orally gave inadequate antidiuresis, but response to injections of vasopressin tannate in oil was sufficient for satisfactory management.     

A case of central diabetes insipidus in the cat: diagnosis and treatment

A case of diabetes insipidus is described in a two-year-old entire male short-haired domestic cat. The clinical signs included a marked polyuria associated with secondary polydipsia and a urine specific gravity of 1–005. Diagnosis was confirmed by water deprivation test and response to desmopressin. Treatment with chlorothiazide diuretics is also described.     

Diabetes Mellitus in two twin male lambs

Summary

A diagnosis of diabetes mellitus in two twin male lambs was based on the clinical signs of emaciation, polydipsia and polyuria, the laboratory findings of glucosuria, ketonuria and hyperglycemia, as well as on the histological findings. In one sheep, an intravenous glucose tolerance test was made which showed glucose intolerance and no insulin response.     

Equine multisystemic eosinophilic epitheliotropic disease: A case report and review of literature

CASE HISTORY: A 2-year-old Standardbred gelding presented with a history of fever over 1 week, anorexia and skin lesions on all four legs. The lesions were associated with severe pruritus and oedema, and there was no response to therapy.

CLINICAL FINDINGS: The horse was in poor body condition, was lethargic and severely pruritic. Skin lesions consisted of diffuse alopecia and crusting of the distal extremities. Initially it was slightly febrile, but subsequently its temperature increased up to 40°C. Ten days after admission it developed profuse watery diarrhoea and the skin lesions progressed. Skin biopsies revealed superficial and deep perivascular dermatitis with lymphoplasmacytic and eosinophilic predominance. Based on the poor prognosis the horse was subject to euthanasia.

PATHOLOGICAL FINDINGS: The most notable lesions included ulcerative gastritis, typhlitis and colitis with prominent oedema of the intestines, marked subcutaneous oedema and severe thickening of the large bile ducts. Histopathology showed marked eosinophilic and lymphoplasmacytic infiltration of various tissues including the skin, gastrointestinal tract, mesenteric lymph nodes, large bile ducts, pancreatic duct and kidney. Immunohistochemistry revealed a clear predominance of CD3-positive cells in the lymphocytic infiltrations.

DIAGNOSIS: Based on the clinical findings and histopathology a diagnosis of multisystemic eosinophilic epitheliotropic disease (MEED) was made.

CLINICAL RELEVANCE: Multisystemic eosinophilic epitheliotropic disease is rare in horses, and usually chronic. In the current case the horse showed an apparently acute onset with high fever and rapid clinical deterioration. A diagnosis of MEED should be considered in horses presenting with weight loss and skin lesions with or without fever. A final diagnosis is based on histological results of biopsy specimens from affected organs.     

Diagnostic approach to polydipsia and polyuria

A variety of metabolic disturbances account for the majority of cases of polydipsia and polyuria. This chapter presents guides to differential diagnosis as well as a discussion of the etiology and clinical features of the primary causes--central diabetes insipidus, nephrogenic diabetes insipidus, and psychogenic polydipsia.     

Antidiuretic response of a horse affected with pituitary pars intermedia dysfunction to desmopressin acetate

Central diabetes insipidus (DI) was diagnosed in a 20‐year‐old American Quarter Horse gelding that was concomitantly affected with pituitary pars intermedia dysfunction (PPID). The diagnosis of DI was supported by a positive response to administered desmopressin acetate. Diagnosis of PPID was supported by physical appearance and elevated plasma adrenocorticotropic hormone concentration following domperidone administration. The horse's physical condition improved following treatment with pergolide but long‐term treatment with desmopressin was not undertaken and severe polyuria and polydipsia persisted. Desmopressin acetate appears to be useful for the diagnosis of DI in mature horses concomitantly affected with PPID.     

Cryptococcal pyelonephritis in a dog

A 5-year-old castrated male Golden Retriever was evaluated for polyuria, polydipsia, and progressive regurgitation thought to be a result of bacterial pyelonephritis and megaesophagus. Bacteriologic culture of urine failed to yield clinically relevant growth, and results of a urine sediment examination were normal. With time, intention tremors and progressive neurologic dysfunction were also observed. At necropsy, a diagnosis of cryptococcal disease was confirmed histologically and immunohistochemically. Findings in the dog of this report were indicative of nephrogenic diabetes insipidus with polyuria and polydipsia caused by cryptococcal pyelonephritis. Neurologic manifestations of systemic cryptococcus infection included megaesophagus, esophageal hypomotility, and regurgitation attributed to localization of cryptococcal organisms in the brain stem in the region of the dorsal motor nucleus of the vagus nerve. To the authors' knowledge, this is the first report of polyuria secondary to cryptococcal pyelonephritis.     

Chronic pancreatitis with secondary diabetes mellitus treated by use of insulin in an adult California sea lion

CASE DESCRIPTION: A 21-year-old neutered male captive California sea lion developed chronic polyuria; polydipsia; polyphagia; accelerated development of existing cataracts; and frequent episodes of gastrointestinal upset including anorexia, signs of abdominal discomfort, diarrhea, and vomiting. CLINICAL FINDINGS: Chronic hypercholesterolemia, hypertriglyceridemia, hyperglycemia, and glucosuria were identified. During episodes of gastrointestinal abnormalities, transient hyperbilirubinemia and increased serum J-glutamyltransferase activities developed. Clinical findings strongly suggested chronic pancreatitis with secondary diabetes mellitus and intermittent cholestasis. Multiple diagnostic tests, including abdominal ultrasonography, serial hematologic and serum biochemical analyses, fecal examinations, urinalyses and bacteriologic culture of urine, measurement of serum fructosamine and insulin concentrations, and evaluation of thyroid and adrenal function, did not reveal any specific parasitic, endocrine, hepatic, or neoplastic etiologies. TREATMENT AND OUTCOME: For 1.5 years, the sea lion received once-daily administration of glargine insulin, gastrointestinal protectants, and a strict high-protein, low-fat diet. Daily monitoring of glucose regulation was achieved by training the sea lion to submit to blood and urine sampling. Glucose regulation ranged from fair to good, and clinical signs of diabetes mellitus lessened. Episodes of gastrointestinal upset still occurred, although the frequency and severity decreased. Ultimately, a severe episode developed, associated with diabetic ketoacidosis and sepsis, and the sea lion died. Severe fibrosing pancreatitis with exocrine and endocrine atrophy and abscesses arising from ectatic pancreatic ducts were found. Peripancreatic fibrosis caused stricture of the common bile duct, resulting in gallbladder distension without cholecystitis. CLINICAL RELEVANCE: Diabetes mellitus can occur secondary to chronic pancreatitis in California sea lions and insulin therapy should be considered.     

Acquired nephrogenic diabetes insipidus in a dog with leptospirosis

A 5 year old male neutered Cairn Terrier was evaluated for signs of polyuria and polydipsia. Initial hematology and chemistry panels were unremarkable and urinalysis showed a persistent hyposthenuria. Eleven days later, the dog became lethargic, inappetent and had developed acute renal failure. The dog was ultimately euthanized due to a poor response to treatment. Microscopic agglutination titres were consistent with a diagnosis of leptospirosis. The initial hyposthenuria in this case was consistent with acquired nephrogenic diabetes insipidus. This is an uncommon presentation of leptospirosis that has not previously been described to progress to acute renal failure. Leptospirosis should be considered as a differential diagnosis in any dog presenting with polyuria and polydipsia and these patients should be treated as a zoonotic risk.     

Evaluation of a modified water-deprivation test for diagnosis of polyuric disorders in dogs.

A modified water-deprivation test was performed on 12 polyuric and 4 clinically normal dogs. Immediately after maximal urine osmolality had been achieved with water deprivation, antidiuretic hormone was injected to test further renal concentrating ability. The test provided accurate diagnosis of severe hypothalamic-neurohypophyseal diabetes insipidus in 3 dogs, partial diabetes insipidus in 2 dogs, and primary (psychogenic) polydipsia in 2 dogs. Five polyuric dogs with hyperadreno corticism had a response to the modified water-deprivation test similar to that of dogs with partial diabetes indipidus.     

Congenital central diabetes insipidus in two sibling Afghan hound pups

Congenital central diabetes insipidus was determined to be the cause of polydipsia and polyuria in sibling pups. Both pups were lacking adequate plasma arginine vasopressin concentration, compared with that in control dogs. Microscopic abnormalities were confined to the brain and pituitary gland in one pup. Without breeding trials of these dogs or their relatives, it cannot be determined whether the cause was familial.     

Concurrent central diabetes insipidus and panhypopituitarism in a German shepherd dog

This report describes a German shepherd dog that was presented with proportionate dwarfism and coat changes typical of hypopituitarism but that was also profoundly polydipsic and polyuric. Investigations established a diagnosis of concurrent central diabetes insipidus. Treatment with desmopressin was successful in managing the polyuria and polydipsia.     

Bilateral ovarian adenocarcinoma in a mare causing haemoperitoneum and colic

Abstract

CASE HISTORY: A 13-year-old Thoroughbred mare was presented with a history of mild colic over 3 days. This colic had acutely exacerbated and was unresponsive to analgesic treatment, and was referred to Massey University Veterinary Teaching Hospital.

CLINICAL FINDINGS: On examination the heart rate was 100 beats per minute, and mucous membranes were pale and tacky. A large mass was detected on transrectal palpation in the caudal abdomen to the left of midline. Explorative laparotomy revealed severe haemoperitoneum and several masses that were associated with the reproductive tract. The mare was then subject to euthanasia. On post-mortem examination, adjacent and attached to each ovary were soft, lobulated dark red masses up to 200 mm in diameter. Similar masses were present in the omentum and on the peritoneal surface of the diaphragm and the serosa of the spleen and liver. Histopathology revealed that the neoplastic component of the masses comprised proliferating cuboidal to columnar cells forming disorganised acini and cords separated by dense collagenous stroma. Immunohistochemistry showed the neoplastic cells were positive for cytokeratin AE1/AE3 and vimentin, but negative for cytokeratin 7 and inhibin α.

DIAGNOSIS: Bilateral ovarian adenocarcinoma with transcoelomic metastasis and terminal decompensation due to rupture of a neoplastic mass and consequent haemoperitoneum.

CLINICAL RELEVANCE: To the authors' knowledge, bilateral ovarian adenocarcinoma has not been previously reported in a horse. Ovarian adenocarcinoma should be considered when horses present with haemoperitoneum and colic. Further research is required on the immunohistochemical differentiation of adenocarcinoma of ovarian and intestinal origin in the horse.