Diabetes insipidus is entirely different to diabetes mellitus and has two presentations:
- Central diabetes insipidus - due to hypothalamic-pituitary trauma, post-transsphenoidal surgery for correction of hyperadrenocorticism, dorsally expanding cysts, inflammatory granuloma, lymphocytic hypophysitis, congenital malformation and neoplasms such as craniopharyngioma, pituitary chromophobe adenoma, pituitary chromophobe adenocarcinoma and metastatic tumors such as metastatic mammary carcinoma, lymphoma, malignant melanoma and pancreatic carcinoma
- - results in lack of vasopressin (antidiuretic hormone) production
- Nephrogenic diabetes insipidus - due to nephron impairment as a result of genetic or acquired disease
- - results in lack of vasopressin sensitivity by nephrons
Central diabetes insipidus (CDI) results in absolute or partial loss of vasopressin (antidiuretic hormone; ADH) production by the central nervous system, causing persistent hyposthenuria (urine specific gravities ≤ 1.006) and severe diuresis, even with severe dehydration.
Nephrogenic diabetes insipidus (NDI), which may be primary (familial; X-linked in humans) or secondary (acquired), results from impaired responsiveness of the nephron to the actions of vasopressin. Plasma vasopressin concentrations are normal or increased in animals with this disorder. Primary NDI is a rare congenital disorder of dogs resulting from a congenital defect involving the cellular mechanisms responsible for insertion of aquaporin-2 water channels into the luminal cell membrane.
Acquired secondary NDI includes a variety of renal and metabolic disorders which interfere with the normal interaction between vasopressin and its renal tubular receptors, affect renal tubular cell function, or decrease the hypertonic renal medullary interstitium, resulting in a loss of the normal osmotic gradient. These disorders are listed below as differential causes od secondary nephrogenic diabetes insipidus.
Common clinical signs in dogs with diabetes insipidus is polyuria and polydipsia.
In dogs with primary (familial) NDI, clinical signs typically become apparent by the time the dog is 8 to 12 weeks of age, with symptoms of excessive thirst, urination and difficulty in house-breaking.
Neurological signs have been reported, due to electrolyte disturbances or pituitary neoplasia, with depression and seizures observed in rare cases.
Water consumption can often be extreme, sometimes exceeding 800 ml/kg/day, with compensatory urine production exceeding 50 mL/kg/day, .
Blood tests are usually within normal limits apart from a polydipsia-induced hyponatremia.
Urinalysis usually shows hyposthenuria or isosthenuria, and hematuria is not regularly observed unless underlying concurrent nephropathy present. Urine culture and sensitivity is required to eliminate underlying cystitis or pyelonephritis.
Diagnosis is initially one of exclusion of other diseases (see list below), followed by low dose dexamethasone suppression test, water-deprivation tests, vasopressin therapy and central nervous imaging studies to diagnose central diabetes insipidus. The main diagnostic dilemma is differentiating between central diabetes insipidus, psychogenic polydipsia and nephrogenic diabetes insipidus.
Standard hematology and biochemistry assessments are usually unrewarding and in most cases, plasma concentrations of thyroid-stimulating hormone, thyroxine, growth hormone, insulin-like growth factor-1, adrenocorticotropic hormone and plasma α-melanocyte-stimulating hormone are within normal reference levels.
A response to synthetic vasopressin therapy (desmopressin; 0.1 - 0.2 mg orally every 8 hours) or urinary aquaporin-2 excretion testing may help clarify nephrogenic from central diabetes insipidus. Other tests include vasopressin measurements during hypertonic saline infusion. However, the occurrence of spontaneous vasopressin pulses may hamper the interpretation of the curve describing the relationship between plasma osmolality and plasma vasopressin concentration during osmotic stimulation.
An increase in urine specific gravity by 50% or more, compared with pre-treatment specific gravities, supports the diagnosis of CDI, especially if urine specific gravity exceeds 1.030. There should be only minimal improvement in dogs with primary NDI. Dogs with psychogenic water consumption may exhibit a mild decline in urine output and water intake because the chronically low plasma osmolality tends to depress vasopressin production.
Pituitary or hypothalamic neoplasia should be considered in older dogs diagnosed with CDI. A renal biopsy may be warranted in the older dog tentatively considered to have primary NDI.
A differential diagnosis would include:
- Diabetes mellitus - osmotic diuresis
- Chronic renal disease osmotic diuresis
- Primary renal glycosuria - osmotic diuresis
- Post-urolithiasis diuresis - osmotic diuresis, down-regulation of aquaporin-2
- Pyometra - bacterial endotoxin-induced reduced tubular sensitivity to vasopressin
- Escherichia coli septicemia - bacterial endotoxin-induced reduced tubular sensitivity to vasopressin
- Hypercalcemia - interference with action of vasopressin on renal tubules
- Hepatitis - loss of medullary hypertonicity, impaired hormone metabolism
- Hyperadrenocorticism - impaired tubular response to vasopressin
- Hyperaldosteronism - impaired tubular response to vasopressin
- Pyelonephritis - bacterial endotoxin-induced reduced tubular sensitivity to vasopressin, damaged countercurrent mechanism
- Fanconi's syndrome - osmotic diuresis
- Hypokalemia - down-regulation of aquaporin-2, loss of medullary hypertonicity
- Hyponatremia - loss of medullary hypertonicity
- Hypoadrenocorticism - loss of medullary hypertonicity
- Hyperthyroidism - loss of medullary hypertonicity
- Leptospirosis - action unknown
- Polycythemia - action of natriuretic peptide
- Pheochromocytoma - excessive catecholamines
- Portosystemic shunt - loss of medullary hypertonicity, increased GFR
- Dwarfism - action unknown
- Acromegaly - osmotic diuresis due to diabetes mellitus
- Psychogenic polydipsia - loss of medullary hypertonicity
- Intestinal leiomyosarcoma - impaired tubular response to vasopressin
- Very low protein diet - loss of medullary hypertonicity
- Gastrointestinal disease (e.g. ulcerative colitis)
- X-linked hereditary nephropathy - loss of medullary hypertonicity, increased GFR
- Renal dysplasia - loss of medullary hypertonicity, increased GFR
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