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Cranial Diabetes Insipidus

Title               

Ñ    Cranial Diabetes Insipidus   

Definition

Ñ    Disorder of the neurohypophysial system

Ñ    Deficiency of anti diuretic hormone (ADH, vasopressin)

Characterised by:

Ñ    Passage of large volumes of dilute urine

Ñ    Excessive thirst

Pathogenesis

Primary

Ñ    Autosomal dominant inheritance

Ñ    DIDMOAD syndrome:

Diabetes insipidus, diabetes mellitus, optic atrophy, deafness

Ñ    Idiopathic:

Often autoimmune

Secondary

Ñ    Trauma:

Head injury, surgery

Ñ    Inflammation:

Meningitis, encephalitis, granulomas, cerebral abscess

Ñ    Neoplasm:

 Pituitary tumours, hypothalamic tumours, secondary deposits, lymphoma, craniopharyngioma

Ñ    Vascular:

Pituitary infarction, pituitary haemorrhage

Pathophysiology

Ñ    Lack of ADH results in failure to reabsorb water in the collecting ducts thus causing polyuria and compensatory polydypsia

Clinical Features

History

Onset

Ñ    Insidious or abrupt

KUS

Ñ    Polyuria

Ñ    Polydypsia

Examination

CVS

Ñ    Hypovolaemia:

If urinary losses are not replaced

Investigations

Fluids

Urine

Ñ    Large volumes:

24 hour urine < 2L excludes need for further investigation

Ñ    Specific gravity:

<1.005

Ñ    Osmolality:

< 200 mOsm/L

Blood

Biochemistry

Ñ    Osmolality:

High or high normal

Ñ    Plasma Sodium:

High or high normal

Ñ    ADH concentration:

Radioimmunoassay of circulating ADH concentration

Physiological studies

Water Deprivation Test

Ñ    Commencement:

Start the test in the morning, check:

·          Body Weight

·          Venous blood:

Osmolality and electrolytes

·          Urine:

Osmolality, specific gravity

Ñ    Do not allow the patient to drink

Ñ    Hourly body weight, urine osmolality or specific gravity, pulse, blood pressure, serum osmolality

Ñ    Stop dehydration if:

·          Orthostatic hypotension, postural tachycardia

·          Loss of 5% of body weight

·          Urinary concentration: 

Does not increase by more than 0.001 specific gravity or 30 mOsm/L osmolality in sequential specimens

Ñ    Inject 2 micrograms of desmopressin or 5 U of aqueous vasopressin s.c. after taking blood for electrolytes and osmolality

Ñ    Terminate Test:

·          One hour later

Collect urine for osmolality and specific gravity

Interpretation

Ñ    Normal Response:

·          Maximum urine osmolality > plasma osmolality:

Urine specific gravity  > 1.020

Urine Osmolality  > 700 mOsm/L

·          Serum osmolality remains within the normal range

Ñ    Cranial Diabetes Insipidus:

·          Unable to concentrate urine osmolality to greater than plasma osmolality

·          Serum osmolality rises above normal

·          Urine osmolality increases > 50 % after vasopressin injection

Ñ    Partial Diabetes Insipidus:

·          Able to concentrate urine to greater than plasma osmolality

·          Urine osmolality rises to > 9% after vasopressin injection

Ñ    Nephrogenic Diabetes Insipidus:

·          Unable to concentrate urine to greater than plasma osmolality

·          No response to vasopressin

Management

Cure

Ñ    Treatment of the cause should either precede or accompany treatment of diabetes insipidus

Control

Drugs

Hormonal Therapy:

Ñ    Desmopressin (DDAVP), synthetic analogue of arginine vasopressin:

·          Intranasal preparations

·          s.c. if intranasal delivery inappropriate :

Upper respiratory tract infection, allergic rhinitis

·          Intravenous:

Acute situations

Ñ    Lypressin (lysine-8-vasopresin):

Nasal spray

Ñ    Vasopressin tannate in oil:

i.m. acts up to 96 hours

Nonhormonal Therapy

Ñ    Diuretics (Thiazides):

Reduces extra-cellular fluid volume and increases proximal tubular reabsorption

Ñ    ADH-releasing drugs:

Chlorpropamide, carbamazepine, clofibrate

Ñ    Prostaglandin inhibitors:

·          Indomethacin:

Probably decreases renal blood flow and glomerular filtration rate

Ñ    Combinations:

May be used

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