DIABETES INSIPIDUS(DI)

Introduction
Vasopressin and oxytocin are formed in the neurons of the hypothalamus, migrate down the axons of the hypothalamic-neurohypophyseal system, are stored in the secretory granules within the nerve terminals of neurohypophysis, and are released into the bloodstream in response to appropriate stimuli. Vasopressin (ADH, AV ! functions to concentrate urine and conserve water, and its release is coordinated with the activity of the thirst centre that regulates fluid inta"e. AV action is mediated via V# receptors on distal tubule and medullary collecting ducts of the "idney AV secretion is regulated primarily by the $effective% osmotic pressure of body fluids. &his control is mediated by speciali'ed hypothalamic cells, "nown as osmoreceptors. D( is commonest disorder of posterior pituitary.

Etiology and classification Diabetes insipidus can be classified as )! Cranial or central diabetes insipidus in which there is deficient production of ADH by the hypothalamus. #! Nep!rogenic diabetes insipidus - in which the renal tubules are unresponsive to ADH.

A" Central DI ). *eoplastic or infiltrative lesions of hypothalamus (pituitary tumours with suprasellar extension, metastases, sarcoidosis, ! #. ituitary or hypothalamic surgery +. ,evere head in-ury, usually associated with s"ull fracture (stal" section! .. /uptured cerebral aneurysms 0. (diopathic B" Nep!rogenic DI ). 1ongenital or familial #. Ac2uired 3 chronic renal diseases, acute tubular necrosis, primary aldosteronism, chronic hypercalcaemias, drug-induced (lithium, demeclocycline! Pat!op!ysiology 4hen the secretion or action of AV is reduced, urine concentration ceases and the rate of urine output increases. 5ut water loss due to increase urine output causes increase in plasma osmolarity and sodium concentration that stimulate thirst and a compensatory increase in water inta"e. ,o overt physical or laboratory signs of dehydration do not develop unless the patient has a defect in thirst or fails to drin" for some other reason. Clinical features# 1haracteri'ed by polydipsia and olyuria in severe cases upto )6-)0l7day. (f the thirst mechanism is lost then patient may present with unconscious and with features of dehydration. 8ild daytime fatigue7somnolence, as a conse2uence of polyuria Any patients with polyuria rule out diabetes mellitus and primary polydipsia. Differential diagnosis of Polyuria Diabetes insipidus

Diabetes mellitus Drugs- diuretics,8annitol. Hypercalcemia 1hronic renal failure

Differential diagnosis of DI rimary or sychogenic polydipsia

9ncontrolled diabetes mellitus

In$estigations#

Diagnosis of polyuria is confirmed if output is : 06 m;7"g daily (:+,066 m; in a <6-"g man!. (ncreased in serum osmolality (:+66mosm7"g! and decreased urine osmolality (=>>6mosm7"g! is very characteristic of D(. ,erum sodium is mar"edly increased esp. severe cases. ,erum ADH levels is not reliable. %ater depri$ation test ? Use &o establish a diagnosis of diabetes insipidus, and differentiate cranial from nephrogenic causes. P!ysiologic principal3 Dehydration causes elevation of plasma osmolality which stimulates AV secretion, causing concentration of urine. atients with excessive thirst will concentrate urine@ patients with D( will not. &est differentiates patients with D( from patients with primary polydipsia. Protocol Step & for diagnosis of DI *o coffee, tea or smo"ing on the test day Aree fluids until 6<+6 hrs on the morning of the test, but discourage patients from Bstoc"ing upB with extra fluid in anticipation of fluid deprivation *o fluids from 6<+6 hrs Attend at 6C+6 hrs for body weight, plasma and urine osmolality /ecord body weight, urine volume, urine and plasma osmolality and thirst score on a visual analogue scale every # hours for up to C hours ,top the test if the patient loses +D of body weight Step ' to differentiate bet(een central and nep!rogenic DI (f plasma osmolality reaches : +66 mEsm7"g and urine osmolality = >66 mEsm7"g, then administer DDAV # Fg i.m. Interpretation Diabetes insipidus is confirmed by a plasma osmolality : +66 mEsm7"g with a urine osmolality = >66 mEsm7"g 1ranial diabetes insipidus is confirmed if urine osmolality rises by at least 06D after DDAV *ephrogenic diabetes insipidus is confirmed if DDAV does not concentrate the urine rimary polydipsia is suggested by low plasma osmolality at the start of the test I)aging- 8/( of pituitary and hypothalamus for cranial D( Nep!rogenic DI is suspected ? /A&, calcium and phosphate and other renal investigations are re2uired.

Treat)ent# &reatment depends on the cause of D(. Central DI

Des-amino, DesArgininineVasoppressin (DDAV or des)opressin! analogue of AV is the drug of choice. 8echanism of action3 acts selectively at V# receptors to increase urine concentration and decrease urine flow &his drug can be given (ntravenous or subcutaneous in-ection, nasal inhalation, or tablet depending on patient condition. Chlorpropamide ( this one of old oral hypoglycemics used for traement of type # D8! 8echanism of action3 potentiates the effect of small amounts of AV or direct activation of the V# receptor Dose - )#0?066 mg E once daily ,ide effects- Hypoglycemia 1arbama'epine can also be used instead of chlorpropamide.

Nep!rogenic DI (nitial therapy should be directed at correcting an underlying disorder or discontinuing an offending medication. olyuria in nephrogenic diabetes insipidus is improved by thia'ide diuretics (e.g. bendroflumethia'ide #.0-0 mg7day!, amiloride (0-)6 mg7day! and *,A(Ds (e.g. indometacin )0 mg C-hourly! Pri)ary polydipsia 1orrected by patient counseling@ however, there is no effective treatment

S*ND+,-E ,. INAPP+,P+IATE ANTIDIU+ETIC /,+-,NE SEC+ETI,N (SIAD/)

Definition - ,(ADH refers to a condition of excess blood level of vasopressin associated with hyponatraemia without oedema Pat!op!ysiology Causes of !yponatrae)ia &) /ypo$olae)ic (sodium deficit with a relatively smaller water deficit! e.g /enal *a losses Diuretic therapy, Gastrointestinal *a losses Vomiting Diarrhoea ') Eu$olae)ic (water retention alone! - SIAD/ 0) /yper$olae)ic (sodium retention with relatively greater water retention!1ongestive cardiac failure 1irrhosis *ephrotic syndrome Hyponatraemia in ,(ADH is due excess ADH, in the absence of an appropriate physiological stimulus. &his results significant promotes renal water retention which inturn causes expansion of extracellular fluid volume without oedema.

 &he extracellular volume expansion produces an increase in atrial natriuretic

hormone, , and a compensatory increase in urinary sodium excretion that serves to reduce the hypervolemia but aggravates the Hyponatremia. &his can result in resultant brain swelling, increases intracranial pressure leading to altered sensorium, coma and even sei'ures. &he ma-or mechanisms for ,(ADH are3 )! Autono)ous synt!esis and release of AV from tumours (e.g. oat cell carcinoma! #! Non tu)orous tissue ac2uires capacity to synthesise and release AV autonomously or stimulate AV release from pituitary (e.g. pulmonary &uberculosis, pneumonias! +! Pituitary A1P is released inappropriately due to inflammation, neoplasia, vascular lesions and drugs Etiology &) Tu)ours ,mall-cell carcinoma of lung 2) -etabolic causes Alcohol withdrawal

rostate ancreas ;ymphomas

') Pul)onary lesions neumonia &uberculosis

orphyria

3) Drugs 1hlorpropamide

;ung abscess 0) CNS causes 8eningitis Head in-ury ,ubdural haematoma 1erebral Abscess
Clinical features 4eight gain, wea"ness, lethargy and

1arbama'epine 1yclophosphamide henothia'ines

8ental confusion which may progress to coma and convulsions 1linical features of cause of ,(ADH are most often very evident.
In$estigations &ypical lad data of ,(ADH are ;ow plasma sodium concentration ( = )+6 mmol7l! (due to renal loss! and ;ow plasma osmolality (= #<6 mmol7"g! ? due to excess water retention. 9rine osmolality is always more than that of serum. Due to water retention by ADH

 9rine sodium concentration is high (: +6 mmol7l! ? due to excess atrial natriuretic

hormone ;ow-normal plasma urea, creatinine, uric acid

other causes of hyponatremia li"e AddisonHs disease, renal causes, hypothyroidism,

drugs, /ypo$olae)ic and /yper$olae)ic hyponatremia have to ruled out before diagnosis of ,(ADH 1auses of ,(ADH have to aggressively loo" for li"e pneumonia, meningitis carcinoma. Treat)ent /estrict total fluid inta"e to less than the sum of insensible losses and urinary output, that is approximate C66ml of fluids per day.

Hypertonic saline infusion (+D! may be necessary for severe hyponatremia or if

patient is in altered sensorium and having sei'ures. 1hronic ,(ADH - Demeclocycline or Fludrocortisone . Demeclocycline interferes with renal action of AV 8anagement should also include eliminating the underlying cause. Co)plications 1oma

,ei'ures Central pontine )yelinolysis- this occurs due to rapid correction of hyponatremia