pituitary Flashcards
diabetes insipidus: recall the pathophysiology of diabetes insipidus (cranial vs nephrogenic), list the principle causes, recall and explain the clinical features, explain how diagnosis may be made, and recall treatment modalities (24 cards)
2 pathophysiological causes of diabetes insipidus
cranial (central), where there is an absence/lack of circulating vasopressin; nephrogenic, where end-organ (kidneys) are resistant to vasopressin, resulting in very dilute urine
2 types of cranial diabetes insipidus and prevalence (aetiology)
acquired (more common), genetic (rare)
5 ways the neurohypophysial system may be damaged in acquired cranial diabetes insipidus
traumatic brain injury, pituitary surgery, pituitary tumours (craniopharyngioma), metastasis to pituitary gland (e.g. from breast), granulomatous infiltration of median eminence (e.g. TB, sarcoidosis; vasopressin travels down stalk so if inflamed it can’t reach posterior pituitary)
nephrogenic diabetes insipidus aetiology: congenital
rare; e.g. mutation in gene encoding V2 receptor or AQP2
nephrogenic diabetes insipidus aetiology: acquired
drugs (e.g. lithium toxicity)
5 signs and symptoms of diabetes insipidus
polyuria, hypo-osmolar urine (unlike diabetes mellitus, which has lots of glucose in it), polydipsia, dehydration (if fluid intake not maintained), possible sleep disruption
how does diabetes insipidus cause expansion of ECF volume [in presence of water availability] (if no access to water, causes dehydration and death)
inadequate production of/response to vasopressin -> large volumes of dilute (hypotonic) urine -> increase in plasma osmolality (and Na+) -> reduction in ECF volume -> [thirst (polydipsia) -> ECF volume expansion]
where is psychogenic (primary) polydipsia most frequently seen and why
psychiatric patients, unclear but may reflect anti-cholinergic effects of medication (‘dry mouth’ due to side effects); can be in patients told to ‘drink plenty’ by healthcare professionals
psychogenic polydipsia vs diabetes insipidus
excess fluid intake (polydipsia) and excess urine output (polyuria), but ability to secrete vasopressin in response to osmotic stimuli is preserved
pathway of psychogenic polydipsia: normal response to drinking lots of fluid but confusion as to whether it is diabetes insipidus or psychogenic polydipsia
increased drinking (polydipsia) -> expansion of ECF volume, reduction in plasma osmolality -> less vasopressin secreted by posterior pituitary -> large volumes of dilute (hypotonic) urine -> ECF volume returns to normal -> increased drinking (polydipsia)
approximate normal (hydrated) range vs diabetes insipidus vs psychogenic polydipsia
approximate normal (hydrated) range: 280 mOsm/kg H2O; diabetes insipidus: 290 mOsm/kg H2O (higher despite trying to drink more water to keep up with passing dilute urine); psychogenic polydipsia: 270 mOsm/kg (dilute plasma osmolality)
water deprivation test: purpose and normal hydrated urine osmolality
to determine cause of diabetes insipidus; about 350 mOsm/kg H2O
water deprivation test: fluid deprived urine osmolality: normal vs psychological poydipsia vs central diabetes insipidus vs nephrogenic diabetes insipidus
normal and psychological poydipsia at 1200 mOsm/kg H2O (has normal vasopressin system so rises); central and nephrogenic diabetes insipidus no change from 350 mOsm/kg H2O (cannot reabsorb water from collecting duct, so must monitor body weight every hour, so if lose more than 3% that is mark of clinical dehydration); therefore normal and psychological polydipsia pass test
water deprivation test: DDAVP (vasopressin analogue) administration urine osmolality: central diabetes insipidus vs nephrogenic diabetes insipidus
central diabetes insipidus at 900 mOsm/kg H2O (can’t produce vasopressin but do respond); nephrogenic diabetes insipidus no change (can’t respond to vasopressin)
4 biochemical features of diabetes insipidus (after confirming not diabetes mellitus)
(exclude diabetes mellitus by taking serum glucose); associated with dehydration so: hypernatraemia, raised urea, increased plasma osmolality, dilute (hypo-osmolar) urine
3 biochemical features of psychogenic polydipsia
mild hyponatraemia (excess water intake), low plasma osmolality, appropriately dilute (hypo-osmolar) urine
how is cranial diabetes insipidus treated, what does this activate and why is this a problem
exogenous vasopressin which activates all V1 and V2 receptors, when the only relevant receptor is V2 in kidney (also present in endothelial cells which is not desired); V1 present in VSMCs, non-VSMCs, anterior pituitary, liver, platelets and CNS
selective V1 peptidergic agonist and when used
terlipressin, when upper GI bleed (strong vasoconstrictive effects)
selective V2 peptideric agonist to treat diabetes insipidus
desmopressin (DDAVP)
how is desmopressin administered
nasally (critical as often forgotten), orally, subcutaneously
effect of desmopressin and type of diabetes insipidus it treats
reduces urine volume and concentration only in cranial diabetes insipidus (no issue with vasopressin resistance in collecting ducts)
risk of desmopressin
risk of hyponatraemia if patient continues to drink large amounts of fluid
how is nephrogenic diabetes insipidus treated
not desmopressin as problem isn’t vasopressin proudction, so treat with thiazides e.g. bendroflumethiazide (despite helping to pass urine)
mechanism of how thiazides treat nephrogenic insipidus
inhibits Na+/Cl- transport in distal convoluted tubule, causing diuretic effect -> volume depletion -> compensatory increase in Na+ reabsorption from proximal tubule (and small decrease in GFR) -> increased proximal water reabsorption -> decreased fluid reaching collecting duct -> reduced urine volume
