pituitary

Question 1

2 pathophysiological causes of diabetes insipidus

Answer 1

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

Question 2

2 types of cranial diabetes insipidus and prevalence (aetiology)

Answer 2

acquired (more common), genetic (rare)

Question 3

5 ways the neurohypophysial system may be damaged in acquired cranial diabetes insipidus

Answer 3

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)

Question 4

nephrogenic diabetes insipidus aetiology: congenital

Answer 4

rare; e.g. mutation in gene encoding V2 receptor or AQP2

Question 5

nephrogenic diabetes insipidus aetiology: acquired

Answer 5

drugs (e.g. lithium toxicity)

Question 6

5 signs and symptoms of diabetes insipidus

Answer 6

polyuria, hypo-osmolar urine (unlike diabetes mellitus, which has lots of glucose in it), polydipsia, dehydration (if fluid intake not maintained), possible sleep disruption

Question 7

how does diabetes insipidus cause expansion of ECF volume [in presence of water availability] (if no access to water, causes dehydration and death)

Answer 7

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]

Question 8

where is psychogenic (primary) polydipsia most frequently seen and why

Answer 8

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

Question 9

psychogenic polydipsia vs diabetes insipidus

Answer 9

excess fluid intake (polydipsia) and excess urine output (polyuria), but ability to secrete vasopressin in response to osmotic stimuli is preserved

Question 10

pathway of psychogenic polydipsia: normal response to drinking lots of fluid but confusion as to whether it is diabetes insipidus or psychogenic polydipsia

Answer 10

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)

Question 11

approximate normal (hydrated) range vs diabetes insipidus vs psychogenic polydipsia

Answer 11

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)

Question 12

water deprivation test: purpose and normal hydrated urine osmolality

Answer 12

to determine cause of diabetes insipidus; about 350 mOsm/kg H2O

Question 13

water deprivation test: fluid deprived urine osmolality: normal vs psychological poydipsia vs central diabetes insipidus vs nephrogenic diabetes insipidus

Answer 13

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

Question 14

water deprivation test: DDAVP (vasopressin analogue) administration urine osmolality: central diabetes insipidus vs nephrogenic diabetes insipidus

Answer 14

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)

Question 15

4 biochemical features of diabetes insipidus (after confirming not diabetes mellitus)

Answer 15

(exclude diabetes mellitus by taking serum glucose); associated with dehydration so: hypernatraemia, raised urea, increased plasma osmolality, dilute (hypo-osmolar) urine

Question 16

3 biochemical features of psychogenic polydipsia

Answer 16

mild hyponatraemia (excess water intake), low plasma osmolality, appropriately dilute (hypo-osmolar) urine

Question 17

how is cranial diabetes insipidus treated, what does this activate and why is this a problem

Answer 17

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

Question 18

selective V1 peptidergic agonist and when used

Answer 18

terlipressin, when upper GI bleed (strong vasoconstrictive effects)

Question 19

selective V2 peptideric agonist to treat diabetes insipidus

Answer 19

desmopressin (DDAVP)

Question 20

how is desmopressin administered

Answer 20

nasally (critical as often forgotten), orally, subcutaneously

Question 21

effect of desmopressin and type of diabetes insipidus it treats

Answer 21

reduces urine volume and concentration only in cranial diabetes insipidus (no issue with vasopressin resistance in collecting ducts)

Question 22

risk of desmopressin

Answer 22

risk of hyponatraemia if patient continues to drink large amounts of fluid

Question 23

how is nephrogenic diabetes insipidus treated

Answer 23

not desmopressin as problem isn’t vasopressin proudction, so treat with thiazides e.g. bendroflumethiazide (despite helping to pass urine)

Question 24

mechanism of how thiazides treat nephrogenic insipidus

Answer 24

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