Diabetes Insipidus Flashcards
Diabetes Insipidus (DI)
Diabetes insipidus (DI) is a condition characterised by either a deficiency of antidiuretic hormone, ADH, (cranial DI) or an insensitivity to antidiuretic hormone (nephrogenic DI).
Features
polyuria
polydipsia
Investigation
high plasma osmolality, low urine osmolality
water deprivation test
Causes of Cranial DI
Causes of cranial DI idiopathic post head injury pituitary surgery craniopharyngiomas histiocytosis X DIDMOAD is the association of cranial Diabetes Insipidus, Diabetes Mellitus, Optic Atrophy and Deafness (also known as Wolfram's syndrome)
Causes of Nephrogenic DI
Causes of nephrogenic DI
genetic: the more common form affects the vasopression (ADH) receptor, the less common form results from a mutation in the gene that encodes the aquaporin 2 channel
electrolytes: hypercalcaemia, hypokalaemia
drugs: demeclocycline, lithium
tubulo-interstitial disease: obstruction, sickle-cell, pyelonephritis
Cranial DI: Example Question
A 40 year old man attended his General Practitioner and reported ongoing frequency of urination for the past few weeks. The patient reported passing very dilute urine. There was no history of hesitancy of micturition or terminal dribbling.
The patient was also under investigation for suspected liver disease after presenting with mild jaundice 3 weeks previously. Some initial investigations had been completed but hepatology clinic review was still awaited. There was no other past medical history and the patient took no regular or illicit medications. The patient worked as an insurance agent, lived alone and drank only minimal amounts of alcohol.
A summary of initial investigations arranged by the General Practitioner and through endocrine clinic are given below.
Haemoglobin 11.5 g / dL
White cell count 6.5 * 109/l
Neutrophils 4.2 * 109/l
Platelets 156 * 109/l
Urea 9.3 mmol / L
Creatinine 145 micromol / L
Sodium 156 mmol / L
Potassium 3.9 mmol / L
Albumin 30 g / L
Alkaline phosphatase 170 U / L
ALT 150 U / L
Bilirubin 80 micromol / L
Ferritin 439 ng / mL
Serum immunoglobulins No abnormality detected
Hepatitis viruses No abnormality detected
Thyroid stimulating hormone 1.0 microU / L (reference 0.4-5.0)
T4 free serum 13.4 pmol / L (reference 8.5-15.2)
Plasma osmolality 390 mmol / L (reference 280-295)
Urine osmolality 80 mmol / L (reference 100-900)
Plasma osmolality (after desmopressin) 267 mmol / L (reference 280-295)
Urine osmolality (after desmopressin) 265 mmol / L (reference 100-900)
Random serum glucose 4.5 mmol / L
What is the cause of the patient’s polydipsia?
Nephrogenic diabetes insipidus Liver cirrhosis secondary to haemachromatosis Primary polydipsia Chronic renal failure > Cranial diabetes insipidus
The patient has a high plasma osmolality and low urine osmolality consistent with diabetes insipidus. The osmolality values correct with desmopressin indicating a cranial aetiology. The likely cause of this is haemachromatosis implied by deranged liver function tests and raised ferritin. The other possible answers would not explain the observed osmolality values.
Nephrogenic DI: Example Question
A 36 year old female patient presents to the endocrinology clinic to see you for follow up. She reports a 1 year history of thirst and drinking a lot of water. She has had a normal fasting glucose and oral glucose tolerance test. On her previous visit, you booked the patient for a water deprivation test and the results are available:
Time> Urine osmolality (mOsm/kg) >Serum osmolality (mOsm/kg) > Weight (kg) >% change in weight
0800 263 263 86.1 n/a 1000 265 278 85.7 -0.46% 1200 279 289 85.4 -0.81% 1400 280 295 84.9 -1.39% 1600 285 301 84.6 -1.74% 1700 DDAVP given 1800 286 302 84.3 -2.09% 2000 289 303 84.1 -2.32%
What is the underlying cause of this lady’s symptoms?
> Nephrogenic diabetes insipidus Psychogenic polydipsia Cranial diabetes insipidus Partial cranial diabetes insipidus None of the above
This lady has symptoms of polydipsia and thirst. The differentials of this are diabetes insipidus, psychogenic polydipsia and diabetes mellitus (which is ruled out in the question body). The water deprivation test is used when diabetes insipidus is suspected and helps to differentiate between nephrogenic diabetes insipidus (kidney is not sensitive enough to ADH release by the posterior pituitary), cranial diabetes insipidus (lack of release of ADH from the posterior pituitary, kidney sensitive to exogenous ADH when administered) and psychogenic polydipsia (a normal outcome to the water deprivation test). In this case we can see that as the patient is deprived of water, their serum osmolality rises, as expected. However, the urine does not concentrate that much, and there is minimal, if any response by the kidneys to DDAVP. This indicates a nephrogenic diabetes insipidus as psychogenic polydipsia would show concentrated urine much earlier in the test with high urine osmolalities and in cranial diabetes insipidus, the kidneys would show a much greater response to DDAVP by concentrating the urine.
Nephrogenic DI - SE of Lithium Therapy - Example Question
A 58-year-old lady with an extensive psychiatric history presents to the Acute Medical unit unwell and dehydrated. She recently had a viral illness and has spent most of the past week in bed. She is mildly confused on arrival and the ambulance sheet states that for the past two weeks she has been passing urine more frequently, particularly at night. She denies any dysuria or fevers.
She has a history of bipolar affective disorder which is currently stable on lithium. She also has a history of irritable bowel syndrome, hypertension, hypercholesterolaemia and migraines. She currently takes amlodipine 10mg once a day, simvastatin 20mg at night, mebeverine 135mg three times a day and lithium carbonate 800mg at night. She has no known drug allergies.
On examination, she looks unwell and dehydrated. Her pulse is 105 bpm and regular, blood pressure 95/65 mmHg, saturations of 98% on air. Numerous linear scars are apparent on both her arms and the tops of her thighs. Her mucous membranes are dry and her JVP is not visible at 45 degrees. Her chest was clear. Abdominal examination demonstrated a soft, non-tender abdomen with no masses or organomegaly and normal bowel sounds.
A set of bloods come back as follows:
Na+ 153 mmol/L K+ 4.9 mmol/L Urea 8 mmol/L Creatinine 110 µmol/L Hb 160 g/L WBC 6.0x10^9/L LFTs Normal Urine osmolality 180 mOsmol/kg
Chest x-ray shows clear lung fields.
Considering the most likely diagnosis which of the following treatments are most likely to treat the underlying condition?
Hypertonic saline resuscitation Low dose DDAVP Observation > Thiazide diuretic and amiloride 1.5L fluid restriction
This lady has a history of bipolar disorder which has been well controlled with lithium. She presents following a viral illness where her mobility and possibly fluid intake has been reduced. She has been passing large quantities of urine associated with a very low (diluted) urine osmolality. She is very dehydrated and hypovolaemic with associated hypernatraemia which may explain the mild confusion.
Nephrogenic diabetes insipidus (DI) is a relatively common side effect of lithium therapy and usually presents with polyuria and polydipsia. Severe dehydration only presents if patients have struggled to keep up with the oral intake as is the case here.
Unlike cranial DI, nephrogenic DI is not usually responsive to low doses of desmopressin (DDAVP) although mild to moderate cases have been successfully treated with high doses.
The patient is clearly very dehydrated, therefore fluid restriction is likely to worsen her condition. Equally, in view of her hypernatraemia, the use of hypertonic saline will likely worsen this.
Observation is likely to result in further deterioration. Ideally, the case should be discussed with the psychiatrists and the lithium discontinued and she should be encouraged to drink plenty of fluids.
As she is markedly dehydrated and affected by her DI, treatment with thiazide diuretics (which produce a paradoxical concentration of the urine) and amiloride has been shown to be effective. This is, therefore, the only correct answer here.
Psychogenic Polydipsia - Example Question
A 52 year old lady presents complaining of polydipsia and polyuria. She has a background of hypertension, hypercholesterolaemia and bipolar affective disorder and a strong family history of diabetes - she is unsure which type.
Results show the following:
Na+ 131mmol/l
urine osmolality 287mOsmol/kg (300 - 900mOsmol/kg)
plasma osmolality 287mOsmol/kg (285 - 295mOsmol/kg)
Which of the following is the most likely explanation for this lady’s symptoms?
> Psychogenic polydipsia Syndrome of inappropriate anti-diuretic hormone (SIADH) Diabetes insipidus Diabetes mellitus type 1 Hyponatraemia
Although this lady is biochemically hyponatraemic, this is unlikely to be the cause of her symptoms.
With a past medical history of bipolar affective disorder, although not stated in the question, there is a good chance she may be on lithium which predisposes her to developing nephrogenic diabetes insipidus. However with this diagnosis, we would expect a much lower urine osmolality and a higher plasma osmolality. She would also have a normal to high serum sodium. The opposite would indicate a diagnosis of SIADH (serum hypo-osmolality and high urine osmolality).
The osmolality results here reflect a diagnosis of psychogenic polydipsia with a low urine osmolality and a low end of normal plasma osmolality.
Nephrogenic DI 2dry to Lithium Therapy again: Example Question
A 30-year-old man with bipolar disorder is admitted with malaise and lethargy. He takes lithium regularly and complains of increased thirst and weakness.
His urine output is 4.5L in 24 hours.
Na+ 154 mmol/l K+ 4.0 mmol/l Urea 6.1 mmol/l Creatinine 72 µmol/l Calcium 2.47 mmol/l Glucose 7.2 mmol/l Urine Osmolarity 254 osmol/l (NR 500-800)
What is the most appropriate next step in management?
5% Dextrose 0.45% Saline Desmopressin Fluid restriction > Thiazide diuretic
This patient has hypernatraemia secondary to nephrogenic diabetes insipidus caused by lithium therapy. This is indicated by polyuria, hypernatraemia, lithium use. The urine is inappropriately dilute for his serum sodium.
Treatment is with thiazide diuretics or NSAIDs. Diuretics act to induce hypovolaemia leading to a subsequent increase in proximal sodium and water reabsorption, thereby diminishing the water delivery to the ADH sensitive sites in the collecting tubules, and reducing the urine output.
Hypernatraemia is usually caused by:
excess of hypertonic fluids (IV saline, enteral or parenteral nutrition);
excessive free water loss - renal (diabetes insipidus, diuretics, osmotic diuresis as with hyperglycaemia), GI (diarrhoea, vomiting), skin (sweating, burns)
reduced thirst - seen in very old and very young patients.
Treatment is aimed at the underlying cause. An acute hypernatraemia can be corrected quickly but if chronic (>24hours) then it should be corrected at <0.5mmol/L/hr. Fluid resuscitation should involve oral water, 0.45% saline or 5% dextrose IV.
Nephrogenic DI 2dry to Lithium again again - Example Question
A 40-year-old woman is brought to the GP by her husband due to her recent onset of lethargy and confusion. For the past few days she has been complaining of intense thirst, craving for ice water and increased urination, particularly at night. Her medications include lithium and olanzapine for bipolar disorder and lansoprazole for acid reflux.
Her temperature is 37.2ºC, blood pressure is 83/59 mmHg, pulse is 122/min and respiratory rate is 15/min. Physical examination shows a disoriented woman with reduced skin turgor and dry mucous membranes.
Laboratory results are as follows:
Na+ 156 mmol/l K+ 4.1 mmol/l Urea 9.6 mmol/l Creatinine 141 µmol/l Chloride 110 mmol/l Bicarbonate 24 mmol/l Serum glucose 9.9 mmol/l Serum osmolality 328 mOsm/kg Urine osmolality 180 mOsm/kg Serum lithium pending
Which of the following is the most appropriate next step in management of this patient?
Haemodialysis I.V. 0.45% normal saline > I.V. 0.9% normal saline I.V. 5% dextrose Water deprivation test
The patient’s clinical presentation (hypotension, tachycardia, poor skin turgor) is consistent with hypovolaemic hypernatraemia. The first step is to restore volume with isotonic fluids (0.9% saline). Isotonic fluid is not usually used in hypernatraemia, but it is recommended in patients with marked volume depletion and haemodynamic instability. Once euvolaemic, the fluid can be switched to a hypotonic fluid (5% dextrose preferred over 0.45% saline) for free water supplementation (Choices 4 and 2). The serum sodium should be corrected by 0.5 mmol/l/hr without exceeding 12 mmol/l in 24 hours. Cerebral oedema can occur if the sodium is corrected too quickly.
This patient’s high serum and low urine osmolality indicate an inability to concentrate the urine due to inadequate anti-diuretic hormone (ADH) response. This is most likely due to lithium-induced nephrogenic diabetes insipidus. Lithium induces ADH resistance by impairing water reabsorption in the collecting duct. Patients typically develop acute-onset nocturia, polyuria and polydipsia. If water intake is inadequate, significant hypernatraemia and central nervous system symptoms can develop. Discontinuing lithium is recommended, with salt restriction and selected diuretics (e.g. amiloride) as an alternative for patients who cannot stop lithium.
Choice 1: Haemodialysis is usually indicated if serum lithium levels >4 mmol/l or >2.5 mmol/l with signs of significant lithium toxicity (e.g. seizures, depressed mental status) or inability to excrete lithium (e.g. renal disease, decompensated heart failure). Haemodialysis may be necessary in this patient once the lithium level is known and hypovolaemia has been corrected.
Choice 5: A water deprivation test can differentiate between central and nephrogenic diabetes insipidus, however this test would not typically be done until the patient is euvolaemic.
Primary Polydipsia
Primary polydipsia is a rare cause of polyuria in the general population but is common among institutionalised psychiatric patients (6-20 %).
Primary polydipsia is a form of polydipsia characterised by excessive fluid intake in the absence of physiological stimuli to drink. This includes psychogenic polydipsia (PPD), which is caused by mental disorders, often schizophrenia, and often accompanied by the sensation of dry mouth.
Polyuria
Polyuria
A recent review in the BMJ categorised the causes of polyuria by how common they were. This does not of course tally with how common they are in exams!
Common (>1 in 10) diuretics, caffeine & alcohol diabetes mellitus lithium heart failure
Infrequent (1 in 100)
hypercalcaemia
hyperthyroidism
Rare (1 in 1000)
chronic renal failure
primary polydipsia
hypokalaemia
Very rare (<1 in 10 000) diabetes insipidus
Post-operative Diabetes Insipidus: Example Question
A 55-year-old man with acromegaly is admitted electively for trans-sphenoidal pituitary surgery. The day after his operation, you are asked to prescribe additional fluids as his urine output has reached 10 litres in the past 24 hours. Urinalysis is unremarkable apart from a low specific gravity.
You organise the following investigations:
Serum Na+ 149 mmol/l
Serum K+ 3.8 mmol/l
Plasma Osmolality 299 mOsm/kg
24 hour Urine Osmolality 325 mOsm/kg
Which of the following is the most useful step in this patient’s immediate management?
Start demeclocycline Start desmopressin MRI imaging of the pituitary Ultrasound imaging of the kidneys > Monitor fluid balance and replace losses
The clue here is that the question asks about immediate managment.
In this case, a post-operative diabetes insipidus is the likely culprit. This may resolve without intervention. If the fluid and electrolyte abnormalities failed to settle, further investigations (i.e. water deprivation and desmopressin challenge) would be appropriate. If this patient had a longstanding DI then pharmacotherapy could be considered; however in this acute (and hopefully transient) setting, it should be sufficient to replace fluid losses and await spontaneous restoration of endogenous AVP secretion.
Psychogenic DI - Example Question
A 34-year-old woman with a body mass index of 28kg/m² and a background of bipolar disorder presents with excessive thirst, polyuria, and nocturia. Her current medications include lithium and occasional over the counter paracetamol. Her investigation results are as shown below.
Hb 120 g/l
Platelets 220 * 109/l
WBC 5.2 * 109/l
Na+ 128 mmol/l
Ca+ 2.32 mmol/l
Urea 3 mmol/l
Fasting plasma glucose 7.2 mmol/L
Water deprivation test: Initial plasma osmolality low Urine osmolality 300-400 mOsm/kg Urine osmolality post desmopressin 400 mOsm/kg Final plasma ADH moderate
What is the most likely cause of her symptoms?
Type 2 diabetes mellitus Nephrogenic diabetes insipidus Type 1 diabetes mellitus > Primary polydipsia Cranial diabetes insipidus
Although this patient is on lithium that can cause nephrogenic diabetes insipidus (DI), her low sodium and plasma osmolality point towards primary/psychogenic polydipsia. This is further supported by the minimal change in urine osmolality post desmopressin.
In nephrogenic and cranial DI, initial plasma osmolality is high and urine osmolality is <300 mOsm/kg. Also one would expect a significant increase in urine osmolality (>600 mOsm/kg) post desmopressin in cranial DI. Nephrogenic DI does not respond to desmopressin and therefore urine osmolality will not change.
Her mildly raised fasting glucose does not account for her low sodium or plasma osmolality.
Water Deprivation Test
Water deprivation test
Method
prevent patient drinking water
ask patient to empty bladder
hourly urine and plasma osmolalities
NORMAL:
Starting plasma osm = Normal
Urine osm post-DDAVP = > 600
Final urine osm = > 600
PSYCHOGENIC POLYDIPSIA:
Starting plasma osm = Low
Final urine osm = > 400
Urine osm post-DDAVP = > 400
CRANIAL DI:
Starting plasma osm = High
Final urine osm = < 300
Urine osm post-DDAVP = > 600
NEPHROGENIC DI:
Starting plasma osm = High
Final urine osm = < 300
Urine osm post-DDAVP = < 300
DDVAP = Desmopressin
DIDMOAD/Wolfram’s Syndrome
DM
Cranial DI
Optic atrophy
Deafness
