Diabetes Insipidus

Diabetes Insipidus Dr Thomas Fox Endocrine SpR RCH

Diabetes from the Greek diabainein
To stand with the legs apart
Insipudus meaning lack of taste

Outline
Anatomy of posterior pituitary
Water physiology and anti-diuretic hormone (arginine vasopressin)
Clinical cases
Investigations and differential diagnoses
Management
Conclusions

Anti-diuretic hormone (Arginine Vasopressin )
Anti-diuretic hormone (ADH)
Molecular weight 1084
Polypeptide hormone
Produced
from prohormone neurophysin II
by the macrocellular neurons
In the suprasellar nucleus
Released in the posterior
Pituitary
Hepatic metabolism
Half life 10-20mins

Water homeostasis
Intake
1.2 litres daily from food/metabolism
1-2 litres daily water intake
Output
Stool
Insensible losses skin, lungs etc)
Urine

Role of ADH
To maintain euvolaemia
Water intake
Stimulated by hypertonic saline and sucrose but not hypertonic urea
Water excretion
Vascular resistance

H20 H20 Collecting Duct Principal cell ADH DNA AQP 2 Synthesis Transport AQP 2 ADH affect on kidney V2 R

ADH production
In response to increased osmolality
Increased osmolality
Cellular dehydration via auaporins in hypothalamic osmoceptors
Linear response with increasing osmolality

ADH Production in response to volume and osmolality changes

ADH Production
In response to reduced reduced extracellular volume
Stimulate baroreceptors in jugular vein
Need a large volume loss to stimulate ADH production
Acts via V1 receptors in vascular systems

Case 1
Initial referral 1999
18y/o male with 3 month history of
dry mouth, thirst
Dinking 10 litres fluid per day
Nocturia 3-4 nightly
No weight loss
PMHx nil
DHx nil
SHx drinks 4-5 unites EtOH weekly

Case cont
Examination normal
Biochemistry
Na 136 mmol/L
K 4.1 mmol/L
Urea 3.3 mmol/L
Creatinine 85 uimol/L
C ca 2.28 mmol/L
Plasma glucose 7.3 mmol/L
Plasma osmolarity 284 mmol/kg
Urine osmolarity 84 mmol/kg

Impression
Biochemistry consistent with psychogenic polydipsia
Pt reviewed 6/12 later
Feeling better
Still thirsty all the time but drinking less in total
discharged

2 years later
Routine contact lens F/U with optician
Pt described reduced vision
Had bitemporal hemianopia
GP referred the patient to neurology who arranged MRI brain
MRI abnormal so patient referred for acute admission

On admission
Na 146 mmol/L
K 4.8 mmol/L
LH and FSH <0.9 IU/L
Testosterone <0.9 mmol/L
Cortisol 15 nmol/L, ACTH <10 ng/L
PRL 1148 miU/L
TSH 5.4 miU/L
FT4 4.9 pmol/L, FT3 4.5 pmol/L
ILGF-1 12.5 nmol/L
synACTHen, GnRH and TRH tests normal response to stimulation

MRI brain showed;
An irregular enhancing suprasellar mass in the region of the hypothalamus and floor of the third ventricle, immediately abutting the optic chiasm.
There wass a further 2.2cm mass seen at the scene in the posterior 3rd ventricle immediately adjacent to the tectum and aqueduct
Appearances consistent with glioblastoma, no evidence of hydrocephalus

Treatment - medical
Dexamethasone 0.5/0.25mg daily
Levothyroxine 100mcg od
Sustanon 250 every 3 weeks
Desmopressin 20mcg nasally od
serum osmolality 300mosm/L (pt chooses not to take 2 nd dose of desmopressin)

Treatment – surgical
Biopsy confirmed a germinoma
Ommaya shunt sited
Subsequently treated with craniospinal radiotherapy

Case 2
64 year-old female
PMHx
Osteoarthritis
Essential hypertension
Fibromyalgia
Previous gallstone pancreatitis
Laparoscopic cholecystectomy

Referred by rheumatology consultant with severe polydipsia, polyuria and nocturia
Drinking 6-8litres daily
Passing 7 litres urine daily
Nocturia 2-3 times
DHx
Irbesartan 300mg
Diltiazem MR 300mg
Amitriptyllijne 10mg
Tramadol MR 400mg
Co-codamol

On examination
Not dehydrated
No visual field defect
BP 152/94
Biochemistry
Cor Ca 2.61 mmol/L
Sodium 139-142 mmol/L
Potassium 4.6 mmol/L
Creatinie 96 umol/L

Further investigations
Plasma osmolality – 300mosm/kg
TSH 2.4mU/L
FT4 8.3pmol/L, FT£ 3.0pmol/L
PRL 1044mU/L
C Ca 2.66 mmol/L, PTH 5.9 mmol/L
Cortisol 564 nmol/L
LH 0.5iU/L, FSH 3.0 iU/L

Ophthalmology review
Bitemporal hemianopia

Pituitary MRI
Suprasellar cystic mass I2 1 x 2.5 x 3 .2 cm. It is predominantly cystic although there are two enhancing nodules within it.
The mass displaced adjacent structures, most notably the optic chiasm which is stretched and compressed.
Mass extended into pituitary fossa but did not arise from the piuitary
Likely craniopharyngeoma

Management
Commenced on
Hydrocortisone 10mg/5mg/5mg
Levothyroxine 50mcg
Desmopressin acetate orally 100mcg bd
Urgent referral to neurosurgeons

Progress
Underwent pituitary surgery
Histology confirmed a chordoma
Awaiting proton beam radiotherapy
Plasma osmolality now 280-285 mosmol/L

Differential diagnosis of polydipsia/polyuria
Diabetes mellitus
Hypercalcaemia
Diabetes insipidus
Cranial
Nephrogenic (genetic X linked, litjium, domeclocycline)
Psychogenic polydipsia

Causes of cranial DI
idiopathic
head injury and neurosurgery
neoplastic - pituitary tumour, craniopharyngioma, dysgerminoma, hypothalamic metastases - often in children
infectious - meningitis, encephalitis
granulomatous disease - sarcoidosis, histiocytosis
vascular - aneurysm, sickle cell anaemia, Sheehan's syndrome
drugs - ADH secretion is suppressed by naloxone, ethanol and phenytoin

Investigations
Electrolytes
Urea/creatinine
Plasma osmolality/urine osmolality
Glucose
Calcium
24 hour urine collection
Pituitary screen (TSH, FT4, PRL, cortisol, LH/FSH, ILGF1)
Visual field tests
Pituitary MRI

Water deprivation test
Baseline
Weight
Plasma and urine osmolality
Serum electrolytes
Deprive of water, and food
Under constant supervision
Monitor hourly serum/urine osmolality, urine output and weight
Primary polydipsia - If urine concentrates and serum osmolality remains low
If plasma osmolality >300 mosmol/L or 5% wt loss then give DDAVP and allow to drink
Recheck serum and urine and expect to see 1:2 ratio (serum to urine osm) in cranial DI, patinents with nephrogenic DI will not concentrate their urine

Treatment
Desmopressin
Inranasally- 10-40mcg daily divided doses
By mouth 0.2-1.2mg daily divided doses
Titrate dose to symptoms
Monitor electrolytes and osmolality

Conclusions
Adequate investigation required
Presentation can often be subtle/missed
Initial urine/plasma osmolality may be falsely reassuring
Can be first presentation of severe intracranial pathology

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Diabetes Insipidus

by PeninsulaEndocrine on Dec 02, 2009

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Diabetes Insipidus — Presentation Transcript