Diabetes Insipidus
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Diabetes Insipidus

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Diabetes Insipidus Diabetes Insipidus Presentation Transcript

  • 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