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Diabetes Insipidus Dr Thomas Fox  Endocrine SpR RCH
<ul><li>Diabetes from the Greek  diabainein   </li></ul><ul><ul><li>To stand with the legs apart </li></ul></ul><ul><li>In...
Outline <ul><li>Anatomy of posterior pituitary </li></ul><ul><li>Water physiology and anti-diuretic hormone (arginine vaso...
Anti-diuretic hormone (Arginine Vasopressin ) <ul><li>Anti-diuretic hormone (ADH) </li></ul><ul><li>Molecular weight 1084 ...
                                                                                          
Water homeostasis <ul><li>Intake </li></ul><ul><ul><li>1.2 litres daily from food/metabolism </li></ul></ul><ul><ul><li>1-...
Role of ADH <ul><li>To maintain euvolaemia </li></ul><ul><ul><li>Water intake </li></ul></ul><ul><ul><ul><li>Stimulated by...
H20 H20 Collecting Duct Principal cell ADH DNA AQP 2 Synthesis Transport AQP 2 ADH affect on kidney V2 R
ADH production <ul><li>In response to increased osmolality </li></ul><ul><ul><li>Increased osmolality </li></ul></ul><ul><...
ADH Production in response to volume and osmolality changes
ADH Production <ul><li>In response to reduced reduced extracellular volume </li></ul><ul><ul><li>Stimulate baroreceptors i...
Case 1 <ul><li>Initial referral 1999 </li></ul><ul><li>18y/o male with 3 month history of </li></ul><ul><ul><li>dry mouth,...
Case cont <ul><li>Examination normal </li></ul><ul><li>Biochemistry </li></ul><ul><ul><li>Na 136 mmol/L </li></ul></ul><ul...
<ul><li>Impression </li></ul><ul><ul><li>Biochemistry consistent with psychogenic polydipsia </li></ul></ul><ul><li>Pt rev...
2 years later <ul><li>Routine contact lens F/U with optician </li></ul><ul><ul><li>Pt described reduced vision </li></ul><...
On admission <ul><li>Na 146 mmol/L </li></ul><ul><li>K 4.8 mmol/L </li></ul><ul><li>LH and FSH <0.9 IU/L </li></ul><ul><li...
<ul><li>MRI brain showed; </li></ul><ul><li>An irregular enhancing suprasellar mass in the region of the hypothalamus and ...
Treatment - medical <ul><li>Dexamethasone 0.5/0.25mg daily </li></ul><ul><li>Levothyroxine 100mcg od </li></ul><ul><li>Sus...
Treatment – surgical <ul><li>Biopsy confirmed a germinoma </li></ul><ul><li>Ommaya shunt sited </li></ul><ul><li>Subsequen...
Case 2 <ul><li>64 year-old female </li></ul><ul><ul><li>PMHx </li></ul></ul><ul><ul><ul><li>Osteoarthritis </li></ul></ul>...
<ul><li>Referred by rheumatology consultant with severe polydipsia, polyuria and nocturia </li></ul><ul><ul><li>Drinking 6...
<ul><li>On examination </li></ul><ul><ul><li>Not dehydrated </li></ul></ul><ul><ul><li>No visual field defect </li></ul></...
Further investigations <ul><li>Plasma osmolality – 300mosm/kg </li></ul><ul><li>TSH 2.4mU/L </li></ul><ul><li>FT4 8.3pmol/...
Ophthalmology review <ul><li>Bitemporal hemianopia </li></ul>
Pituitary MRI <ul><li>Suprasellar cystic  mass I2  1  x  2.5  x  3  .2  cm.  It  is predominantly  cystic  although  there...
 
Management <ul><li>Commenced on </li></ul><ul><ul><li>Hydrocortisone 10mg/5mg/5mg </li></ul></ul><ul><ul><li>Levothyroxine...
Progress <ul><li>Underwent pituitary surgery </li></ul><ul><li>Histology confirmed a chordoma </li></ul><ul><li>Awaiting p...
Differential diagnosis of polydipsia/polyuria <ul><li>Diabetes mellitus </li></ul><ul><li>Hypercalcaemia </li></ul><ul><li...
Causes of cranial DI <ul><li>idiopathic  </li></ul><ul><li>head injury and neurosurgery  </li></ul><ul><li>neoplastic - pi...
Investigations <ul><li>Electrolytes </li></ul><ul><li>Urea/creatinine </li></ul><ul><li>Plasma osmolality/urine osmolality...
Water deprivation test <ul><li>Baseline </li></ul><ul><ul><li>Weight </li></ul></ul><ul><ul><li>Plasma and urine osmolalit...
Treatment <ul><li>Desmopressin </li></ul><ul><ul><li>Inranasally- 10-40mcg daily divided doses </li></ul></ul><ul><ul><li>...
Conclusions <ul><li>Adequate investigation required </li></ul><ul><li>Presentation can often be subtle/missed </li></ul><u...
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Diabetes Insipidus

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  1. 1. Diabetes Insipidus Dr Thomas Fox Endocrine SpR RCH
  2. 2. <ul><li>Diabetes from the Greek diabainein </li></ul><ul><ul><li>To stand with the legs apart </li></ul></ul><ul><li>Insipudus meaning lack of taste </li></ul>
  3. 3. Outline <ul><li>Anatomy of posterior pituitary </li></ul><ul><li>Water physiology and anti-diuretic hormone (arginine vasopressin) </li></ul><ul><li>Clinical cases </li></ul><ul><li>Investigations and differential diagnoses </li></ul><ul><li>Management </li></ul><ul><li>Conclusions </li></ul>
  4. 4. Anti-diuretic hormone (Arginine Vasopressin ) <ul><li>Anti-diuretic hormone (ADH) </li></ul><ul><li>Molecular weight 1084 </li></ul><ul><li>Polypeptide hormone </li></ul><ul><li>Produced </li></ul><ul><ul><li>from prohormone neurophysin II </li></ul></ul><ul><ul><li>by the macrocellular neurons </li></ul></ul><ul><ul><li>In the suprasellar nucleus </li></ul></ul><ul><li>Released in the posterior </li></ul><ul><ul><li>Pituitary </li></ul></ul><ul><ul><li>Hepatic metabolism </li></ul></ul><ul><ul><li>Half life 10-20mins </li></ul></ul>
  5. 5.                                                                                           
  6. 6. Water homeostasis <ul><li>Intake </li></ul><ul><ul><li>1.2 litres daily from food/metabolism </li></ul></ul><ul><ul><li>1-2 litres daily water intake </li></ul></ul><ul><li>Output </li></ul><ul><ul><li>Stool </li></ul></ul><ul><ul><li>Insensible losses skin, lungs etc) </li></ul></ul><ul><ul><li>Urine </li></ul></ul>
  7. 7. Role of ADH <ul><li>To maintain euvolaemia </li></ul><ul><ul><li>Water intake </li></ul></ul><ul><ul><ul><li>Stimulated by hypertonic saline and sucrose but not hypertonic urea </li></ul></ul></ul><ul><ul><li>Water excretion </li></ul></ul><ul><ul><li>Vascular resistance </li></ul></ul>
  8. 8. H20 H20 Collecting Duct Principal cell ADH DNA AQP 2 Synthesis Transport AQP 2 ADH affect on kidney V2 R
  9. 9. ADH production <ul><li>In response to increased osmolality </li></ul><ul><ul><li>Increased osmolality </li></ul></ul><ul><ul><li>Cellular dehydration via auaporins in hypothalamic osmoceptors </li></ul></ul><ul><ul><li>Linear response with increasing osmolality </li></ul></ul>
  10. 10. ADH Production in response to volume and osmolality changes
  11. 11. ADH Production <ul><li>In response to reduced reduced extracellular volume </li></ul><ul><ul><li>Stimulate baroreceptors in jugular vein </li></ul></ul><ul><ul><li>Need a large volume loss to stimulate ADH production </li></ul></ul><ul><ul><li>Acts via V1 receptors in vascular systems </li></ul></ul>
  12. 12. Case 1 <ul><li>Initial referral 1999 </li></ul><ul><li>18y/o male with 3 month history of </li></ul><ul><ul><li>dry mouth, thirst </li></ul></ul><ul><ul><li>Dinking 10 litres fluid per day </li></ul></ul><ul><ul><li>Nocturia 3-4 nightly </li></ul></ul><ul><ul><li>No weight loss </li></ul></ul><ul><li>PMHx nil </li></ul><ul><li>DHx nil </li></ul><ul><li>SHx drinks 4-5 unites EtOH weekly </li></ul>
  13. 13. Case cont <ul><li>Examination normal </li></ul><ul><li>Biochemistry </li></ul><ul><ul><li>Na 136 mmol/L </li></ul></ul><ul><ul><li>K 4.1 mmol/L </li></ul></ul><ul><ul><li>Urea 3.3 mmol/L </li></ul></ul><ul><ul><li>Creatinine 85 uimol/L </li></ul></ul><ul><ul><li>C ca 2.28 mmol/L </li></ul></ul><ul><ul><li>Plasma glucose 7.3 mmol/L </li></ul></ul><ul><ul><li>Plasma osmolarity 284 mmol/kg </li></ul></ul><ul><ul><li>Urine osmolarity 84 mmol/kg </li></ul></ul>
  14. 14. <ul><li>Impression </li></ul><ul><ul><li>Biochemistry consistent with psychogenic polydipsia </li></ul></ul><ul><li>Pt reviewed 6/12 later </li></ul><ul><ul><li>Feeling better </li></ul></ul><ul><ul><li>Still thirsty all the time but drinking less in total </li></ul></ul><ul><ul><li>discharged </li></ul></ul>
  15. 15. 2 years later <ul><li>Routine contact lens F/U with optician </li></ul><ul><ul><li>Pt described reduced vision </li></ul></ul><ul><ul><li>Had bitemporal hemianopia </li></ul></ul><ul><li>GP referred the patient to neurology who arranged MRI brain </li></ul><ul><li>MRI abnormal so patient referred for acute admission </li></ul>
  16. 16. On admission <ul><li>Na 146 mmol/L </li></ul><ul><li>K 4.8 mmol/L </li></ul><ul><li>LH and FSH <0.9 IU/L </li></ul><ul><li>Testosterone <0.9 mmol/L </li></ul><ul><li>Cortisol 15 nmol/L, ACTH <10 ng/L </li></ul><ul><li>PRL 1148 miU/L </li></ul><ul><li>TSH 5.4 miU/L </li></ul><ul><li>FT4 4.9 pmol/L, FT3 4.5 pmol/L </li></ul><ul><li>ILGF-1 12.5 nmol/L </li></ul><ul><li>synACTHen, GnRH and TRH tests normal response to stimulation </li></ul>
  17. 17. <ul><li>MRI brain showed; </li></ul><ul><li>An irregular enhancing suprasellar mass in the region of the hypothalamus and floor of the third ventricle, immediately abutting the optic chiasm. </li></ul><ul><li>There wass a further 2.2cm mass seen at the scene in the posterior 3rd ventricle immediately adjacent to the tectum and aqueduct </li></ul><ul><li>Appearances consistent with glioblastoma, no evidence of hydrocephalus </li></ul>
  18. 18. Treatment - medical <ul><li>Dexamethasone 0.5/0.25mg daily </li></ul><ul><li>Levothyroxine 100mcg od </li></ul><ul><li>Sustanon 250 every 3 weeks </li></ul><ul><li>Desmopressin 20mcg nasally od </li></ul><ul><ul><li>serum osmolality 300mosm/L (pt chooses not to take 2 nd dose of desmopressin) </li></ul></ul>
  19. 19. Treatment – surgical <ul><li>Biopsy confirmed a germinoma </li></ul><ul><li>Ommaya shunt sited </li></ul><ul><li>Subsequently treated with craniospinal radiotherapy </li></ul>
  20. 20. Case 2 <ul><li>64 year-old female </li></ul><ul><ul><li>PMHx </li></ul></ul><ul><ul><ul><li>Osteoarthritis </li></ul></ul></ul><ul><ul><ul><li>Essential hypertension </li></ul></ul></ul><ul><ul><ul><li>Fibromyalgia </li></ul></ul></ul><ul><ul><ul><li>Previous gallstone pancreatitis </li></ul></ul></ul><ul><ul><ul><li>Laparoscopic cholecystectomy </li></ul></ul></ul>
  21. 21. <ul><li>Referred by rheumatology consultant with severe polydipsia, polyuria and nocturia </li></ul><ul><ul><li>Drinking 6-8litres daily </li></ul></ul><ul><ul><li>Passing 7 litres urine daily </li></ul></ul><ul><ul><li>Nocturia 2-3 times </li></ul></ul><ul><li>DHx </li></ul><ul><ul><li>Irbesartan 300mg </li></ul></ul><ul><ul><li>Diltiazem MR 300mg </li></ul></ul><ul><ul><li>Amitriptyllijne 10mg </li></ul></ul><ul><ul><li>Tramadol MR 400mg </li></ul></ul><ul><ul><li>Co-codamol </li></ul></ul>
  22. 22. <ul><li>On examination </li></ul><ul><ul><li>Not dehydrated </li></ul></ul><ul><ul><li>No visual field defect </li></ul></ul><ul><ul><li>BP 152/94 </li></ul></ul><ul><li>Biochemistry </li></ul><ul><ul><li>Cor Ca 2.61 mmol/L </li></ul></ul><ul><ul><li>Sodium 139-142 mmol/L </li></ul></ul><ul><ul><li>Potassium 4.6 mmol/L </li></ul></ul><ul><ul><li>Creatinie 96 umol/L </li></ul></ul>
  23. 23. Further investigations <ul><li>Plasma osmolality – 300mosm/kg </li></ul><ul><li>TSH 2.4mU/L </li></ul><ul><li>FT4 8.3pmol/L, FT£ 3.0pmol/L </li></ul><ul><li>PRL 1044mU/L </li></ul><ul><li>C Ca 2.66 mmol/L, PTH 5.9 mmol/L </li></ul><ul><li>Cortisol 564 nmol/L </li></ul><ul><li>LH 0.5iU/L, FSH 3.0 iU/L </li></ul>
  24. 24. Ophthalmology review <ul><li>Bitemporal hemianopia </li></ul>
  25. 25. Pituitary MRI <ul><li>Suprasellar cystic mass I2  1  x  2.5  x  3  .2  cm.  It  is predominantly  cystic  although  there  are  two  enhancing nodules  within  it.  </li></ul><ul><li>The  mass  displaced  adjacent  structures, most  notably  the  optic  chiasm  which  is  stretched  and compressed.  </li></ul><ul><li>Mass extended into pituitary fossa but did not arise from the piuitary </li></ul><ul><li>Likely craniopharyngeoma </li></ul>
  26. 27. Management <ul><li>Commenced on </li></ul><ul><ul><li>Hydrocortisone 10mg/5mg/5mg </li></ul></ul><ul><ul><li>Levothyroxine 50mcg </li></ul></ul><ul><ul><li>Desmopressin acetate orally 100mcg bd </li></ul></ul><ul><li>Urgent referral to neurosurgeons </li></ul>
  27. 28. Progress <ul><li>Underwent pituitary surgery </li></ul><ul><li>Histology confirmed a chordoma </li></ul><ul><li>Awaiting proton beam radiotherapy </li></ul><ul><li>Plasma osmolality now 280-285 mosmol/L </li></ul>
  28. 29. Differential diagnosis of polydipsia/polyuria <ul><li>Diabetes mellitus </li></ul><ul><li>Hypercalcaemia </li></ul><ul><li>Diabetes insipidus </li></ul><ul><ul><li>Cranial </li></ul></ul><ul><ul><li>Nephrogenic (genetic X linked, litjium, domeclocycline) </li></ul></ul><ul><li>Psychogenic polydipsia </li></ul>
  29. 30. Causes of cranial DI <ul><li>idiopathic </li></ul><ul><li>head injury and neurosurgery </li></ul><ul><li>neoplastic - pituitary tumour, craniopharyngioma, dysgerminoma, hypothalamic metastases - often in children </li></ul><ul><li>infectious - meningitis, encephalitis </li></ul><ul><li>granulomatous disease - sarcoidosis, histiocytosis </li></ul><ul><li>vascular - aneurysm, sickle cell anaemia, Sheehan's syndrome </li></ul><ul><li>drugs - ADH secretion is suppressed by naloxone, ethanol and phenytoin </li></ul>
  30. 31. Investigations <ul><li>Electrolytes </li></ul><ul><li>Urea/creatinine </li></ul><ul><li>Plasma osmolality/urine osmolality </li></ul><ul><li>Glucose </li></ul><ul><li>Calcium </li></ul><ul><li>24 hour urine collection </li></ul><ul><li>Pituitary screen (TSH, FT4, PRL, cortisol, LH/FSH, ILGF1) </li></ul><ul><li>Visual field tests </li></ul><ul><li>Pituitary MRI </li></ul>
  31. 32. Water deprivation test <ul><li>Baseline </li></ul><ul><ul><li>Weight </li></ul></ul><ul><ul><li>Plasma and urine osmolality </li></ul></ul><ul><ul><li>Serum electrolytes </li></ul></ul><ul><li>Deprive of water, and food </li></ul><ul><li>Under constant supervision </li></ul><ul><li>Monitor hourly serum/urine osmolality, urine output and weight </li></ul><ul><li>Primary polydipsia - If urine concentrates and serum osmolality remains low </li></ul><ul><li>If plasma osmolality >300 mosmol/L or 5% wt loss then give DDAVP and allow to drink </li></ul><ul><li>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 </li></ul>
  32. 33. Treatment <ul><li>Desmopressin </li></ul><ul><ul><li>Inranasally- 10-40mcg daily divided doses </li></ul></ul><ul><ul><li>By mouth 0.2-1.2mg daily divided doses </li></ul></ul><ul><li>Titrate dose to symptoms </li></ul><ul><li>Monitor electrolytes and osmolality </li></ul>
  33. 34. Conclusions <ul><li>Adequate investigation required </li></ul><ul><li>Presentation can often be subtle/missed </li></ul><ul><li>Initial urine/plasma osmolality may be falsely reassuring </li></ul><ul><li>Can be first presentation of severe intracranial pathology </li></ul>
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