Pituitary Insufficiency William Harper, MD, FRCPC Endocrinology & Metabolism Assistant Professor of Medicine McMaster Univ...
Pituitary Disorders <ul><li>Mass effect </li></ul><ul><ul><ul><li>Headaches </li></ul></ul></ul><ul><ul><ul><li>CN II, III...
Mass Effect: H/A, CN II, EOM, V 1 , V 2 (LR 6 SO 4 ) 3 V 1 V 2
 
 
 
H-P-A Axis
Cushing’s Disease Ectopic ACTH High ACTH Cushing’s
Establish hypercortisolism (Cushing’s syndrome) <ul><li>“ Screening” tests </li></ul><ul><li>1 mg O/N DMST </li></ul><ul><...
Establish hypercortisolism (Cushing’s syndrome) <ul><li>“ Confirmatory Tests” </li></ul><ul><li>24 UFC </li></ul><ul><ul><...
Clinical Suspicion Screen Test:  24 UFC or 1mg O/N DST (+/- evening plasma/salivary cortisol) Confirmatory Testing: Repeat...
Case <ul><li>49 year old female </li></ul><ul><li>Adie’s pupil x 2 years </li></ul><ul><li>L frontoparietal H/A </li></ul>...
 
Pituitary Hyperplasia <ul><li>Another cause of sellar mass! </li></ul><ul><li>Physiological enlargement of pituitary </li>...
 
Prolactinoma <ul><li>Most common pituitary tumor </li></ul><ul><ul><ul><li>Dx: elevated PRL with size/level correlation (s...
Prolactinoma: pregnancy <ul><li>Microadenoma:  </li></ul><ul><ul><ul><li>1.6% symptomatic growth </li></ul></ul></ul><ul><...
 
Anterior Pituitary Dysfunction <ul><li>Gold standard diagnosis = 3x bolus test </li></ul><ul><ul><ul><li>Insulin    ACTH,...
Diagnosis of AI <ul><li>8AM Plasma Cortisol (Pcortisol at 8AM or during “Stress”): </li></ul><ul><ul><ul><li>< 83  nM    ...
Diagnosis of AI <ul><li>Short Cortrosyn/ACTH test </li></ul><ul><ul><ul><li>Must be performed  within a few days  of start...
Short Cortrosyn Test <ul><li>High (Standard) Dose: </li></ul><ul><ul><ul><li>250 ug IV or IM, measure cortisol t = 0, 30, ...
Short Cortrosyn Test (cont’d) <ul><li>Criteria requiring a minimum cortisol increment (i.e. 2x baseline or absolute rise o...
Distinguish 1 ˚   from Central AI <ul><li>Plasma ACTH </li></ul><ul><li>Measure with basal cortisol during short ACTH test...
Distinguish 1 ˚   from Central AI <ul><li>Long Cortrosyn Test </li></ul><ul><li>Rarely needed </li></ul><ul><li>Done if pl...
Anterior Pituitary Dysfn Rx <ul><li>Corticosteroids </li></ul><ul><ul><ul><li>Prednisone 5 mg qhs or qam to 5/2.5 mg daily...
Pituitary Apoplexy <ul><li>Acute pituitary hemorrhage </li></ul><ul><li>Sudden severe H/A, diploplia, visual loss </li></u...
 
P Na  (mEq/L) 130 135 140 145 0 5 ADH (pM) Thirst ↓  ECFv Normal Serum [Na] (135-145 mEq/L) Closely Guarded
Diabetes Insipidus  <ul><ul><ul><ul><ul><li>Ddx </li></ul></ul></ul></ul></ul><ul><ul><ul><li>Diabetes Mellitus </li></ul>...
Diabetes Insipidus Ddx <ul><li>Central (CDI) </li></ul><ul><li>Idiopathic </li></ul><ul><ul><li>autoimmune </li></ul></ul>...
Diabetes Insipidus   <ul><li>Intact thirst & access to water </li></ul><ul><ul><ul><li>Hi-normal serum sodium (142-145 mEq...
Diabetes Insipidus   <ul><li>Healthy out-patients </li></ul><ul><li>DI with Intact thirst or access to water </li></ul><ul...
1 ˚ Polydipsia: “What came first?” The Chicken or the Egg?  (Egg) The Polyuria or the Polydipsia?
Water Deprivation Test <ul><li>Hold water intake for 2-3h prior to coming in. </li></ul><ul><li>Continue to hold water & M...
Diabetes Insipidus   <ul><li>Impaired thirst or access to water </li></ul><ul><ul><ul><li>Elevated serum sodium/OSM </li><...
Pituitary Surgery/Trauma <ul><li>Triphasic response to surgery </li></ul><ul><li>Phase 1: DI </li></ul><ul><ul><ul><li>Axo...
1 6 11 POD # 50 100 150 P Na (mEq/L) 50 100 400 U/O (cc/h) U/O #1 U/O #2
1 6 11 POD # 50 100 150 P Na (mEq/L) 50 100 400 U/O (cc/h) Na #1 U/O #1
1 6 11 POD # 50 100 150 P Na (mEq/L) 50 100 400 U/O (cc/h) Na #2 U/O #2
1 6 11 POD # 50 100 150 P Na (mEq/L) 50 100 400 U/O (cc/h) Na #1 Na #2 U/O #1 U/O #2 #1 DI #2 Normal
PITUITARY SURGERY  PROTOCOL   <ul><li>Immediately Postop (in recovery room) : </li></ul><ul><ul><li>Send serum for electro...
Treatment of DI <ul><li>Rx Dehydration </li></ul><ul><ul><ul><li>NS initially if ECFv contraction </li></ul></ul></ul><ul>...
Treatment of DI <ul><li>AVP, Aqueous vasopressin (Pitressin) </li></ul><ul><ul><ul><li>Only parenteral form, 5-10 U SC q2-...
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Pituitary Insufficency

  1. 1. Pituitary Insufficiency William Harper, MD, FRCPC Endocrinology & Metabolism Assistant Professor of Medicine McMaster University
  2. 2. Pituitary Disorders <ul><li>Mass effect </li></ul><ul><ul><ul><li>Headaches </li></ul></ul></ul><ul><ul><ul><li>CN II, III, IV, V 1 , V 2 , VI </li></ul></ul></ul><ul><li>Pituitary hypersecretory Syndrome </li></ul><ul><ul><ul><li>PRL, GH, ACTH, > > TSH </li></ul></ul></ul><ul><li>Anterior Pituitary Dysfunction </li></ul><ul><ul><ul><li>ACTH, TSH, LH/FSH > > GH </li></ul></ul></ul><ul><li>Posterior Pituitary Dysfunction </li></ul><ul><ul><ul><li>ADH </li></ul></ul></ul>
  3. 3. Mass Effect: H/A, CN II, EOM, V 1 , V 2 (LR 6 SO 4 ) 3 V 1 V 2
  4. 7. H-P-A Axis
  5. 8. Cushing’s Disease Ectopic ACTH High ACTH Cushing’s
  6. 9. Establish hypercortisolism (Cushing’s syndrome) <ul><li>“ Screening” tests </li></ul><ul><li>1 mg O/N DMST </li></ul><ul><ul><ul><li>DXM 1 mg po 11PM  8AM plasma cortisol </li></ul></ul></ul><ul><ul><ul><li>< 140 nM R/O Cushing’s Syndrome </li></ul></ul></ul><ul><ul><ul><ul><ul><li>SEN 98% SPEC 71-80% </li></ul></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>< 50 nM SEN ~100% SPEC ? (Poor), still some cases missed! </li></ul></ul></ul></ul></ul><ul><li>24 UFC </li></ul><ul><ul><ul><li>< 248 nM/d R/O Cushing’s Syndrome (SEN 95-100%) </li></ul></ul></ul><ul><ul><ul><li>248-840 nM/d Equivocal </li></ul></ul></ul><ul><ul><ul><li>> 840 nM/d consistent with Cushing’s Syndrome (SPEC 98%) </li></ul></ul></ul>
  7. 10. Establish hypercortisolism (Cushing’s syndrome) <ul><li>“ Confirmatory Tests” </li></ul><ul><li>24 UFC </li></ul><ul><ul><ul><li>> 840 nM/d Establishes Cushing’s Syndrome on 2 or more collections AND clear clinical findings of Cushing’s makes diagnosis of Cushing’s with SPEC 98% </li></ul></ul></ul><ul><ul><ul><li>Otherwise, need an additional confirmatory test. </li></ul></ul></ul><ul><li>LDDST (Liddle Test) </li></ul><ul><ul><ul><li>2 baseline 24h urine for cortisol and 17-OH steroids </li></ul></ul></ul><ul><ul><ul><li>DXM 0.5 mg q6h x 48h (8 doses) </li></ul></ul></ul><ul><ul><ul><li>During 2 nd day on DXM repeat 24h urine collection </li></ul></ul></ul><ul><ul><ul><ul><li>UFC > 100 nM/d or 17OHS > 11 uM/d indicates Cushing’s </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Historical gold standard but SEN 56-69%, SPEC 74-100% </li></ul></ul></ul></ul><ul><ul><ul><li>Plasma cortisol < 50 nM measured 2 or 6 hours after last dose has SEN 90-100% and SPEC 97-100% </li></ul></ul></ul>
  8. 11. Clinical Suspicion Screen Test: 24 UFC or 1mg O/N DST (+/- evening plasma/salivary cortisol) Confirmatory Testing: Repeat 24 UFC +/- CRH/DXM Test (+/- evening plasma/salivary cortisol) ACTH ACTH Independent CT abdo Adrenal Surgery ACTH dependent 1 st 8mg O/N DST or HDDST 2 nd CRH Test if above test negative CRH Test Pituitary MRI Pituitary Surgery IPSS <ul><li>Ectopic ACTH </li></ul><ul><li>CT thorax, abdo </li></ul><ul><li>Thyroid U/S </li></ul><ul><li>Octreotide Scan </li></ul>Continue search for ectopic source Remove ectopic source < 1.1pM >2.2pM 1.1-2.2pM No Stim Positive Stim Conclusive (>0.8-1.0cm) Inconclusive >2 basal >3 CRH <1.5 basal <2 CRH Conclusive No CRH stim No DXM suppression Stim by CRH or DXM suppresses
  9. 12. Case <ul><li>49 year old female </li></ul><ul><li>Adie’s pupil x 2 years </li></ul><ul><li>L frontoparietal H/A </li></ul><ul><li>Neurologist ordered MRI </li></ul><ul><ul><ul><li>Enlarged Pituitary! </li></ul></ul></ul><ul><li>Subsequent Endo referral </li></ul><ul><ul><ul><li>TSH 31.7 mU/L, FT4 6 pM  Hypothyroid! </li></ul></ul></ul><ul><ul><ul><li>FSH 63 (menopausal) </li></ul></ul></ul>
  10. 14. Pituitary Hyperplasia <ul><li>Another cause of sellar mass! </li></ul><ul><li>Physiological enlargement of pituitary </li></ul><ul><ul><ul><li>Lactotroph Hyperplasia (pregnancy) </li></ul></ul></ul><ul><ul><ul><ul><ul><li>Pregnancy, most common </li></ul></ul></ul></ul></ul><ul><ul><ul><li>Thyrotroph, Gonadotroph Hyperplasia </li></ul></ul></ul><ul><ul><ul><ul><ul><li>Primary gland failure </li></ul></ul></ul></ul></ul><ul><ul><ul><li>Somatotroph, Corticotroph Hyperplasia </li></ul></ul></ul><ul><ul><ul><ul><ul><li>GHRH or CRH secreting neuroendocrine tumors </li></ul></ul></ul></ul></ul>
  11. 16. Prolactinoma <ul><li>Most common pituitary tumor </li></ul><ul><ul><ul><li>Dx: elevated PRL with size/level correlation (stalk-effect!) </li></ul></ul></ul><ul><li>Treatment: </li></ul><ul><ul><ul><li>Dopamine Agonist </li></ul></ul></ul><ul><ul><ul><ul><ul><li>Bromocriptine, Cabergoline, Pergolide, Quinagolide </li></ul></ul></ul></ul></ul><ul><ul><ul><li>TSSx </li></ul></ul></ul><ul><ul><ul><li>XRT </li></ul></ul></ul><ul><li>Treatment goals: </li></ul><ul><ul><ul><li>Macroadenoma: shrink tumor (mass effect, H/A) </li></ul></ul></ul><ul><ul><ul><li>Stop galactorrhea </li></ul></ul></ul><ul><ul><ul><li>Reestablish menses/fertility </li></ul></ul></ul><ul><ul><ul><ul><ul><li>OCP if fertility not wanted </li></ul></ul></ul></ul></ul>
  12. 17. Prolactinoma: pregnancy <ul><li>Microadenoma: </li></ul><ul><ul><ul><li>1.6% symptomatic growth </li></ul></ul></ul><ul><ul><ul><li>Stop bromocriptine once conception achieved </li></ul></ul></ul><ul><li>Macroadenoma </li></ul><ul><ul><ul><li>13-36% symptomatic growth during pregnancy </li></ul></ul></ul><ul><ul><ul><li>Continue bromocriptine througout pregnancy </li></ul></ul></ul><ul><li>Monitoring PRL useless </li></ul><ul><li>Formal VF tests q3mos </li></ul><ul><li>MRI if any change in vision </li></ul>
  13. 19. Anterior Pituitary Dysfunction <ul><li>Gold standard diagnosis = 3x bolus test </li></ul><ul><ul><ul><li>Insulin  ACTH, GH (Insulin Tolerance Test) </li></ul></ul></ul><ul><ul><ul><li>LHRH  LH, FSH </li></ul></ul></ul><ul><ul><ul><li>TRH  TSH, PRL </li></ul></ul></ul><ul><li>Done > 6 weeks post pituitary surgery </li></ul><ul><li>ITT contraindicated: elderly, cardiac disease </li></ul><ul><ul><ul><li>8AM plasma cortisol </li></ul></ul></ul><ul><ul><ul><li>1 mcg ACTH stimulation testing </li></ul></ul></ul>
  14. 20. Diagnosis of AI <ul><li>8AM Plasma Cortisol (Pcortisol at 8AM or during “Stress”): </li></ul><ul><ul><ul><li>< 83 nM  AI confirmed </li></ul></ul></ul><ul><ul><ul><li>< 138 nM  suggests AI present (SEN 36%, SPEC ~100%) </li></ul></ul></ul><ul><ul><ul><li>> 552 nM  excludes AI (>552 nM @ anytime of day, SEN~100%) </li></ul></ul></ul><ul><ul><ul><li> [with possible exception of critically-ill patients] </li></ul></ul></ul>
  15. 21. Diagnosis of AI <ul><li>Short Cortrosyn/ACTH test </li></ul><ul><ul><ul><li>Must be performed within a few days of starting exogenous glucocorticoid Rx or else H-P-A axis will be suppressed by steroid Rx </li></ul></ul></ul><ul><ul><ul><li>Exogenous glucocorticoid must be dexamethasone (isn’t picked up by the cortisol RIA) </li></ul></ul></ul>
  16. 22. Short Cortrosyn Test <ul><li>High (Standard) Dose: </li></ul><ul><ul><ul><li>250 ug IV or IM, measure cortisol t = 0, 30, 60 min </li></ul></ul></ul><ul><ul><ul><li>Normal: any cortisol > 550 nM (even pre-injection t = 0) </li></ul></ul></ul><ul><ul><ul><li>Rules out 1 ˚ AI (SEN 100%) but only 90% SEN for 2 ˚ AI </li></ul></ul></ul><ul><li>Low Dose: </li></ul><ul><ul><ul><li>1 ug IV (can’t be IM), measure cortisol t = 0, 30 min </li></ul></ul></ul><ul><ul><ul><li>t = 30 min cortisol > 500 nM rules out 1 ˚ or 2 ˚ AI </li></ul></ul></ul><ul><ul><ul><li>(exception is 2 ˚ AI of recent onset < 2wk) </li></ul></ul></ul><ul><ul><ul><li>SEN 95% SPEC 96% ( > 600 nM SEN 100%, SPEC 83%) </li></ul></ul></ul><ul><ul><ul><li>1 ug dose stimulates maximal adrenal cortex secretion 30 min after injection and in normal subjects results in a peak plasma ACTH concentration 2X that seen in an ITT </li></ul></ul></ul>
  17. 23. Short Cortrosyn Test (cont’d) <ul><li>Criteria requiring a minimum cortisol increment (i.e. 2x baseline or absolute rise of 250 nM) now considered invalid </li></ul><ul><li>High basal cortisol due to stress or normal diurnal variation may represent near maximal stimulation with an inability to increase secretion further in upwards of 20% of normal patients </li></ul><ul><li>Possible exception of critically-ill patients </li></ul>
  18. 24. Distinguish 1 ˚ from Central AI <ul><li>Plasma ACTH </li></ul><ul><li>Measure with basal cortisol during short ACTH test </li></ul><ul><li>Primary AI: ACTH > 11 pM </li></ul><ul><li>Central AI: ACTH < 2.2 pM </li></ul><ul><li>Must measure BEFORE exogenous glucocorticoid administration as will be suppressed almost immediately </li></ul><ul><li>2 phases of steroid feedback suppression on ACTH: </li></ul><ul><ul><ul><li>Fast Phase (sec-min): membrane stabilizing effect </li></ul></ul></ul><ul><ul><ul><li>Delayed phase (hrs-days): mediated by glucocorticoid receptor </li></ul></ul></ul>
  19. 25. Distinguish 1 ˚ from Central AI <ul><li>Long Cortrosyn Test </li></ul><ul><li>Rarely needed </li></ul><ul><li>Done if plasma ACTH equivocal (2.2-11 pM) or result not available (i.e. not sent before the initiation of exogenous glucocorticoids) </li></ul><ul><li>250 ug IV infusion over 8h x 3d </li></ul><ul><li>Plasma cortisols during infusion (0, 4, and 8h) </li></ul><ul><li>24h UFC day prior to and on 3 days with infusion </li></ul><ul><li>1˚AI: no response </li></ul><ul><li>Central AI: some response </li></ul>
  20. 26. Anterior Pituitary Dysfn Rx <ul><li>Corticosteroids </li></ul><ul><ul><ul><li>Prednisone 5 mg qhs or qam to 5/2.5 mg daily </li></ul></ul></ul><ul><ul><ul><li>Cortef 20 mg qhs or qam to 20/10 mg daily </li></ul></ul></ul><ul><ul><ul><li>Medic-alert, 2-3x dose during acute-illness </li></ul></ul></ul><ul><ul><ul><li>Surgery: 50mg IV preop & q8h postop </li></ul></ul></ul><ul><li>Levothyroxine </li></ul><ul><ul><ul><li>Titrate dose to mid-normal FT4 not TSH </li></ul></ul></ul><ul><li>Sex steroids </li></ul><ul><ul><ul><li>Male: testosterone 100 mg/wk IM, androgel 5g/d </li></ul></ul></ul><ul><ul><ul><li>Female: premenopausal OCP, postmenopausal HRT? </li></ul></ul></ul><ul><li>Growth hormone? </li></ul>
  21. 27. Pituitary Apoplexy <ul><li>Acute pituitary hemorrhage </li></ul><ul><li>Sudden severe H/A, diploplia, visual loss </li></ul><ul><li>Shock due to adrenal crisis </li></ul><ul><li>Diagnosis: pituitary MRI or CT </li></ul><ul><li>Rx: </li></ul><ul><ul><ul><li>urgent surgical decompression </li></ul></ul></ul><ul><ul><ul><li>Solucortef 50 mg IV q8h </li></ul></ul></ul><ul><ul><ul><li>Dopamine agonist if high PRL/known prolactinoma </li></ul></ul></ul>
  22. 29. P Na (mEq/L) 130 135 140 145 0 5 ADH (pM) Thirst ↓ ECFv Normal Serum [Na] (135-145 mEq/L) Closely Guarded
  23. 30. Diabetes Insipidus <ul><ul><ul><ul><ul><li>Ddx </li></ul></ul></ul></ul></ul><ul><ul><ul><li>Diabetes Mellitus </li></ul></ul></ul><ul><ul><ul><li>Hypercalcemia </li></ul></ul></ul><ul><ul><ul><li>Solute diuresis: </li></ul></ul></ul><ul><ul><ul><ul><ul><li>Volume expansion 2 ° saline loading </li></ul></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>High-protein feeds (urea as osmotic agent) </li></ul></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>Post-obstructive diuresis </li></ul></ul></ul></ul></ul><ul><ul><ul><li>Diabetes Insipidus: </li></ul></ul></ul><ul><ul><ul><ul><ul><li>Central (CDI) </li></ul></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>Nephrogenic (NDI) </li></ul></ul></ul></ul></ul><ul><ul><ul><li>Primary (Psychogenic) Polydipsia </li></ul></ul></ul>Polyuria: > 3 L/d + Polydipsia: > 3.5 L/d
  24. 31. Diabetes Insipidus Ddx <ul><li>Central (CDI) </li></ul><ul><li>Idiopathic </li></ul><ul><ul><li>autoimmune </li></ul></ul><ul><li>Neurosurgery, head trauma </li></ul><ul><li>Cerebral hypoperfusion </li></ul><ul><li>Tumor </li></ul><ul><ul><li>Craniopharyngioma, pituitary adenoma, suprasellar meningioma, pineal gland, metastasis </li></ul></ul><ul><li>Infiltration </li></ul><ul><ul><li>Fe, Sarcoid, Histiocytosis X </li></ul></ul><ul><li>Nephrogenic (NDI) </li></ul><ul><li>X-linked recessive </li></ul><ul><li>Hypokalemia </li></ul><ul><li>Hypercalcemia (2 ° to HPT in particular) </li></ul><ul><li>Renal disease : after ATN, postobstructive uropathy, RAS, renal transplant, amyloid, Sickle cell anemia </li></ul><ul><li>Sjogren’s </li></ul><ul><li>Drugs : </li></ul><ul><ul><li>Lithium, 20% of chronic users </li></ul></ul><ul><ul><li>Demeclocycline, amphotericin, colchicine </li></ul></ul>
  25. 32. Diabetes Insipidus <ul><li>Intact thirst & access to water </li></ul><ul><ul><ul><li>Hi-normal serum sodium (142-145 mEq/L) </li></ul></ul></ul><ul><ul><ul><li>Polydipsia (crave cold fluids) </li></ul></ul></ul><ul><ul><ul><li>Polyuria, Nocturia  sleep disturbance </li></ul></ul></ul><ul><ul><ul><li>1 ° treatment is pharmacological </li></ul></ul></ul><ul><li>Impaired thirst or access to water: </li></ul><ul><ul><ul><li>Hypernatremia </li></ul></ul></ul><ul><ul><ul><li>Insufficiently concentrated urine </li></ul></ul></ul><ul><ul><ul><li>1 ° treatment is free water (enteral or IV D5W) </li></ul></ul></ul>
  26. 33. Diabetes Insipidus <ul><li>Healthy out-patients </li></ul><ul><li>DI with Intact thirst or access to water </li></ul><ul><ul><ul><li>Hi-normal serum sodium (142-145 mEq/L) </li></ul></ul></ul><ul><ul><ul><li>Polydipsia (crave cold fluids) </li></ul></ul></ul><ul><ul><ul><li>Polyuria, Nocturia  sleep disturbance </li></ul></ul></ul><ul><li>1 ˚ Psychogenic Polydipsia </li></ul><ul><ul><ul><li>Low-normal serum sodium (135-137 mEq/L) </li></ul></ul></ul><ul><ul><ul><li>Anxious middle-aged women </li></ul></ul></ul><ul><ul><ul><li>Psychiatric illness, phenothiazine (dry mouth) </li></ul></ul></ul>
  27. 34. 1 ˚ Polydipsia: “What came first?” The Chicken or the Egg? (Egg) The Polyuria or the Polydipsia?
  28. 35. Water Deprivation Test <ul><li>Hold water intake for 2-3h prior to coming in. </li></ul><ul><li>Continue to hold water & Monitor: </li></ul><ul><ul><ul><li>Urine volume, U OSM q1h </li></ul></ul></ul><ul><ul><ul><li>Serum Na, OSM q2h </li></ul></ul></ul><ul><li>If serum OSM/sodium do not rise above normal ranges & UOSM reaches 600  1 ˚ Polydipsia </li></ul><ul><li>If serum OSM reaches 295-300 mM & U OSM doesn’t ↑ </li></ul><ul><ul><ul><li>Diabetes Insipidus established </li></ul></ul></ul><ul><ul><ul><li>Endogenous ADH should be maximal, check serum ADH </li></ul></ul></ul><ul><ul><ul><ul><li>2 green rubber stopper tubes, pre-chilled, on ice, need biochemist </li></ul></ul></ul></ul><ul><ul><ul><li>Give DDAVP 10 ug IN </li></ul></ul></ul><ul><ul><ul><ul><li>CDI: U OSM ↑ by 100-800% (complete CDI), ↑ by 15-50% (partial CDI) with absolute U OSM > 345mM </li></ul></ul></ul></ul><ul><ul><ul><ul><li>NDI: U OSM ↑ by up to < 9%, sometimes ↑ as high as 45% but absolute U OSM always < isotonic (290 mM) </li></ul></ul></ul></ul>
  29. 36. Diabetes Insipidus <ul><li>Impaired thirst or access to water </li></ul><ul><ul><ul><li>Elevated serum sodium/OSM </li></ul></ul></ul><ul><ul><ul><li>U OSM < 500 mM, U SG < 1.017 </li></ul></ul></ul><ul><li>If serum sodium/OSM not elevated </li></ul><ul><ul><ul><li>Not DI! </li></ul></ul></ul><ul><ul><ul><li>U OSM and U SG are irrelevant </li></ul></ul></ul>
  30. 37. Pituitary Surgery/Trauma <ul><li>Triphasic response to surgery </li></ul><ul><li>Phase 1: DI </li></ul><ul><ul><ul><li>Axonal injury 2 ° surgery/swelling </li></ul></ul></ul><ul><ul><ul><li>Begins after POD #1 (pre-existing DI can occur earlier) </li></ul></ul></ul><ul><ul><ul><li>Lasts 1-5d </li></ul></ul></ul><ul><li>Phase 2: SIADH </li></ul><ul><ul><ul><li>Axonal necrosis of AVP secreting neurons with uncontrolled AVP release </li></ul></ul></ul><ul><ul><ul><li>Lasts 1-5 days </li></ul></ul></ul><ul><li>Phase 3: DI </li></ul><ul><ul><ul><li>Axonal death with cessation of AVP production </li></ul></ul></ul><ul><ul><ul><li>Usually permanent </li></ul></ul></ul>
  31. 38. 1 6 11 POD # 50 100 150 P Na (mEq/L) 50 100 400 U/O (cc/h) U/O #1 U/O #2
  32. 39. 1 6 11 POD # 50 100 150 P Na (mEq/L) 50 100 400 U/O (cc/h) Na #1 U/O #1
  33. 40. 1 6 11 POD # 50 100 150 P Na (mEq/L) 50 100 400 U/O (cc/h) Na #2 U/O #2
  34. 41. 1 6 11 POD # 50 100 150 P Na (mEq/L) 50 100 400 U/O (cc/h) Na #1 Na #2 U/O #1 U/O #2 #1 DI #2 Normal
  35. 42. PITUITARY SURGERY PROTOCOL <ul><li>Immediately Postop (in recovery room) : </li></ul><ul><ul><li>Send serum for electrolytes, creatinine, blood sugar </li></ul></ul><ul><ul><li>Send urine for U SG (specific gravity) </li></ul></ul><ul><li>Then monitor : </li></ul><ul><ul><li>Accurate I&O: fluid intake & urine output hourly (q1h) with complete tally q12 hours (q12h) </li></ul></ul><ul><ul><li>Serum electrolytes and U SG : q12h </li></ul></ul><ul><ul><li>If on steroids (decadron, solucortef, etc.) do capillary blood glucose bid </li></ul></ul><ul><li>If urine output > 400cc/hour : </li></ul><ul><ul><li>Serum OSM & urine OSM now and then q12h </li></ul></ul><ul><ul><li>Serum lytes, creatinine now and then q6h </li></ul></ul><ul><ul><li>U SG now and then q4h </li></ul></ul><ul><ul><li>Call Endocrinology Service once serum electrolytes and U SG results are back for possible DDAVP and IV fluid orders </li></ul></ul><ul><li>Call Endocrinology Service whenever : </li></ul><ul><ul><li>Serum sodium > 148 </li></ul></ul><ul><ul><li>Serum sodium < 130 </li></ul></ul><ul><ul><li>Urine output > 400 cc/h (see above 3.) </li></ul></ul>
  36. 43. Treatment of DI <ul><li>Rx Dehydration </li></ul><ul><ul><ul><li>NS initially if ECFv contraction </li></ul></ul></ul><ul><ul><ul><li>Then IV D5W or enteral free water to lower serum [Na] </li></ul></ul></ul><ul><ul><ul><ul><ul><li>1-2 mEq/h if Na > 160, symptomatic (coma, SZ), acute </li></ul></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>Otherwise 0.5-1.0 mEq/h </li></ul></ul></ul></ul></ul><ul><ul><ul><li>Insensible losses? (0.5 L/d) </li></ul></ul></ul><ul><ul><ul><li>Do NOT replace U/O if giving DDAVP </li></ul></ul></ul><ul><li>DDAVP (Desmopressin) </li></ul><ul><ul><ul><li>Reduces U/O and therefore simplifies fluid therapy </li></ul></ul></ul><ul><ul><ul><li>Long t½: duration 8-12h, up to 24h </li></ul></ul></ul><ul><ul><ul><li>Therefore use judiciously </li></ul></ul></ul><ul><ul><ul><ul><ul><li>DDAVP 1ug IV/SC x 1 </li></ul></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>Only repeat if breaks-thru again (i.e. becomes hypernatremic with dilute polyuria) </li></ul></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>Once nasal mucosa stable can switch to intranasal </li></ul></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>Also oral form DDAVP now available </li></ul></ul></ul></ul></ul><ul><li>DDAVP: 1ug IV/SC = 10 ug IN = 0.1 mg PO </li></ul>
  37. 44. Treatment of DI <ul><li>AVP, Aqueous vasopressin (Pitressin) </li></ul><ul><ul><ul><li>Only parenteral form, 5-10 U SC q2-4h </li></ul></ul></ul><ul><ul><ul><li>Lasts 2-6h </li></ul></ul></ul><ul><ul><ul><li>Can cause HTN, coronary vasospasm </li></ul></ul></ul><ul><li>Chlorpropamide (OHA which stimulates AVP secretion) </li></ul><ul><ul><ul><li>100-500 mg po OD-bid </li></ul></ul></ul><ul><ul><ul><li>Only useful for partial DI, can cause hypoglycemia </li></ul></ul></ul><ul><li>HTCZ (induces volume contraction which diminishes free water excretion) </li></ul><ul><ul><ul><li>50-100 mg OD-bid </li></ul></ul></ul><ul><ul><ul><li>Mainstay of Rx for chronic NDI </li></ul></ul></ul><ul><li>Amiloride (blunts Lithium uptake in distal tubules & collecting ducts) </li></ul><ul><ul><ul><li>5-20 mg po OD-bid </li></ul></ul></ul><ul><ul><ul><li>Drug of choice for Lithium induced DI </li></ul></ul></ul><ul><li>Indomethacin 100-150 mg po bid-tid (PGs antagonize AVP action) </li></ul><ul><li>Clofibrate 500 mg po qid (augments AVP release in partial CDI) </li></ul><ul><li>Tegretol 200-600 mg po od (augments AVP release in partial CDI) </li></ul>

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