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MEDICAL GRANDROUNDS ON DIABETES INSIPIDUS

MEDICAL GRANDROUNDS ON DIABETES INSIPIDUS. Desiree B. Yano-Simbulan, M.D. Maricel B. Peniero, M.D. November 8, 2007. LEARNING OBJECTIVES. To present a case of a 50 year old female with diabetes insipidus To provide an overview in the diagnostic approach to polyuria and diabetes insipidus

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MEDICAL GRANDROUNDS ON DIABETES INSIPIDUS

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  1. MEDICAL GRANDROUNDSONDIABETES INSIPIDUS Desiree B. Yano-Simbulan, M.D. Maricel B. Peniero, M.D. November 8, 2007

  2. LEARNING OBJECTIVES • To present a case of a 50 year old female with diabetes insipidus • To provide an overview in the diagnostic approach to polyuria and diabetes insipidus • To discuss nephrogenic versus central diabetes insipidus: etiology, clinical manifestation, work up and management

  3. IDENTIFYING DATA • A.G. • 50y/o female • Filipino • cc: epigastric pain

  4. HISTORY OF PRESENT ILLNESS 2 weeks PTA (+)epigastric pain (+)bloatedness (+)loss of appetite (-) nausea, vomiting (-)changes in bowel habit EGD: Gastritis Gastric polyp Few days PTA (+)persistence of symptoms A

  5. REVIEW OF SYSTEMS • No fever • No blurring of vision, no visual loss • No throat pain, tinnitus, no hearing loss • No dyspnea, no cough, no hemoptysis • No chest pain, no palpitation, no orthopnea • (+) polydipsia (+) polyphagia (+) nocturia • (+) right hip pain (+) low back pain • No skin rash or skin changes

  6. PAST MEDICAL HISTORY • Invasive Ductal Carcinoma, Left Breast s/p Modified Radical Mastectomy,left breast 2003 s/p Chemotherapy 2003, 2004 s/p Radiotherapy, 2006 • Hypertension, 2004 Atenolol (Therabloc) 50mg 1/2tab OD Imidapril (Vascor) 5mg OD • Diabetes Mellitus, 2000 Acarbose (Glucobay) 50mg OD Repaglinide (Novonorm) 0.5mg OD • s/p laparoscopic cholecystectomy, 2004

  7. FAMILY HISTORY • (+) Breast cancer – 2 cousins • (+) Diabetes Mellitus – mother, brother

  8. PERSONAL/SOCIAL HISTORY • non smoker • non alcoholic beverage drinker • no history of substance abuse • worked as a general accountant

  9. PHYSICAL EXAMINATION Gen. Survey: Awake, alert not in cardiorespiratory distress Vital Statistics: Ht:157cm Wt:58kgs BMI: 23 Vital Signs: BP:110/70 CR:95 RR:20 To:36.6 Skin: warm, moist, no rash HEENT: pink palpebral conjunctivae, anicteric sclerae, supple neck, no tonsillopharyngeal congestion, no neck vein distention, JVP = 10cm

  10. PHYSICAL EXAMINATION Chest: symmetrical chest expansion, (-) intercostal retraction (-) rales (-) wheezes (+) 10cm well healed incisional scar left chest Cardiac: Adynamic Precordium, regular S1S2, apex beat at 5th LICS MCL, (-) murmur (-) thrill Abdomen: Globular, NABS, (-) bruits, normo-tympanic, (+)epigastric tenderness (-) organomegaly Extremities: (-)edema (-) cyanosis, full and equal pulses

  11. ADMITTING DIAGNOSIS • Gastritis, Gastric polyp s/p EGD • Hypertensive Cardiovascular Disease II • Diabetes Mellitus Type II • Invasive Ductal Carcinoma, Left Breast, 2003 s/p MRM, left breast s/p chemotherapy s/p radiotherapy

  12. COURSE IN THE WARDS

  13. 1st HOSPITAL DAY • Diagnostics • CBC • Spec 16 • CT of chest and abdomen • Endocrine Referral for blood sugar control • CBG monitoring (initial CBG= 243mgs%) • FBS (207mgs%), HbA1c (9.6%) • Acarbose (Glucobay) 50mg TID • Glimepiride (Solosa) 2mg OD

  14. CBC

  15. Urinalysis Color yellow Transparency clear pH acidic Specific Gravity 1.020 (1.015-1.025) Sugar (-) Protein (-) Ketones (-) Nitrites (-) Leucocyte Esterases +1 Blood (-) RBC 0.1 WBC 2.5 Epithelial cells 0.2 Bacteria 82 Mucus Threads (-) Crystals (-) Cast(-)

  16. SPEC 16 (done as OPD) Corrected Na 136 (CBG-100) x0.016 +Na Corrected Ca 12.6 (4-albumin) x0.8 +Ca

  17. K = 2.9 • KCL incorporation (30meqsKCL +PNSS1L x10h)  Repeat K 5.0 (n.v. 3.5-5.1) • Ca = 12.6 • ionized Ca (1.66mmol/L) (n.v. 1.12-1.32) • phosphorus (3.7mgs%) (n.v. 2.3-4.7) • intact PTH (1.637pg/ml)(n.v. 10-65)

  18. 3rd Hospital Day NEPHROLOGY referral for electrolyte management • Ca = 12.0 ( 12.1) • Hydration with PNSS at 200cc/h x 4hours, then back to 120cc/h • Diuresis with Lasix 20mg IV q8 • Serial electrolyte monitoring • Accurate I/O monitoring

  19. 4th Hospital Day • Ca = 12.2 12.0 after Lasix and PNSS • Impression Hypercalcemia of Malignancy • Plan Ibandronic Acid (6mg in PNSS500cc x1hr) Lasix discontinued Continue hydration, PNSS 1Lx120cc/h

  20. CT Scan of Chest and Abdomen • Multiple osseous lytic lesions in the thoracolumbar spine, likely metastatic • Minimal bilateral pleural effusion with parenchymal consolidation in the right lower lobe, atelectasis vs pneumonia • No interval change in size of subcm nodule in lingula • Mediastinal, right hilar and right axillary lymphadenopathy showing significant increase in size since september 27, 2006 • Heterogeneous enhancement with slight nodularity of the right breast tissue. • Post mastectomy, left

  21. 4th Hospital Day • Medical Oncology Referral • Impression Breast Ca IV, bone and lung metastases with inflammatory breast changes, right breast • Plan For repeat chemotherapy

  22. 4th Hospital Day • Pain Management Referral for right hip pain, low back pain • Paracetamol/Tramadol (Dolcet) 1 tab TID • Gabapentin 100mg BID • Fentanyl 25mcg IV  Fentanyl PCA

  23. 5th Hospital Day • uncontrolled Hyperglycemia (CBG = 406mgs%) • OHA discontinued • Insulin drip • Hourly CBG monitoring • K monitoring ( K = 3.3) • KCL incorporation

  24. 6th Hospital Day – Bone Scan Foci of increased radioactivity situated in several areas of the body, namely: frontal, parietal, and occipital regions of the skull, both shoulder regions, both scapulae, both humerii, sternum, all levels of the thoracic and lumbosacral spine, both sides of the pelvis, both femora, both tibia, and multiple rib segments bilaterally. Above findings are not demonstrated in the previous study done in October 2006 Impression: Findings are compatible with Osseous Metastases

  25. Zoledronic acid (Zometa) 4mg in D5W100cc x20min • Allopurinol 300mg OD

  26. 8th HOSPITAL DAY – MRI of the Cervical and Thoracic Spine Extensive bone metastases involving the cervical and thoracic spine with compression deformities of T2 and T6 vertebral bodies. No evidence of spinal canal metastasis Extensive mediastinal lymphadenopathy

  27. Dexamethasone 5mg IV q 6hr RTC • Nexium 40mg IV OD

  28. 10th Hospital Day • Radiation Oncology Referral for spinal cord compression • For radiation therapy • 900 cGy to upper thoracic spines, 10 sessions over 2 weeks

  29. 12th Hospital Day • Polyuria (Urine output 8.8/L) • Na (155) • Urine Osmolality (120 mosm/kg) (n.v.301-1093) • Plasma Osmolality (326 mosm/kg) (n.v.275-295) • Increase oral fluid intake • Increased hydration with D5W 1L x100cc/h  150cc/h, later shifted to 0.3% NSS 1L x 150cc/h

  30. Urinalysis Color yellow Transparency hazy pH neutral Specific Gravity 1.010(1.015-1.025) Sugar +2 Protein trace Ketones (-) Nitrites (-) Leucocyte Esterases +1 Blood (-) RBC 0.2 WBC 6.6 Epithelial cells 1.3 Bacteria 291 Mucus Threads (-) Crystals (-) Cast(-)

  31. Osmolar Clearance vs Free Water Clearance Solute H20 urine Uosm x V -------------- Posm Osmolar Clearance (Cosm) =

  32. Uosm = 120 Posm = 326 Vol = 8.8L Cosm = 120 x 8.8 326 Cosm = 3.23L 3.3L (Osm) Urine vol =8.8L 5.5L (H20)

  33. Conclusion • Polyuria is secondary to water diuresis

  34. Polyuria secondary to water diuresis • Nephrogenic DI (? hypercalcemia) • vs Central DI (? metastasis) • Trial of DESMOPRESSIN (0.2mcg 1/2tab BID) • Effect on urine volume and osmolality

  35. After the trial of Desmopressin • Urine Volume 100% 8.8L  4.6L • Urine Osmolality 100% 120  423 WITHDRAWAL OF DESMOPRESSIN Urine OSMOLALITY: 423  213 Conclusion : CENTRAL Diabetes Insipidus

  36. Urine Osmolality Urine Volume

  37. Input and Output Monitoring

  38. 16th HOSPITAL DAY – Brain MRI Nodules in the pineal region and hypothalamus withthickening of the pituitary stalk. Enhancing nodules in the left parieto occipital area, head of the right caudate nucleus, left basal ganglia, left cerebellar hemisphere. Leptomeningeal thickening and enhancement, left temporal area. Enhancing bone foci in both frontoparietal and left temporal bones. Above findings considered metastases

  39. Clinical Outcome • Discharged stable on the 24th hospital day

  40. POLYURIA AND DIABETES INSIPIDUS

  41. POLYURIA • Polyuria can be arbitrarily defined as a urine output exceeding 3 L/day in adults and 2 L/m2 in children • Causes • Primary polydipsia • Central Diabetes Insipidus • Nephrogenic Diabetes Insipidus

  42. Diagnostic Approach to Polyuria • Onset of polyuria • Family history • Plasma Na concentration • Na <137 meq/L, due to water overload, is usually indicative of primary polydipsia • Na >142 meq/L, due to water loss, points toward DI • Water restriction test • Plasma ADH measurement

  43. Water Restriction Test

  44. Solute Diuresis • Glucosuria • High-protein feedings • Volume expansion due to saline loading • Differentiated from diabetes insipidus • Water diuresis Uosm <250 • Solute diuresis Uosm >300 mosmol/kg • Total solute excretion markedly increased

  45. Central Diabetes Insipidus • Decreased release of ADH • Lack of ADH can be caused by disorders that act at one or more of the sites involved in ADH secretion: • hypothalamic osmoreceptors • supraoptic or paraventricular nuclei • superior portion of the supraopticohypophyseal tract

  46. Etiology of central diabetes insipidus • Idiopathic • Neurosurgery a. Craniopharyngioma b. Transphenoidal surgery • Head trauma • Hypoxic or ischemic encephalopathy a. Cardiopulmonary arrest b. Shock c. Sheehan syndrome • Neoplastic a. Primary : craniopharyngioma, cyst, pinealoma b. Metastatic : breast, lung • Miscellaneous

  47. Review of Literature SYSTEMIC CANCER PRESENTING AS DIABETES INSIPIDUS - Clinical and radiographic features of 11 patients with a review of metastatic-induced diabetes insipidus “…of 100 consecutive cases of DI of any cause, diabetes insipidus was the initial presentation in 11 patients with systemic cancer. In these 11 patients, the most common sources metastatic to the posterior pituitary-hypothalamic region were lung, breast, leukemia and lymphoma. CT scanning demonstrated pituitary stalk enlargement, suprasellar masses, or both…” Kimmel D.W., O'Neill B.P., Systemic cancer presenting as diabetes insipidus. Clinical and radiographic features of 11 patients with a review of metastatic-induced diabetes insipidus. Cancer 1983 Dec 15;52(12):2355-8.

  48. Review of Literature PITUITARY METASTASIS IN BREAST CARCINOMA “…the incidence of metastasis to pituitary in breast cancer is reported as0.95%. Breast cancer and lung cancer are the most common primary sites, in women and men respectively, which metastasize to the pituitary. The presenting symptoms include diabetes insipidus, anterior pituitary insufficiency and retro-orbital pain. Metastases to the posterior lobe are more common than to the anterior lobe...” Rao SR, Rao RS, Pituitary metastases in carcinoma breast. Shushrusha Hospital, Mumbai, India. JPGM 2001 Volume 47 Issue2 Page 135-6

  49. Drug therapy of central diabetes insipidus • ADH preparations a. Desmopressin nasal spray b. Aqueous vasopressin c. Lysine vasopressin nasal spray d. Vasopressin tannate in oil • Drugs that potentiate ADH effect a. Chlorpropamide b. Carbamazepine c. NSAIDS • Drugs that increase ADH secretion a. Clofibrate • Drugs not requiring ADH b. Thiazide diuretics

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