Endocrine Emergencies

1. Endocrine Emergencies Resident Rounds May 22, 2003 Rob Hall PGY3

2. Outline

3. 16yo female, DM1 Drinking, ecstacy at a rave, no insulin Confused, dry, borderline hypotension, tachy Chemstrip 25 Urine gluc/ketone+ve Fruity breath Na 129 K+ 5.1 HCO3 8 pH 6.95 PC02 20 Mg low P04 low Case

4. What is your approach to DKA? • Resuscitate the patient: ABCs • Assess the severity of the DKA: physical exam, dehydration, lytes, ABG • Correct the metabolic derrangements: hyperglycemia, acidosis, ketosis, dehydration • Look for precipitant……….. • Lack of insulin: non-compliant, new dx • Physiologic stress: infection, pregnancy, ischemia, drugs, alcohol, GI bleed, • Poor oral intake or vomiting

5. What is a differential dx? • Hyperglycemia: DKA, HONKs, glucose administration • Ketoacidosis: DKA, AKA, starvation, 3rd trimester pregnancy • AGMA: AMUDPILECATO • Hyperglycemia + Ketoacidosis + AGMA = DKA • There isn’t really a ddx • HONKS could potentially fool you b/c ketoacidosis can be present but it should be MINIMAL/MILD

6. Is there any value in measuring serum ketones? • Maybe! • Serum ketones measures betahydroxybutyrate • Urine dip for ketones measures acetoacetate • Acetoacetate rises EARLIER but betahydroxybutyrate rises HIGHER in DKA • Acetoacetate: betahydroxybutyrate ratio normally 1:3 • Can be as high as 1:30 • Could potentially have –ve urine dip for ketones despite very high levels of betahydroxybutyrate

7. How will you manage the DKA patient? • Fluids • Insulin • Electrolyte disorders • Look for precipitant • Generally no bicarb • Chemstrip q1hr, lytes q2hr initially

8. Fluid management of DKA • ADULT • Principles • DKA develops in days and can does NOT need to be reversed within hours unless very unstable • Some evidence that too rapid fluid rehydration decreases serum osmolarity too fast and causes cerebral edema • NS boluses for shock • Otherwise give 2-3L NS over 2 hours (slower with CHF/CRF) • Some advocate 1/2NS or colloid but most use NS (1/2NS decreases osmolarity faster) • Switch to D51/2NS when glucose 14-16 and decrease rate to 2X maintenance

9. Insulin and DKA • Humulin R iv Bolus 0.1 unit/kg: ????? • Humulin R iv Infusion 0.1 unit/kg/hr • Must prime tubing • Adjust infusion as glucose drops • Chemstrips q1hr • Target drop in 2-3 mmol/hr • Note: low doses as effective as higher doses with less complications

10. Bolus insulin? • Controversial • No RCT to compare bolus vs no bolus • Recommendations change • Don’t give a bolus in peds • CMAJ Review article April 2003 • No evidence to recommend an iv bolus • Diabetes Care26: Supplement. 2003 • Concensus statement from American Diabetic Association • Recommends iv bolus 0.15 Unit/kg iv for adults but not peds

11. Case • You have initiated fluid resuscitation and started Humulin R at 0.1 U/kg/hr • One hour later the c/s is still 25 • Why? What do you do? • Insulin resistance • Double the infusion rate, recheck glucose in one hour, double rate q hourly until glucose is dropping by 2-3 mmol/hr

12. What disorders do you expect? How are they managed? Hypokalemia Always deficient in K+ Ensure urine output b/f replacing K+ > 5.0: no K+, recheck in 1hr K+ 4 – 5: 20 mmol KCl/L K+ 3 – 4: 40 mmol KCl/L K+ < 3: 60 mmol KCl/L or iv bolus Electrolyte disorders inDKA

13. Electrolyte disorders: disorders of Na, Mg, P04 common • Na • False: dilutional b/c of hyperosmolarity (10:3) • True: vomiting, poor intake, renal loss • No specific mx • Mg • Level may be low, normal, or high b/c shift • Total body depletion common: replace 2gm iv • P04 • Level may be low, normal, or high b/c shift • Total body depletion common • Generally no need to replace unless very low or complications (resp depression, arrythmias)

14. Case: she’s sick, pH was 6.95, would you give bicarb? • Controversial: NO RCT • Glaser NEJM Jan 2001: retrospective study of cerebral edema in peds DKA • Predictors: bicarb, lower C02, higher BUN • Adults • Give bicarb if pH < 7.0 AFTER 1hr of fluids • How: 100 mmol sodium bicarb to 400 ml of sterile water and run at 200 ml/hr • Peds • CMAJ: Don’t give bicarb • ADA: consider bicarb if pH<6.9 after 1hr of fluids • 1-2 mEq/kg added to NS (max sodium is 155 mEq/L)

15. 5hrs in ED waiting for bed RN calls you to bedside She’s confused Dx? Mx? CEREBRAL EDEMA More common in peds (1%) 50% of mortality of DKA 6-10 hrs after initiation of tx Mechanism unknown: shifts? Highest risk New dx, < 5yo, pH < 7.1 Predictors (Glaser) Bicarb, low C02, high BUN Case

16. Presentation Failure to improve LOC with treatment Deterioration of LOC despite treatment Seizures Pupillary changes (unequal, unresponsive) Hemodynamic instability Decrease u/o despite fluids Management ABCs Elevate head of bed Hyperventilate Mannitol ? Decrease iv rate ICU NO steroids DKA: Cerebral Edema

17. What’s different in adult vs pediatric DKA • The same principles but more cautious on the fluids, no insulin bolus, no bicarb, insulin started if in ED > 2hrs (fluids before insulin) • Mild: pH >7.25, C02 >12, normal LOC, <10% dry • NS at 1.5X maintenance (no bolus) • Mod: pH 7.15-7.25, C02 8-12, 10-15% dry • NS bolus 10 cc/kg then 1.5X maintenance • Severe: pH , 7.15, C02 < 8, > 15% dry or shocky • NS bolus 20 cc/kg X 1 or until shock resolves • Then NS at 1.5X maintenance

18. 85 yo female Dementia Nursing home More confused RN did chemstrip = 30 Tachy, hypotensive, GCS 12, parched Glucose 55 K+ 5 C02 19 BUN 25 Urine glucose 3+ Urine ketones 1+ Dx? Mx? Case

19. HONKS • HHNKs, HHS • Pathophysiology • Relative lack of insulin (enough to prevent significant ketoacidosis though) • Physiologic stress • Hyperglycemia • Profound osmotic diuresis and dehydration • Compounded by poor oral intake • Dementia, CVA, mental illness, mentally challenged, SCI, hip #, elderly, etc

20. Features Usually elderly, dementia, CVA, etc Very, very dry Severe hyperglycemia Minimal or absent ketoacidosis Any CNS finding Precipitants to consider Sepsis CVA Fall, hip#, trauma Ischemia, MI Poor oral intake Drugs Diuretics Dilantin HONKS

21. HONKS management • Treat essentially the same as DKA • Fluids: deficit larger (10L) • Bolus prn for shock • Replace ½ deficit over 8hrs and ½ over 16hrs • Most use NS X 2-3L then switch to ½ NS • Slower rates with CRF and CHF • Switch to D5 ½ NS when glucose 14-16 • Case reports of cerebral edema with fast replacement • Insulin: controversial, safe and effective, +/-bolus • Manage electrolyte disorders; No bicarb

22. Case • She has a generalized seizure • What are you thinking as an etiology? • Could be any cause: structural vs metabolic • Think of CNS events, cerebral edema, rapid lyte changes, hypoglycemia from insulin • Management after correcting lytes, glucose prn? • Benzodiazepines, phenobarb 2nd line • NO dilantin • Can cause HONKS b/c inhibits release of insulin

23. Compare and Contrast:DKA, HONKS, AKA

24. Glucose of 1.9 Not known to be diabetic Ddx? Investigations? Mx? Case

25. Insulinoma Insulin Oral hypoglycmics Sepsis Critical Illness Liver Failure Adrenal failure Alimentary hyperinsulinism Labs Insulin level Pro-insulin level Cpeptide level Sulphonyurea LFTs, cortisol Mx IV Dextrose Glucagon: 1-2 mg im or sc Non-diabetic Hypoglycemia

26. Etiology of Thyroid Emergencies Undiagnosed or Undertreated thyroid disorder (hypo or hyperthyroid) Thyroid Storm Or Myxedemic coma Acute Precipitant

27. KEY FEATURES of Thyroid Storm • FEVER • TACHYCARDIA • ALTERED LOC • Features of underlying Hyperthyroidism • Weight loss, heat intolerance, tremors, anxiety, diarrhea, palpitations, sweating, CP, SOB • Goiter, eye findings, pretibial myxedema

28. When should you consider Thyroid Storm and what is the ddx? • Infectious: sepsis, meningitis, encephalitis • Vascular: ICH, SAH • Heat stroke • Toxicologic • Sympathomimetics, seritonin syndrome, neuroleptic malignant syndrome, Delirium Tremens, anticholinergic syndrome

29. PTU: 1gm po then 250 q4hr PROPRANOLOL: 1-2mg iv q10min POTASSIUM IODIDE: SSKI 5 drops po q6hr STERIODS: dexamethasone 4mg iv SUPPORTIVE CARE P3S2 Summary of Thyroid Storm Management

30. KEY FEATURES of Myxedema

31. When should Myxedema be considered and what is the ddx? • Altered LOC • Structural vs metabolic causes of decreased LOC • Hypoventilatory Resp Failure • Narcotics, Benzodiazepines, EtOH intoxication, OSA, obesity hypoventilation, brain stem CVA, neuromuscular disorders (MG, GBS) • Hypothermia • Environmental • Medical: pituitary or hypothalamic lesion, sepsis

32. Management of Myxedemic Coma • Levothyroxine is the cornerstone of Mx • Levothyroxine 500 ug po/iv (preferred over T3) • Ischemia and arrythmias possible: monitor • When in doubt, treat en spec • Other • Intubate/ventilate prn • Fluids/pressors/thyroxine for hypotension • Thyroxine for hypothermia • Stress Steroids: hydrocortisone 100 mg iv

33. Etiology of Adrenal Crisis Underlying Adrenal Insufficiency (Addision’s and Chronic Steriods) Acute Precipitant Adrenal Crisis

34. Nonspecific Nausea, vomiting, abdominal pain Shock Distributive shock not responsive to fluids or pressors Laboratory (variable) Hyponatremia, hyperkalemia, metabolic acidosis Known Adrenal insufficiency Features of undiagnosed adrenal insufficiency Weakness, fatigue, weight loss, anorexia, N/V, abdo pain, salt craving, hyperpigmentation Key Features of Adrenal Crisis

35. Adrenal Crisis • Consider on the differential diagnosis of SHOCK NYD

36. Management of Adrenal Crisis • Corticosteroid replacement • Dexamethasone 4mg iv q6hr is the drug of choice (doesn’t affect ACTH stim test) • Hydrocortisone 100 mg iv is an option • Mineralocorticoid not required in acute phase • Other • Correct lytes, fluid resuscitation (2-3L) • Glucose for hypoglycemia

37. The end…….