Non Diabetic Endocrine Emergencies

1. Non � Diabetic Endocrine Emergencies �What an emerg doc needs to know� Rob Hall PGY3 December 5th, 2002

2. Non � Diabetic Endocrine Emergencies WHY? Uncommon Potentially lethal Diagnostic dilemmas ED treatment may be life-saving

3. Outline

4. Objectives How uncommon? What defines thyroid storm, myxedemic coma, adrenal crisis? What are the main clinical features? When should these dx be considered? What investigations are pertinent? What is the emergency management? When and how do you give stress dosing for chronic adrenal insufficiency?

5. Case 37 yo female Chest Pain and SOB Denies any PMHx Recent weight loss Sinus tach 130 Temp 40 Agitated Tremulous

6. CASE

7. CASE NOT GOOD!

8. Thyroid Storm

9. What is Thyroid Storm?

10. What is Thyroid Storm?Burch 1993

11. Etiology of Thyroid Storm Undiagnosed Undertreated (Grave�s disease or Mulitnodular toxic goiter)

12. Thyroid Storm 1% of all hyperthyroids Mortality 30% Precipitants Vascular Infectious Trauma Surgery Drugs Obstetrics Any acute medical illness

13. 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

14. 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

15. INVESTIGATIONS Thyroid Testing TSH Free T4 Don�t need to order total T3/4, TBG, T3RU, FT3 Look for precipitant ECG CXR Urine Labs Blood cultures Tox screen ? CT head ? CSF

16. Thyroid Storm: Goals of Management 1 - Decrease Hormone Synthesis 2 - Decrease Hormone Release 3 - Decrease Adrenergic Symptoms 4 - Decrease Peripheral T4 -> T3 5 - Supportive Care

17. Decrease Hormonal Synthesis Inhibition of thyroid peroxidase Propylthiouracil (PTU) or Methimazole (Tapazole) PTU is the drug of choice PTU 1000 mg po/ng/pr then 250 q4hr No iv form Safe in pregnancy S/E: rash, SJS, BM suppression, hepatotoxic Contraindications: previous hepatic failure or agranulocytosis from PTU

18. Decrease Hormone Release Iodine or lithium decreases release from hormone stored in colloid cells MUST not be given until 1hr after PTU Potassium Iodide (SSKI) 5 drops po/ng q6hr Lugol�s solution 8 drops q6hr

19. Decrease Adrenergic Effects Most important maneuver to decrease morbidity/mortality Decreases HR, arrythmias, temp, etc Propranolol 1 � 2 mg iv q 10 min prn Propranolol preferred over metoprolol Contraindications to beta-blockers Reserpine 2.5 � 5.0 mg im q4hr Guanethidine 20 mg po q6hr Diltiazem

20. Decrease T4 -> T3 Corticosteriods PTU and propranolol also have some effect Dexamethasone 2 � 4 mg iv Relative or absolute adrenal insufficiency also common

21. Supportive Care Fluid rehydration Correct electrolyte abnormalities Control temperature aggressively Ice, cooling blanket, tylenol, fans Search for precipitant Think vascular, infectious, trauma, drugs, etc

22. Summary of Management PTU PROPRANOLOL POTASSIUM IODIDE STERIODS SUPPORTIVE CARE P3S2

23. Apathetic Hyperthyroidism Elderly (can be any age) Altered LOC, Afib, CHF Minimal fever, tachycardia No preceeding hx of hyperthyroidism except weight loss More COMMON than thyroid storm Check TSH in any elderly patient with altered LOC, psych presentation, Afib, CHF

24. Outline

25. What is Myxedemic Coma? Myxedema = swelling of hands, face, feet, periorbital tissues Myxedemic coma = decreased LOC associated with severe hypothyroidism Myxedemic coma/Myxedema generally used to mean severe hypothyroidism

26. Myxedemic Coma Hypothyroidism Myxedemic Coma

27. Etiology of Myxedemic Coma Undiagnosed Undertreated (Hashimoto�s thyroiditis, post surgery/ablation most common)

28. Myxedemic Coma Precipitants of Myxedemic Coma Infection Trauma Vascular: CVA, MI, PE Noncompliance with Rx Any acute medical illness Cold

29. KEY FEATURES of Myxedema

30. 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

31. Myxedemic Coma Investigations TSH and Free T4 Look for ppt ECG Labs Septic work up (CXR/BC/urine/ +/- LP) Random cortisol CT head

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. Outline

34. Adrenal Insufficiency Primary = Adrenal disease = Addison�s Idiopathic, autoimmune, infectious, infiltrative, infarction, hemorrhage, cancer, CAH, postop Secondary = Pituitary Tertiary = Hypothalamus Functional = Exogenous steroids

35. Etiology of Adrenal Crisis Underlying Adrenal Insufficiency (Addision�s and Chronic Steriods)

36. Acute adrenal crisis? Underlying Adrenal insufficiency Addison�s disease Chronic steroids No underlying Adrenal insufficiency Adrenal infarct or hemorrhage Pituitary infarct or hemorrhage Precipitants of Adrenal crisis Surgery Anesthesia Procedures Infection MI/CVA/PE Alcohol/drugs Hypothermia

37. Adrenal Hemorrhage Overwhelming sepsis (Waterhouse-Friderichsen syndrome) Trauma or surgery Coagulopathy Adrenal tumors or infiltrative disorders Spontaneous Eclampsia, post-parturm, antiphospholipid Ab syndromes

38. Key Features of Adrenal Crisis 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

39. Features of Adrenal Insufficiency

40. Hyperpigmentation

41. Hyperpigmentation

42. Adrenal Crisis Consider on the differential diagnosis of SHOCK NYD

43. Investigations Adrenal Function Electrolytes Random cortisol ACTH Look for Precipitant ECG CXR Labs EtOH Urine

44. 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

45. Outline

46. Corticosteriod Stress Dosing:Who? When? How much? Who needs stress steroids? ?Addison�s ?Chronic prednisone ?Chronic Inhaled Steroids When? ? Laceration suturing ? Colle�s fracture reduction ? Cardioversion for Afib ? Trauma or septic shock How Much?

47. Effects of Exogenous Corticosteroids Hypothalamic � Pituitary � Adrenal axis suppression Has occurred with ANY route of administration (including oral, dermal, inhaled, intranasal) Adrenal suppresion may last for up to a year after a course of steroids HPA axis recovers quickly after prednisone 50 po od X 5/7

48. Streck 1979: Pituitary � Adrenal Recovery Following a Five Day Prednisone Treatment

49. Who needs Corticosteroid Stress Dosing? Coursin JAMA 2002: Corticosteroid Supplementation for Adrenal Insufficiency All patients with known adrenal insufficiency All patients on chronic steroids equivalent to or greater than PREDNISONE 5 mg/day

50. Corticosteroid Stress Dosing: La Rochelle Am J Med 1993 ACTH stimulation test to patients on chronic prednisone Prednisone < 5 mg/day No patient had suppressed HPA axis Three had intermediate responses Prednisone > or = 5 mg/day 50% had suppressed HPA axis, 25% were intermediate, 25% had normal response

51. Corticosteroid Stress Dosing What duration of prednisone is important? What about intermittent steroids? What about inhaled steroids?

52. Corticosteroid Stress Dosing: Summary of literature review Short courses of steroids are safe Many studies in literature documenting safety of prednisone X 5 � 10 days Wilmsmeyer 1990 Documented safety of 14 day course of prednisone Sorkess 1999 Documented HPA axis suppression in majority of patients receiving prednisone 10 mg/day X 4 weeks Many studies documenting HPA axis suppression with steroid use for > one month

53. Corticosteroid Stress Dosing Inhaled Corticosteroids: Allen 2002. Safety of Inhaled Corticosteroids. Adrenal suppression has occurred in moderate doses of ICS (Flovent 200 � 800 ug/day) Adrenal suppression is more common and should be considered with chronic high doses of ICS (Flovent > 800 ug/day)

54. Corticosteroid Stress Dosing �There is NO consistent evidence to reliably predict what dose and duration of corticosteroid treatment will lead to H-P-A axis suppression� Why?

55. Corticosteroid Stress Dosing: The bottom line Consider potential for adrenal suppression: Chronic Prednisone 5 mg/day or equivalent Prednisone 20 mg/day for one month within the last year > 3 courses of Prednisone 50 mg/day for 5 days within the last year Chronic high dose inhaled corticosteroids

56. When are stress steroids required? When is stress dosing required? (Cousin JAMA 2002) Any local procedure with duration < 1hr that doesn�t involve general anesthesia or sedatives does NOT require stress dosing All illnesses and more significant procedures require stress dosing

57. Corticosteroid Stress Dosing

58. Corticosteroid Stress Dosing MINOR Double chronic steroid dose for duration of illness (only needs iv if can�t tolerate po) MODERATE Hydrocortisone 50 mg po/iv q8hr MAJOR Hydrocortisone 100 mg iv q8hr

59. Corticosteroid Stress Dosing What about procedural sedation? ? Stress dose just before sedation/procedure Recommended by Coursin JAMA 2002 but NO supporting literature specific to procedural sedation in emerg Should be done --------> Hydrocortisone 50 mg iv just before procedure and then continue with normal steroid dose

60. Outline

61. Non �diabetic Hypoglycemia Fasting Insulinoma Insulin Sulfonylureas Liver dz H-P-A axis Fed Alimentary hyperinsulinism Congenital deficiency What labs to order BEFORE glucose administration???? Serum glucose C-peptide level Insulin level Cortisol Sulfonylurea level

62. Non-diabetic Endocrine Emergencies Recognize key features Pattern of underlying dz + precipitant Emergent management P3S2, levothyroxine, dex Supportive care and look for precipitant Consider corticosteroid stress dosing

63. The End�