1. ICU Endocrine Emergencies
Bradley J. Phillips, MD
Burn-Trauma-ICU
Adults & Pediatrics

2. ICU - Endocrine Disorders
Glucose metabolism
Thyroid dysfunction
Adrenal disorders
Pituitary disorder
Unusual
Carcinoid crisis
Hyperparathyroidism

3. ICU - Glucose Metabolism
Hyperglycemia
Hypoglycemia
Diabetic Ketoacidosis (DKA)
Hyperglycemic Hyperosmolar Syndrome

4. Diabetes in the ICU Diagnosis Complications Fasting glucose > 126
Random glucose > 200 x 2
Complications
Diuresis and dehydration
Acidosis
Hyponatremia
Hypocalcemia
Immune dysfunction

5. DKA Presentation Anorexia, nausea, emesis, polyuria Kussmaul breathing
“Fruity” breath
Deterioration mental status
Hypotension
Progressive acidosis
Chest and/or abdominal pain

6. DKA Occurs in absence or near-absence of insulin
NIDDM (type 2) at risk during catabolic stress
More common in adults than children
40% over 40
20% over 55
Infectious cause most common
Mortality
5-10%
Increases with age ( > 65 = 20-40%)

7. DKA Tests Hyperglycemia (> 250) Ketonemia (ß-hydroxybutyrate)
Glycosuria and ketonuria
Acidosis (pH < 7.3) with anion gap
Low serum bicarbonate (< 15)
Moderate hyperosmolality

8. DKA - Associated Abnormalities
Sodium
variable
fall by 1.6 for every 100 increase in glucose
falsely low with hypertriglyceridemia
Chloride
hyper in ketoacidosis
hypo associated with severe emesis
Potassium
high with acidosis
at high risk for severe hypokalemia

9. DKA Management Fluid resuscitation Insulin
Normal saline cc/hr with bolus of 1L
If UOP good and NA > 140, slow IVF and change to .45 NS
Add D5 once BS < 300
Insulin
0.4u/kg with 1/2 IV and 1/2 SQ
IV qtt or hourly IV injections
continue until ketones in urine resolved
change to SQ once BS< 200, pH > 7.3, Bicarb > 18

10. DKA Management Potassium Replete hypophosphatemia
K< 3.5 add 40 meq/l
K > 3.5 and < meq/l
check q 2 hrs
Replete hypophosphatemia
Give bicarbonate if pH < 7.1
Treat underlying cause

11. DKA Complications Hypotension and shock Thrombosis Cerebral edema
Renal failure
Hypoglycemia

12. Hyperglycemic Hyperosmolar Syndrome
Present with severe hydration without ketosis and acidosis
Glucose > 1000
Coma, seizures, tremors, hemiplegia
Causes
infection MI
hemorrhage and trauma
burns
Treat the same as DKA

13. ICU - Thyroid Dysfunction
Hypothyroidism
Myxedema coma
Thyrotoxicosis
Thyrotoxic crisis

14. Hypothyroidism cold intolerance hypothermia apathy
depressed mental status
weight gain
alopecia
dry coarse skin
arthralgia and myalgia
hoarseness
enlarged tongue
goiter
periorbital edema
hyponatremia
hypoventilation
hypotension
cardiac dysfunction
bradycardia
pericardial effusion

15. Myxedema Coma Acute exacerbation of hypothyroidism Highly lethal = 50%
Precipitating factors
CVA
CHF
drugs (narcotics, diuretics, sedative)
surgery/trauma
GI hemorrhage
bowel obstruction
hypoadrenalism

16. Myxedema coma Non-pitting edema “doughy” Severe sensorial depression
Airway obstruction
Respiratory muscle weakness
Severe hypoventilation

17. Thyrotoxicosis Etiology Graves toxic goiter thyroiditis drugs
amiodarone
iodine
thyroxine (particularly IV)
Pituitary adenoma
Molar pregnancy

18. Thyrotoxicosis Thyroid crisis / “storm”
life-threatening 10-20% mortality
precipitation factors
Infection
Thyroid manipulation (operation, palpation)
Metabolic disorders (DKA)
Trauma MI PE
Pregnancy

19. Thyrotoxicosis Vs “Storm”
Neuro
emotional lability
tremors
weakness CV
tachycardia
systolic HTN
afib
Thermo
heat intolerance GI
diarrhea
Neuro
delirium
seizures
coma CV
CHF
arrhythmias
Thermo
fevers GI
emesis
diarrhea
jaundice

20. Thyroid - Diagnostic Tests
TSH
Free T4 ( or FTI)
T3 –RIA (Radioimmune Assay)

21. Thyrotoxicosis Differential Diagnosis
Check free T4
if high, r/o euthyroid hyperthyroxinemia
etiology
high TBG (pregnancy, estrogen)
acute illness
liver disease
drug-induced (amiodarone, heparin, narcotics, anti-psychotics)
differeriate with history/clinical exa,
If low, check T3 to r/o T3 toxicosis
Radioactive iodine uptake test

22. Therapy - Hyperthyroidism
Uncomplicated hyperthyroidism
outpatient
methimazole or PTU
B-blockers for adrenergic
+/- I31 ablation
Severe hyperthyroidism
possible hospitalization
restricted activity
compliance with medications
education

23. Management of Thyroid “Storm”
Always ICU management
Supportive
Fever reduction
decreases metabolic rate
decreases percentage of free T4
tylenol avoid salicylates (alters protein binding)
Aggressive fluid resuscitation
large losses from sweating, emesis, diarrhea
replete glucose and vitamins
? Hemodynamic monitoring
rate control - first line digoxin
avoid B-Blockers

24. Management of Thyroid “Storm”
Pharmacologic control
Antithyroid drugs
methimazole or PTU
give po/NGT/rectally
Inhibit release of T4 and T3
SSKI or Lugol’s solution
initial of dose of antithyroid drug must be given
consider lithium

25. Management of Thyroid “Storm”
Pharmacologic control
Inhibit conversion of T4 to T3
consider steroids or PTU
ipodate sodium (Oragrafin) highly effective
caution long-term use (“escape”
Reduction of hyperadrenergic state
propranolol (historical)
cautious of B-blockers in CHF
Removal of T4
plasmaphresis or hemoperfusion
emergent thyroidectomy

26. ICU Complications of Hyperthyroidism
Atrial arrthythmias
most convert within 3 weeks of euthyroidism
never after 4 months
no prospective study on anticoagulation
CVA age-dependent not atrial fib -dependent
CHF
Malnutrition/dehydration
Metabolic failure
Drug metabolism

27. Therapy - Hypothyroidism
Uncomplicated
outpatient treatment
full dose 1.7 ug/kg
age dependent
young ug/d
old 12.5 to 25 ug/d
check TSH at 4-6 weeks
change doses 12.5 to 25 ug increments

28. Therapy - Hypothyroidism
Profound or myxedema coma
endocrine emergency
supportive care
correct hypothermia
blood volume restoration
monitor electrolytes (free water clearance impaired)
glucose replacement
check for drug toxicity (digoxin etc)
r/o underlying infection

29. Therapy - Hypothyroidism
Thyroxine replacement
loading dose uq IV
no CV complications in critically ill
? Higher mortality in high T3 toxicosis
maintenance ug/d

30. Hypothyroidism in Surgical Patients
Historical complications peri-op more common
Recent studies
mild-moderate - little influence
no increased cardiopulmonary difficulties, wound healing impairment, or infections
Critically ill
? respiratory dysfunction and vent weaning
T4 and T3 reduced, TSH high/low/normal
Controlled studies of T4/T3 administration
no benefit overall in trauma, burns
? Benefit in organ transplantation

31. Adrenal disorders Adrenal insufficiency Pheochromocytoma and “ crisis”
Aldosterone deficiency

32. Adrenal Insufficiency
Incidence
General population 40-60/million
ICU %
SICU %
SICU trauma 0.23%
SICU nontrauma 0.98%
SICU
> 14 days 6%
age > %
> 14 days and age > 55 11%
Blunt adrenal injury 5%

33. Risk Factors - AI Age > 55 Malnutrition
Prolonged hospital or ICU stay
Chronic alcoholism
High APACHE score
Stress in form of trauma, surgery, infection, and dehydration

34. Presentation of AI Non-ICU ICU insidious
nonspecific (weakness, wt loss, lethargy, GI symptoms)
ICU
acute adrenal crisis
altered by co-existing disease
usually precipitated by physical stressor (trauma, surgery, infection, dehydration)
other causes AIDS, TB, or pituitary tumor

35. ICU Clinical Presentation
Refractory hypotension
High-output circulatory failure
CI > 4
tachycardia
low SVR with normal wedge
Electrolytes disturbances
high K , low Na, and low glucose
Febrile (> 39C)
Mental status changes
Dehydration
GI disturbances

36. “Clues” to AI History Eosinophilia other endocrine abnormalities
family h/o endocrine abnormalities
Eosinophilia

37. AI Differential Diagnosis
Sepsis
Neurogenic shock
Overdose of vasodilator
Severe anemia
AV shunt
Thyrotoxicosis
Beriberi
Pregnancy

38. Adrenal Insufficiency - AI
Primary
Central
Relative

39. Adrenal Insufficiency - AI
Primary
autoimmune, infection, hemorrhage(bilateral), medications (ketaconazole, etc), metastatic carcinoma, lymphoma
Central
long-standing steroid use
Relative
increased degradation
resistance
increased demand

40. Primary AI Pathological process within adrenal gland Etiology
90% o f gland destruction
Etiology
Autoimmune %
Infectious - 35%
Hemorrhagic
Risk factors (Rao et al , Ann Intern Med, 1989)
coagulopathy
thromboembolic disease
postoperative state

41. Central AI Central dysfunction Etiology pituitary (secondary)
hypothalamus (teritary)
Etiology
 long-term glucocorticoid therapy
uncommon
post-partum pituitary necrosis (Sheehan’s syndrome)
transient ACTH deficiency (alcoholics)
pituitary radiation
empty sella syndrome

42. Steroid and Potency

43. Glucocorticoid vs Mineralocorticoid
Steroid Glucocorticoid Mineralocorticoid
Hydrocortisone
Prednisolone
Dexamethasone
Aldosterone
Fludrocortisone

44. Potential for HPA Suppression
Higher risk for suppression
higher glucocorticoid potency
short frequency of dosing
evening dosing
systemic therapy
duration > 1 week

45. Relative AI Relative increased degradation of glucocorticoids
drugs that activate hepatic metabolism
treatment of hypothyroidism
resistance to glucocorticoid activity
AIDS
increased demand (stress response)
numerous ICU studies

46. HPA Axis Assessment - Tests
H-P Axis and Adrenal
Low-dose ACTH stimulation (1 ug)
Adrenal only
Short ACTH stimulation test (250 ug)
H -P Axis only
Insulin-induced hypoglycemia test
Metyrapone
CRH stimulation

47. Laboratory Assessment
Random cortisol level
draw before steroids given
draw between 6-8 am
decadron generally consider not cross-reactive
positive if < 10 in normal or < 15 in critically ill
10-20 indeterminant
Cosyntropin testing
Corticotropin-releasing hormone test (CRH)
Plasma renin and aldosterone measurements

48. Cosyntropin stimulation test
Standard short
baseline cortisol level
0.25 mg cosyntropin with level 60 minutes later
peak > 20 or rise of 7 in critically ill
Low-dose short ( more sensitive for central)
more accurate and physiologic
same as standard but only 1 ug dose
Long
differentiation of primary vs central
replaced by ACTH measurement

49. HPA Axis Assessment - Test Summary

50. Treatment Hemodynamically unstable Hemodynamically stable
Baseline cortisol
Treat with Hydrocortisone 100 IV bolus and q8
+/- cosyntropin testing
Isotonic IVF with D5
treat underlying disease or precipitating factors
Hemodynamically stable
same as above
cosyntropin testing

51. uncommonly required for mineralocorticoid activity
Treatment - Steroids
Hydrocortisone
provides glucocorticoid and mineralocorticoid
physiological doses
max 300 mg/day
normal daily adrenal output
AM 25 mg /PM mg
Dexamethasone
not cross-reactive with cortisol assays
no mineralocorticoid activity
useful while diagnostic testing being completed
Fludrocortisone (Florinef)
uncommonly required for mineralocorticoid activity

52. Outcome Untreated = 100% mortality
Treated in critically ill = 50% mortality
Cortisol level
positively correlated to severity of illness
negatively correlated to survival

53. ICU Endocrine Emergencies
Questions…?
Bradley J. Phillips, MD
Burn-ICU
SBH-UTMB