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

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

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

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

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

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%)

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

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

DKA Management Fluid resuscitation Insulin Normal saline 500-1000 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

DKA Management Potassium Replete hypophosphatemia K< 3.5 add 40 meq/l K > 3.5 and < 5.5 20 meq/l check q 2 hrs Replete hypophosphatemia Give bicarbonate if pH < 7.1 Treat underlying cause

DKA Complications Hypotension and shock Thrombosis Cerebral edema Renal failure Hypoglycemia

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

ICU - Thyroid Dysfunction Hypothyroidism Myxedema coma Thyrotoxicosis Thyrotoxic crisis

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

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

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

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

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

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

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

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

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

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

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

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

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

Therapy - Hypothyroidism Uncomplicated outpatient treatment full dose 1.7 ug/kg age dependent young 50-100 ug/d old 12.5 to 25 ug/d check TSH at 4-6 weeks change doses 12.5 to 25 ug increments

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

Therapy - Hypothyroidism Thyroxine replacement loading dose 300-500 uq IV no CV complications in critically ill ? Higher mortality in high T3 toxicosis maintenance 50-100 ug/d

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

Adrenal disorders Adrenal insufficiency Pheochromocytoma and “ crisis” Aldosterone deficiency

Adrenal Insufficiency Incidence General population 40-60/million ICU 1-20% SICU 0.66% SICU trauma 0.23% SICU nontrauma 0.98% SICU > 14 days 6% age > 55 1.7% > 14 days and age > 55 11% Blunt adrenal injury 5%

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

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

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

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

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

Adrenal Insufficiency - AI Primary Central Relative

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

Primary AI Pathological process within adrenal gland Etiology 90% o f gland destruction Etiology Autoimmune - 65-80% Infectious - 35% Hemorrhagic Risk factors (Rao et al , Ann Intern Med, 1989) coagulopathy thromboembolic disease postoperative state

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

Steroid and Potency

Glucocorticoid vs Mineralocorticoid Steroid Glucocorticoid Mineralocorticoid Hydrocortisone 1 1 Prednisolone 4 0.7 Dexamethasone 40 2 Aldosterone 0.1 400 Fludrocortisone 10 400

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

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

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

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

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

HPA Axis Assessment - Test Summary

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

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 12..5 mg Dexamethasone not cross-reactive with cortisol assays no mineralocorticoid activity useful while diagnostic testing being completed Fludrocortisone (Florinef) uncommonly required for mineralocorticoid activity

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

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