Non – Diabetic Non – Diabetic Endocrine Endocrine

EmergenciesEmergencies

“What an emerg doc needs to know”

Rob Hall PGY3

December 5th, 2002

Non – Diabetic Endocrine Non – Diabetic Endocrine EmergenciesEmergencies

WHY? Uncommon Potentially lethal Diagnostic dilemmas ED treatment may be

life-saving

OutlineOutline

T h yro id S to rm M yxe d e m ic C o m a

T H Y R O ID

A cu te A dre n a lin su ficc ie n cy

S te ro id S tre ssd o sing

A D R E N A LS

N o n - d iab e ticE n d oc rin e E m e rg en c ies

ObjectivesObjectives

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?

CaseCase

37 yo female Chest Pain and SOB Denies any PMHx Recent weight loss

Sinus tach 130 Temp 40 Agitated Tremulous

CASECASE

CASECASE

NOT GOOD!

Thyroid StormThyroid Storm

What is Thyroid Storm?What is Thyroid Storm?

What is Thyroid Storm?What is Thyroid Storm?Burch 1993Burch 1993

Etiology of Thyroid StormEtiology of Thyroid Storm

Undiagnosed Undertreated (Grave’s disease

or Mulitnodular toxic goiter)

Acute Precipitant

ThyroidStorm

Thyroid StormThyroid Storm

1% of all hyperthyroids

Mortality 30%

Precipitants– Vascular– Infectious– Trauma– Surgery– Drugs– Obstetrics– Any acute medical

illness

KEY FEATURES of Thyroid StormKEY FEATURES of Thyroid Storm

FEVERTACHYCARDIAALTERED LOCFeatures of underlying Hyperthyroidism

– Weight loss, heat intolerance, tremors, anxiety, diarrhea, palpitations, sweating, CP, SOB

– Goiter, eye findings, pretibial myxedema

When should you consider Thyroid When should you consider Thyroid Storm and what is the ddx?Storm and what is the ddx?

Infectious: sepsis, meningitis, encephalitisVascular: ICH, SAHHeat strokeToxicologic

– Sympathomimetics, seritonin syndrome, neuroleptic malignant syndrome, Delirium Tremens, anticholinergic syndrome

INVESTIGATIONSINVESTIGATIONS

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

Thyroid Storm: Thyroid Storm: Goals of ManagementGoals of Management

1 - Decrease Hormone Synthesis2 - Decrease Hormone Release3 - Decrease Adrenergic Symptoms4 - Decrease Peripheral T4 -> T35 - Supportive Care

Decrease Hormonal SynthesisDecrease 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

Decrease Hormone ReleaseDecrease Hormone Release

Iodine or lithium decreases release from hormone stored in colloid cells

MUST not be given until 1hr after PTUPotassium Iodide (SSKI) 5 drops po/ng

q6hrLugol’s solution 8 drops q6hr

Decrease Adrenergic EffectsDecrease 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

Decrease T4 -> T3Decrease T4 -> T3

CorticosteriodsPTU and propranolol also have some effectDexamethasone 2 – 4 mg ivRelative or absolute adrenal insufficiency

also common

Supportive CareSupportive Care

Fluid rehydrationCorrect electrolyte abnormalitiesControl temperature aggressively

– Ice, cooling blanket, tylenol, fans

Search for precipitant– Think vascular, infectious, trauma, drugs, etc

Summary of ManagementSummary of Management

PTU PROPRANOLOL POTASSIUM

IODIDE STERIODS SUPPORTIVE CARE

P3S2

Apathetic HyperthyroidismApathetic Hyperthyroidism

Elderly (can be any age)Altered LOC, Afib, CHFMinimal fever, tachycardiaNo preceeding hx of hyperthyroidism

except weight lossMore COMMON than thyroid stormCheck TSH in any elderly patient with

altered LOC, psych presentation, Afib, CHF

OutlineOutline

T h yro id S to rm M yxe d e m ic C o m a

T H Y R O ID

A cu te A dre n a lin su ficc ie n cy

S te ro id S tre ssd o sing

A D R E N A LS

N o n - d iab e ticE n d oc rin e E m e rg en c ies

What is Myxedemic Coma?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

Myxedemic ComaMyxedemic Coma

Hypothyroidism Myxedemic Coma

Etiology of Myxedemic ComaEtiology of Myxedemic Coma

Undiagnosed

Undertreated (Hashimoto’s thyroiditis,

post surgery/ablation most common)

Acute Precipitant

MyxedemicComa

Myxedemic ComaMyxedemic Coma

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

KEY FEATURES of KEY FEATURES of MyxedemaMyxedema

ALTER ED LO C H YPO VEN TILATIO N /R ESP FA ILU R E

H YPO TH ER M IA

U nderlying/preceeding featuresof H ypothyro id ism

When should Myxedema be When should Myxedema be considered and what is the ddx?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

Myxedemic ComaMyxedemic Coma

Investigations– TSH and Free T4– Look for ppt

ECG Labs Septic work up (CXR/BC/urine/ +/- LP) Random cortisol CT head

Management of Myxedemic Management of Myxedemic ComaComa

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

OutlineOutline

T h yro id S to rm M yxe d e m ic C o m a

T H Y R O ID

A cu te A dre n a lin su ficc ie n cy

S te ro id S tre ssd o sing

A D R E N A LS

N o n - d iab e ticE n d oc rin e E m e rg en c ies

Adrenal InsufficiencyAdrenal Insufficiency

Primary = Adrenal disease = Addison’s– Idiopathic, autoimmune, infectious, infiltrative,

infarction, hemorrhage, cancer, CAH, postop

Secondary = PituitaryTertiary = HypothalamusFunctional = Exogenous steroids

Etiology of Adrenal CrisisEtiology of Adrenal Crisis

Underlying Adrenal Insufficiency

(Addision’s and Chronic Steriods)

Acute Precipitant

AdrenalCrisis

Acute adrenal crisis?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

Adrenal HemorrhageAdrenal Hemorrhage

Overwhelming sepsis (Waterhouse-Friderichsen syndrome)

Trauma or surgeryCoagulopathyAdrenal tumors or infiltrative disordersSpontaneous

– Eclampsia, post-parturm, antiphospholipid Ab syndromes

Key Features of Adrenal CrisisKey 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

Features of Adrenal Features of Adrenal InsufficiencyInsufficiency

H yperp igm en ta tionH ypona trem iaH ype rka lem ia

M e tabo lic A c idos is

PRIMARYADRENAL INSUFF

N O H ype rpigm en ta tionM ild hypona trem iaN O hyperka lem iaN O m e t ac idos is

SECONDARY /TERTIARY ADRENAL

INSUFFICIENCY

HyperpigmentationHyperpigmentation

HyperpigmentationHyperpigmentation

Adrenal CrisisAdrenal Crisis

Consider on the differential diagnosis of SHOCK NYD

InvestigationsInvestigations

Adrenal Function– Electrolytes– Random cortisol– ACTH

Look for Precipitant– ECG– CXR– Labs– EtOH– Urine

Management of Adrenal CrisisManagement 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

OutlineOutline

T h yro id S to rm M yxe d e m ic C o m a

T H Y R O ID

A cu te A dre n a lin su ficc ie n cy

S te ro id S tre ssd o sing

A D R E N A LS

N o n - d iab e ticE n d oc rin e E m e rg en c ies

Corticosteriod Stress Dosing:Corticosteriod Stress Dosing:Who? When? How much?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?

Effects of Exogenous Effects of Exogenous CorticosteroidsCorticosteroids

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

Streck 1979: Pituitary – Adrenal Recovery Streck 1979: Pituitary – Adrenal Recovery Following a Five Day Prednisone Following a Five Day Prednisone

TreatmentTreatment

0

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Day-1

Day1

Day3

Day5

Day7

Day9

Day11

Cortisol

Who needs Corticosteroid Who needs Corticosteroid Stress Dosing?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

Corticosteroid Stress Dosing: Corticosteroid Stress Dosing: La Rochelle Am J Med 1993La 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

Corticosteroid Stress DosingCorticosteroid Stress Dosing

What duration of prednisone is important?What about intermittent steroids?What about inhaled steroids?

Corticosteroid Stress Dosing: Corticosteroid Stress Dosing: Summary of literature reviewSummary 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

Corticosteroid Stress DosingCorticosteroid 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)

Corticosteroid Stress DosingCorticosteroid 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?

Corticosteroid Stress Dosing: Corticosteroid Stress Dosing: The bottom lineThe 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

When are stress steroids When are stress steroids required?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

Corticosteroid Stress DosingCorticosteroid Stress Dosing

V ira l in fe c tio n , U R T I,U T I, fra c tu re , e tc,

w h ich do n o t req u ireh o sp ita l ad m iss ion

M IN O RS tre ss

M e d ica l o rtra u m a tic co n d ito nsth a t re q u ire h o sp ita l

a d m iss ion

M O D E R A T ES tre ss

C rit ica l co n d it ionre q u irin g IC U /C C UE m erg e n t S urg e ry

M A JO RS tre ss

C o rticos te ro idS tre ss D o s ing

Corticosteroid Stress DosingCorticosteroid 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

Corticosteroid Stress DosingCorticosteroid 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

OutlineOutline

T h yro id S to rm M yxe d e m ic C o m a

T H Y R O ID

A cu te A dre n a lin su ficc ie n cy

S te ro id S tre ssd o sing

A D R E N A LS

N o n - d iab e ticE n d oc rin e E m e rg en c ies

Non –diabetic HypoglycemiaNon –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

Non-diabetic Endocrine Non-diabetic Endocrine EmergenciesEmergencies

Recognize key featuresPattern of underlying dz + precipitant Emergent management

– P3S2, levothyroxine, dex– Supportive care and look for precipitant

Consider corticosteroid stress dosing

The End…The End…