Endocrine EmergenciesEndocrine Emergencies

Natasa Janicic-Kahric, MDDivision of Endocrinology and MetabolismDivision of Endocrinology and Metabolism

Georgetown University HospitalWashington, DC

Classification of HypoglycemiaClassification of Hypoglycemia

FastingFasting::

Postprandial:Postprandial:

FactitiousFactitious

Increase in glucagon and epinephrine is impaired in many patients with type 1 DM

Symptoms of HypoglycemiaSymptoms of Hypoglycemia

AdrenergicAdrenergic

sweating sweating anxietyanxietytremortremornauseanauseapalpitationspalpitationstachycardiatachycardia

NeuroglycopenicNeuroglycopenic

dizzinessdizzinessheadacheheadachevisual disturbancesvisual disturbancesdifficulty speakingdifficulty speakinginability to concentrateinability to concentrateloss of memory, loss of memory,

confusionconfusionloss of consciousness or loss of consciousness or seizuresseizures

Treatment of HypoglycemiaTreatment of Hypoglycemia

Mild to moderate hypoglycemia in conscious patient:Mild to moderate hypoglycemia in conscious patient:

Fast-acting carbs (glucose tablets, juice) usually 15-30g Fast-acting carbs (glucose tablets, juice) usually 15-30g followed by long acting carbohydrate to prevent recurrent followed by long acting carbohydrate to prevent recurrent hypoglycemiahypoglycemia

Repeat BG in 15-30 minRepeat BG in 15-30 min

Severe hypoglycemia/unconscious patient:Severe hypoglycemia/unconscious patient:

25-50g of 50% glucose (1/2-1 amp D50W) IV25-50g of 50% glucose (1/2-1 amp D50W) IV

0.5-1.0 mg glucagon sc/IM if no IV access0.5-1.0 mg glucagon sc/IM if no IV access

Causes of HypercalcemiaCauses of Hypercalcemia

Parathyroid hormone-relatedParathyroid hormone-related

Primary HyperparathyroidismPrimary Hyperparathyroidism

(sporadic, familial, associated with (sporadic, familial, associated with MEN 1 or 2)MEN 1 or 2)Tertiary HyperparathyroidismTertiary Hyperparathyroidism(chronic renal failure)(chronic renal failure)

Vitamin D-relatedVitamin D-related

( vitamin D intoxication, ( vitamin D intoxication, granulomatous diseases)granulomatous diseases)

MedicationsMedications

thiazides, thiazides,

lithium lithium

vit A intoxicationvit A intoxication

Malignancy associated Malignancy associated HypercalcemiaHypercalcemia

Causes of HypercalcemiaCauses of Hypercalcemia

EndocrinopathiesEndocrinopathiesThyrotoxicosisThyrotoxicosisAddison’s diseaseAddison’s diseasePheochromocytomaPheochromocytomaAcromegalyAcromegaly

ImmobilizationImmobilization Milk-Alkali syndrome (from Milk-Alkali syndrome (from

calcium amtacids)calcium amtacids) TPNTPN HypophosphatemiaHypophosphatemia Manganese toxicityManganese toxicity Chronic liver diseaseChronic liver disease

Evaluation of HypercalcemiaEvaluation of Hypercalcemia

Confirm Hypercalcemia: total Calcium> 10.5 mg/dl or ionized calcium > 5.6 mg/dlConfirm Hypercalcemia: total Calcium> 10.5 mg/dl or ionized calcium > 5.6 mg/dl History, PE, Medications- stop and recheck calcium levelHistory, PE, Medications- stop and recheck calcium level

PTH normal or high measure 24-hour urine calcium PTH normal or high measure 24-hour urine calcium level:level:

low urine calcium- FHH low urine calcium- FHH

high urine calcium- HPThigh urine calcium- HPT

intact PTH measurement:intact PTH measurement:

measure PTHrP, malignancy work-upmeasure PTHrP, malignancy work-up

Hypocalcemia - DifferentialHypocalcemia - Differential

HypoparathyroidismHypoparathyroidism

Type I Polyglandular Autoimmune syndromeType I Polyglandular Autoimmune syndrome

Sporadic / Familial / diGeorgeSporadic / Familial / diGeorge

Infiltrative DiseasesInfiltrative Diseases

Disorders of Vitamin D metabolismDisorders of Vitamin D metabolism

MalignancyMalignancy

Postparathyroidectomy- hungry bone syndromePostparathyroidectomy- hungry bone syndrome

After thyroidectomyAfter thyroidectomy

HyperphosphatemiaHyperphosphatemia

MalabsorptionMalabsorption

Hypocalcemia - signs & symptomsHypocalcemia - signs & symptoms

Neuromuscular manifestations:Neuromuscular manifestations:

Tetany (neuromuscular irritability)Tetany (neuromuscular irritability)

Mild (circumoral numbness, muscle cramps, Mild (circumoral numbness, muscle cramps, parathesiasparathesias

Severe (carpopedal spasm, laryngospasm, Severe (carpopedal spasm, laryngospasm, seizures)seizures)

Trousseau’s signTrousseau’s sign

Chvostek’s signChvostek’s sign

Hypocalcemia - Medical TherapyHypocalcemia - Medical Therapy

Emergent - iv CalciumEmergent - iv Calcium1 amp Ca gluconate = 90mg elemental Ca 1 amp Ca gluconate = 90mg elemental Ca ++++ 2mg/kg ivp over 5 min2mg/kg ivp over 5 min15mg/kg iv over 6-12 hrs15mg/kg iv over 6-12 hrsUse if severe hypocalcemia associated with muscleUse if severe hypocalcemia associated with musclecramps, tetany, EKG abnormalities or mental statuscramps, tetany, EKG abnormalities or mental statuschangeschanges

Long term therapyLong term therapyrequires Calcium and Vitamin Drequires Calcium and Vitamin Dgoal = Cagoal = Ca++++ low normal (8.0 - 8.5mg/dl) low normal (8.0 - 8.5mg/dl)Ergocalciferol - long half life, can become toxicErgocalciferol - long half life, can become toxic

Adrenal CrisisAdrenal Crisis

Life-threatening, decompensated presentation of Life-threatening, decompensated presentation of adrenal insufficiencyadrenal insufficiency

High mortality if unrecognized & untreatedHigh mortality if unrecognized & untreated

Predominant manifestation is shockPredominant manifestation is shock

Hormonal deficiency responsible for crisis is mainly Hormonal deficiency responsible for crisis is mainly mineralocorticoid deficiencymineralocorticoid deficiency

Adrenal Crisis: ManifestationsAdrenal Crisis: Manifestations

FindingFinding % present% present

Fever > 39.4˚CFever > 39.4˚C 7070

Blood pressure < 80 mm HgBlood pressure < 80 mm Hg 2323

Serum Na < 130 mEq/LSerum Na < 130 mEq/L 3939

Hematocrit > 45%Hematocrit > 45% 3232

BUN > 25 mg/dlBUN > 25 mg/dl 1818

Serum K > 6 mEq/LSerum K > 6 mEq/L 1818

Blood glucose < 70 mg/dlBlood glucose < 70 mg/dl 1313

Diagnosis: Adrenal InsufficiencyDiagnosis: Adrenal Insufficiency

Therapy always takes precedence over diagnosis in Therapy always takes precedence over diagnosis in unstable patientunstable patient

Cornerstone of diagnosis is failure to raise cortisol Cornerstone of diagnosis is failure to raise cortisol levels in response to ACTH stimulation (cortisol level > levels in response to ACTH stimulation (cortisol level > 18 µg/dl)18 µg/dl)

ACTH stimulation test does not localize site of ACTH stimulation test does not localize site of deficiencydeficiency

Treatment: Adrenal InsufficiencyTreatment: Adrenal Insufficiency

Immediately:Immediately:

– Glucocorticoid administration (stress doses of 100 Glucocorticoid administration (stress doses of 100 mg hydrocortisone IV q 8 hr)mg hydrocortisone IV q 8 hr)

– Intravenous fluid, electrolyte, and glucose Intravenous fluid, electrolyte, and glucose administrationadministration

– Treatment of precipitating illnessTreatment of precipitating illness

Treatment: Adrenal InsufficiencyTreatment: Adrenal Insufficiency

As patient stabilizes:As patient stabilizes:– Taper glucocorticoids to physiologic replacement (15 Taper glucocorticoids to physiologic replacement (15

- 30 mg/day)- 30 mg/day)– Initiate mineralocorticoid replacement (for 1˚ AI)Initiate mineralocorticoid replacement (for 1˚ AI)– Screen patient for other endocrine dysfunction Screen patient for other endocrine dysfunction

(hypothyroidism, diabetes, hypogonadism etc)(hypothyroidism, diabetes, hypogonadism etc)– Patient education (sick day guidelines, medic-alert Patient education (sick day guidelines, medic-alert

bracelet)bracelet)

Myxedema Coma: DefinitionMyxedema Coma: Definition

Life threatening state associated with long-Life threatening state associated with long-standing untreated hypothyroidismstanding untreated hypothyroidism

Slowed functioning of virtually every organ Slowed functioning of virtually every organ systemsystem

Degree of hypothyroidism in which precipitating Degree of hypothyroidism in which precipitating illness or events produce cardiovascular and illness or events produce cardiovascular and central nervous system decompensationcentral nervous system decompensation

Myxedema Coma: Physical examMyxedema Coma: Physical exam

HypothermiaHypothermia

Hypotension Hypotension

Bradycardia Bradycardia

HypoventilationHypoventilation

Decreased mental statusDecreased mental status

Carotenemia, pallor Carotenemia, pallor

? Presence of thyroidectomy scar? Presence of thyroidectomy scar

Myxedema Coma: DiagnosisMyxedema Coma: Diagnosis

Three key diagnostic featuresThree key diagnostic features

Altered mental statusAltered mental status

Defective thermoregulationDefective thermoregulation

absolute or absolute or relativerelative hypothermia hypothermia

Precipitating illnessPrecipitating illness

infection most commoninfection most common

Myxedema Coma: ImportanceMyxedema Coma: Importance

30 - 40% mortality30 - 40% mortality

Early recognition and therapy essentialEarly recognition and therapy essential

Cardiopulmonary dysfunction reversible Cardiopulmonary dysfunction reversible with thyroid hormonewith thyroid hormone

Myxedema Coma: TherapyMyxedema Coma: Therapy

Parenteral form of thyroid hormone (gastrointestinal Parenteral form of thyroid hormone (gastrointestinal absorption impaired)absorption impaired)

Loading dose of levothyroxine to restore thyroxine Loading dose of levothyroxine to restore thyroxine pool (approx 300 µg/mpool (approx 300 µg/m22))

Daily intravenous dose of 50 - 100 µg LT4Daily intravenous dose of 50 - 100 µg LT4

Controversy exists as to whether to give T3, in Controversy exists as to whether to give T3, in addition to T4addition to T4

Thyroid Storm: DefinitionThyroid Storm: Definition

Life threatening thyrotoxicosisLife threatening thyrotoxicosis

The extreme of a clinical spectrum of The extreme of a clinical spectrum of hyperthyroidismhyperthyroidism

20% mortality if left untreated20% mortality if left untreated

Thyroid Storm: Physical ExamThyroid Storm: Physical Exam

TemperatureTemperature

HyperpyrexiaHyperpyrexia

CardiovascularCardiovascular

accelerated tachycardia, accelerated tachycardia, atrial dysrhythmia, atrial dysrhythmia, congestive heart failurecongestive heart failure

GastrointestinalGastrointestinal

nausea, vomiting, diarrhea, nausea, vomiting, diarrhea, jaundicejaundice

Central Nervous SystemCentral Nervous System

agitation, delirium,agitation, delirium,

psychosis, stupor, comapsychosis, stupor, coma

Thyroid Storm: PrecipitantsThyroid Storm: Precipitants

Rapid Rise in Thyroid Rapid Rise in Thyroid Hormone LevelsHormone Levels

withdrawal of antithyroidwithdrawal of antithyroid

drug therapydrug therapy

radioiodine therapyradioiodine therapy

vigorous thyroid palpationvigorous thyroid palpation

iodinated contrast dyesiodinated contrast dyes

Acute or Subacute non-Acute or Subacute non-thyroidal illnessthyroidal illness

infectioninfection

cerebrovasc. accidentcerebrovasc. accident

pulmonary embolismpulmonary embolism

parturitionparturition

diabetic ketoacidosisdiabetic ketoacidosis

hypoglycemiahypoglycemia

emotional stress, traumaemotional stress, trauma

Prevention of Thyroid StormPrevention of Thyroid Storm

Precautions with use of radioactive iodine therapyPrecautions with use of radioactive iodine therapy

Render patient euthyroid prior to treatmentRender patient euthyroid prior to treatment

Continue ß-blockersContinue ß-blockers

Monitor for exacerbation of hyperthyroidismMonitor for exacerbation of hyperthyroidism

Adequate treatment of hyperthyroidism prior to Adequate treatment of hyperthyroidism prior to surgical proceduressurgical procedures

Monitor patient if withdrawal of thionamides is Monitor patient if withdrawal of thionamides is indicatedindicated

Thyroid Storm: TreatmentThyroid Storm: Treatment

directed against peripheral effects of thyroid hormonedirected against peripheral effects of thyroid hormone

inhibition of T4 to T3 conversioninhibition of T4 to T3 conversion

PTUPTU

CorticosteroidsCorticosteroids

PropranololPropranolol

Ipodate, iopanoic acid, amiodaroneIpodate, iopanoic acid, amiodarone

ß-adrenergic blockadeß-adrenergic blockade

propranolol, cardioselective ß-blockerspropranolol, cardioselective ß-blockers

removal of excess circulating thyroid hormoneremoval of excess circulating thyroid hormone

plasmapheresis, charcoal plasmaperfusionplasmapheresis, charcoal plasmaperfusion

HyponatremiaHyponatremia

Most common electrolyte disorder and is Most common electrolyte disorder and is associated with variety of underlying diseases associated with variety of underlying diseases and conditionsand conditions

Hyponatremia is important clinically because:Hyponatremia is important clinically because:– Acute severe hyponatremia causes substantial Acute severe hyponatremia causes substantial

morbidity and mortalitymorbidity and mortality– Rapid correction of hyponatremia can cause severe Rapid correction of hyponatremia can cause severe

neurological damage and deathneurological damage and death

Differential diagnosis Differential diagnosis

Based on ECF volume status, hypo-osmolar Based on ECF volume status, hypo-osmolar hyponatremia can be divided into 3 categories:hyponatremia can be divided into 3 categories:1.1. Decreased ECF volume (hypovolemia)Decreased ECF volume (hypovolemia)

2.2. Increased ECF volume (hypervolemia)Increased ECF volume (hypervolemia)Congestive heart failure, cirrhosisCongestive heart failure, cirrhosis

3.3. Normal ECF volume (euvolemia): Most common type of Normal ECF volume (euvolemia): Most common type of hyponatremia in hospitilized patientshyponatremia in hospitilized patients

SIADHSIADH

Glucocorticoid deficiencyGlucocorticoid deficiency

HypothyroidismHypothyroidism

Clinical manifestations of hyponatremiaClinical manifestations of hyponatremia

The severity of symptoms correlates with the degree of The severity of symptoms correlates with the degree of hyponatremia and the rate at which it developshyponatremia and the rate at which it develops

Neurological manifestationsNeurological manifestations– Mild, nonspecific early symptomsMild, nonspecific early symptoms

Headache, nausea, fatigue, muscular cramps, anorexia, weakness, Headache, nausea, fatigue, muscular cramps, anorexia, weakness, lethargylethargy

– Severe symptomsSevere symptomsConfusion, focal neurological deficits, delirium, seizures and comaConfusion, focal neurological deficits, delirium, seizures and coma

Safe correction of hyponatremia entails balancing the risks of the hyponatremia versus the risks of the correction. These, in turn, depend on the degree of brain volume regulation that has occurred.

Verbalis, Trends Endocrinol Metab 3:1-7, 1992

Treatment of hyponatremiaTreatment of hyponatremia

central pontine myelinolysis:white areas in the middle of the pons indicate massive demyelination of descending axons (corticobulbar and corticospinaltracts)

Wright, Laureno & Victor Brain 102:361-385, 1979

Limited Controlled Correction

• Correct at a rate appropriate for the neurological symptoms (mild: 0.5 mmol/L/h; severe: 2 mmol/L/h).

• Use 0.9% NaCl if the patient is clinically volume depleted or has a urine Na+ < 30 mmol/L, otherwise use 3% NaCl.

• Monitor plasma [Na+] every 2-4 hours to ensure that the correction stays within the chosen parameters.

• Stop active correction when suitable end-points are reached:- the patient becomes asymptomatic;- a safe plasma [Na+] (generally > 120 mmol/L) is reached;- a total magnitude of correction of 12-15 mmol/L in the first 24h or

18-20 mmol/L in the first 48h is achieved.

• Complete correction using slower means (fluid restriction).

Treatment of Treatment of SIADH

Vaprisol Vaprisol (conivaptan)(conivaptan)Dual AVP V1A and V2 receptor antagonist Dual AVP V1A and V2 receptor antagonist Inhibits the effects of AVP on receptors in the kidneys Inhibits the effects of AVP on receptors in the kidneys Indicated for the treatment of hospitalized patients with Indicated for the treatment of hospitalized patients with euvolemic hyponatremia resulting from inappropriate or euvolemic hyponatremia resulting from inappropriate or excessive secretion of AVPexcessive secretion of AVPThe recommended regimen of treatment is a loading dose of 20 The recommended regimen of treatment is a loading dose of 20 mg of the drug delivered via 30 minute infusion, followed by an mg of the drug delivered via 30 minute infusion, followed by an additional infusion of 20 mg continuously over 24 hours. additional infusion of 20 mg continuously over 24 hours. Subsequent infusions should be administered every 1-3 days at Subsequent infusions should be administered every 1-3 days at 20 mg/day via continuous infusion. Dose may be titrated up to 20 mg/day via continuous infusion. Dose may be titrated up to 40 mg/day if response is not sufficiently rapid.40 mg/day if response is not sufficiently rapid.