Transcript Non Diabetic Endocrine Emergencies

Endocrine Emergencies
Maude Latulippe
Dr. Arun Abbi
January 21st 2010
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Objectives
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Thyroid Storm
Thyrotoxicosis
Myxedema Coma
Adrenal Insufficiency/Crisis
Pheochromocytoma
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Thyroid Physiology
• Hypothalamus
– Thyrotropin releasing
hormone (TRH)
• Anterior Pituitary
– Thyroid stimulating
hormone (TSH)
• Thyroid
– T3 and T4
Hypothalamic-Pituitary-Thyroid
Axis
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Thyroid Hormone Synthesis
bloodstream
lumen
T3
T4
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Case 1: Cranked!!
• 60 yr old female presents to PLC ED
concerned because she might have a “clot
in the veins”.
• States feels heart beating fast and very
sweaty.
• HR 140, BP 180/90, 98% RA, Temp 37.6,
glucose 11.
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Cranked!!
• Review of Systems
– 5 days ago had radioactive iodine therapy.
– No fevers/chills/malaise
– “Thyroid disorder for years”
– States hx of previous DVT
– Hyperactive
– Remainder of review unremarkable.
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Cranked!!
• Exam
– Hyperactive, speaking fast, restless
– Tremulous
– No tenderness to thyroid (why is this
important??)
– Normal cardiopulmonary exam
– Hyperreflexive otherwise normal neurological
examination
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Cranked!!
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LABS: All normal. TSH sent
Doppler U/S legs normal
Cardiac markers negative
CXR normal.
ECG: sinus tachycardia
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Cranked!!
• Treatment
– In ED gave Propranolol 2mg IV q10minutes x 3
---> heart rate decreased to 70 - 80
• During the day so discussed case with her
primary endocrinologist.
• Wished her started back on Propanolol and
Tapazole (methimazole).
• Agreed to see her the next day in clinic.
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Hyperthyroidism/
Thyrotoxicosis/Thyroid Storm
• Non-synonymous terms
– But no consensus on definitions
• Hyperthyroidism: the result of excessive
thyroid function
• Thyrotoxicosis: a state of thyroid hormone
excess
• Thyroid Storm: acute, life-threatening
exacerbation of thyrotoxicosis
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Symptoms/Signs of Hyperthyroidism
Symptoms
Signs
Hyperactivity/Irritable/Dysphoria
Tachycardia/A. fib in elderly
Heat Intolerance/Sweating
Tremor
Palpitations
Goiter
Fatigue/Weakness
Warm, moist skin
Weight loss/Hyperphagia
Muscle Weakness/Proximal Myopathy
Diarrhea
Lid retraction/Lag
Polyuria
Gynecomastia
Oligomenorrhea/Dec. Libido
Harrison’s Principles of Internal Medicine 16th Ed. p2113
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Causes of Thyrotoxicosis
Causes of Thyrotoxicosis
Toxic Diffuse Goiter (Graves’ Disease)
Toxic Multinodular Goiter
Toxic Uninodular Goiter
Factitious Thyrotoxicosis (external supplementation)
T3 Toxicosis
Thyrotoxicosis associated with Thyroiditis (eg: Hashimoto’s, de Quervain’s)
Iodine Loads (eg: amiodarone)
Metastatic Follicular Carcinoma
Malignancies with circulating thyroid stimulators
TSH – producing pituitary tumours
Struma Ovarii with hyperthyroidism
Hypothalamic hyperthyroidism
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Precipitant of Thyroid Storm
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V – vascular accidents, PE, infarction
I – infection
T – trauma, surgery, burns, palpation
A - ***
M – hypoglycemia, DKA, HONK
I – I131 therapy, thyroid hormone, contrast,
amiodarone, iodine, Li, withdrawal thyroid
meds
• N - ***
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Thyroid Storm
Thyrotoxicosis + altered mental status + fever
• Temp > 37.8 oC
• Tachycardia out of proportion to fever
• CNS sx (excitation early, depress later)
• Cardiovasc or GI signs and sx
-dysrythmias
-severe Do
-PVCs
-No ,Vo
-AV block
-Cramps
20-30% surgical emerg!!
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“Apathetic Hyperthyroidism”
• Elderly (>70yo)
– Lethargy, Slow mentation, Apathetic facies
– Goiter
– Blepharoptosis
– Excessive weight loss (average=40lbs)
– Prox muscle weakness
– Masked thyrotoxicosis by cardiovasc sx:
a fib with CHF
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Diagnosis
• Low TSH, High FT4 or FT3
• Differential Diagnosis:
– Sepsis – CXRay, Blood, Urine, Skin
– Intoxication (Cocaine, Amphetamines) –
toxidrome?
– Withdrawal (EtOH, benzo)
– Heat Stroke – history
– Malignant hyperthermia
– Neuroleptic malignant syndrome
– Hypoglycemia or DKA
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Treatment of Thyroid Storm
• 5 Goals of Treatment:
– 1) Inhibit Hormone Synthesis
• Propylthiouracil (PTU) 600-1200mg PO/NG, then
200-250mg q4-6h
• Methimazole 20mg PO q4h
– 2) Block Hormone Release (>1 hr post PTU)
• Iodine: Saturated Solution of KI (SSKI) 5 drops
PO/NG q6h (iopanoic acid, Lugol’s iodine),
• Iodine Anaphylaxis: Lithium Carbonate 300mg PO
q6h
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– 3) Prevent Peripheral effects
Conversion of T4 to T3
• Propylthiouracil (PTU)
• Propranolol
• Dexamethasone 10mg
Peripheral Adrenergic Blockade
• Propranolol 1-2mg IV bolus q5mins until effect
• Alternative: esmolol, guanethidine, reserpine
– 4) Supportive Care
• Treat fever: Acetaminophen (Not ASA)
• Treat CHF (diuretics, oxygen)
• Stress dose steroids
5) Treat Precipitating factors
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Case 2: “I Can’t Move!”
• 21 yr old male woke up at 0300 hrs
feeling unwell.
• Progressive weakness migrating from
lower extremities to upper extremities.
• Now unable to move.
• Has had similar episodes in the past but
not as severe and always resolved on
their own.
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“I Can’t Move!!”
• Vitals: 130/75, 105HR, 96% RA, 18RR, glucose
7.6, Temp 36.4
• Recent URTI, no chest pain, shortness of breath,
difficulty swallowing, back pain or bowel or
bladder dysfunction.
• Recently immigrated from Mexico.
• Denies any medications or any medical history.
• Denies any drug or EtOH abuse.
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“I Can’t Move!!”
– HEENT: no palpable lymph nodes, normal
oropharynx
– CVS: S1S2, no murmurs
– RESP: Clear
– ABDO: soft, non-tender, no organomegaly
– NEURO: Cranial nerve exam normal, complete
paralysis both upper and lower extremities,
markedly hyporeflexia bilaterally (upper and
lower), sensation and proprioception remained
intact, rectal tone normal
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Labs
• Arterial Blood Gas
– Na: 144, K: <1.5, Cl: 109, CO2: 16, Cr: 61, gluc:
8.0
– WBC: 15.1, Ca: 2.57, Mg: 0.77, Phos: 0.15, Urea:
7.5
– TSH: <0.01A, Free T4: 37, CK: 218
– CXR: normal, CT head: normal
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Thyrotoxic Periodic Paralysis
• Asian Males most common
– Native Americans/African
Americans/South Americans
• Vigorous exercise/high carb
meal
• Flaccid, ascending
paralysis (proximal > distal)
– Spares facial and respiratory
muscles
• Depressed/Absent DTR
– Due to weakness
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Thyrotoxic Periodic Paralysis
• Low serum potassium
– Shift
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Thyrotoxic Periodic Paralysis
• Management:
– 1) Block β-adrenergic stimulation of Na/K
ATPase
• Propranolol 60mg PO q6h
– 2) Replete Potassium
– 3) Treat Hyperthyroidism
• AVOID: IV glucose, β-agonists
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Case 1: “I Can’t Move!”
• DX: Thyrotoxic Periodic Paralysis
• Improvement in ED after
K+ 10mEqK IV
B-blocker therapy
• Admitted to Internal Medicine
• During Admission diagnosed with 1st
Presentation Graves Disease.
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Post Partum Thyroiditis
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“Silent/Painless” thyroiditis
5-10% postpartum cases
6 wks to 6 months months post-delivery
Transient hyperthyroid followed by
transient hypothyroid then euthyroid
• Propranolol if needed
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Case 2: “I Can’t Warm Up!”
• 70 yr old non-English speaking female
brought by EMS because of decline in
LOC and function of past few days.
• Multiple recent ED visits for
hyponatremia.
• Complaints of malaise, fatigue,
weakness and confusion.
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Case 2: “I Can’t Warm Up!”
• Vitals 35.2, 45-55HR, 10RR, 150/74
(initial), glucose 5.7
• Past Medical History: HTN, RA,
Shingles, Bilateral Hip Replacement
• Meds: BP med (water pill), acyclovir
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Case 2: “I Can’t Warm Up!”
• Collateral History from son states multiple visits
over past months for low salt, confusion and
lethargy.
• Had been referred to Outpatient Internal Med
Clinic.
• EXAM: puffy face, dry mm, tender epigastrium,
tremulous, depressed reflexes, initial GCS
14/15, remainder of exam unremarkable.
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• LABS: Hgb: 109, WBC 3.9, Plts 100, ESR
111, Na 132, K 5.0, Glucose 4.1, Lipase
410, Urea 10.8, CK pending, TnT normal
• Initial ABG 7.43/38/78/25 lactate 0.6
• TSH: not back in ED
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• CT head: normal
• CXR: normal
• Urine normal
• CT abdo/pelvis: probable ovarian mass, no
diverticulitis or pancreatic
abscess/pseudocyst, small bilat effusions
seen.
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Case 2: “I Can’t Warm Up!”
• In ED declining GCS to 8/15
• profoundly bradycardic,
• borderline hypotensive,
• hyponatremia and hypoglycemia
• hypothermic (31.4C despite external rewarming techniques)
• decreased RR --> increasing CO2 on ABG
• Intubated and lined in ED
• After induction agents and paralytics had worn
off pt made no respiratory effort on own, nor
response to painful stimuli
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• DX: ? Myxedema Coma
• Given steroids and thyroxine (also given
dose of Abx after cultures drawn)
• Sent to ICU
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Hypothyroidism
Subclinical Disease
Myxedema Coma
• Primary disease most common
– Autoimmune
– Iatrogenic
• Elderly Obese Females
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Medications associated with hypothyroidism
Decreased TSH secretion
Dopamine
Glucocorticoids
Octreotide
Decreased thyroid hormone secretion
Lithium
Iodide
Amiodarone
Decreased T4 absorption
Colestipol
Cholestyramine
Aluminum hydroxide
Ferrous sulfate
Sucralfate
Increased thyroid hormone metabolism
Phenobarbital
Rifampin
Phenytoin
Carbamazepine
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Signs/Symptoms of Hypothyroidism
Symptoms
Signs
Fatigue/Weakness
Dry /Cool Skin
Dry Skin
Puffy face, hands, feet (myxedema)
Cold intolerance
Diffuse alopecia
Hair Loss
Bradycardia
Difficulty Concentrating/Poor Memory
Peripheral Edema
Constipation
Delayed DTRs
Weight Gain/Poor Appetite
Carpal Tunnel Syndrome
Dyspnea
Serous Cavity Effusion
Hoarse Voice
Menorrhagia
Paresthesia
Seizures 25% cases
Impaired Principles
Hearing of Internal Medicine
Harrison’s
(low Na+, low glycemia)
16th
Ed. p2109
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Myxedema Coma
• Most dramatic of untreated/inadequately treated dz
– Rarely first presentation of hypothyroidism
– Most common:
• Thyroid hormone discontinuation
• Precipitating event
• Misnomer! ±Coma ±Myxedema
• Myxedema Coma:
– Severe Hypothyroidism + Hypothermia + Altered LOC
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Myxedema Coma
Precipitants of Myxedema Coma
Cold Exposure
Infection (usually pulmonary)
CHF
Trauma
Drugs
Iodides
CVA
Hemorrhage (esp. GI)
Hypoxia
Hypercapnea
Hyponatremia
Hypoglycemia
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Myxedema Coma
• Cardiovascular:
– Sinus bradycardia
– BP variable
– Leaky capillaries
• Effusions
• Respiratory:
– Depressed respiratory drive (hypoxic +
hypercapneic)
– Airway obstruction (from edema)
– Muscle weakness
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• Gastrointestinal:
– Decreased peristalsis
• Abdominal pain, distension, constipation
• Neurological:
– Paresthesias
– Cerebellar-Like Symptoms
• Due to increased muscle tone/prolonged
contraction
– Coma
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• Mortality 15%
• Predictors
– Age
– temp < 34
– HR < 40
– large amounts of T4 iv
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Investigation
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Hyponatremia
Blood glucose N to low
↑CPK/AST/LDH
ABG: resp acidosis (Hypoventilation)
Urinalysis: source infection
CXR
+- Abdo XR
+- Head CT
+- Echo
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Diagnosis
• High TSH and Low Free T4
– Note: Dopamine, Glucocorticoids, and
Somatostatin suppress TSH at pharmacologic
doses.
• Low/Normal TSH and Low Free T4?
– Hypothalamic/Pituitary Disease
– Critically ill patients
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Differential Diagnosis
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Sepsis
Accidental Hypothermia
Nephrotic Syndrome/Renal Failure
Apathetic Hyperthyroidism
Hyperglycemia
Intoxication (sedatives)
CHF
Electrolytes imbalance
Depression
Hepatic encephalopathy
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Treatment of Myxedema Coma
• ABC
• 4 Goals:
– 1) Thyroid Hormone Replacement
• Levothyroxine 300µg slow IV, then 100µg/day
– 2) Correct Metabolic Abnormalities
• Hypoventilation – Intubate + Ventilate
• Hyponatremia – water restriction
• Hypoglycemia – D5W IV
– 3) Identify/Correct Precipitating Factors
• Infection? CHF?
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– 4) Supportive Care
• Hypotension – Fluids
• Hypothermia – GENTLE Rewarming
• Stress Dose Steroids – Hydrocortisone 100mg IV
q8h
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Some Pearls
• ***beware when giving IV thyroxine and pressors
together as may result in VF/VT (should stop
pressor when giving IV thyroxine)
• ***try to avoid use of ASA in setting of storm as
may worsen disease.
• ***can use CK if TSH not available in setting of
presumed myxedema coma.
• ***be diligent re: searching for precipitating
causes!!!
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Case 3: “The Disappearing Tan
Lines”
• 29 yr old male with fatigue, heart
palpitations, vomiting and lightheadness
for 1yr.
• Presented to ED because of frustration
and multiple physician visits for similar.
• Vitals: 36.6, 67HR, 14RR, 112/65, 99%
RA, gluc 8.0
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Case 3: “The Disappearing Tan
Lines”
• Review of Systems
– Low BP (states at time as low as 85
systolic), wt loss of 20lbs over past year,
Tingling and muscle weakness, shortness
of breath on exertion, no chest pain, denies
any drug or EtOH abuse
– Previously treated for depression
– Family hx of hypothyroid and diabetes
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Case 3: “The Disappearing Tan
Lines”
• Exam
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HEENT: normal
CVS: S1 S2, no murmurs
RESP: clear
NEURO: no focal
ABDO: benign
DERM: Bronze skin, no tan lines
MSK: muscle wasting
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Case 3: “The Disappearing Tan
Lines”
• Labs: all normal in ED
• However, outpt lab work one month ago
shows:
– Na 131, K: 5.8, Cl: 99, CO2: 23, CK: 410,
Ferritin 364, Fe: 7, TSH 3.3
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Adrenal Insufficiency
• An absolute or relative deficiency of
adrenal hormones
– Cortisol, Aldosterone, Androgen
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Adrenal Physiology
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Steroid Hormones
• Cortisol:
– Intermediary metabolism (carbs,protein,fat,NA)
– Immune response (depressed)
– Fonction of catecholamines on cardiac muscle and
arterioles
Hypothalamus
CRH
Anterior Pituitary
Negative Feedback
ACTH
Negative Feedback
Adrenal Cortex
(Cortisol)
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Steroid Hormones
• Aldosterone
– Blood Pressure
– Vascular Volume
– Electrolytes
• Regulation
– Primarily by Renin-Angiotensin-Aldosterone
Axis
• Small role by ACTH
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Steroid Hormones
• Androgens
– Male sex steroids
• Secondary sexual characteristics in females
• Small proportion of total androgen in males
– Minimal effect of males
• Regulation:
– ACTH stimulates release
– Does NOT feedback to decrease ACTH
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Etiologies of Adrenal
Insufficiency
• BIG CAUSE TODAY: HIV-RELATED
• Primary
– Idiopathic – autoimmune, idiopathic
– Infectious – granulomatous, viral, fungal
– Infiltrative – neoplasm, amyloidosis,
sarcoidosis
– Iatrogenic – post-adrenalectomy, RX
– Hemorrhage
– CAH – lack of 21β-Hydroxylase deficiency
– Congenital Unresponsiveness to ACTH
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Etiologies
• Secondary
– Pituitary Insufficiency
• Infarction, Hemorrhage, Tumour/Infiltration, ACTH
deficiency
– Hypothalamic Insufficiency
– Head Trauma
• Functional Disease
– Exogenous glucocorticoids
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Acute Adrenal Insufficiency
• Acute illness on Chronic Adrenal
Insufficiency
Precipitants of Acute Adrenal Insufficiency
Exogenous Steroids
Infection
Vascular Event (MI, CVA)
Trauma
Surgery
Hypoglycemia
Pain
Psychiatric Event
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Special Cases
• Adrenal Hemorrhage
– Waterhouse-Friedrickson Syndrome
• Sepsis from meningococcemia with associated adrenal
hemorrhage (amongst hypotension,shock,DIC)
• Can also occur from Pseudomonas sepsis
– Acute, severe illness + anticoagulation/coagulopathy
• Pituitary Infarction
– Sheehan Syndrome
• Delayed effect of intrapartum/post-partum hemorrhage
leading to pituitary infarction
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The Usual Suspects
Symptom/Sign
Frequency (%)
Weakness
99
Pigmentation of Skin
98
Weight Loss
97
Anorexia/Nausea/Vomiting
90
Hypotension (<110/70)
87
Pigmentation of mucous membranes
82
Abdominal Pain
34
Salt Craving
22
Diarrhea
20
Constipation
19
Syncope
16
Vitiligo
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Hyperpigmentation
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Adrenal Crisis
• Hypotension
– Decreased myocardial contractility
– Decreased responsiveness to catecholamines
– Hypovolemia (Na wasting, N/V)
• HypoNa, HyperK, HyperCa
• Hypoglycemia
– Decreased gluconeogenesis
– Increased peripheral glucose use
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Treatment
• Correct the greatest threats to life!
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Hypotension: Fluid resuscitate ± pressors
Correct hyper K (hyper Ca, hypo Na)
Hypoglycemia: D5W or D50.9% saline
Correct hormone deficiency:
• Corticotropin Stimulation Test
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Baseline cortisol
250mcg cosyntropin IV/IM
Serum cortisol at time: 0, 30 mins, 60 mins
Normal: cortisol baseline or after test >550nmol/L or 2xbaseline
• Dexamethasone 4mg IV q6-8h (during test)
• Hydrocortisone 100mg IV/IM q6-8h
• Treat the Precipitating Factor!
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Case 3: “The Disappearing Tan
Lines”
• DX: Primary Adrenal
Insufficiency/Addison’s Disease
• Referral made to Urgent Internal
Medicine/Endo
– Cosyntropin stim test performed
– Started on Decadron
– Marked improvement within 48hrs
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Prevention
• Cortisol:
– Acute Illness
• Double dose of hydrocortisone
– Severe Illness
• 75-150mg hydrocortisone/day
• Aldosterone:
• Increase salt in diet
• Fludrocortisone 0.05-0.2mg
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Adrenal Medulla
Norepinephrine
Epinephrine
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Precipitants!!
Exercice
Stress
Naloxone
Glucagon,
Metoclopramide
5-HT
BB
Rocuronium
If those drug precipitate HTN crise = pheo!!
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Catecholamine Effects
• Norepinephrine/Epinephrine:
– α and β effects
• Increased CV contractility, excitability, heart rate
– Increased gluconeogenesis/glycogenolysis
– Increased metabolic rate
– Increased alertness/anxiety/fear
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Pheochromocytoma
• Catecholamine secreting tumour
– Adrenal or Extra-adrenal
– Rare!
– Young to Mid-Adult Life
• Clinical Presentation:
– Hypertension – most common
– Paroxysms
• Hypertension, Headache, Sweating, Palpitations,
Apprehension, Sense of impending doom, Chest
Pain, Abdo Pain, N/V, pallor/flushing
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Differential Diagnosis
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Sympathomimetic Intoxication
MAOI Crisis
Withdrawal of Clonidine therapy
Seizures
Intracranial Lesions – posterior fossa
tumours
• SAH
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Pheochromocytoma
• Cardiovascular
– Hypertension (DBP >120)
– ECG
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Sinus tachycardia, SVT, VT, V.Fib.
Non-specific ST changes, U-waves (hypoK)
Ventricular Strain
RBBB, LBBB
Prolonged QT
• Endocrine
– Impaired glucose tolerance
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Diagnosis
• 24 Hour Urine Studies
– Catecholamines and Metabolites
• Free Catecholamines
• Free Metanephrines
• Vanillylmandelic acid (VMA)
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Treatment
• α-adrenergic Blockade
– Phentolamine 5 mg IV q1-2min
– Phenoxybenzamine 10mg PO q12h (long term)
• β-blockade
– ONLY AFTER stable α-blockade achieved
– usually reserved for tachydysrrhythmias
– Propranolol 10mg PO q6-8h
• Mg, Nitroprusside, CCB, ACEi
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Conclusion
• Endocrine emergencies are RARE!
– High index of suspicion in certain patient
populations
• Most diagnoses are CLINICAL!!!!!
• Search for precipitating causes!!
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Questions?
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