Download Non Diabetic Endocrine Emergencies

Non Diabetic Endocrine
Emergencies
Ping-Wei Chen
Dr. Stefan DaSilva
December 18th 2008
Objectives
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Brief review of HPA axis physiology
Thyroid Storm
Thyrotoxicosis
Myxedema Coma
Adrenal Insufficiency/Crisis
Pheochromocytoma
Pituitary Apoplexy
Thyroid Physiology
• Hypothalamus
– Thyroptropin releasing
hormone (TRH)
• Anterior Pituitary
– Thyroid stimulating
hormone (TSH)
• Thyroid
– T3 and T4
Hypothalamic-Pituitary-Thyroid
Axis
Thyroid Hormone Synthesis
bloodstream
lumen
T3
T4
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.
5
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
7
Cranked!!
• Treatment
– In ED gave Propranolol 2mg IV q10minutes x 3
---> heartrate 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
• Rosen’s: “They refer to the continuum of
disease that results from thyroid
hyperfunction”.
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
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
Precipitant of Thyroid Storm
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V – vascular accidents, PE, infarction
I – infection
T – trauma, surgery, burns
A - ***
M – hypoglycemia, DKA, HONK
I – I131 therapy, thyroid hormone, contrast
N - ***
Thyroid Storm
• Exaggerated hyperthyroidism + Fever + Altered
LOC
• Cardiovascular: hyperdynamic + excitable
– Sinus tachycardia/Atrial tachycardia (A. fib)
– CHF (±underlying heart disease)
– Chest pain, Dyspnea, Palpitations, Inc. Pulse
Pressure, “Water Hammer” pulse
• Gastrointestinal:
– Diarrhea, N/V, Abdominal pain
– Liver dysfunction
Thyroid Storm
• Neurological/Behavioural:
– Proximal myopathy/Weakness
– Tremor
– Agitation/Anxiety/Restlessness/Delirium
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“Apathetic Hyperthyroidism”
• Elderly
– Fatigue and Weight Loss
– Multinodular Goiter
• Apathetic Thyroid Storm?
• Exaggerated Hyperthyroidism + Fever + Altered
LOC
– NOT agitated/restless/anxious
– CV, GI, Neuro signs/symptoms still present
Diagnosis
• Low TSH, High FT4 or FT3
• Differential Diagnosis:
– Sepsis – CXRay, Blood, Urine, Skin
– Intoxication (Cocaine, Amphetamines) –
toxidrome?
– Withdrawal (EtOH, benzodiazapene)
– Heat Stroke - history
– Hypothyroidism
Treatment of Thyroid Storm
• 5 Goals of Treatment:
– 1) Inhibit Hormone Synthesis
• Propylthiouracil (PTU) 600-1000mg PO/NG, then
200-250mg q4-6h
– 2) Block Hormone Release (>1 hr post PTU)
• Saturated Solution of KI (SSKI) 5 drops PO/NG q6h
• Iodine Anaphylaxis: Lithium Carbonate 300mg PO
q6h
• Iodine Overload Hyperthyroidism: Potassium
Perchlorate 500mg PO OD.
– 3) Prevent Peripheral Conversion of T4 to T3
• Propylthiouracil (PTU)
• Dexamethasone 2mg IV q6h
• Propranolol
– 4) Peripheral Adrenergic Blockade
• Propranolol 1-2mg IV bolus q10-15mins until effect
– 5) Supportive Care
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Treat fever: Acetaminophen (Not ASA)
Treat CHF (digitalis, diuretics, oxygen)
Stress dose steroids (Hydrocortisone 100mg IV q8h)
Treat Precipitating Factors
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.
“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
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
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
Thyrotoxic Periodic Paralysis
• Low serum potassium
– Shift
Thyrotoxic Periodic Paralysis
• Management:
– 1) Block β-adrenergic stimulation of Na/K
ATPase
• Propranolol 60mg PO q6h
– 2) Replete Potassium
• ORAL potassium (given not decreased total stores)
– 3) Treat Hyperthyroidism
• AVOID: IV glucose, β-agonists
Case 1: “I Can’t Move!”
• DX: Thyrotoxic Periodic Paralysis
• Improvement in ED with Potassium
Replacement and B-blocker therapy
• Admitted to Internal Medicine
• During Admission diagnosed with 1st
Presentation Graves Disease.
Post Partum Thyroiditis
• “Silent/Painless” thyroiditis
• 5% postpartum cases
• 3-4 months post-delivery
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• Clinical Features:
• Transient hyperthyroid followed by
transient hypothyroid
• Triphasic course
• Non-tender thyroid, Normal ESR (cf.
subacute thyroiditis)
• No eye findings (cf. Graves’ Disease)
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Post Partum Thyroiditis
• Laboratory Findings
– FT4 >> T3 – leakage of hormone from gland
• Treatment (if needed)
– Propranolol 20mg-40mg q6-8h
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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.
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
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,
tremelous, depressed reflexes, initial GCS
14/15, remainder of exam unremarkable.
• 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
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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
• 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
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
Impaired Hearing
Harrison’s Principles of Internal Medicine 16th Ed. p2109
Myxedema Coma
• Most dramatic of untreated/inadequately treated
dz
– Rarely first presentation of hypothyroidism
– Most common:
• Thyroid hormone discontinuation
• Precipitating event
• Misnomer! ±Coma
• Myxedema Coma:
– Severe Hypothyroidism + Hypothermia + Altered LOC
Myxedema Coma
Precipitants of Myxedema Coma
Cold Exposure
Infection (usually pulmonary)
CHF
Trauma
Drugs
Iodides
CVA
Hemorrhage (esp. GI)
Hypoxia
Hypercapnea
Hyponatremia
Hypoglycemia
Myxedema Coma
• Cardiovascular:
– Sinus bradycardia
– BP variable
– Leaky capillaries
• Effusions
• Respiratory:
– Depressed respiratory drive (hypoxic +
hypercapneic)
– Airway obstruction (from edema)
Myxedema Coma
• Gastrointestinal:
– Decreased peristalsis
• Abdominal pain, distension, constipation
• Neurological:
– Paresthesias
– Cerebellar-Like Symptoms
• Due to increased muscle tone/prolonged
contraction
– Coma
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
Differential Diagnosis
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Sepsis
Accidental Hypothermia
Nephrotic Syndrome/Renal Failure
Apathetic Hyperthyroidism
Hyperglycemia
Intoxication (sedatives)
Treatment of Myxedema Coma
• 4 Goals:
– 1) Thyroid Hormone Replacement
• Levothyroxine 500µg PO/IV, then 100µg/day
– 2) Correct Metabolic Abnormalities
• Hypoventilation – Intubate + Ventilate
• Hyponatremia – water restriction
• Hypoglycemia – D5W IV
– 3) Identify/Correct Precipitating Factors
• Infection? CHF?
– 4) Supportive Care
• Hypotension – Fluids, Pressors
• Hypothermia – GENTLE Rewarming
• Stress Dose Steroids – Hydrocortisone 300mg IV,
then 100mg q6-8h.
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 as poor man’s TSH 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
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
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
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
Adrenal Insufficiency
• An absolute or relative deficiency of
adrenal hormones
– Cortisol, Aldosterone, Androgen
Adrenal Physiology
Steroid Hormone Synthesis
Steroid Hormone Synthesis
17α-Hydroxylase
Steroid Hormones
• Cortisol:
– Intermediary metabolism (carbs,protein,fat,NA)
– Immune response (depressed)
Hypothalamus
CRH
Anterior Pituitary
ACTH
Negative Feedback
Adrenal Cortex
(Cortisol)
Negative Feedback
Steroid Hormones
• Aldosterone
– Blood Pressure
– Vascular Volume
– Electrolytes
• Regulation
– Primarily by Renin-Angiotensin-Aldosterone
Axis
• Small role by ACTH
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
Etiologies of Adrenal
Insufficiency
• Primary
– Idiopathic – autoimmune, idiopathic
– Infectious – granulomatous, viral, fungal
– Infiltrative – neoplasm, amyloidosis,
sarcoidosis
– Iatrogenic – post-adrenalectomy
– Hemorrhage
– CAH – lack of 21β-Hydroxylase deficiency
– Congenital Unresponsiveness to ACTH
Etiologies
• Secondary
– Pituitary Insufficiency
• Infarction, Hemorrhage, Tumour/Infiltration, ACTH
deficiency
– Hypothalamic Insufficiency
– Head Trauma
• Functional Disease
– Exogenous glucocorticoids
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
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
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
9
Hyperpigmentation
Adrenal Crisis
• Hypotension
– Decreased myocardial contractility
– Decreased responsiveness to catecholamines
– Hypovolemia (Na wasting, N/V)
• Hypoglycemia
– Decreased gluconeogenesis
– Increased peripheral glucose use
Treatment
• Correct the greatest threats to life!
– Hypotension: Fluid resuscitate ± pressors
– Hypoglycemia: D5W or D50.9% saline
• Glucagon 1-2mg IM/SC
– Correct hormone deficiency:
• Cortrosyn Stimulation Test
– 0.25mg (25U) cosyntropin IV/IM
– Serum cortisol at time: 0, 30 mins, 60 mins
– Normal: cortisol >500nmol/L or >200nmol/L over baseline
• Dexamethasone 4mg IV q6-8h (during test)
• Hydrocortisone 100mg IV/IM q6-8h
• Treat the Precipitating Factor!
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
Prevention
• Cortisol:
– Acute Illness
• Double dose of hydrocortisone
– Severe Illness
• 75-150mg hydrocortisone/day
• Aldosterone:
• Fludrocortisone 0.05-0.1mg
• Increase salt in diet
Adrenal Medulla
Norepinephrine
Epinephrine
Catecholamine Effects
• Norepinephrine/Epinephrine:
– α and β effects
• Increased CV contractility, excitability, heart rate
– Increased gluconeogenesis/glycogenolysis
– Increased metabolic rate
– Increased alertness/anxiety/fear
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
Differential Diagnosis
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Sympathomimetic Intoxication
MAOI Crisis
Withdrawal of Clonidine therapy
Seizures
Intracranial Lesions – posterior fossa
tumours
• SAH
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
Diagnosis
• 24 Hour Urine Studies
– Catecholamines and Metabolites
• Free Catecholamines
• Free Metanephrines
• Vanillylmandelic acid (VMA)
– Provocative and Adrenolytic Tests obsolete
Treatment
• α-adrenergic Blockade
– Phentolamine 1-2mg IV q5mins
– Phenoxybenzamine 10mg PO q12h (long term)
• β-blockade
– ONLY AFTER stable α-blockade achieved
– usually reserved for tachydysrrhythmias
– Propranolol 10mg PO q6-8h
• Nitroprusside, CCB, ACEi
Pituitary Gland
Growth Hormone
ACTH
Prolactin
TSH
LH
FSH
ADH
Oxytocin
Pituitary Apoplexy
• Infarction or Hemorrhage of Pituitary Gland
– Pre-existing tumour
– Head trauma
– Pregnancy
– Anti-coagulation
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Hypertension
DKA
Irradiation
Estrogen
Diuretic use
Bromocriptine
Clinical Presentation
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Sudden onset headache
Visual abnormalities
Oculomotor abnormalities
Meningeal irritation
Altered mental status
Pituitary Insufficiency
Adrenal Insufficiency
Diagnosis
• MRI – gold standard
• CT
• Treatment
• Dexamethasone 4mg IV q6-8h
• Hydrocortisone 100mg IV/IM q6-8h
• ±Emergent Neurosurgery
Conclusion
• Endocrine emergencies are RARE!
– High index of suspicion in certain patient
populations
• Most diagnoses are CLINICAL!!!!!
• Search for precipitating causes!!
Questions?