Thyroid
Emergencies
Jim Holliman, M.D., F.A.C.E.P.
Professor of Military and Emergency Medicine
Uniformed Services University of the Health Sciences
Clinical Professor of Emergency Medicine
George Washington University
Bethesda, Maryland, U.S.A.
Thyroid Emergencies
Lecture Goals
Review pathophysiology of thyroid
related illnesses
Present information on recognition and
management of medical emergencies
related to thyroid diseases
The Thyroid Emergencies
Previously undiagnosed
hyperthyroidism
"Apathetic thyrotoxicosis"
Thyroid Storm
Myxedema coma
Airway compression or superior vena
cava syndrome from goiter or tumor
Ancient
Greek and
Roman
coins
showing
goiters
Maria de
Medici, wife of
King Henry IV
of France in
1625, with a
goiter
Thyroid Physiology
Thyroid gland secretes 2 hormones :
–Thyroxine (tetraiodothyronine or T4)
–Triiodothyronine (T3)
–Secretion ratio T4 to T3 is 15:1
–Iodine is attached to tyrosine amino acid
residues of thyroglobulin in the gland
(organification)
–Coupling of these residues then produces
T4 & T3
Thyroid Physiology (cont.)
T4 & T3 released by the gland are bound &
transported by serum proteins :
–Thyroxine-Binding Globulin (TBG) : 75 %
–Thyroxine-Binding Prealbumin (TBPA)
–Albumin
The free (or unbound) hormone levels are
the levels which are maintained constant by
feedback & regulate thyroid function
Total measured serum T4 includes bound &
unbound
Variations in Thyroxine Binding
Proteins
Causes of increased TBG levels :
–Pregnancy, estrogens, cirrhosis, hepatitis,
porphyrias
Causes of decreased TBG levels :
–Protein malnutrition, nephrotic syndrome,
hepatic failure, androgenic steroids, high
dose glucocorticoids
Free T4 (FT4) usually constant in the
above conditions
Thyroid Hormone Action in the
Tissues
T4 deiodonated in periphery to T3
–This is 80 % of T3 produced
Other metabolite of T4 is reverse T3 (rT3)
which is metabolically inactive
T3 enters cells & binds to group of
nuclear receptors, then affects wide
range of cellular metabolic functions
Thyroid hormone required for normal
cell metabolism
Feedback Regulation of Thyroid
Hormone Levels
Normal regulation requires intact hypothalamicpituitary system
Hypothalamus secretes Thyrotropin-Releasing
Hormone (TRH)
TRH then stimulates synthesis & release of
thyrotropin (Thyroid Stimulating Hormone or TSH)
by the anterior pituitary
TSH then stimulates the thyroid gland to uptake
iodine, synthesize & release T4 & T3
T4 & T3 levels feedback to both hypothalamus &
pituitary affecting TRH & TSH release
Thyroid Function Tests
Radioimmunoassay for T4 (T4RIA) is most useful
single test of thyroid function
–Normal levels 4 to 12 mcg / dl
Free thyroid homone difficult to measure directly,
so "indirect" tests developed
–T3 Resin Uptake (T3RU) measures amount of
radioactive T3 unbound when added to patient's
serum
–Reflects # of sites available for binding T4 &T3
–Is indirect measure of level of circulating T4
–Normal is 25 to 35 %
Other Thyroid Function Tests
Free T4 Index (FT4I)
–Correlates with level of Free T4
–Is the product of T4RIA & T3RU
T3 radioimmunoassay (less useful)
–Normal 75 to 195 ng / dl
Serum TSH
–Normal is 0.3 to 5.0 mcU / ml
TRH Stimulation Test
–Measures TSH response to TRH IV injection
–Normal is increase in TSH to 30 mcU / ml
Clinical Interpretation of
Thyroid Function Tests
T3RU :
–Low in hypothyroidism & high TBG states
–High in hyperthyroidism & low TBG states
–T4RIA & the T3RU go in same direction with thyroid
disease & in opposite directions with TBG level
abnormalities
TSH
–Elevated in primary hypothyroidism
–If patient hypothyroid & TSH is low, then lesion is in
hypothalamic-pituitary axis, and TRH Stimulation
Test should be done
Directional Changes in Thyroid
Function Tests
Clinical
State
FT4I
Free T4
N
N
N
High TBG
N
N
N
Low TBG
N
N
N
N or
N or
Euthyroid
Total T4
N
T3RU
N
TSH
Hyperthyroid
Hypothyroid
Nonthyroid
Illness
N or
N or
(N = Normal)
Medications Which May Cause
"Euthyroid Hyperthyroxinemia"
Oral contraceptives
Narcotics (methadone, heroin)
Perphenazine
Clofibrate
5-flurouracil
Heparin
Amiodarone
Iodine contrast agents
Disorders of Thyroid Hormone
Excess
"Thyrotoxicosis" is the term for all
disorders with increased levels of
circulating thyroid hormones
"Hyperthyroidism" refers to disorders in
which the thyroid gland secretes too
much hormone
Radioactive iodine uptake test (RAUI)
distinguishes hyperthyroidism from
other forms of thyrotoxicosis
The Radioactive Iodine Uptake
Test (RAIU)
Quantitates the fraction of a dose of radioiodine
I-123 taken up by the thyroid gland within 24
hours
Normal is 5 to 30 %
Elevated when thyroid gland is overstimulated
Decreased when thyroid gland is suppressed
(as by ectopic production of T4 or T3)
Is decreased falsely by recent iodine load (as
from contrast computed tomography scan)
Thyroid scans
Graves Disease
Toxic
multinodular
goiter with hot
nodule
Causes of Thyrotoxicosis with
Elevated RAUI
Graves' Disease
Pituitary tumor secreting excess TSH
Pituitary insensitivity to feedback
Hydatidiform mole
Choriocarcinoma
Testis embryonal carcinoma
Toxic multinodular goiter
Toxic uninodular goiter
Causes of Thyrotoxicosis with
Decreased RAUI
Acute autoimmune thyroiditis (may later
lead to hypothyroidism)
Infectious thyroiditis
Postpartum thyroiditis
Factitious (taking PO excess thyroid
hormone)
Metastatic thyroid cancer
Struma ovarii (dermoid tumors or
teratomas of the ovary)
Medications Which Can Induce
Hyperthyroidism
Iodine
Amiodarone
Lithium
Also rarely due to ground beef
contaminated with bovine
thyroid glands
Features of Graves' Disease
(Toxic Diffuse Goiter)
Most common cause of hyperthyroidism (70
to 85 % of all cases)
Caused by thyroid stimulating
immunoglobulins
Mainly in young adults ages 20 to 50
5 times more frequent in women
Half of cases have infiltrative
ophthalmopathy with exopthalmos (not seen
with other causes of hyperthyroidism)
5 % have pretibial myxedema
51 year old male who presented with urinary retention and
proved to have Graves Disease
Pretibial
myxedema
and “square
toes” in the
same patient
on the prior
slide
Ophthalmopathy
associated
with Graves
Disease
Asymmetric
ophthalmopathy with
lag
ophthalmos
in Graves
Disease
Features of Toxic Multinodular
Goiter
Second most common cause of
hyperthyroidism
Most cases in women in 5th to 7th
decades
Often have long standing goiter
Symptoms usually develop slowly
Symptoms Suggestive of
Thyrotoxicosis
Nervousness, restlessness,shortened
attention span, emotional lability,
difficulty sleeping
Increased appetite
Weight loss
Heat intolerance, perhaps low fever
Diaphoresis
Weakness
Menstrual irregularities
Signs Suggestive of
Thyrotoxicosis
Sinus tachycardia, PVC's, PAC's, atrial
fibrillation
Tremor, hyperreflexia, muscle wasting
Warm, erythematous, moist skin
Alopecia, nail friability & separation from bed
Hyperventilation
Eyelid retraction, lid lag, persistent stare
Hyperactive bowel sounds
With Graves' : may have exopthalmos, tender
enlarged thyroid, & pretibial myxedema
Patient with
thyrotoxicosis
from Graves
Disease
Onycholysis (irregular separation of nail plate from nail bed near
distal end) in the same patient on the prior slide
Possible Complications of
Thyrotoxicosis at Presentation
High output congestive heart failure
Dehydration
Electrolyte imbalance (from diarrhea)
Corneal lesions from exopthalmos
Worsening of preexistent angina
Syndrome of "Apathetic" or
"Nonactivated" Thyrotoxicosis
Represents potentially dangerous
degree of hyperthyroidism masked by
other preexistent chronic conditions or
illnesses
High mortality if not recognized & patient
has surgery or another new illness
Most cases in elderly or patients with
compromised communication ability
Clinical Features of Apathetic
Thyrotoxicosis
May present with any of these seemingly
isolated symptoms :
–Congestive heart failure
–Atrial fibrillation
–Recent weight loss > 20 kg
–Somnolence, apathy
–Irritability and uncooperative behavior
If not recognized and treated, patients
may slip into coma and die
Thyroid Storm, A True Medical
Emergency
Exact pathogenesis not understood
No clear cut clinical feature separation
from thyrotoxicosis
Represents diffuse life-threatening
decompensated dysfunction of the
body's metabolism
Cases now very rare and sporadic
Thyroid Storm
Definitions
"Exaggerated or florid state of thyrotoxicosis"
"Life threatening, sudden onset of thyroid
hyperactivity"
May represent end stage of a continuum :
–Thyroid hyperactivity to thyrotoxicosis to
thyrotoxic crisis to thyroid storm
"Probably reflects the addition of adrenergic
hyperactivity, induced by a nonspecific stress,
into the setting of untreated or undertreated
hyperthyroidism"
Thyroid Storm
Background Etiology
Most cases secondary to Graves'
disease
Some due to toxic multinodular goiter
Rare causes :
–Acute thyroiditis
–Factitious
–Malignancies (most do not efficiently
produce thyroid hormones)
Very rare in children
Thyroid Storm
Prognosis
Old references quote almost 100 %
mortality untreated, and 20 % treated (but
these reports were before use of beta
blockers)
Current mortality ? should be < 5%
(although not well studied or reported
due to rarity of cases)
Thyroid Storm
Clinical Presentation
2 most important defining features :
–High fever (usually over 40 degrees C)
–Significantly abnormal mental status
ƒ Agitation, confusion, psychosis, coma
May also exhibit :
–Marked tachycardia
–Vomiting, diarrhea
–Jaundice (in 20 %)
–Associated signs of Graves' disease
Thyroid Storm
Precipitating Factors
Infection, especially pneumonia
Cerebrovascular accident
Acute coronary syndrome, Congestive heart failure
Pulmonary embolus
Diabetic ketoacidosis
Parturition / toxemia
Major trauma
Surgery
Iodine 131 Rx or iodine contrast agents
Rapid withdrawl of antithyroid medications
Thyroid Storm
Differential Diagnosis
Environmental heatstroke
Cocaine, amphetamine, or phencyclidine
toxicity
Neuroleptic malignant syndrome
Meningitis or encephalitis
Intracranial hemorrhage
Malignant hyperthermia
Falciparum cerebral malaria
Progression of Neurologic
Findings in Thyroid Storm
Emotional lability
Restlessness
Hyperkinesis
Confusion
Psychosis
Lethargy
Somnolence
Obtundation
Coma
Cardiovascular Findings in
Thyroid Storm
Marked tachycardia
–Sinus tach or atrial fibrillation
Increased myocardial irritability
–PVC's, PAC's, first degree AV block
Wide pulse pressure
Apical systolic murmur
Loud S1 and S2 valve sounds
Some have high output CHF
Case Reports of Unusual
Presentations of Thyroid Storm
Coma without prominent cardiovascular
findings
Status epilepticus
Nonembolic cerebral infarction
Abdominal pain and fever
Acute renal failure / rhabdomyolysis
Usual Indicated Initial Lab
Studies for Thyroid Storm
Glucose (stat fingerstick because of
altered mental status)
Pulse oximetry (+/- ABG)
CBC, electrolytes, BUN, creatinine
T4RIA, T3RU, TSH, +/- T3RIA
Urinalysis
Liver function tests
Serum cortisol
Thyroid Storm
Usual Lab Results
Lab studies do NOT distinguish
thyrotoxicosis from thyroid storm
Usually T4 and T3 are elevated, but may
only be elevated T3
Usually plasma cortisol is low for degree
of stress present
Hyperglycemia common
Thyroid Storm
Emergent Rx
High flow O2
Rapid cooling if markedly hyperthermic
–Ice packs, cooling blanket, mist / fans,
nasogastric tube lavage, acetominophen
(Salicylates contraindicated because cause
peripheral deiodination to T3)
IV fluid bolus if dehydrated
–May need inotropes instead if in CHF
Propranolol 1 mg doses or labetolol 10 to 20
mg doses IV & repeat doses as needed
Thyroid Storm
Further Rx
IV diltiazem +/- digoxin for rate control for
atrial fib
IV diuretics if in CHF
IV hydrocortisone (or equivalent) 100 mg
Propylthiouracil (PTU) 600 to 1200 mg PO
or by NG
Sodium iodide 1 gram IV one hour after the
PTU
Find and treat the precipitating cause
Thyroid Storm
Additional Optional Meds
Lithium carbonate 600 mg PO
–Follow-on dose 300 mg PO tid
Colestipol (resin which binds T4 in the
gut) 10 grams PO
–Follow-on dose 10 grams PO tid
Consider sedatives such as
benzodiazepines (but beta blockers are
the mainstay of therapy)
Actions of Antithyroid Meds for
Thyroid Storm Rx
PTU inhibits hormone synthesis by the thyroid
gland & also inhibits T4 to T3 conversion
peripherally (this is why it is preferred over
methimizole which just acts at the thyroid)
Iodine inhibits secretion of T4 & T3 from the
thyroid (it must be given AFTER synthesis block
from PTU or else it may provide more substrate
for gland hormone synthesis)
Lithium can be used in patients alergic to iodine
but can cause relapse when stopped
Follow-on Doses of Meds for
Thyroid Storm
PTU 100 to 300 mg PO tid
–Monitor for later agranulocytosis or liver
dysfunction
–Or Methimizole 20 mg PO tid to qid
Sodium iodide 500 mg IV q 12 hours
–Or SSKI 5 to 20 gtts PO tid
50 to 100 mg hydrocortisone IV daily till
stable, then wean as appropriate
Propranolol or labetolol or metoprolol (same
daily doses as for hypertension)
Additional Rx for Thyroid Storm
Not Responding to Initial Rx
Plasma exchange or plasmapheresis
Peritoneal dialysis or charcoal
hemoperfusion
Emergency surgery for partial or total
thyroidectomy
Myxedema Coma : The Other
Thyroid Emergency
Represents end stage of improperly treated,
neglected, or undiagnosed primary
hypothyroidism
Occurs in 0.1 % or less of cases of
hypothyroidism
Very rare under age 50
50 % of cases become evident after hospital
admission
Mortality is 100 % untreated, 50 % even if treated
Most cases present in winter (cold exposure)
General Causes of Thyroid
Failure
Diseases of the :
–Thyroid (primary hypothyroidism) : 95 %
–Pituitary (secondary hypothyroidism) : 4 %
–Hypothalamus (tertiary hypothyroidism) : < 1%
Can be associated with the multiple
endocrine failure syndromes
Etiologies of Primary
Hypothyroidism
Autoimmune : most common
–Some have lymphocytic infiltration variant
Post surgical thyroidectomy
External radiation
Iodine 131 Rx for hyperthyroidism
Severe prolonged iodine deficiency
Antithyroid meds (such as lithium)
Inherited enzymatic defects
True idiopathic
Symptoms of Hypothyroidism
Cold intolerance
Dyspnea
Anorexia
Constipation
Menorrhagia or amenorrhea
Arthralgias, myalgias
Fatigue
Depression
Irritability
Decreased attention & memory
Paresthesias
Signs Related to
Hypothyroidism
Dry, yellow (carotenemic ) skin
Weight gain (41 % of cases)
Thinning, coarse hair
Myxedema signs (mucopolysaccharide
deposition in tissues) :
–Puffy eyelids
–Hoarse voice
–Dependent edema
–Carpal tunnel syndrome
Anemia
Signs of
advanced
hypothyroidism
60 year old male
who presented
with fatigue and
alopecia ; his FTI
was 0.2 and his
TSH was > 75
Same patient on prior slide after 6 months treatment with T4
Hypothyroidism and Myxedema
Coma : Cardiac Signs
Hypotension
Bradycardia
Pericardial effusion
Low voltage EKG
Prolonged QT interval
Inverted / flattened T waves
EKG of 52 year old
female presenting
with fatigue and
weight gain ; her T4
was 2.7 and her
TSH was 40
EKG of same
patient on prior
slide after
treatment with
T4
Precipitants of Myxedema
Coma
Cold exposure
Infection
–Pneumonia
–Urinary tract infection
Trauma
CNS depressants
Narcotics
ƒ Barbiturates, Tranquilizers
ƒ General anesthetics
ƒ
Cerebrovascular accident
Congestive heart failure
Myxedema Coma
Typical Presentation
Usual symptoms & signs of
hypothyroidism, plus :
–Hypothermia (80 % of cases)
ƒ If temp. is normal, consider infection
present
–Hypotension / bradycardia
–Hypoventilation / respiratory failure
–Ileus
–Depressed mental status / coma
Patient with
myxedema
coma
Contributing Factors to Coma in
Myxedema Coma
Hypothyroidism itself
Hypercapnia
Hypoxia
Hypothermia
Hypotension
Hypoglycemia
Hyponatremia
Drug (sedative) side effect
+/- sepsis
Lab Studies to Order for
Suspected Myxedema Coma
Stat glucose (because of altered mental status)
Pulse oximetry (ABG usually indicated)
CBC, Lytes, BUN, creat., calcium
T4RAI, T3RU, TSH
Serum cortisol
Liver function tests
Relevant drug / alcohol levels
Emergency Treatment of
Myxedema Coma
O2 +/- intubation / ventilation if resp. failure
Rapid blood glucose check +/- IV D50 +/naloxone
Hydrocortisone 100 to 250 mg IV
Cautious slow rewarming (warm O2, scalp, groin,
& axilla warm packs, +/- NG lavage)
Thyroxine (T4) 500 mcg IV, then 50 mcg IV q day
Add 25 mcg T3 PO or by NG q 12 h (if T4 to T3
peripheral conversion possibly impaired)
Careful IV fluid rehydration (watch for CHF)
Other Aspects of Treatment for
Myxedema Coma
Search for and treat precipitating cause
Use lower doses of most other meds
(drug metabolism is impaired &
decreased until T4 physiology is
restored)
Follow TSH levels
–Should decrease in 24 hours and normalize
by day 7 of Rx
"Mechanical " Symptoms
Associated with Goiter
Frequent :
–Dyspnea, dysphagia
–Fullness, choking or pressure sensation in neck
Less common :
–Acute respiratory failure
–Superior vena cava syndrome
–Esophageal varices
Uncommon but reported :
–New onset asthma, phrenic nerve paralysis,
Horner's syndrome, chylothorax, neck abscess,
sleep apnea
70 year old male with a substernal goiter causing tracheal
compression
Surgical
excision
of a goiter
Causes of Airway Distress Due
to Thyroid Disease
Preoperative :
–Direct tracheal deviation & compression
–Intrathyroid bleeding causing tracheal
compression
–Tracheal invasion by anaplastic cancer
–Bleeding into trachea
–Resp. failure from pulmonary metastases of
thyroid cancer
Postoperative :
–Wound hematoma
–Laryngeal edema
–Bilateral vocal cord paralysis
–Tracheomalacia
Thyroid Emergencies
Summary
Important to remember interpretation of
thyroid function tests to avoid overdiagnosis
Keep high index of suspicion for "apathetic
thyrotoxicosis" in the elderly
Usual "ABC" care & correction of
temperature are important aspects of
emergency care for both thyroid storm &
myxedema coma
Consider thyroid disease in differential Dx for
upper airway symptoms