Thyroid Emergencies

Lecture Goals

Review pathophysiology of thyroid related

illnesses
Present information on recognition and
management of medical emergencies related
to thyroid diseases
 common Thyroid Emergencies

Thyroid Storm
Myxedema coma
 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
Feedback Regulation of Thyroid
Hormone Levels
Normal regulation requires intact hypothalamic-
pituitary 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
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
 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
Ophthalmo-
pathy
associated
with Graves
Disease
Asymmetric
ophthalmo-
pathy 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
 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
 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
 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
 Precipitants of Myxedema
Coma
Cold exposure
Infection
–Pneumonia
–Urinary tract infection
Trauma
CNS depressants
ƒ Narcotics
ƒ Barbiturates, Tranquilizers

ƒ General anesthetics

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