Thyroid Emergencies

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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.
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Thyroid Emergencies Lecture Goals

• Review pathophysiology of thyroid related
  illnesses
• Present information on recognition and management
  of medical emergencies related to thyroid diseases

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The Thyroid Emergencies

• Previously undiagnosed hyperthyroidism
• "Apathetic thyrotoxicosis"
• Thyroid Storm
• Myxedema coma
• Airway compression or superior vena cava syndrome
  from goiter or tumor

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Ancient Greek and Roman coins showing goiters
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Maria de Medici, wife of King Henry IV of France
in 1625, with a goiter
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Thyroid Physiology

• Thyroid gland secretes 2 hormones
• Thyroxine (tetraiodothyronine or T4)
• Triiodothyronine (T3)
• Secretion ratio T4 to T3 is 151
• Iodine is attached to tyrosine amino acid
  residues of thyroglobulin in the gland
  (organification)
• Coupling of these residues then produces T4 T3

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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

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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

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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

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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

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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

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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

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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

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Directional Changes in Thyroid Function Tests
Clinical State
Total T4
T3RU
FT4I
Free T4
TSH
Euthyroid
N
N
N
N
N
Hyper- thyroid
Hypothyroid
High TBG
N
N
N
Low TBG
N
N
N
Nonthyroid Illness
N or
N or
N or
N or
(N Normal)
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Medications Which May Cause "Euthyroid
Hyperthyroxinemia"

• Oral contraceptives
• Narcotics (methadone, heroin)
• Perphenazine
• Clofibrate
• 5-flurouracil
• Heparin
• Amiodarone
• Iodine contrast agents

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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

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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)

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Thyroid scans
Graves Disease
Toxic multinodular goiter with hot nodule
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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

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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)

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Medications Which Can Induce Hyperthyroidism

• Iodine
• Amiodarone
• Lithium

Also rarely due to ground beef contaminated with
bovine thyroid glands
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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

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51 year old male who presented with urinary
retention and proved to have Graves Disease
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Pretibial myxedema and square toes in the same
patient on the prior slide
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Ophthalmo- pathy associated with Graves Disease
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Asymmetric ophthalmo- pathy with lag ophthalmos
in Graves Disease
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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

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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

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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

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Patient with thyrotoxicosis from Graves Disease
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Onycholysis (irregular separation of nail plate
from nail bed near distal end) in the same
patient on the prior slide
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Possible Complications of Thyrotoxicosis at
Presentation

• High output congestive heart failure
• Dehydration
• Electrolyte imbalance (from diarrhea)
• Corneal lesions from exopthalmos
• Worsening of preexistent angina

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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

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Clinical Features of Apathetic Thyrotoxicosis

• May present with any of these seemingly isolated
  symptoms
• Congestive heart failure
• Atrial fibrillation
• Recent weight loss gt 20 kg
• Somnolence, apathy
• Irritability and uncooperative behavior
• If not recognized and treated, patients may slip
  into coma and die

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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

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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"

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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

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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 lt 5 (although not
  well studied or reported due to rarity of cases)

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Thyroid Storm Clinical Presentation

• 2 most important defining features
• High fever (usually over 40 degrees C)
• Significantly abnormal mental status
• Agitation, confusion, psychosis, coma
• May also exhibit
• Marked tachycardia
• Vomiting, diarrhea
• Jaundice (in 20 )
• Associated signs of Graves' disease

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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

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Thyroid Storm Differential Diagnosis

• Environmental heatstroke
• Cocaine, amphetamine, or phencyclidine toxicity
• Neuroleptic malignant syndrome
• Meningitis or encephalitis
• Intracranial hemorrhage
• Malignant hyperthermia
• Falciparum cerebral malaria

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Progression of Neurologic Findings in Thyroid
Storm

• Emotional lability
• Restlessness
• Hyperkinesis
• Confusion
• Psychosis
• Lethargy
• Somnolence
• Obtundation
• Coma

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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

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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

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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

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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

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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

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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

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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)

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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

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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)

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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

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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)

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General Causes of Thyroid Failure

• Diseases of the
• Thyroid (primary hypothyroidism) 95
• Pituitary (secondary hypothyroidism) 4
• Hypothalamus (tertiary hypothyroidism) lt 1
• Can be associated with the multiple endocrine
  failure syndromes

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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

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Symptoms of Hypothyroidism

• Cold intolerance
• Dyspnea
• Anorexia
• Constipation
• Menorrhagia or amenorrhea
• Arthralgias, myalgias
• Fatigue
• Depression
• Irritability
• Decreased attention memory
• Paresthesias

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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

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Signs of advanced hypothyroidism
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60 year old male who presented with fatigue and
alopecia his FTI was 0.2 and his TSH was gt 75
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Same patient on prior slide after 6 months
treatment with T4
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Hypothyroidism and Myxedema Coma Cardiac Signs

• Hypotension
• Bradycardia
• Pericardial effusion
• Low voltage EKG
• Prolonged QT interval
• Inverted / flattened T waves

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EKG of 52 year old female presenting with fatigue
and weight gain her T4 was 2.7 and her TSH was
40
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EKG of same patient on prior slide after
treatment with T4
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Precipitants of Myxedema Coma

• Cold exposure
• Infection
• Pneumonia
• Urinary tract infection
• Trauma
• CNS depressants
• Narcotics
• Barbiturates, Tranquilizers
• General anesthetics
• Cerebrovascular accident
• Congestive heart failure

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Myxedema Coma Typical Presentation

• Usual symptoms signs of hypothyroidism, plus
• Hypothermia (80 of cases)
• If temp. is normal, consider infection present
• Hypotension / bradycardia
• Hypoventilation / respiratory failure
• Ileus
• Depressed mental status / coma

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Patient with myxedema coma
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Contributing Factors to Coma in Myxedema Coma

• Hypothyroidism itself
• Hypercapnia
• Hypoxia
• Hypothermia
• Hypotension
• Hypoglycemia
• Hyponatremia
• Drug (sedative) side effect
• /- sepsis

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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

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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)

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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

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"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

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70 year old male with a substernal goiter causing
tracheal compression
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Surgical excision of a goiter
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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

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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