Thyroid storm and myxedema coma are life-threatening emergencies caused by excess or deficiency of thyroid hormones respectively. Thyroid storm results from excessive thyroid hormones and causes hypermetabolism affecting multiple systems. Myxedema coma occurs in severe long-standing hypothyroidism when precipitated by an event and causes physiological decompensation. Both require rapid diagnosis and aggressive treatment in an ICU setting to prevent high mortality rates. Treatment involves supportive care, thyroid hormone replacement, glucocorticoids, and correcting underlying conditions.

1. THYROID
EMERGENCIES
THYROID STORM
MYXEDEMA COMA

2. THYROID STORM

3. Background
• Thyroid storm, also referred to as thyrotoxic crisis, is an acute, life-
threatening, hypermetabolic state induced by excessive release of
thyroid hormones (THs) in individuals with thyrotoxicosis.
• May be the initial presentation of thyrotoxicosis in undiagnosed
children especially neonates
• Because thyroid storm is almost invariably fatal if left untreated (90%
mortality), rapid diagnosis and aggressive treatment are critical
• In the past, thyroid storm was commonly observed during thyroid
surgery, especially in older children and adults, but improved
preoperative management has markedly decreased the incidence of
this complication. Today, thyroid storm occurs more commonly as a
medical crisis rather than a surgical crisis.

4. Pathophysiology
• Thyroid storm is a decompensated state of thyroid hormone–induced, severe
hypermetabolism involving multiple systems.
• The clinical picture relates to severely exaggerated effects of THs.
• Heat intolerance and diaphoresis common in thyrotoxicosis manifest as
hyperpyrexia.
• Cardiac findings of mild-to-moderate sinus tachycardia in thyrotoxicosis
intensify to accelerated tachycardia, hypertension, high-output cardiac failure,
and a propensity to develop cardiac arrhythmias.
• Irritability and restlessness in thyrotoxicosis progress to severe agitation,
delirium, seizures, and coma.
• GI manifestations of thyroid storm include diarrhea, vomiting, jaundice, and
abdominal pain, in contrast to only mild elevations of transaminases and simple
enhancement of intestinal transport in thyrotoxicosis.

5. Precipitating factors
• Sepsis
• Surgery
• Anesthesia induction
• Radioactive iodine (RAI) therapy
• Drugs (anticholinergic and adrenergic drugs, eg, pseudoephedrine;
salicylates; nonsteroidal anti-inflammatory drugs [NSAIDs]; chemotherapy
• Excessive thyroid hormone (TH) ingestion
• Withdrawal of or noncompliance with antithyroid medications
• Diabetic ketoacidosis
• Direct trauma to the thyroid gland
• Vigorous palpation of an enlarged thyroid
• Toxemia of pregnancy and labor in older adolescents; molar pregnancy
• Most commonly associated with Graves disease.

6. Diagnosis
• Known Hx of thyrotoxicosis
• Burch and Wartofsky criteria – next slide
• General Sx: Fever, fatigue, profuse sweating, respiratory distress,
poor feeding and wt loss
• GI Sx: abdominal pain, nausea, vomiting, diarrhea and jaundice.
• Neurologic sx: Anxiety, altered behavior, seizures, coma

7. Diagnosis

8. Physical Examination
•Fever: Temperature consistently exceeds 38.5°C, Patients may progress
to hyperpyrexia, Temperature frequently exceeds 41°C.
•Excessive sweating
•Cardiovascular signs: Hypertension with wide pulse pressure,
Hypotension in later stages with shock, Tachycardia disproportionate to
fever, Signs of high-output heart failure, Cardiac arrhythmia
(Supraventricular arrhythmias are more common, [eg, atrial flutter and
fibrillation], but ventricular tachycardia may also occur.)
•Neurologic signs: Agitation and confusion, Hyperreflexia and transient
pyramidal signs, tremors, seizures, Coma
•Signs of thyrotoxicosis: Orbital signs, Goiter

9. Workup
• Thyroid storm diagnosis is based on clinical features, not on
laboratory test findings. If the patient's clinical picture is consistent
with thyroid storm, do not delay treatment pending laboratory
confirmation of thyrotoxicosis.
• Results of TFTs are usually consistent with hyperthyroidism i.e.
elevated T3, T4 and suppressed TSH.
• ECG is useful in monitoring for cardiac arrhythmias. Atrial fibrillation
is the most common cardiac arrhythmia associated with thyroid
storm

10. Treatment and Management (1)
• ICU setting – close monitoring and inotropic support.
• Supportive measures include: if needed oxygen, ventilatory support,
IV fluids preferably dextrose solution, correct any electrolyte
abnormalities, treat any cardiac arrhythmias and aggressively control
hyperthermia by ice packs, cooling blankets, PCM (PO or PR)
• Antiadrenergic drugs – beta blockers e.g. propanolol administered
orally or via NGT 60 – 80 mg every 4 – 6 hrs or IV when necessary Use
cardioselective beta blockers in cases of reactive airway disease e.g
metoprolol, use calciul channel blockers if beta blockers is
contraindicated. The use of intravenous short acting beta-1 blockers,
such as esmolol (loading dose of 250-500 mcg/kg, followed by an
infusion of 50-100 mcg/kg per minute), allows quick dose titration
with minimization of side effects.

11. Treatment and Management (2)
• Thionamides: Correct the hyperthyroid state. Administer antithyroid
medications to block further synthesis of THs. High dose PTU is
preferred over methimazole because of rapid onset and capacity to
inhibit peripheral conversion of T4 to T3. Methimazole may be used
in less severe cases. PTU 200mg every 4 hours or methimazole 20mg
every 4 to 6 hours orally through an NGT.
• Iodine compounds: lugol iodine or potassium iodide to block the
release of THs (atleast 1 hr after antithyroid drug therapy)
• Glucocorticoids: to decrease peripheral conversion of T4 to T3. HC is
administered 100mg IV or dexamethasone 1 – 2 mg every 6 to 8 hrs

12. Treatment and Management (3)
• Bile acid sequestrants: prevent reabsorption of free THs in the gut. A
recommended dose is 4 g of cholestyramine every 6 hours via a
nasogastric tube
• Treat any underlying conditions – infections should be treated with
antibiotics and treat comorbidities such as DKA
• If the patient is given PTU during treatment of thyroid storm, this should
be switched to methimazole at the time of discharge unless methimazole
is contraindicated. If there is a contraindication for the use of
methimazole, alternative methods to treat hyperthyroidism should be
considered after discharge, such as radioactive iodine or surgery.
• Patients with contraindications to thionamides need to be managed with
supportive measures, aggressive beta blockade, iodine preparations,
glucocorticoids and bile acid sequestrants for about a week in preparation
for a thyroidectomy.
• Plasmapheresis may be attempted if other measures are not effective.

13. MYXEDEMA COMA

14. Background
• Myxedema is a term generally used to denote severe hypothyroidism.
• Myxedema is also used to describe the dermatologic changes that occur in
hypothyroidism. In this setting, myxedema refers to deposition of
mucopolysaccharides in the dermis, which results in swelling of the
affected area.
• Myxedema coma, occasionally called myxedema crisis, is a rare life-
threatening clinical condition that represents severe hypothyroidism with
physiological decompensation. The condition usually occurs in patients
with long-standing, undiagnosed hypothyroidism and is usually
precipitated by infection, cerebrovascular disease, heart failure, trauma,
or drug therapy.
• Patients with myxedema coma are generally severely-ill with significant
hypothermia and depressed mental status.

15. Pathophysiology

16. Pathophysiology
• Myxedema coma can result from any of the causes of
hypothyroidism, most commonly chronic autoimmune thyroiditis. It
can also occur in patients who had thyroidectomy or underwent
radioactive iodine therapy for hyperthyroidism.
• Rare causes may include secondary hypothyroidism and medications
such as lithium and amiodarone
• Given the importance of thyroid hormones in cell metabolism, long-
standing hypothyroidism is associated with reduced metabolic rate
and decreased oxygen consumption, which affects all body systems.
• Another consequence is decreased drug metabolism leading to
overdosing of medications particularly sedatives, hypnotics, and
anesthetic agents; this can precipitate myxedema coma.

17. • CVS – cardiac contractility is impaired leading to reduced stroke volume,
low CO, bradycardia and sometimes hypotension. Reduced stroke volume
may also be due to pericardial effusion
• CNS – despite the term coma, many patients don’t present with coma but
with variable degrees of consciousness Brain function is affected by
reduction in oxygen delivery and subsequent consumption, decreased
glucose utilization and reduced cerebral blood flow.
• Pulmonary – hypoventilation due to central depression of ventilatory drive
with decreased responsiveness to hypoxia and hypercapnia
• Renal - Hyponatremia is common in patients with myxedema coma and is
caused by increased serum antidiuretic hormone and impaired water
excretion and reduced GFR due to low CO.
• GI - malabsorption, gastric atony, impaired peristalsis, paralytic ileus, and
megacolon.Ascites may occur due to increased capillary permeability,
heart failure, or other mechanisms.Gastrointestinal bleeding secondary to
an associated coagulopathy may occur

18. Causes/ Precipitating Factors
•Infection
•Exposure to cold temperatures
•Trauma
•Burns
•Cerebrovascular accident
•Myocardial infarction
•Congestive heart failure
•Respiratory acidosis
•Medications – sedatives, narcotics, amiodarone, rifampin, beta
blockers, lithium
•GI hemorrhage
•Metabolic disturbances – hypoglycemia, hyponatremia, acidosis
and hypercapnia

19. Clinical Presentation - History
• Most patients with myxedema coma have a history of hypothyroidism.
Some patients may have developed hypothyroidism after thyroidectomy
or iodine therapy for hyperthyroidism. However, some patients will have
undiagnosed hypothyroidism and myxedema coma will be the initial
presentation.
• Symptoms of hypothyroidism, including fatigue, weight gain, cold
intolerance, constipation, and dry skin, may be elicited.
• Patients have depressed mental state with lethargy, delirium, or coma.
• Symptoms of the precipitating illness can be seen such as infection
(commonly pneumonia), stroke, myocardial infarction, trauma, or heart
failure.

20. Physical Examination
• Hypothermia, which may not be recognized initially because many automatic
thermometers do not register low body temperatures (It may be necessary to
use special thermometers.)
• Hypotension, bradycardia
• Decreased / slow respiratory rate
• Periorbital puffiness, Macroglossia, Dry, brittle nails, ecchymoses, purpura ,
coarse or thinning hair, Cool, pale, dry, scaly, and thickened skin
• Thyroid is commonly small (Look for scar suggesting previous thyroidectomy.)
• Soft or distant heart sounds, diminished apical impulse, pericardial effusion,
pleural effusion
• Abdominal distension due to ascites, diminished or absent bowel sounds due
to ileus
• Bladder distension
• Cold extremities, nonpitting edema of the upper and lower extremities
• Confusion, stupor, slow speech, delayed reflexes, seizures, coma

21. Workup
• Laboratory studies are important to confirm the diagnosis of
myxedema coma. However, if the condition is suspected, treatment
should be started immediately without waiting for the results.
• TFTs – TSH is elevated, fT3 and fT4 is low. A low or normal TSH level
with low levels of free T4 and free T3 may indicate that the disorder is
due to pituitary or hypothalamic dysfunction
• Other tests – Serum osmolality (hyponatremia), serum creatinine
(because of decreased renal perfusion), CBC (r/o infection), serum
cortisol.
• Imaging studies – CXR (signs of PE, cardiomegaly, CHF, pericardia
effusion), ECG (sinus bradycardia, low-amplitude QRS complexes, a
prolonged QT interval, flattened or inverted T waves, or arrhythmias).

22. Treatment and Management
• ICU setting with continuous cardiac monitoring
• Airway maintenance is crucial, mechanical ventilation is commonly
required during the first 36-48 hours, but some patients require
prolonged respiratory support for as long as 2-3 weeks.
• Thyroid hormone replacement – controversial, some favor
levothyroxine (T4) while others favor combination of T4 and
liothyronine (T3). (preferable combination by American Thy. Asso),
because of reduced GI absorption IV therapy is advised. An
intravenous loading dose of 300-600 micrograms of levothyroxine
(T4) is followed by a daily intravenous dose of 50-100 micrograms.

23. Treatment and Management (2)
• Because the rate of conversion of T4 to the active hormone T3 can be
reduced in these patients, the addition of T3 along with T4 has been
recommended. T3 has a quicker onset of action than T4, as increases
in body temperature and oxygen consumption has been reported to
be faster with T3 therapy compared to T4.T3 therapy is given as bolus
of 5-20 micrograms intravenously and to be continued at a dosage of
2.5-10 micrograms every 8 hours.
• Measurement of thyroid hormones every 1-2 days is suggested.
Failure of TSH to decrease or of thyroid hormone levels to increase
suggests the need to increase doses of T4 and/or add T3.
• The treatment is changed to the oral form once the patient is able to
take medications by mouth.

24. Treatment and Management (3)
• Glucocorticoid therapy - Patients with primary hypothyroidism may
have concomitant primary adrenal insufficiency while patients with
secondary hypothyroidism may have associated hypopituitarism and
secondary adrenal insufficiency. The other rationale for the treatment
with corticosteroids is the potential risk of precipitating acute adrenal
insufficiency caused by the accelerated metabolism of cortisol that
follows T4 therapy.
• Hydrocortisone at a dose of 50-100 mg every 8 hours is administered.
An alternative is dexamethasone at a dose of 2-4 mg every 12 hours.
Dexamethasone has the advantage of not affecting the serum cortisol
concentration and can be used immediately without affecting the
results of the ACTH stimulation test, which can be performed at any
time.
• If the test is normal, corticosteroids can be stopped without tapering.

25. Treatment and Management (4)
• Supportive measures – treat hypothermia with passive rewarming
using ordinary blankets and a warm room.
• Treat associated infection.
• Correct severe hyponatremia with saline and free water restriction.
• Correct hypoglycemia with IV dextrose.
• Hypotension is usually corrected with thyroid hormone therapy. If
blood pressure continues to be low, cautious use of intravenous fluids
with normal saline is advised. Refractory hypotension can be
cautiously treated with vasopressors such as dopamine.