Myxedema coma is a life-threatening complication of severe hypothyroidism. It is characterized by decreased level of consciousness, hypothermia, and other symptoms. Precipitating factors include infection, medications, and cold exposure. Diagnosis involves finding very high TSH and low T4 levels. Treatment requires intensive care, addressing precipitants, fluid management, warming, and thyroid hormone replacement therapy with intravenous T4 or T3. Even with treatment, mortality rates are high at 50-60%.

1. MYXEDEMA COMA
DR LAVANYA BONNY
SR, DEPT OF ENDOCRINOLOGY
ST JOHNS MEDICAL COLLEGE
BANGALORE

2. INTRODUCTION
 most extreme form of hypothyroidism
 May readily progress to death unless diagnosed promptly and treated vigorously.
 The term myxedema coma is a misnomer
 myxedema crisis may be an apt term - patients are obtunded, rather than frankly
comatose.

3. EPIDEMIOLOGY
 Around 300 cases reported in the literature
 most patients are women.
 More in the elderly
 even with reasonably early diagnosis and therapy, the mortality rate - 50% to
60%.

4. PRECIPITATING EVENTS
 most patients present in winter
 Extremely cold weather seems to lower the threshold for vulnerability
 incidence of severe hypothermia may be lower in tropical countries

5. PRECIPITATING EVENTS

6. PRECIPITATING EVENTS
 Typical infections - pneumonia, urinary tract infections, and cellulitis
 Diuretics may mask some of the myxedematous features
 may also aggravate the hyponatremia associated with myxedema crisis

7. PRECIPITATING EVENTS
 Metabolic disturbances exacerbating myxedema coma
 Hypoglycemia
 Hyponatremia
 Acidosis
 Hypercalcemia
 Hypoxemia
 Hypercapnia

8. PRECIPITATING EVENTS
 Recently, Chu and Seltzer reported a case of myxedema crisis precipitated by
consumption of raw bok choy
 Bok choy or Chinese white cabbage contains glucosinolates.
 Some of the breakdown products of glucosinolates, such as thiocyanates, nitriles,
and oxazolidines have inhibitory effects on the thyroid as they may inhibit the
uptake of iodine.

9. PRECIPITATING EVENTS
 When eaten raw, brassica vegetables release the enzyme myrosinase, which
accelerates the hydrolysis of glucosinolates.
 Cooking deactivates myrosinase

10. PATHOGENESIS
 Low intracellularT3 secondary to hypothyroidism is the basic underlying
pathology in myxedema crisis
 This leads to hypothermia and suppression of cardiac activity.
 The body tries to compensate by neurovascular adaptations including chronic
peripheral vasoconstriction, mild diastolic hypertension, and diminished blood
volume.

11. PATHOGENESIS
 Low intracellularT3 leads to depressed cardiac functions with decreased
inotropism and chronotropism with vasoconstriction
 The hypothyroid heart tries to perform more work at a given amount of oxygen by
better coupling of ATP to contractile events.
 A precipitating factor pushes this precarious balance over the brink

12. PATHOGENESIS
 In the decompensated state, low cardiac output and hypotension will result in
cardiogenic shock
 may not be responsive to vasopressors without thyroid hormone replacement

14. CLINICAL FEATURES
 course is typically one of lethargy progressing to stupor and then coma, with
respiratory failure and hypothermia
 may be hastened by the administration of drugs that depress respiration and
other brain functions

15. CLINICAL FEATURES
 Physical examination should focus on features of severe hypothyroidism
 dry skin
 sparse hair
 a hoarse voice
 Hypothermia
 delayed tendon reflexes
 Macroglossia
 nonpitting edema
 Goiter
 surgical scar of thyroidectomy

16. CLINICAL FEATURES
 Presence of orbitopathy may indicate underlying GD which may have been
treated with radioiodine or surgery
 Study by Dutta et al - 39% of them had hypothyroidism detected only at the time
of crisis.

17. CLINICAL FEATURES
 NEUROPSYCHIATRIC MANIFESTATIONS
 may be a history of lethargy, slowed mentation, poor memory, cognitive
dysfunction, depression, or even psychosis, as can also be seen in patients with
uncomplicated hypothyroidism.
 Pts do not complain of these symptoms because of their impaired state of
consciousness.

18. CLINICAL FEATURES
 NEUROPSYCHIATRIC MANIFESTATIONS
 Focal or generalized seizures - in up to 25% of patients
 D/t hyponatremia
 Hypoglycemia
 hypoxemia because of reduced cerebral blood flow
 generalized depression of cerebral function

19. CLINICAL FEATURES
 HYPOTHERMIA
 hypothermia is present in virtually all patients and may be quite profound (<80F).
 In many of the reported cases, hypothermia was the first clinical clue to the
diagnosis of myxedema coma.
 survival has been shown to correlate with the degree of hypothermia (worst
prognosis with a core body temperature < 90F)

20. CLINICAL FEATURES
 CARDIOVASCULAR MANIFESTATIONS
 Low stroke volume and cardiac output occur as a result of the reduction in cardiac
contractility
 frank CCF is rare.
 Cardiac enlargement – d/t ventricular dilatation or pericardial effusion.

21. CLINICAL FEATURES
 CARDIOVASCULAR MANIFESTATIONS
 Hypotension – d/t decreased intravascular volume and cardiovascular collapse
 shock may occur late in the course of the disease.
 hypotension may be refractory to vasopressor therapy unless thyroid hormone is
also being given

22. CLINICAL FEATURES
 ECG – non specific
 Sinus bradycardia, low voltage complexes, bundle branch blocks, complete heart
blocks, and nonspecific ST-T changes
 Rare - Prolongation of QT interval and increased QT dispersion, a marker of
electrical instability
 Increased myocardial fibrosis in severe hypothyroidism may lead to a resistance in
improvement of QT dispersion with thyroid hormone supplementation

23. CLINICAL FEATURES
 RESPIRATORY SYSTEM
 reduced hypoxic respiratory drive and decreased ventilatory response to
hypercapnia
 impaired respiratory muscle function and obesity may exacerbate the
hypoventilation
 The respiratory depression leads to alveolar hypoventilation and progressive
hypoxemia and, ultimately, to carbon dioxide narcosis and coma.

24. CLINICAL FEATURES
 RESPIRATORY SYSTEM
 Respiration may be impaired by the presence of
 pleural effusions or ascites
 by reduced lung volume
 by macroglossia
 And myxedema of the nasopharynx and larynx

25. CLINICAL FEATURES
 GASTROINTESTINAL SYSTEM
 anorexia, nausea, abdominal pain, and constipation with fecal retention.
 distended quiet abdomen may be present
 reduced intestinal motility is common, and paralytic ileus and megacolon may
occur.

26. CLINICAL FEATURES
 GASTROINTESTINAL SYSTEM
 neurogenic oropharyngeal dysphagia
 Pts have delayed swallowing, aspiration, and risk of aspiration pneumonia
 Gastric atony may reduce absorption of oral medications.

27. CLINICAL FEATURES
 INFECTIONS
 the presence of a ‘‘normal’’ temperature should be a clue to underlying infection.
 Other signs of infection, such as diaphoresis and tachycardia, are also absent
 The possibility of an underlying infection should always be considered while
maintaining a low threshold for initiation of systemic antibiotic coverage

28. CLINICAL FEATURES
 HYPOGLYCEMIA
 Causes:
 Decreased gluconeogenesis
 precipitating factors like sepsis
 concomitant adrenal insufficiency

29. CLINICAL FEATURES
 RENAL AND ELECTROLYTE MANIFESTATIONS
 bladder atony with urinary retention.
 Reduced GFR
 Hyponatremia may cause lethargy and confusion

30. CLINICAL FEATURES
 RENAL AND ELECTROLYTE MANIFESTATIONS
 The hyponatremia results from an inability to excrete a water load, which is
caused by decreased delivery of water to the distal nephron and excess
vasopressin secretion
 Urinary sodium excretion is normal or increased
 urinary osmolality is high relative to plasma osmolality.

31. DIAGNOSIS
 The probable diagnosis of myxedema coma should be considered in a patient with
a history of or physical findings compatible with hypothyroidism
 in the presence of stupor, confusion, or coma, especially in the setting of
hypothermia.
 markedly elevated serumTSH would be expected

32. DIAGNOSIS
 patients with severe nonthyroidal systemic illness may demonstrate a
phenomenon parallel to the ‘‘euthyroid sick’’ syndrome
 can be called the ‘‘hypothyroid sick’’ syndrome.
 In such circumstances, pituitaryTSH secretion is reduced and the blood levels may
not be as high as expected

33. DIAGNOSIS
 5% - may be due to central hypothyroidism
 The deciding factor here will be associated pituitary hormone deficiencies as
isolated central hypothyroidism is rare.
 all patients with myxedema coma have low serum total and freeT4 andT3
 In patients with the hypothyroid sick syndrome, serumT3 levels may be unusually
low (<25 ng/mL).

34. HASHIMOTO’S ENCEPHALOPATHY
 rare complication of Hashimoto’s thyroiditis
 may present as a subacute or acute encephalopathy with seizures, stroke-like episodes,
myoclonus, and tremor
 Patients will have elevated thyroid-specific autoantibodies (Anti-TPO), elevated CSF
protein without pleocytosis, and abnormal EEG
 most patients are euthyroid and the condition is steroid responsive

35. INVESTIGATIONS
 normocytic normochromic anemia - secondary to decreased oxygen requirement
and erythropoietin
 Macrocytic blood picture - low folate absorption and pernicious anemia
 Severely hypothyroid patients - prolonged bleeding time and clotting time,
decreased platelet adhesiveness, elevated APTT, and low or normal factorVIII
activity.

36. INVESTIGATIONS
 Acquired vonWillebrand’s disease
 Due to decreased synthesis of vonWillebrand factor in the absence of adequate
levels of thyroxine

37. INVESTIGATIONS
 Other common biochemical anomalies
 increased levels of creatine phosphokinase
 lactate dehydrogenase
 aspartate transaminase
 hypercholesterolemia

39. TREATMENT
COMPONENTS
 (a) intensive care treatment with ventilator support, central venous pressure
monitoring, and pulmonary capillary wedge pressure if feasible in patients with
cardiac disease
 (b) appropriate fluid management and correction of hypotension and
dyselectrolytemia
 (c) aggressive management of precipitating factors and steroid supplementation
if required
 (d) thyroid hormone replacement.

40. GENERAL MEASURES
 AIRWAY
 Management of airway and airway protection from aspiration in case of patients
with poor consciousness level should be the utmost priority.
 Endotracheal intubation or tracheostomy with mechanical ventilation may be
performed.
 Frequent ABG to ensure adequate oxygenation and correction of hypercarbia.

41. GENERAL MEASURES
 FLUID MANAGEMENT
 the choice is between fluid supplementation for hypotension and fluid restriction
for hyponatremia.
 mild hyponatremia - fluid restriction with replacement to cover the daily losses
taking care to supplement glucose, sodium, and potassium
 severe hyponatremia (<120 mEq/L) - 3% saline along with furosemide, so that Na
may be elevated by 3-4 meq/L to tide over the immediate crisis

42. GENERAL MEASURES
 FLUID MANAGEMENT
 A rapid correction of chronic hyponatremia might put patients at risk for central
pontine myelinolysis
 Treatment with furosemide will prevent fluid overloading associated with
hypertonic saline

43. GENERAL MEASURES
 HYPOTHERMIA
 may be managed by external warming
 the accompanying vasodilatation may precipitate hypotension.

44. GENERAL MEASURES
 HYPOTENSION
 Hypotension requires careful infusion of dextrose saline solutions and
vasopressors if required.
 search for other causes of hypotension like sepsis, myocardial infarction,
pericardial effusion, and occult bleeding
 hydrocortisone supplementation for concomitant adrenal insufficiency

45. GENERAL MEASURES
 HYPOCORTISOLEMIA
 may be due to primary or secondary adrenal insufficiency.
 Hyperpigmentation, hyperkalemia, hypercalcemia, and previous history of on and
off steroid use must be sought.
 Thyroid hormone replacement may increase cortisol clearance and may
aggravate cortisol deficiency

46. GENERAL MEASURES
 HYPOCORTISOLEMIA
 Intravenous hydrocortisone is preferred at a rate of 50 mg every 6 hours

47. GENERAL MEASURES
 PRECIPITATING FACTOR
 antibiotics in case of infection
 hemodialysis for associated renal failure
 comprehensive care of multiorgan dysfunction.

48. THYROID HORMONETHERAPY
 T4 therapy
 provides a steady, smooth, and slow onset of action with relatively few adverse
events.
 avoids major peaks and troughs in body, and values of serumT4 may be easy to
interpret
 However,T3 is the active hormone in the body, and in a setting of severe illness
there may be a decreased conversion ofT4 toT3

49. THYROID HORMONETHERAPY
 ParenteralT4 may be used at a dose of 300–500 µg as bolus to saturate the body
pool.
 The usual protocol then is to continueT4 at a dose of 50–100 µg daily.
 T4 concentrations rise acutely to levels above normal and slowly gets converted
toT3

50. THYROID HORMONETHERAPY
 Oral administration ofT4 through Ryles tube has proved to be equally effective
 Drawback - gastric atony may prevent absorption and put the patient at risk for
aspiration.
 Dutta and colleagues compared 500 µg of oral loading dose ofT4 with 150 µg of
maintenance dose orally and 200 µg ofT4 intravenously followed by 100 µgT4
intravenously - did not find any difference in outcome among the patients

51. THYROID HORMONETHERAPY
 Advantages of usingT3
 rapid onset of action
 earlier beneficial effect on neuropsychiatric symptoms
 significant clinical improvement within 24 hours.
 dose of 10 to 20 µg, followed by 10 µg every 4 hours for the first 24 hours and then
10 µg every 6 hours for 1 or 2 days till the patient is alert enough to continue
therapy through oral route.

52. THYROID HORMONETHERAPY
 Measurable increases in body temperature and oxygen consumption occur within
2 to 3 hours after i.vT3
 may take 8 to 14 hours or longer after i.vT4

53. THYROID HORMONETHERAPY
 DISADVANTAGES OFT3
 poor availability ofT3
 fluctuations in serum levels ofT3
 adverse cardiac effects
 Yamamoto et al. reported that doses of LT4 more than 500 µg per day and LT3
more than 75 µg/day were associated with increased mortality

54. THYROID HORMONETHERAPY
 Combined therapy ofT4 andT3 may also prove to be useful.
 T4 may be initiated at a dose of 4 µg/kg lean bwt, followed by 100 µg 24 hours
later and then 50 µg daily i.v or orally.
 T3 may also be started simultaneously withT4 at a dose of 10 µg iv, and the same
dose is given every 8 to 12 hours until the patient can take maintenance oral doses
ofT4

55. PREDICTORS OF MORTALITY
 Hypotension
 bradycardia at presentation
 need for mechanical ventilation
 hypothermia unresponsive to treatment
 Sepsis
 intake of sedative drugs
 lower GCS
 high APACHE II

56. PREDICTORS OF MORTALITY
 Sequential organ failure assessment (SOFA) score was more effective than other
predictive models.
 Baseline and day 3 SOFA scores of more than 6 were highly predictive of poor
outcome
 treatment defaulters had more severe manifestations than de novo patients

57. PREDICTORS OF MORTALITY
 higher doses ofT3 are associated with increased mortality, and lower doses ofT3
andT4 may be associated with favorable prognosis
 Other factors associated with mortality include advanced age and cardiovascular
disease

58. THANKYOU