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
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
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
13.
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.
37. INVESTIGATIONS
Other common biochemical anomalies
increased levels of creatine phosphokinase
lactate dehydrogenase
aspartate transaminase
hypercholesterolemia
38.
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
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
Glucosinolates are relatively stable in plant cell. However, when the plant tissue containing glucosinolates is damaged, as is the case in the preparation (cutting, chopping, mixing) or chewing food, a β-thioglucosidase called myrosinase is released. The enzyme is normally stored separately from glucosinolates in different cells, or in different intracellular compartments, depending on the plant species (6). The hydrolysis of glucosinolate by myrosinase produces a molecule of β-d-glucose and an unstable aglycone; thiohydroximate-O-sulfonate (Figure 1). Spontaneous reorganization of this intermediate (chemical rearrangement of Lossen) results in the release of sulfate ion and in the formation of metabolites, the structures of which depend on the nature of the side chain (R) of glucosinolate, and the physico-chemical conditions of the medium
QT dispersion is simply defined as the difference between the longest (QTmax) and the shortest (QTmin) QT intervals within a 12‐lead ECG.
Both a prolonged QT interval and increased QT interval dispersion (QTD) have been proposed as surface ECG markers of vulnerability to ventricular arrhythmias and potential predictors of mortality.
384 pmol/L
Acquired von Willebrand’s disease is very likely to be type 1 in all cases because of a normal ratio of von Willebrand’s factor antigen to ristocetin cofactor r
partial quantitative deficiency (low levels) of von Willebrand factor (type 1), qualitative deficiency (type 2), or virtually complete deficiency (type 3)
First, adrenal insufficiency causes hypovolemia and a consequent reduction in glomerular infiltration rate. Decreased glomerular infiltration rate results in reduction in the amount of calcium filtered at the glomerulus, and increased calcium renal reabsorption in proximal tubule.8,9 Rehydration with normal saline will normalize the glomerular filtration rate as well as the level of filtered calcium. Second, the enzyme activity of 1-alpha-hydroxylase may be increased in adrenal insufficiency. The 1-alpha-hydroxylase is a renal enzyme that participates in conversion of calcidiol to the active form of vitamin D, calcitriol, leading to increased intestinal absorption of calcium.10 As prednisone inhibits 1-alpha-hydroxylase, thus reducing hypercalcemia, adrenal insufficiency may result in hypercalcemia. Third, a decrease in circulating stanniocalcin, a paracrine hormone secreted from the adrenal gland, could result in reduced levels of circulating calcium. Deficient adrenal hormone and decreased level of stanniocalcin may affect skeletal calcium efflux into circulation and result in hypercalcemia
CYTOMEL – T3 brand
Acute Physiology and Chronic Health Evaluation (
AaDO2 or PaO2 (depending on FiO2)
Temperature (rectal)
Mean arterial pressure
pH arterial
Heart rate
Respiratory rate
Sodium (serum)
Potassium (serum)
Creatinine
Hematocrit
White blood cell count
Glasgow Coma Scale
SOFA – resp, CVS, CNS, kidney, liver, coagulation total 24
