What is a myxoedema coma and how can I identify it?
A myxoedema coma is a severe decompensated state of hypothyroidism due to prolonged depletion of thyroid hormone. Because thyroid hormone (otherwise called thyroxine) is involved in regulating a large number of bodily functions and processes, lack of thyroid hormone can become dangerous and life-threatening. Thyroxine is involved in regulating body temperature, glycaemia, cardiac, neurologic, respiratory and gastrointestinal functions. Untreated, mortality rates range between 20-50% and inpatient mortality can be up to 30%. Hence early recognition is vital.
Key features in a patient's presentation that might give you a clue to the diagnosis would be drowsiness, bradycardia, hypothermia and hypoglycemia in the setting of known Hashimoto's hypothyroidism or previous history (or scar) of a total thyroidectomy. Also remember that the degree of TSH elevation does not indicate the severity of hypothyroidism.
Systematic assessment of the patient with myxoedema coma
In a patient with suspected myxoedema coma, a rapid but systematic assessment is essential, starting with the basic airway, breathing and circulation assessments. Drowsy patients may be unable to protect their airway and may even be bradypneic,. Patients with frank hypothyroidism may have glycosaminoglycan infiltration into their tongue resulting in macroglossia and hence a difficult airway. If there is any concern, get help with airway management and consider intubation.
Systemic features:
Thermoregulatory: Hypothermia (warming blankets may be necessary)
Menorrhagia (check for this in the history)
Hypoglycaemia (simple bedside POCT glucose would suffice if the patient has a good blood pressure)
Cardiac manifestations:
Bradycardia
Arrhythmias
Small QRS complexes suggestive of pericardial effusion
Heart failure - with congestive hepatopathy - jaundice
GI manifestations:
Constipation/ileus
Toxic megacolon
Abdominal pain
Neurological manifestations:
Drowsiness/reduced GCS
Coma
Any evidence of precipitating factors
What are the possible precipitating causes for a myxoedema coma?
These include sepsis, exposure to cold environment, trauma, an acute myocardial infarction, a cerebrovascular accident, a gastrointestinal bleed and medications (sedatives, anaesthetics, lithium, amiodarone, sunitinib, phenytoin) amongst other causes.
What are the underlying causes for hypothyroidism?
Although this can be left till later, clues in the history and examination can help us to understand why the patient developed hypothyroidism. Causes include:
Previous thyroidectomy
RAI treatment
Cancer treatment requiring immunotherapy (immunotherapy related thyroiditis)
Autoimmune thyroiditis (Hashimoto's thyroiditis)
Previous history of subacute thyroiditis/amiodarone-induced thyroiditis
Acute management of the patient with myxoedema coma
As with all emergencies, after a quick assessment of the patient's ABCs, make a decision as to where this patient should be best sited. For any patient with suspected myxoedema coma, an ICU setting is most appropriate as there is a high risk of needing intubation and vasopressor support.
Supportive measures
Airway management – consider intubation
Cardiovascular – consider vasopressor support for hypotension and consult a cardiologist if there are concerns for a pericardial effusion (muffled heart sounds/small QRS complexes on ECG)
Hypothermia – gentle rewarming with blankets
Glucocorticoid supplementation
This is usually administered prior to any IV thyroxine to treat for any concurrent adrenal insufficiency
Consider checking a random cortisol before administration of IV hydrocortisone (though don't wait for the results - at a later point the cortisol value can help to determine whether a short synacthen test is needed to assess the HPA axis once the patient is more stable)
Administer 100mg of IV hydrocortisone stat followed by 100mg Q8H
Thyroid hormone replacement
Patients in myxoedema coma have poor GI absorption due to gut oedema and ileus. Therefore, the IV route is preferred for administering levothyroxine.
IV levothyroxine (T4)
Loading dose of 200-400mcg (4mcg/kg lean body weight) (Lower doses are given in smaller/elderly patients and those with known coronary artery disease/arrhythmias) - as per ATA 2014 guidelines
Maintenance dose of 50-100mcg daily until the patient is able to take orally and transition to oral formulation. (ATA 2014 guidelines suggest 75% of the 1.6mcg/kg oral dose can be given daily in IV formulation)
Doses of more than 500mcg/day are associated with increased mortality
Liothyronine (T3)
if there is no response to T4 in the first 24-48hrs, consider adding on T3 (locally, in Singapore, liothyronine or T3 is only available in the oral form)
Loading dose of 10-20mcg of PO T3
Maintenance dose of 10mcg q4h for 24h, followed by 10mcg q6h for 1-2 days
Doses >75mcg/day are associated with increased mortality
ATA 2014 suggests that T3 can be administered in addition to LT4 right from the beginning due to reduced conversion of T4 to T3 in an acutely unwell patient, though high doses are associated with increased mortality
It may be useful to know the Wartofsky regimen:
IV T4 4mcg/kg followed by 100mcg 24h later, then 50mcg daily
IV T3 10mcg then 10mcg every 8-12h
Change to weight-based oral formulation when the patient is more alert and can take orally (i.e. 1.6mcg/kg/day)
Target a normal T4/T3 level by the end of 1 week and trend T3/T4 levels every 1-2 days to ensure an appropriate trajectory and guide dosing
The patient should also demonstrate improvement in GCS, cardiovascular, respiratory, renal, metabolic and GI functions within a week
Fluids and electrolytes
If there is hypotension, resuscitate as necessary, however be aware that many of these patients may have hyponatraemia and assessing their fluid status will be important
In addition to the above, it is essential to address any precipitating factors urgently and also determine the underlying cause of the hypothyroidism. Cover patients with broad spectrum antibiotics if sepsis is on the list of differentials.
Scoring systems
The Popoveniuc scoring system can be used to assess if a patient is likely to be in myxoedema coma.
* Table from Popoveniuc G, Wartofsky L (2014). "A diagnostic scoring system for myxedema coma". Endocr Pract. 20 (8): 808–17
A score of 60 out of 100% had a sensitivity of 100% and a specificity of 85.7% suggesting that while it is useful - it is not very specific and clinical suspicion is still the most important for assessing and diagnosing such a patient.
Possible Exam Questions
Why is a loading dose of LT4 necessary in the treatment of myxoedema coma?
A loading dose is usually given for three reasons:
To saturate the empty binding sites and still leave enough free thyroxine to act at the hormone receptors.
In hypothyroidism there is fluid retention and hence a larger volume of distribution
There is impaired T4 to T3 conversion and hence a higher T4 dose is even to help overcome this bottleneck (this is also the reasoning behind addition of T3 liothyronine)
What is the evidence behind the dose of 200-400mcg used for loading levothyroxine?
The table above is from Yamamoto et al 1999 (full reference below) and gives evidence that loading doses > 500mcg levothyroxine for treatment of myxoedema coma were associated with increased mortality with p<0.02.
Last thoughts
In conclusion, early diagnosis and treatment is important to ensure a good outcome for patients with myxoedema coma. Remember to educate and counsel your patient on the importance of continuing regular levothyroxine medication lifelong and for regular check ups with their primary doctor before they are discharged.
References
Popoveniuc G, Wartofsky L (2014). "A diagnostic scoring system for myxedema coma". Endocr Pract. 20 (8): 808–17
ATA 2014 Guidelines: Jonklaas J, Bianco AC, Bauer AJ, et al. Guidelines for the treatment of hypothyroidism: prepared by the american thyroid association task force on thyroid hormone replacement. Thyroid. 2014;24(12):1670-1751.
Yamamoto T, Fukuyama J, Fujiyoshi A. Factors associated with mortality of myxedema coma: report of eight cases and literature survey. Thyroid. 1999;9(12):1167-1174.
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