The "myx-up" of Myxedema Coma
In this case, does a different diagnosis mean a much different treatment strategy?
A transport team is called to a free-standing emergency/urgent care center for a 72-year-old female who is obtunded with a glasgow coma score (GCS) of 6 (localizes painful stimuli; does not open eyes; no verbal response). The patient's daughter, who had driven her mother in, reported that her mother had been feeling generally ill for the better part of a week after "getting over a pretty bad pneumonia." She states that the patient had been generally lethargic, not interested in eating, and that she noticed her mother's "eyes were a bit more swollen" over the last couple of days.
Upon arrival of the transport team, the patient was being mask ventilated by a very frantic nurse and medical assistant. She had previously been receiving oxygen via mask when her oxygen saturation dropped to 81 percent. Her saturation has since stabilized at 91 percent. She has one, 20-guage peripheral intravenous line in her right forearm.
She had received 1 mg of atropine for a sustained heart rate of 48 beats per minute. Her last recorded blood pressure, which was her blood pressure upon arrival to the urgent care center, was 94/56 (69). Her oral temperature was 85 degrees Fahrenheit (29.4o Celsius). She has non-palpable radial pulses and weak femoral pulses.
The referring physician's transfer diagnosis is septic shock. He orders 2 liters of crystalloid to be infused along with broad-spectrum antibiotics for transport. The transport team's conversation with the receiving physician leads him to believe that "something just does not add up." The magic question, as always, is what are the transport team's priorities? In this case, does a different diagnosis mean a much different treatment strategy?
What is Myxedema Coma? Something to consider
Myxedema Coma is a severe form of hypothyroidism, which precedes physiologic deterioration if gone untreated. It is manifested by altered mentation, delayed deep tendon reflexes, respiratory depression, carbon dioxide narcosis, bradycardia, and decreased cardiac output. Altered laboratory studies include hypoglycemia, hyponatremia, evidence of respiratory acidosis with blood gas analysis, increased thyrotropin (TSH) levels and low thyroxine (T4) levels.1,3,4,7
While definitive diagnosis can only be made with serum thyroid studies (which take up to several hours to run), high clinical suspicion should point to this diagnosis in comatose patients with hypothermia (the most common and ominous sign)6, hypocapnea and/or hyponatremia4. Other common clinical manifestations that may lead the clinician to consider this diagnosis include orbital edema, dry skin and a hoarse voice4. Awaiting definitive diagnosis should not delay management.
- Medication overdose
- Adrenal Insufficiency
- Severe sepsis/Septic Shock
- Cerebral Vascular Accident
- Severe Hypoglycemia
Function of thyroid
The function of the thyroid gland is to make take thyroid hormones: thyroxine (T4) and triiodothyronine (T3). This is done through combining tyrosine (an amino acid) with Iodine. Resultant T3 and T4 is released into the blood stream. The function of thyroid hormones is to aid in the regulation of cellular metabolism throughout the body. Regulation of this process is controlled by the pituitary gland through the release and/or regulation of thyrotropin (i.e., thyroid stimulating hormone) (TSH).
Susceptible patient populations
There are numerous etiologies of hypothyroidism. The most common in the United States is primary thyroid failure secondary to autoimmune destruction of the gland (Hashimoto's Thyroiditis)5. Other etiologies and susceptible patient populations include4:
- Drug induced
- Irradiation of the neck
- Iodine deficiency
- Pituitary or hypothalamic disease
- Precipitating or Exacerbating factors4,6
o Exposure to the cold / winter months (elderly women especially susceptible to this)
o Infection / Illness (e.g., pneumonia)
o Other metabolic derangements
o Hypoxia / Acidosis
o Co-morbidities (e.g., Cardiac Failure, CVA)
Management and transport considerations
In answer to the question during the introduction of the case, no, a different diagnosis does not necessarily indicate an alteration in treatment strategy. Myxedema coma is difficult to diagnose, as indicated by the numerous differentials and vague, nonspecific clinical manifestations. Management goals are mainly supportive and include1,2,3:
- Ventilatory management and treatment of hypercapnea
- Management of hypotension
o Management of hypothermia with passive rewarming
Note: Use active rewarming only in severe cases of hypothermia as it causes peripheral vasodilatation and circulatory collapse as well as increased oxygen consumption3
o Isotonic crystalloid
o Vasopressor agents
Note: Exercise caution with these agents as their effectiveness is questionable and patients with myxedema coma are very sensitive to their potentially toxic effects3
- Management of altered laboratory values (i.e., intravenous glucose and reversal of hyponatremia
Having said this, without a definitive diagnosis, primary shock management is definitely indicated. Hypotension refractory to fluid and catecholamines will typically lead the clinician to giving steroids. It is an acceptable assumption that these patients would be presumed to have adrenal insufficiency and therefore would necessitate 100 mg of hydrocortisone (or an acceptable glucocorticoid substitute)2.
Definitive management of Myxedema coma involves thyroid hormone replacement. Many of the above symptoms, including refractory hypotension will improve with the administration of this medication. Typical intravenous dosing is between 0.2 and 0.5 mg of T4.3 Elderly patients and those with heart disease are typically started on lower doses (in the area of 0.1 mg).
Management and transport of the previously mentioned patient
The patient received her previously ordered 2 liters of crystalloid with minimial results. She was intubated by the transport team and the ventilator was set at conservative settings with rate and tidal volume titrated to the capnography reading. Additional vascular access was obtained and a norepinephrine drip was initiated.
Enroute, high dose dexamethasone was administered. The patient was given warm IV fluids and covered with warm blankets. She was also given IV dextrose per the transport team's unconscious protocol. The patient's mean arterial pressure remained between 50 and 60 mmHg. Her heartrate was between 60 and 80 beats per minute during the flight.
Upon her arrival to the emergency department, she was continued on the management initiated by the transport team and given 300 mcg of Levothyroxine. She was subsequently transported to the medical intensive care unit (ICU) where she was treated for sepsis and severe hypothyroidism. She also received hemodialysis. She awoke several days later with minor neurological deficits. She was subsequently admitted to an extended care facility upon hospital discharge.
While myxedema coma is quite rare, if left untreated it carries a very high mortality. While diagnosis is difficult, management is fairly standard while attempting to narrow down differential diagnoses. The purpose of this month's discussion was to simply offer an additional thought to the challenge of refractory hypotension during transport.
1. Hackstadt, D, & Korley, F. (2008). Thyroid disorders. In J Adams (Ed.), James G. Adams Emergency Medicine (pp. 1796-1798). Philadelphia, PA: Saunders Elsevier.
2. Sipos , JA, & Cance , WG. (2009). Thyroid disease in the intensive care unit. In A Gabrielli (Ed.), Civetta, Taylor and Kirby's Critical Care (4th ed) (pp. 2458-2461). Philadelphia, PA: Lippincott, Williams and Wilkins.
3. Emerson, CH. (2008). Myxedema coma. In RS Irwin (Ed.), Irwin and Rippe's Intensive Care Medicine (pp. Chapter 104). Philadelphia, PA: Lippincott, Williams and Wilkins.
4. Kwaku, MP, & Burman, KD. (2007). Myxedema coma. Journal of Intensive Care Medicine, 22(4), 224-231.
5. Zull, D. (2010). Thyroid and adrenal disorders. In J Marx (Ed.), Rosen's Emergency Medicine (7th ed) (pp. 1666-1671). Philadelphia, PA: Mosby Elsevier.
6. Braithwaite, SS. (2008). Thyroid disorders. In J Parrillo (Ed.), Critical Care Medicine: Principles of Diagnosis and Management in the Adult (pp. 1290-1292). Philadelphia, PA: Mosby Elsevier.
7. Wartofsky, L. (2006). Myxedema coma. Endocrinology and Metabolism Clinics of North America, 35, 687-698.