Myxedema Coma or Crisis Treatment & Management
- Author: Mohsen S Eledrisi, MD, FACP, FACE; Chief Editor: George T Griffing, MD more...
Myxedema coma is a medical emergency that requires immediate attention. If the diagnosis is suspected, immediate management is necessary before confirming the diagnosis due to the high associated mortality rate. Patients with myxedema coma should be managed in an intensive care unit with continuous cardiac monitoring. Initial steps in management include the elements below.
Maintenance of adequate airway is crucial, since most patients have depressed mental status along with respiratory failure. 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
The ideal mode of therapy and doses of thyroid hormone therapy in myxedema coma remain controversial due to the rarity of the condition and lack of clinical trials. Some clinicians favor the administration of levothyroxine (T4), while others prefer a combination of T4 and liothyronine (T3).[1, 2, 26, 27] The American Thyroid Association recommends combination therapy with T4 and T3.
Because of reduced gastrointestinal absorption, intravenous thyroid hormone 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. Larger doses of T4 probably have no advantage and may be dangerous. The lower end of the dosing range is recommended in older patients, those at risk for cardiac complications such as myocardial infarction and arrhythmias, and in patients with coronary artery disease, since full-dose T4 therapy may worsen myocardial ischemia by increasing myocardial oxygen consumption.
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 depending on the patient's age and coexistent cardiac risk factors.
Intravenous levothyroxine treatment in severely hypothyroid patients usually leads to improvement in cardiovascular, renal, pulmonary, and metabolic parameters within a week. Serum T4 and T3 concentrations may improve or normalize with a similar time frame, with more gradual improvement in serum TSH. Thus, the therapeutic endpoints in myxedema coma should be improved mental status, improved cardiac function, and improved pulmonary function.
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.
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.
Stress doses of intravenous glucocorticoids should be administered until the possibility of adrenal insufficiency is excluded by a random serum cortisol, which is helpful only if very low, or, better, by an ACTH stimulation test.
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.
Treat hypothermia with passive rewarming using ordinary blankets and a warm room. Active rewarming using external devices carries a risk of vasodilatation and worsening hypotension and should be avoided. The use of a rectal probe helps to determine the true core temperature and to monitor rewarming.
Treat associated infection. Given the severity of the condition, infection should always be considered and empiric broad-spectrum of antibiotics be considered until appropriate cultures are proven negative.
Correct severe hyponatremia with saline and free water restriction.
Correct hypoglycemia with intravenous 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 treated with vasopressors such as dopamine, but patients should be weaned off the vasopressor as soon as possible because of the risk of pressor-induced ischemic event.
Patients who are awake, no longer dependent on a ventilator, and medically stable may be transferred from the intensive care unit to a medical ward.
Patients with myxedema coma who require surgical intervention are considered high risk for complications of anesthesia as well as intraoperative and postoperative complications. Stabilization of these patients before proceeding to surgery is preferred unless the procedure is urgent.
In life-threatening situations, the loading dose of T4 and glucocorticoids are administered before induction of anesthesia. Careful administration of anesthetic agents with consideration of using lower doses should be exercised given the decreased metabolism of these agents in patients with myxedema coma.
Close monitoring during surgery and in the postoperative period in a critical care unit is imperative. Monitoring includes respiratory, cardiac, and volume and temperature status.
Consultations include endocrinologists and critical care specialists. Depending on complications, consultations with pulmonologists and/or cardiologists may be appropriate.
Most patients will be initially ill and will not be given any food by mouth. Many patients require nasogastric feeding, and if mechanical ventilation is prolonged, total parenteral nutrition may be required.
Once stable, patients may progress to usual activity as their strength allows. Physical therapy may be needed for incapacitated patients.
Patients with a history of thyroid resection or ablation for hyperthyroidism and persons with a history of Hashimoto thyroiditis are at risk for developing hypothyroidism, and the TSH level should be monitored yearly. Such patients should be informed that hypothyroidism could occur in the future. They should understand the symptoms that signal the condition and the need to seek medical attention for appropriate testing.
In cold climates, inadequately heated residences are a significant cause of myxedema coma/crises in patients with undiagnosed or inadequately treated hypothyroidism.
Thyroid function tests should be monitored regularly in patients with hypothyroidism until the appropriate dose of levothyroxine is reached. Adherence to thyroid hormone therapy should be assessed regularly and to ensure maintenance of euthyroid state. Patients who are deemed nonadherent or have issues that may hinder adherence should have their thyroid function closely monitored.
Patients are advised to report to their physicians if they are prescribed any new medications since some drugs may interfere with the absorption, production, secretion, or clearance of thyroid hormone therapy. Patients should also contact their health care provider if symptoms of inadequately-treated hypothyroidism persist.
Follow-up care after discharge is necessary to ensure adherence with thyroid hormone replacement.
If primary hypothyroidism was diagnosed, TSH levels are assessed every 4-6 weeks, and the dose of T4 is adjusted accordingly.
If hypothyroidism is secondary to pituitary dysfunction, free T4 levels are monitored. TSH level is not an accurate measure of thyroid function in this setting.
Kwaku MP, Burman KD. Myxedema coma. J Intensive Care Med. 2007 Jul-Aug. 22(4):224-31. [Medline].
Klubo-Gwiezdzinska J, Wartofsky L. Thyroid emergencies. Med Clin North Am. 2012 Mar. 96(2):385-403. [Medline].
Waldman SA, Park D. Myxedema coma associated with lithium therapy. Am J Med. 1989 Sep. 87 (3):355-6. [Medline].
Mazonson PD, Williams ML, Cantley LK, Dalldorf FG, Utiger RD, Foster JR. Myxedema coma during long-term amiodarone therapy. Am J Med. 1984 Oct. 77 (4):751-4. [Medline].
Nicoloff JT, LoPresti JS. Myxedema coma. A form of decompensated hypothyroidism. Endocrinol Metab Clin North Am. 1993 Jun. 22(2):279-90. [Medline].
Klein I. Thyroid hormone and the cardiovascular system. Am J Med. 1990 Jun. 88 (6):631-7. [Medline].
Schenck JB, Rizvi AA, Lin T. Severe primary hypothyroidism manifesting with torsades de pointes. Am J Med Sci. 2006 Mar. 331 (3):154-6. [Medline].
Mathew V, Misgar RA, Ghosh S, Mukhopadhyay P, Roychowdhury P, Pandit K, et al. Myxedema coma: a new look into an old crisis. J Thyroid Res. 2011. 2011:493462. [Medline]. [Full Text].
Zwillich CW, Pierson DJ, Hofeldt FD, Lufkin EG, Weil JV. Ventilatory control in myxedema and hypothyroidism. N Engl J Med. 1975 Mar 27. 292 (13):662-5. [Medline].
Ladenson PW, Goldenheim PD, Ridgway EC. Prediction and reversal of blunted ventilatory responsiveness in patients with hypothyroidism. Am J Med. 1988 May. 84 (5):877-83. [Medline].
Ardalan MR, Ghabili K, Mirnour R, Shoja MM. Hypothyroidism-induced rhabdomyolysis and renal failure. Ren Fail. 2011. 33 (5):553-4. [Medline].
Birewar S, Oppenheimer M, Zawada ET Jr. Hypothyroid acute renal failure. S D J Med. 2004 Mar. 57 (3):109-10. [Medline].
Skowsky WR, Kikuchi TA. The role of vasopressin in the impaired water excretion of myxedema. Am J Med. 1978 Apr. 64 (4):613-21. [Medline].
Derubertis FR Jr, Michelis MF, Bloom ME, Mintz DH, Field JB, Davis BB. Impaired water excretion in myxedema. Am J Med. 1971 Jul. 51 (1):41-53. [Medline].
Bergeron E, Mitchell A, Heyen F, Dube S. Acute colonic surgery and unrecognized hypothyroidism: a warning. Report of six cases. Dis Colon Rectum. 1997 Jul. 40 (7):859-61. [Medline].
Ji JS, Chae HS, Cho YS, Kim HK, Kim SS, et al. Myxedema ascites: case report and literature review. J Korean Med Sci. 2006 Aug. 21 (4):761-4. [Medline].
Fukunaga K. Refractory gastrointestinal bleeding treated with thyroid hormone replacement. J Clin Gastroenterol. 2001 Aug. 33 (2):145-7. [Medline].
Manfredi E, van Zaane B, Gerdes VE, Brandjes DP, Squizzato A. Hypothyroidism and acquired von Willebrand's syndrome: a systematic review. Haemophilia. 2008 May. 14 (3):423-33. [Medline].
Ford HC, Carter JM. Haemostasis in hypothyroidism. Postgrad Med J. 1990 Apr. 66 (774):280-4. [Medline].
Rodriguez I, Fluiters E, Perez-Mendez LF, et al. Factors associated with mortality of patients with myxoedema coma: prospective study in 11 cases treated in a single institution. J Endocrinol. 2004 Feb. 180(2):347-50. [Medline]. [Full Text].
Dutta P, Bhansali A, Masoodi SR, et al. Predictors of outcome in myxoedema coma: a study from a tertiary care centre. Crit Care. 2008. 12(1):R1. [Medline]. [Full Text].
Yamamoto T, Fukuyama J, Fujiyoshi A. Factors associated with mortality of myxedema coma: report of eight cases and literature survey. Thyroid. 1999 Dec. 9(12):1167-74. [Medline].
Hylander B, Rosenqvist U. Treatment of myxoedema coma--factors associated with fatal outcome. Acta Endocrinol (Copenh). 1985 Jan. 108(1):65-71. [Medline].
Jordan RM. Myxedema coma. Pathophysiology, therapy, and factors affecting prognosis. Med Clin North Am. 1995 Jan. 79(1):185-94. [Medline].
Popoveniuc G, Chandra T, Sud A, Sharma M, Blackman MR, Burman KD, et al. A diagnostic scoring system for myxedema coma. Endocr Pract. 2014 Aug 1. 20(8):808-17. [Medline].
MacKerrow SD, Osborn LA, Levy H, Eaton RP, Economou P. Myxedema-associated cardiogenic shock treated with intravenous triiodothyronine. Ann Intern Med. 1992 Dec 15. 117 (12):1014-5. [Medline].
Arlot S, Debussche X, Lalau JD, Mesmacque A, Tolani M, Quichaud J, et al. Myxoedema coma: response of thyroid hormones with oral and intravenous high-dose L-thyroxine treatment. Intensive Care Med. 1991. 17 (1):16-8. [Medline].
Jonklaas J, Bianco AC, Bauer AJ, Burman KD, Cappola AR, Celi FS, et al. Guidelines for the treatment of hypothyroidism: prepared by the american thyroid association task force on thyroid hormone replacement. Thyroid. 2014 Dec. 24 (12):1670-751. [Medline].
Ridgway EC, McCammon JA, Benotti J, Maloof F. Acute metabolic responses in myxedema to large doses of intravenous L-thyroxine. Ann Intern Med. 1972 Oct. 77 (4):549-55. [Medline].
Fliers E, Wiersinga WM. Myxedema coma. Rev Endocr Metab Disord. 2003 May. 4(2):137-41. [Medline].
Dutta P, Bhansali A, Masoodi SR, Bhadada S, Sharma N, Rajput R. Predictors of outcome in myxoedema coma: a study from a tertiary care centre. Crit Care. 2008. 12(1):R1. [Medline]. [Full Text].