Chief Complaint:

Lethargy

HPI:

56-year-old male who uses a wheelchair at baseline arrives via EMS from home with complaints of lethargy. EMS was originally contacted because occupants of the patient’s home thought his blood glucose level was low. The patient had slowed respirations and was bradycardic upon EMS arrival. His blood glucose was 264 and he was in atrial fibrillation on the field monitor. He was also slow to answer questions.

History limited by patients’ mental status.

Past Medical History: diabetes, Atrial fibrillation, end-stage renal disease.

Pertinent Exam Findings:

General Appearance: Patient is awake, somnolent, and in no acute distress
Eyes: Pupils equal, eye movements normal
HENT: Moist mucus membranes
Respiratory: Clear to auscultation, no respiratory distress, no accessory muscle use, speaking in full sentences
Cardiac: Normal rate, regular rhythm
Gastrointestinal: Abdomen soft, no abdominal tenderness, no guarding
Skin: Warm and dry, no rash
Musculoskeletal: Full range of motion of 3 extremities, right lower extremity with below knee amputation
Neurologic: Somnolent, oriented x3, cranial nerves 2-12 intact, symmetrical extremity 5/5 strength

ED Course:

The patient confirms that he took his Metoprolol today. He is also complaining of some nausea. Glucagon and Zofran ordered. No significant change in heart rate.
Cardiology consulted and suspects sepsis after bedside evaluation and requests admit to hospital. Admitted to medicine.

EKG 1 @ 10:50

EKG 2 @ 12:10

Hospital Course:

Persistently bradycardic, hypotensive despite IV fluids and with goal to hold beta-blockers was admitted to the ICU for care and management of symptomatic bradycardia. No clear source of infection identified with negative Covid PCR, chest x-ray consistent with bibasilar atelectasis

CT head without CVA or hemorrhage

Thyroid studies ordered in ICU and found to have TSH 83, free T4 low 0.3

Blood cultures obtained without growth. Started on IV T4, IV steroids, no T3 available in hospital. Midodrine after initiation of HD.

Eventually vitals stabilized and patient discharged.

DISCUSSION:

Background:

Myxedema coma is a rare, life-threatening presentation of severe hypothyroidism consisting of multi-organ dysfunction and physiologic decompensation. It can be the result of long-standing hypothyroidism or precipitated by an acute event such as an infection or surgery in a patient with poorly controlled hypothyroidism. Any patient with hypothyroidism is at risk for developing myxedema coma, but it is noted to be more prevalent in patients with chronic autoimmune thyroiditis due to it having a more insidious onset. The estimated incidence of myxedema coma is only 0.22 cases per 1,000,000 per year, but it is associated with high mortality rates ranging from 30-50%. Myxedema coma has a higher prevalence in women and most cases almost exclusively occur in patients over the age of 60

Diagnosis:

The hallmark symptoms associated with myxedema coma are a decrease in mental status (i.e. confusion, lethargy) along with hypothermia defined as a temperature below 36 C due to decreased metabolism. Patients may also present with hypotension, bradycardia and hypoventilation. Other clinical findings may include swelling of the hands, face, lips, and tongue due to deposition of mucopolysaccharides in the dermis. A comatose state is not necessary for the diagnosis of myxedema coma since this is a late finding in the disease.

Clinicians should have a high index of suspicion for myxedema coma in patients that present with such symptoms noted above, while also having a history of hypothyroidism or any previous thyroid dysfunction. An extensive workup is necessary since multiple organ systems are involved in myxedema coma. Because primary hypothyroidism is vastly more common, thyroid studies will reveal very low serum T3 and T4 concentrations along with an elevated TSH. A normal or low thyroid stimulating hormone (TSH) may indicate pituitary or hypothalamic dysfunction. Blood chemistry may reveal hyponatremia and hypoglycemia due to metabolic abnormalities. Hypotension can result in poor perfusion which may lead to organ damage related lab changes such as elevated creatine and liver function tests (LFTs). Venous blood gas (VBG) or arterial blood gas (ABG) should be ordered to reveal the extent of hypercapnia and hypoxia. Other lab abnormalities may include elevated creatinine protein kinase (CPK) and lipid levels and decreased cortisol levels. Additionally, an EKG may show sinus bradycardia, non-specific ST wave changes or a prolonged QT interval.

In addition to evaluating thyroid and metabolic dysfunction, a diagnostic work up should investigate precipitating factors, such as infection, hemorrhage, trauma, stroke, recent surgery, medication use, and burns. Of note, typical signs of infection like tachycardia or hyperthermia may not be present due to the pathophysiology of myxedema coma. It is recommended to obtain blood cultures and imaging studies to determine a primary precipitating event. A chest-xray may show pleural effusions and a point of care cardiac ultrasound may reveal a pericardial effusion. While a diagnostic scoring system for myxedema coma has been proposed, it has not yet been widely adopted for clinical use due to the limited number of patients involved in creating the scoring system.

Management in ED:

Myxedema coma is an endocrine emergency and, if suspected, treatment should begin before laboratory confirmation. Optimal hormone replacement protocol is not agreed upon within the literature, but should consist of either T4 (levothyroxine) and T3 (liothyronine) or T4 alone. T3 has increased biologic activity and more rapid onset, but high concentrations should be avoided due to risk of precipitating fatal tachycardia or myocardial infarction. Gastrointestinal absorption of these agents may be impaired, so hormone replacement is best given initially via slow intravenous bolus. Successful management of myxedema coma will require supportive measures in addition to thyroid hormone replacement. Patients may require mechanical intubation, intravenous fluids for hypotension and electrolyte replacement as needed, and rewarming. Underlying or precipitating conditions must be concurrently treated. Liberal prophylactic use of antibiotics should be applied as signs of infection may be absent. Additionally, glucocorticoids should be administered until coexisting adrenal insufficiency (such as from central hypopituitarism) can be ruled out.

Prognosis:

Myxedema coma is exceedingly uncommon, thus there are few case reports and a lack of overall data on prognosis. A major prognosticating factor is the degree of hypothermia, which directly correlates to mortality outcomes in patients with myxedema coma. There is one study from Japan looking at data from 2010-2013, which found in-hospital mortality with myxedema coma diagnosis to be 29.5% among a cohort of 149 patients. Overall, myxedema coma remains a serious diagnosis with published mortality rates up to 50%.

Differential Diagnoses:

• • Myxedema Coma
  • Hypothyroidism
  • Heart Failure
  • Alcohol Intoxication
  • Opioid Intoxication
  • Sepsis
  • Hypothermia
  • CVA

Clinical Pearls:

• • Myxedema coma is a rare, life-threatening condition associated with hypothyroidism resulting in multiorgan dysfunction and decompensation.
  • Patients may present with lethargy, confusion, hypotension, hypothermia, bradycardia, or soft tissue swelling
  • Diagnosis can be difficult, labs and imaging can help to clarify the metabolic condition of the patient and identify any precipitating factors.
  • Management should be started early when clinical suspicion is high, T3 or T4 should be given although there is no clear consensus dosing.
  • Prophylactic antibiotics, IV fluids, mechanical ventilation, rewarming measures, and glucocorticoids should be considered.
  • Prognosis is poor with mortality rates up to 50%.

References:

1. Bridwell RE, Willis GC, Gottlieb M, Koyfman A, Long B. Decompensated hypothyroidism: A review for the emergency clinician. Am J Emerg Med. 2021;39:207-212. doi:10.1016/j.ajem.2020.09.062
2. Elkattawy S, Dhanoa P, Kotys J, Fichadiya H, Eckman A. Myxedema Coma: Case Report and Literature Review. Cureus. 2021;13(5):e15277-e15277.
3. Elshimy G, Chippa V, Correa R. Myxedema. In: StatPearls. Treasure Island (FL): StatPearls Publishing. Copyright © 2022, StatPearls Publishing LLC.; 2022.
   
4. Klubo-Gwiezdzinska. (2012). Thyroid emergencies. Medical Clinics of North America., 96(2), 385–403. https://doi.org/10.1016/j.mcna.2012.01.015
5. Mathew V, Misgar RA, Ghosh S, et al. Myxedema coma: a new look into an old crisis. J Thyroid Res. 2011;2011:493462. doi:10.4061/2011/493462
6. Ono Y, Ono S, Yasunaga H, Matsui H, Fushimi K, Tanaka Y. Clinical characteristics and outcomes of myxedema coma: Analysis of a national inpatient database in Japan. J Epidemiol. 2017;27(3):117-122.
7. Popoveniuc G, Chandra T, Sud A, et al. A diagnostic scoring system for myxedema coma. Endocr Pract. 2014;20(8):808-817.
8. Wall C. R. (2000). Myxedema coma: diagnosis and treatment. American family physician, 62(11), 2485–2490.
9. Wiersinga WM. Myxedema and Coma (Severe Hypothyroidism) [Updated 2018 Apr 25]. In: Feingold KR, Anawalt B, Boyce A, et al., editors. Endotext [Internet]. South Dartmouth (MA): MDText.com, Inc.; 2000-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK279007/

Authors

Jack Spartz MSIV

Peter Haskins, MSIV

Josh Wahba, MSIV

Kirsten Hughes MSIII

Mark O’Brien MSIII