The patient was extremely ill and rapidly decompensating with multisystem organ failure including respiratory failure, altered mental status, acute on chronic renal failure, and cardiac dysfunction. The primary concerns for the stability of the patient revolved around the respiratory failure coupled with altered mental status. In the intensive care unit (ICU), she rapidly began to fail BiPAP therapy. Subsequently, the patient was emergently intubated in the ICU.  A systemic review of therapies and hospital course is as follows:

Endocrine

Considering the primary diagnosis of myxedema coma, early supplementation with thyroid hormone is essential. Healthcare providers followed the American Thyroid Association recommendations which recommend giving combined T3 and T4 supplementation; however, T4 alone may also be used. T3 therapy is given as a bolus of 5 to 20 micrograms intravenously and continued at 2.5 to 10 micrograms every 8 hours. An intravenous loading dose of 300 to 600 micrograms of T4 is followed by a daily intravenous dose of 50 to 100 micrograms. Repeated monitoring of TSH and T4 should be performed every 1 to 2 days to evaluate the effect and to titrate the dose of medication. The goal is to improve mental function. Until coexistent adrenal insufficiency is ruled out using a random serum cortisol measurement, 50 to 100 mg every 8 hours of hydrocortisone should be administered. In this case, clinicians used hydrocortisone 100 mg IV every 8 hours. Dexamethasone 2 to 4 mg every 12 hours is an alternative therapy.

Neurologic

The patient’s mental status rapidly worsened despite therapy. In the setting of her hypothyroidism history, this may be myxedema coma or due to the involvement of another organ system. The thyroid supplementation medications and hydrocortisone were continued. A CT head without contrast was normal.

Respiratory

For worsening metabolic acidosis and airway protection, the patient was emergently intubated. Her airway was deemed high risk due to having a large tongue, short neck, and extreme obesity. As the patient’s heart was preload dependent secondary to pericardial effusion, a 1-liter normal saline bolus was started. Norepinephrine was started at a low dose for vasopressor support and ketamine with low dose Propofol was used for sedation. Ketamine is a sympathomimetic medication and usually does not cause hypotension as all other sedatives do. The patient was ventilated with AC mode of ventilation, tidal volume of 6 ml/kg ideal body weight, flow 70, initial fio2 100 %, rate 26 per minute (to compensate for metabolic acidosis), PEEP of 8.

Cardiovascular

She was determined to be hemodynamically stable with a pericardial effusion. This patient’s cardiac dysfunction was diastolic in nature as suggested by an ejection fraction of 66% to 70%. The finding of posterior pericardial effusion further supported this conclusion. The posterior nature of this effusion was not amenable to pericardiocentesis. As such, this patient was preload dependent and showed signs of hypotension. The need for crystalloid fluid resuscitation was balanced against the impact increased intravascular volume would have on congestive heart failure and fluid overload status. Thyroid hormone replacement as above should improve hypotension. However, vasopressor agents may be used to maintain vital organ perfusion targeting a mean arterial pressure of greater than 65 mm Hg as needed. BP improved after fluid bolus and eventually the norepinephrine was stopped. Serial echocardiograms were obtained to ensure that the patient did not develop tamponade physiology. Total CK was elevated which was likely due to Hypothyroidism compounded with the chronic renal disease.

Infectious Disease

Blood cultures, urine analysis, and sputum cultures were obtained. The patient's white blood cell count was normal. This is likely secondary to her being immunocompromised due to hypothyroidism and diabetes. In part, the pulmonary findings of diffuse edema and bilateral pleural effusions can be explained by the cardiac dysfunction. Thoracentesis of pleural fluid was attempted and the fluid analyzed for cytology and gram staining to rule out infectious or malignant causes as both a therapeutic and diagnostic measure. Until these results return, broad-spectrum antibiotics are indicated and may be discontinued once the infection is ruled out completely.

Gastrointestinal

Nasogastric tube feedings were started on the patient after intubation. She tolerated feedings well. AST and ALT were mildly elevated which was thought to be due to hypothyroidism and as the TSH and free T4 improved her AST and ALT improved. Eventually, these values became normal once her TSH level was close to 50.

Renal

Her baseline creatinine was found to be close to 1.08 in prior medical records. She presented with a creatinine of 1.8 in the emergency department. As hypothyroidism causes fluid retention in part due to the fact that thyroid hormone encourages excretion of free water and partly due to decreased lymphatic function in returning fluid to vascular circulation.  Aggressive diuresis was attempted. As a result, her creatinine increased initially but improved on repeated evaluation and patient had a new baseline creatinine of 1.6. Overall she had a net change in the fluid status of 10 liters negative by her ten days of admission in the ICU.

Hematology

Mildly anemic otherwise WBC and platelet counts were normal. Electrolyte balance should be monitored closely paying attention to sodium, potassium, chloride, and calcium specifically as these are worsened in both renal failure and myxedema. 

Daily sedation vacations were done, patients mental status improved and was much better when TSH was around 20. The bilateral pleural effusions improved with aggressive diuresis. Breathing trials were initiated when the patient's fio2 requirements decreased to 60% and a PEEP of 8. She was eventually extubated on to BiPAP and then high flow nasal cannula while off of BiPAP. Pericardial fluid remained stable, and no cardiac tamponade pathology developed. As a result, it was determined that a pericardial window was unnecessary. Furthermore, she was not a candidate for pericardiocentesis as the pericardial effusion was located posterior to the heart. Her renal failure improved with improved cardiac function, diuretics, and thyroid hormone replacement.

After extubation patient had speech and swallow evaluations and was able to resume an oral diet. The patient was eventually transferred out of the ICU to the general medical floor and then eventually to a rehabilitation unit.

Despite the name myxedema coma, most patients will not present in a coma status. This illness is at its core a severe hypothyroidism crisis that leads to systemic multiorgan failure. Thyroid hormones T3, and to a lesser extent, T4 act directly on a cellular level to upregulate all metabolic processes in the body. Therefore, deficiency of this hormone is characterized by systemic decreased metabolism and decreased glucose utilization along with increased production and storage of osmotically active mucopolysaccharide protein complexes into peripheral tissues resulting in diffuse edema and swelling of tissue.[1]

Myxedema coma is an illness that occurs primarily in females at a rate of 4:1 compared to men. It typically impacts the elderly at the age of greater than 60 years old and approximately 90% of cases occur during winter months. Myxedema coma is the product of longstanding unidentified or undertreated hypothyroidism of any etiology. Thyroid hormone is necessary throughout the body and acts as a regulatory hormone, that affects many organ systems.[2]In cardiac tissues, myxedema coma manifests as decreased contractility with subsequent reduction in stroke volume and overall cardiac output.  Bradycardia and hypotension are typically present also. Pericardial effusions occur due to the accumulation of mucopolysaccharides in the pericardial sac which leads to worsened cardiac function and congestive heart failure from diastolic dysfunction. Capillary permeability is also increased throughout the body leading to worsened edema. Electrocardiogram findings may include bradycardia and low-voltage, non-specific ST waveform changes with possible inverted T waves.

Neurologic tissues are impacted in myxedema coma leading to the pathognomonic altered mental status as a result of hypoxia and decreased cerebral blood flow secondary to cardiac dysfunction as above. Additionally, hypothyroidism leads to decreased glucose uptake and utilization in neurological tissue thus worsening the cognitive function.

The pulmonary system typically manifests this disease process through hypoventilation secondary to central nervous system (CNS) depression of the respiratory drive with blunting of the response to hypoxia and hypercapnia. Additionally; metabolic dysfunction in the muscles of respiration leads to respiratory fatigue and failure, macroglossia from mucopolysaccharide driven edema of the tongue leads to mechanical obstruction of the airway, and obesity hypoventilation syndrome with the decreased respiratory drive as most hypothyroid patients suffer from obesity.

Renal manifestations include decreased glomerular filtration rate from the reduced cardiac output and increased systemic vascular resistance coupled with acute rhabdomyolysis lead to acute kidney injury. In the case of our patient above who has a pre-existing renal disease status post-nephrectomy, this is further worsened.  The net effect is worsened fluid overload status compounding the cardiac dysfunction and edema.[3]

The gastrointestinal tract is marked by mucopolysaccharide driven edema as well leading to malabsorption of nutrients, gastric ileus, and decreased peristalsis. Ascites are a common occurrence because of increased capillary permeability in the intestines coupled with coexistent congestive heart failure and congestive hepatic failure. Coagulopathies are common to occur as a result of this hepatic dysfunction.

Evaluation: The diagnosis of myxedema coma, as with all other diseases, is heavily reliant on the history and physical exam. A past medical history including hypothyroidism is highly significant whenever decreased mental status or coma is identified. In the absence of identified hypothyroidism myxedema coma is a diagnosis of exclusion when all other sources of coma have been ruled out. If myxedema coma is suspected, evaluation of thyroid stimulating hormone (TSH), free thyroxine (T4), and serum cortisol is warranted. T4 will be extremely low. TSH is variable depending on the etiology of hypothyroidism with a high TSH indicating primary hypothyroidism and a low or normal TSH indicating secondary etiologies. Cortisol may be low indicating adrenal insufficiency because of the hypothyroidism. [4]

Prognosis: Myxedema coma is a medical emergency. With proper and rapid diagnosis and initiation of therapy the mortality rate is still as high as 25% to 50%. The most common cause of death is due to respiratory failure. The factors which suggest a poorer prognosis include increased age, persistent hypothermia, bradycardia, low score Glasgow Coma Scale, or multi-organ impairment indicated by high APACHE (Acute Physiology and Chronic Health Evaluation) II score. For these reasons, placement in an intensive care unit with a low threshold for intubation and mechanical ventilation can improve mortality outcomes.[3][5]

• Not every case of shortness of breath is COPD or congestive heart failure (CHF). While less likely, a history of hypothyroidism should raise suspicion of myxedema coma in a patient with any cognitive changes.
• Myxedema is the great imitator illness that impacts all organ system. It can easily be mistaken for congestive heart failure, COPD exacerbation, pneumonia, renal injury or failure, or neurological insult.
• Initial steps in therapy include aggressive airway management, thyroid hormone replacement, glucocorticoid therapy, and supportive measures.
• These patients should be monitored in an intensive care environment with continuous telemetry.[6]