Case Study
SS is an 84-year-old White female with a history of coronary artery disease, coronary artery bypass grafting, essential hypertension, dyslipidemia, and hypothyroidism. Medics found SS lying on the floor of her house after a neighbor expressed concern over not seeing her for several days. SS's chief complaint was profound weakness to the extent that she could not rise after the fall.
Initial vital signs were: BP, 163/97 mm Hg; temperature, 96.1[degrees] F (35.6[degrees] C, tympanic); pulse, 57 beats/minute; respirations, 23 breaths/minute; and peripheral arterial oxygen saturation (SpO2), 96% on room air. Physical assessment findings included decreased mentation, bilateral peripheral and pedal edema, periorbital edema, and dry skin. An ECG revealed sinus bradycardia without ischemia or infarct.
As the initial encounter was due to a ground-level fall, computerized tomography scans of the head, chest, abdomen, and pelvis were ordered but revealed no signs of injury.
Initial lab findings included an elevated thyroid-stimulating hormone (TSH) level of 110.00 [mu]U/L (normal, 2-10 [mu]U/L) and a decreased free thyroxine (T4) level of 0.08 ng/dL (normal, 0.8-2.8 ng/dL) indicating hypothyroidism.1Based on her severely weakened state, altered mental status, and correlated thyroid hormone levels, SS's admitting diagnosis was adult myxedema. She was also diagnosed with acute metabolic encephalopathy due to myxedema coma (MC), B12 deficiency, and a urinary tract infection. The prompt, life-saving diagnosis was aided by the patient's history of hypothyroidism which led the healthcare provider to assess thyroid hormone levels.
Thyroid hormone physiology
The thyroid gland is anterior to the trachea and synthesizes and releases thyroxine (T4), triiodothyronine (T3), and calcitonin.2 The most abundant thyroid hormone is T4, which makes up 90% of thyroid hormones. While T4 is larger in quantity, T3 is more potent and has a greater effect on metabolism. The thyroid gland is responsible for secreting some T3, but 80% of circulating T3 is produced extra-thyroidally from T4 deiodination.2 These hormones have a significant effect on metabolic rate, carbohydrate and lipid metabolism, caloric requirements, growth and development, oxygen consumption, brain function, and numerous other nervous system activities.2
When low circulating levels of T4 and T3 are detected, the hypothalamus secretes thyrotropin-releasing hormone (TRH), which initiates the release of TSH by the anterior pituitary gland. TSH stimulates thyroid hormone synthesis and secretion3 (see Hypothalamic-pituitary-thyroid axis in health and disease).
Pathophysiology of hypothyroidism
Hypothyroidism occurs when the thyroid gland does not produce enough thyroid hormones and results in a decrease in the metabolic rate.2 This is generally an uncomplicated, frequently diagnosed, and easily treatable disease.4
Hypothyroidism is classified as either primary or secondary.2 Primary hypothyroidism is caused either by the destruction of thyroid tissue or insufficient hormone synthesis. Secondary hypothyroidism is due to either pituitary disease with decreased TSH secretion or hypothalamic dysfunction with decreased TRH secretion. While hypothyroidism worldwide is usually caused by iodine deficiency, hypothyroidism in the US is usually caused by thyroid gland atrophy often secondary to Hashimoto thyroiditis or Graves disease.2
Myxedema coma
MC is a rare and life-threatening endocrine emergency related to pronounced thyroid hormone deficiency.5 A retrospective observational study determined the incidence of MC to be as low as 1.08 per million people per year.6 The rare incidence of MC may be attributed to the increased accessibility to both TSH level testing and medications used to treat hypothyroidism. The mortality of MC can be as high as 60% even with the appropriate treatment.6 Diagnosis of MC can be challenging due to its nonspecific signs and symptoms, resulting in delayed treatment. The misleading terminology and misconception that the coma must be present to diagnose MC also result in delayed treatment.
MC develops from long-standing, unrecognized, or untreated hypothyroidism.5 Approximately 95% of MC cases are secondary to primary hypothyroidism.6 Common precipitating factors of MC include infections, heart failure, cerebrovascular events, trauma, and surgery.5 Additional factors include the use of opioids, lithium, amiodarone, checkpoint inhibitors like pembrolizumab, and gastrointestinal bleeding.7 Typically, MC is diagnosed during the winter months, suggesting that the cold may also be a provoking factor.5
MC is more common in female older adults with chronic undiagnosed hypothyroidism due to a higher frequency of gastrointestinal disorders which can inhibit T4 absorption.5 Nonadherence is the leading cause of oral hypothyroid therapy failure, leading to patients with untreated hypothyroidism.6 This is similar to the case of SS, who had reportedly stopped taking her levothyroxine (T4 replacement therapy) for an undetermined length of time.
Clinical manifestations
The principal features of MC include altered mental status, decreased thermogenesis that accompanies the decrease in metabolism leading to hypothermia, and a precipitating event.7 In addition to hypothermia, signs of MC include hypotension, hyponatremia, hypoglycemia, hypoventilation, bradycardia, and soft tissue nonpitting edema of the hands and face.6 Facial and orbital edema are typically related to deposits of albumin and mucin in the skin and surrounding soft tissue.6 Additional signs include dry coarse skin, macroglossia, and decreased deep tendon reflexes.7 Neurologic-specific signs include lethargy and obtundation.6
SS presented with decreased mentation, hyponatremia, bradycardia, dry skin, peripheral and periorbital edema, and hypothermia.
Complications
MC compromises organ system functions and many metabolic pathways and can result in numerous complications.2 Patients with MC have a higher risk of developing shock and life-threatening dysrhythmias. The reduction of intravascular volume in MC may result in hypotension, cardiovascular collapse, and cardiogenic shock.2 Undiagnosed infections may also contribute to sudden vascular collapse and deaths, so it is crucial to monitor for signs of infection. Respiratory manifestations of MC include hypoventilation with respiratory acidosis due to respiratory center depression and a decreased response to hypoxia and hypercapnia.2
Hypothermia may be further complicated by hypoglycemia and can increase mortality, as there is a poor prognosis for patients with temperatures below 89.6[degrees] F (32[degrees] C).2
MC may also alter the renal function and result in decreased renal blood flow and glomerular filtration rate. A decrease in the renal excretion of free water causes hyponatremia, and when severe, can cause coma and significantly increase the mortality in critically ill patients by about 60 times.2
Hematologic manifestations include an increased risk of bleeding from the reduction in coagulation factors V, VII, VIII, IX, and X. The combination of granulocytopenia and immunosuppression increases the risk of sepsis in patients with MC. Additionally, macrocytic anemia due to vitamin B12 deficiency may worsen neurologic status.4
Lab studies
The most common lab tests for evaluating thyroid function are TSH and free T4.1 In MC, the serum T4 concentration is usually very low. The serum TSH concentration may be high, indicating primary hypothyroidism, or it may be low, normal, or slightly high, indicating central hypothyroidism. Most patients with MC have primary hypothyroidism. SS had an elevated TSH level and a decreased free T4 level.
Other lab studies associated with MC include anemia, hyponatremia, hypoglycemia, hypercholesterolemia, and high serum creatine kinase concentrations.7 Additional lab results may include decreased glomerular filtration rate and leukopenia. Arterial blood gases may show hypoxemia, hypercapnia, and acidosis.4
SS's other lab results revealed anemia, hyponatremia, bacteriuria, and an elevated urine specific gravity. Urine culture revealed Gram-negative bacilli greater than 100,000 colony-forming units/mL, indicating a urinary tract infection (UTI).
Diagnosis
Diagnosis of MC is based on clinical criteria and a high index of suspicion.5 Important clues to possible MC in a poorly responsive patient are the presence of a thyroidectomy scar or a history of radioiodine therapy or hypothyroidism. This life-threatening emergency requires an early diagnosis and the prompt initiation of multimodal therapy, supportive intensive care, and identification and treatment of precipitating causes.5 Through early recognition and prompt treatment, a patient will have a decreased risk of permanent end-organ damage and an estimated reduction in mortality to about 20% to 25%.6 Multimodal therapy includes thyroid hormone replacement, glucocorticoids, and fluid resuscitation. Additional care measures include passive rewarming for patients with hypothermia.6
Treatment
Due to the low incidence of MC and limited availability of clinical trials comparing different treatment regimens, treatment guidelines are most often based on expert opinion and provider experience.6
One mainstay of pharmacotherapy is T4.8 It should be administered I.V. as a slow bolus due to concerns regarding compromised gastrointestinal absorption of oral T4. When SS was admitted, she was immediately started on I.V. levothyroxine daily. By the sixth day of admission, SS was sitting up, appeared significantly more energetic, was more alert, and had a notable improvement in edema. Due to the improvement in clinical status, SS was switched to oral levothyroxine.
The American Thyroid Association recommends I.V. glucocorticoid administration followed by T4 replacement, with T3 replacement as an optional supplement.6
Glucocorticoids are used as empiric treatment for adrenal insufficiency and due to the decreased adrenal response to stress in MC.4 Glucocorticoids are only administered until coexisting adrenal insufficiency has been ruled out. Thyroid hormones are administered after glucocorticoids because thyroid hormone accelerates the metabolism of cortisol, the body's main stress hormone.4
TSH typically falls at a rate of 50% per week and failure to do so indicates inadequate therapy. Once a patient with MC is clinically improving, daily oral levothyroxine can be administered.6
In older adults, T4 to T3 conversion may be weakened, supporting the idea of administering T3 replacement with I.V. liothyronine.6 Additionally, intracellular T3 deficiency can lead to cardiogenic shock, hypoxia, and coma. However, T3 administration may not be safe in patients with cardiac dysfunction, which may suggest why T3 was not administered to SS, who had a history of hypertension and coronary artery disease.6 Lower doses are recommended for older adults and those with cardiovascular disease.
To ensure effective dosing and to monitor improvement, thyroid hormones should be monitored every 24 to 48 hours.6 Aggressive thyroid hormone treatment carries significant risks as rapid administration may cause myocardial infarction or fatal dysrhythmias.6,8
Electrolytes and dextrose may also be administered to correct hyponatremia and hypoglycemia.4 Broad-spectrum antibiotic coverage may be administered due to the high incidence of infections and the correlated higher mortality of undiagnosed infections.4 SS's UTI was treated with I.V. ceftriaxone. SS also received I.M. cyanocobalamin (vitamin B12) daily to address her vitamin B12 deficiency.
Nursing considerations
Early recognition and treatment are crucial.8 Those with MC are often admitted to the ICU and require mechanical ventilation and continuous cardiac monitoring.2 However, SS was deemed to be stable enough to admit to a medical-surgical unit. It is important to frequently monitor patients with MC and their cardiovascular system as circulatory collapse and respiratory failure are common complications.9
Closely monitor core body temperature to assess for hypothermia.2 To combat hypothermia, provide blankets. Avoid thermal blankets or hot baths as these can cause increased vasodilation and increase the risk of vascular collapse.4
Use a gentle soap and moisturizer to help promote skin health and prevent skin breakdown.2
Frequent assessment includes obtaining vital signs and body weight measurements, monitoring intake and output, and monitoring edema. Administer I.V. fluids as prescribed to maintain systolic BP greater than 90 mm Hg. Vasopressor agents may be used if hypotension is refractory to volume administration and if thyroid replacement has not had time to act.2 Measure urine output hourly, and determine fluid balance every 8 hours. The patient's energy level and mentation should improve within 2 to 14 days and steadily progress to baseline levels.2 TSH levels and neurologic status can aid the decision of continuing treatment.
Patients must be informed about the importance of medication adherence and to identify situations where they are at high risk for nonadherence with home medication regimens (see Patient education10).
Promote health and identify thyroid deficiencies by educating high-risk populations to be screened for subclinical thyroid disease. These populations include females, white ethnicity, older adults, those with type 1 diabetes, those with Down syndrome, those with a family history of thyroid disease, patients with goiters, previous hypothyroidism, and external beam radiation in the head or neck area.2
Conclusion
MC is a rare complication of severe hypothyroidism and is associated with high mortality. Considering the poor prognosis in those who have a late diagnosis, healthcare professionals must know and recognize the signs of MC. Patients with hypothyroidism should also be informed about the importance of adhering to their medication regimen.
Hypothalamic-pituitary-thyroid axis in health and disease3
A. In the normal axis, TRH stimulates thyrotropes of the anterior pituitary gland to release TSH. TSH stimulates the synthesis and release of thyroid hormone by the thyroid gland. Thyroid hormone, in addition to its effects on target tissues, inhibits further release of TRH and TSH by the hypothalamus and anterior pituitary gland, respectively. B. In Graves disease, a stimulatory autoantibody autonomously activates the TSH receptor in the thyroid gland, resulting in a sustained stimulation of the thyroid gland, increased plasma thyroid hormone (thick lines), and suppression of TRH and TSH release (dashed lines). C. In Hashimoto thyroiditis, a destructive autoantibody attacks the thyroid gland, causing thyroid insufficiency and decreased synthesis and secretion of thyroid hormone (dashed lines). Consequently, feedback inhibition on the hypothalamus and anterior pituitary gland does not occur, and plasma TSH levels rise (thick lines).
Source: Golan DE, Armstrong EJ, Armstrong AW. Principles of Pharmacology: The Pathophysiologic Basis of Drug Therapy: Fourth Edition. Philadelphia, PA: Wolters Kluwer Health; 2005.
Patient education10
MC is a severe form of hypothyroidism (low thyroid function) that occurs when thyroid hormone levels are not treated or controlled. Thyroid hormones help control body temperature, heart rate, growth, and weight. It can be triggered by not taking medication to treat hypothyroidism. It may also be triggered by an infection, medication, or a sudden stressful event, such as trauma or surgery.
Medications:
* Take prescribed medications as directed to increase and maintain thyroid hormone levels.
* Contact your healthcare provider if you think your medication is not helping or if you have adverse reactions, including rapid or irregular heartbeat, chest pain, shortness of breath, leg cramps, headache, nervousness, irritability, sleeplessness, tremors, change in appetite, weight gain or loss, vomiting, diarrhea, excessive sweating, heat intolerance, fever, changes in menstrual periods, hives, or skin rash.
How to prevent MC:
* Manage your low thyroid. Follow up with your healthcare provider or endocrinologist regularly to make sure your thyroid levels are in a healthy range.
* Keep warm. Especially during the winter months. Being exposed to the cold may increase your risk for MC.
Contact your healthcare provider if you have:
* Fever or feel ill
* Increasing fatigue
* Swelling in your face, arms, or feet
* Difficulty obtaining thyroid medicine
* Questions or concerns about your care
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