What negative history should be asked in a patient with myxedema coma, including previous episodes of hypothyroidism, thyroid surgery, or radiation therapy to the neck, medication history, and history of adrenal insufficiency?

Negative History to Elicit in Myxedema Coma

Critical Precipitating Factors to Exclude

The most important negative history elements focus on identifying precipitating factors that triggered myxedema coma, as these acute stressors can unmask severe hypothyroidism in patients with previously undiagnosed or poorly controlled disease.

Recent Surgical Procedures or Trauma

• Ask specifically about any recent surgery, as this represents a major physiologic stressor that commonly precipitates myxedema coma 1, 2.
• Inquire about any recent trauma or significant injury, which can also trigger decompensation 1.
• Postoperative myxedema coma can occur even after routine procedures like hip replacement, particularly when underlying hypothyroidism was inapparent preoperatively 2.

Infection and Acute Illness

• Question about recent infections, particularly pneumonia or sepsis, as intercurrent illness is a common precipitant 3, 4.
• Ask about symptoms of respiratory infection, urinary tract infection, or other systemic infections in the days to weeks preceding presentation 3.

Medication Exposure

• Specifically ask about recent use of sedatives, anesthetics, or opioid medications, as these drugs can precipitate myxedema coma in hypothyroid patients 3, 4.
• Inquire about any new medications that might suppress thyroid function or central nervous system activity 3.

Environmental Cold Exposure

• Ask about prolonged exposure to cold temperatures, as hypothermia can both result from and precipitate myxedema coma 3.

Thyroid Disease History

Previous Thyroid Dysfunction

• Obtain detailed history of any prior hypothyroidism diagnosis, including duration and severity 5, 3, 6.
• Ask about previous thyroid function test results, particularly TSH and free T4 levels 6.
• Even patients with subclinical hypothyroidism (elevated TSH with normal free T4) can develop myxedema coma under stress, though this is extremely rare 6.

Thyroid Treatment History

• Question about radioactive iodine therapy, as this is a common cause of iatrogenic hypothyroidism 4.
• Ask about previous thyroid surgery, including thyroidectomy or partial thyroid resection 5.
• Inquire about radiation therapy to the neck region for any malignancy 7.

Medication Adherence

• Specifically ask about levothyroxine compliance, including missed doses, dosing schedule, and barriers to adherence 5, 4.
• Determine if the patient has been taking thyroid hormone replacement as prescribed, as poor compliance is a major risk factor 4.
• Ask about recent changes in thyroid medication dose or formulation 5.

Pituitary and Adrenal History

Pituitary Disease

• Ask about history of pituitary tumors or pituitary surgery, as central hypothyroidism can lead to myxedema coma 5.
• Inquire about symptoms of other pituitary hormone deficiencies, including amenorrhea, loss of libido, or visual field defects 5.

Adrenal Insufficiency

• Critically important: Ask about symptoms of adrenal insufficiency, including salt craving, hyperpigmentation, unexplained weight loss, or orthostatic hypotension 8, 5, 3.
• Before initiating thyroid hormone replacement, adrenal insufficiency must be excluded or treated, as starting levothyroxine before corticosteroids can precipitate life-threatening adrenal crisis 8, 5, 3.
• Question about previous diagnosis of Addison's disease or secondary adrenal insufficiency 8.

Cardiovascular History

Cardiac Disease

• Ask about history of coronary artery disease, myocardial infarction, or angina, as these conditions increase risk during thyroid hormone replacement 8, 3.
• Inquire about recent cardiac events, as myocardial infarction can precipitate myxedema coma 3.
• Question about heart failure symptoms, as hypothyroidism causes impaired myocardial contractility 5, 2.

Pericardial Disease

• Ask about previous pericardial effusion, as this commonly occurs in severe hypothyroidism 5.

Metabolic and Endocrine History

Diabetes Mellitus

• Ask about diabetes history and recent hypoglycemic episodes, as hypoglycemia must be identified and corrected immediately in myxedema coma 1.
• Inquire about changes in insulin or oral hypoglycemic requirements 8.

Autoimmune Conditions

• Question about other autoimmune diseases, particularly those associated with autoimmune thyroiditis (Hashimoto's disease) 6, 4.

Medication and Substance History

Drug Interactions

• Ask about medications that can interfere with thyroid hormone absorption, including iron supplements, calcium supplements, proton pump inhibitors, and antacids 9.
• Inquire about recent iodine exposure from radiographic contrast agents 9.

Common Pitfalls to Avoid

• Never assume normal thyroid function based on previous normal tests—even patients with subclinical hypothyroidism can develop myxedema coma under sufficient stress 6.
• Do not overlook medication non-adherence as a precipitating factor, even in previously compliant patients 5, 4.
• Always consider adrenal insufficiency before initiating thyroid hormone replacement, as this oversight can be fatal 8, 5, 3.
• Do not miss recent surgical procedures as precipitants, even routine operations can trigger myxedema coma in undiagnosed hypothyroid patients 2.