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  In a critically ill patient with a goiter or history of hyperthyroidism, consider and treat thyroid storm early.

  
  
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  Thyroid storm and myxedema coma are clinical diagnoses that do not depend on the absolute levels of thyroid-stimulating hormone and free thyroxine.

  
  
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  Myxedema coma should be considered in elderly hypothyroid patients who present with hypothermia and confusion.

  
  
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  For successful treatment, it is important to try to identify a trigger that pushed the patient into the extreme state of thyroid storm or myxedema coma.

Thyroid hormone (TH) is synthesized within the follicular cells of the thyroid gland. Production begins with the uptake of iodine into the follicular lumen. Thyroglobulin, produced within the follicular cell, is bound to iodine and then coupled to produce the thyroid hormones, thyroxine (T₄) and triiodothyrinine (T₃). Release of thyroid hormone is stimulated by one of the hormones secreted by the pituitary gland, thyroid-stimulating hormone (TSH). In turn, TSH is regulated by thyroid-releasing hormone (TRH) secreted by the hypothalamus. High levels of T₄ and T₃ act to suppress production of TSH and TRH via a negative feedback loop. TH released from the thyroid gland is in its less active form, T₄, which is converted in peripheral organs (kidney and liver) into its 10 times more active derivative, T₃. The half-life of T₃ is significantly shorter, approximately a day, compared with 1 week for T₄. In the serum, the majority of TH is bound to thyroid-binding globulin (TBG), making it inactive. The only active forms are free T₃ and T₄. After TH enters cells, it binds to its nuclear receptor and regulates expression of genes involved in lipid and carbohydrates metabolism and protein synthesis. As a net result of its action, there is an increase in basal metabolic rate.

Emergencies related to the thyroid gland can be caused by both excess and deficiency of TH. Excess of TH can cause a syndrome referred to as thyrotoxicosis and can be caused either by excessive production of TH or its exogenous administration. In its extreme state, thyrotoxicosis can lead to a life-threatening condition called thyroid storm, a state manifesting with fever, tachycardia, and altered mental status.

Hyperthyroidism is the term used when excessive production of TH by the thyroid is the cause of thyrotoxicosis. One of the most common causes of hyperthyroidism is Graves disease (approximately 80% of cases), in which autoimmune antibodies that bind to TSH receptors on the surface of thyroid cells stimulate production and release of TH. Other significant causes of hyperthyroidism include toxic multinodular goiter, thyroiditis, pituitary adenoma, and reaction to drugs (eg, lithium, amiodarone and iodine). Hyperthyroidism is 10 times more common in women.

Insufficiency of TH is referred to as hypothyroidism, and 95% of the time it is caused by dysfunction of the thyroid gland. One of the more common causes of hypothyroidism is Hashimoto thyroiditis, an autoimmune condition in which the body produces antibodies to the TSH receptor, which block signaling, and does not allow production of TH. Other causes include iodine deficiency, infiltrative diseases affecting the thyroid gland, or administration of drugs (eg, amiodarone). At its extreme, hypothyroidism can manifest as myxedema coma, a severe and life-threatening state that occurs more frequently in the elderly.

History

Depending on the degree of abnormality, patients will present with varied severity of symptoms. Patients with earlier stages of thyrotoxicosis will report excessive sweating, weight loss, palpitations, anxiety, and heat intolerance. Patients in thyroid storm will present with symptoms of thyrotoxicosis in addition to fever, tachycardia, altered mental status, and often congestive heart failure. In elderly patients, there is a rare form of thyrotoxicosis referred to as apathetic hyperthyroidism, presenting with lethargy, altered mental status, blepharoptosis (drooping of the upper eye lid), weight loss, and atrial fibrillation leading to congestive heart failure.

On the opposite side of the spectrum, patients with hypothyroidism complain of fatigue, depression, weight gain, cold intolerance, and dry skin. In its severe state, myxedema coma, patients present with altered mental status, bradycardia, hypothermia, hypoventilation, and hypotension.

Both thyroid storm and myxedema coma usually occur in patients with previously diagnosed thyroid disorders and are usually precipitated by other factors, such as infection, trauma, diabetic ketoacidosis, stroke, surgery, or medication noncompliance.

Physical Examination

Clinical findings in both hyper- and hypothyroidism are summarized in Table 68-1. Not all the signs and symptoms will be present in every patient. Frequent findings in patients with hyperthyroidism owing to Graves disease include goiter, exopthalmos, palmar erythema, and tachycardia (Figure 68-1). In thyroid storm, in addition to those findings, patients will have altered mental status, fever, hypertension, and frequently atrial fibrillation. Hypothyroid patients will present with fatigue, periorbital edema, hair loss, and dry skin. Myxedema coma patients will have altered mental status, hypothermia, hypotension, and myxedema (non-pitting peripherial edema owing to the accumulation of mucopolysaccharides in the skin).