The classic findings in thyroid storm suggest a sudden and severe exacerbation of hyperthyroidism. There is fever, rapid tachycardia, tremor, nausea and vomiting, diarrhea, dehydration, and delirium or coma. Fever is perhaps the most characteristic feature; the temperature may rise above 105.8 ^oF (41 ^oC). Occasionally, patients have a true toxic psychosis or a marked deterioration in previously abnormal behavior. Sometimes thyroid crisis takes a strikingly different form, which has been called apathetic storm. This condition is characterized by extreme weakness, emotional apathy and sometimes confusion. The wild delirium and agitation of the classic victim of thyroid storm are missing, and fever, if present, does not rise so high.

Signs and symptoms of decompensation in various organ systems may be present. Delirium is one example. Congestive heart failure may occur, with edema, congestive hepatomegaly, and respiratory distress. Extreme tachycardia or atrial fibrillation is common. Liver damage and jaundice may occur from congestive heart failure or possibly from a direct action of thyroid hormone on the liver coupled with malnutrition (Chapter 10). Fever and vomiting may produce dehydration and prerenal azotemia. Abdominal pain may be a prominent feature. The temperature may rise alarmingly, perhaps because the usual thermal controls have broken down in a manner similar to that occurring in the heat stroke. Frequently the clinical picture is clouded by a secondary infection such as pneumonia, a viral infection, or infection of the upper respiratory tract. Death may be caused by cardiac arrhythmia, congestive heart failure, hyperthermia, or other unidentified factors.

Storm is typically associated. with Graves' disease, but it has also been reported in patients with toxic nodular goiter. ¹In years past, death was the final outcome of storm with awesome regularity. ²In an unusually large series reported in 1969, three-fourths of the patients with thyroid storm succumbed to their disease. ³These patients typically were nutritionally depleted., had severe thyrotoxicosis, and had coincident serious disease, such as cardiac decompensation ^3a. In later series the mortality has been 30-75%. ^{1 , 4}At present, although still life-threatening, death from thyroid storm becomes rare provided that prompt recognition and aggressive treatment is initially in an intensive care unit. ⁵

In Nelson and Becker's series reported. in 1969 ³there were 21 cases of storm among 2,329 thyrotoxic admissions. Reports from other clinics, which included all cases manifesting febrile reactions of 38.3oC or more in the postoperative period, set the incidence of storm as high as 10% of patients opera. on. ⁴Few patients are now seen who fit the classic pattern of storm, but patients are occasionally encountered with marked accentuation of the symptoms of thyrotoxicosis in conjunction with infection. Most reports in the literature in recent years have been accounts of single cases. The incidence of thyroid storm is very low at present.

Thyroid storm classically began a few hours after a thyroidectomy performed on a patient prepared for surgery by potassium iodide alone. Many such patients were not euthyroid and would not be considered appropriately prepared for surgery by contemporary standards. Exacerbations of thyrotoxicosis are still seen in patients taken too soon to surgery but are unusual in the antithyroid drug-controlled patient. Thyroid storm occasionally occurs in patients operated on for some other illness while severely thyrotoxic. Severe exacerbations of thyrotoxicosis are seen rarely following 131I therapy; some of these may merit the term storm. ⁶

As reported. in the series of Nelson and Becker, ³thyroid storm appears most commonly following infection, which seems to induce an escape from control of the thyrotoxicosis. Pneumonia, upper respiratory tract infection, enteric infections, or any other infection can produce an acute exacerbation of the symptoms of thyrotoxicosis. The pathophysiology is incompletely understood. ⁷A finding of possible significance is an elevated. free T4 in patients with thyroid storm while total T4 levels were similar as compared with patients with uncomplicated. thyrotoxicosis. ⁸

These data suggest that events like infection may decrease serum binding of T4 resulting in increase in free T4 that may play a role in the precipitation of the storm.

The decreased incidence of thyroid storm can be largely attributed. to the improved methods of diagnosis and therapy available today. In most cases, thyrotoxicosis is recognized before extreme debilitation occurs and is treated. by measures of predictable therapeutic value. Patients are routinely made euthyroid before surgery or treatment with 131-I. Under present-day therapy, using thiocarbamides, the glands have only minimal amounts of stored hormone, in contrast to the iodized gland facing the surgeons of six decades ago. Postoperative storm, formerly the most frequent kind of storm, has now been largely eliminated.

I-131 is increasingly being used as a first line of treatment of hyperthyroidism (Chapter 10 and Chapter 17), but thyroid storm is rarely seen after this form of treatment, due to proper medical pre-treatment, and only isolated. cases have been reported. ^{9 ,9a}

The diagnosis of thyroid storm is made entirely on clinical grounds and involves the usual diagnostic measures for thyrotoxicosis. There are no distinctive laboratory abnormalities. Total and free T4 and if possible total T3 should be measured. T3 may rarely be normal or even decreased because of co-existing non-thyroidal illness. ¹⁰Electrolytes, blood urea nitrogen (BUN), blood sugar, liver function tests, and plasma cortisol should be monitored.

It should be emphasized that a thyroid storm is a major medical emergency that has to be treated. in an intensive care unit (Table 12-1).

It should be noted that if any possibility is present that orally given drugs will not be appropriately absorbed (e.g. due to stomach distention, vomiting, diarrhea or severe heart failure), the intravenous route should be used. If the patient has not been under prior treatment, an antithyroid drug should be given. PTU, 150-250 mg every 6 hours should be given, if possible, in preference to methimazole, since PTU prevents peripheral conversion of T4 to T3. Since peripheral formation of T3 is a major source of the hormone, PTU more rapidly reduces the circulating level of T3 and thus aids recovery. Methimazole (15 mg every 6 hours) can be given orally, or if necessary, the pure compound can be made up in a 10 mg/ml solution for parenteral administration. Methimazole is also absorbed when given rectally in a suppository. ¹¹An hour after thiocarbamide has been given, iodide should be administered. A dosage of 0.1g twice daily is more than sufficient. Unless congestive heart failure contraindicates it, propranolol or other beta blocker should be given at once, orally or parenterally in large doses, depending on the patient's clinical status. Permanent correction of the thyrotoxicosis by either radioactive iodide or immediate surgery should be deferred. Other supporting measures should be fully exploited. These include the use of sedation, oxygen, treatment for tachycardia or congestive heart failure, rehydration, multivitamins, occasionally supportive transfusions, and cooling the patient to bring the temperature down to a reasonable level. An antibiotic may be given on the presumption of infection while the results of culture are awaited.

The adrenal gland may be limited. in its ability to augment steroid production during thyrotoxicosis. ¹²If there is any suspicion of hypoadrenalism, hydrocortisone (100-200 mg/day) or its equivalent should be given. The dose can be rapidly reduced when the acute process subsides. Pharmacological doses of steroids (2 mg dexamethasone every 6 h) acutely depress serum T3 levels in normal subjects and in Graves' disease patients by reducing T4 to T3 conversion. This effect of steroids is beneficial in thyroid storm and supports the routine use of corticosteroids. Propranolol may not reverse the metabolic insults of thyrotoxicosis but does dramatically suppress tachycardia, restlessness, and other symptoms. ^13,14

Usually rehydration, repletion of electrolytes, treatment of coincident disease such as infection, and specific agents (antithyroid drugs, iodine, propranolol, and corticosteroids) produce a marked improvement within 24 hours. A variety of additional approaches have been reported, but indications for their use are not well defined. For example, oral gallbladder contrast agents such as ipodate and iopanoic acid in doses of 1-2 g, which inhibit peripheral T4 to T3 conversion, may have value. ¹⁵Peritoneal dialysis can remove circulating thyroid hormone, and plasmapheresis can do likewise, but at the expense of serum protein loss. Orally administered ion-exchange resin ¹⁶(20-30g/day as Colestipol-HCl) can trap hormone in the intestine and prevent recirculation. Probably these treatments will rarely be needed.

The antithyroid treatment should be continued until euthyroidism is achieved, at which point a final decision regarding antithyroid drugs, surgery, or 131I therapy can be made.