Most patients with thyrotoxic storm have rather obvious symptoms and signs of thyrotoxicosis, including goiter and, in the presence of Graves’ disease, ophthalmopathy, although it can occur in patients with masked or apathetic thyrotoxicosis. There is usually a several-month history of untreated or partially treated thyrotoxicosis, but in an occasional patient the onset of thyrotoxicosis seems to be recent. Typically, those cases of more recent onset will be more rapidly progressive in severity of manifestations.

Two types of events have been associated with the precipitation of thyrotoxic crisis (Table 30.2). One is an intercurrent illness or injury that exacerbates the effects of thyrotoxicosis either systemically or on one or more particular organ systems. The other, now rare, is an acute event that suddenly increases thyroid secretion. This latter situation is best exemplified by the occurrence of thyrotoxic storm soon after thyroidectomy, which was relatively common before the need for preoperative antithyroid therapy was recognized. The presumed explanation was increased thyroxine (T₄) and triiodothyronine (T₃) release caused by manipulation of the thyroid gland, compounded by the systemic effects of surgical stress. The rare occurrence of thyrotoxic storm after radioiodine therapy for thyrotoxicosis is the modern counterpart of this phenomenon.

Many illnesses and trauma, including the trauma of surgery, can precipitate thyrotoxic storm in patients with previously undiagnosed or poorly treated thyrotoxicosis, and storm has been seen following the trauma of an automobile accident. Rare cases of storm have been noted after intoxication with organophosphates (8), exposure to neurotoxins (9), or after chemotherapy for a coincident malignancy (10). The most common precipitating event now is probably an infection, and in a patient with thyrotoxicosis and infection it is difficult if not impossible to determine whether fever and tachycardia herald impending crisis or merely reflect the infection. Excessive diaphoresis with high fever out of proportion to the infection may be a clue to the presence of thyrotoxic storm. Indeed, when it is not recognized and treated, the fever may reach an extremely high and life-threatening level. An exception to this may be the elderly “apathetic” patient or those with concomitant pituitary or adrenal insufficiency (11). Signs and symptoms of CNS dysfunction indicative of metabolic encephalopathy, with anxiety, emotional lability, restlessness, agitation, seizure, confusion, psychosis, and coma, are common, and are important further clues to the diagnosis. The encephalopathy in one case was associated with magnetic resonance imaging (MRI) typical of limbic encephalitis (12). In other cases, thyrotoxic storm was associated with status epilepticus and stroke, or with bilateral basal ganglia infarction, and there may be a greater risk of superior sagittal thrombosis in these patients (13) presumably secondary to a hypercoagulable state (14,15). Storm associated with hydatidiform mole (16), due to subacute thyroiditis (17), metastatic thyroid carcinoma (18,19), or to excessive ingestion of thyroid hormone (20,21) have been reported but must be extremely rare.

In addition to marked sinus tachycardia, atrial tachyarrhythmias may be present, as may symptoms and signs of congestive heart failure. Although the latter is more likely to occur in elderly patients with underlying heart disease, it can occur in relatively young or middle-aged patients with no known antecedent (or subsequently demonstrable) heart disease. A reversible dilated cardiomyopathy may be the etiology of heart failure (22) and thyrotoxic crisis has been seen in the setting of myocardial infarction (23). Systolic hypertension with widened pulse pressure is likely to be noted in most patients, at least initially, although some patients have postural hypotension, particularly those with volume depletion due to vomiting or diarrhea, and vascular collapse may supervene. Other gastrointestinal manifestations include presentation as an acute abdomen or intestinal obstruction, or with
diffuse abdominal pain, hepatomegaly, splenomegaly, and various abnormalities in liver function. The liver may be tender, as a result of either congestion or hepatic necrosis. The presence of jaundice is a poor prognostic sign.

Serum total T₄ and T₃ concentrations and thyroid radioiodine uptake values are high in patients with thyrotoxic storm, but not necessarily more so than in patients with uncomplicated thyrotoxicosis. Serum free T₄ and T₃ concentrations are also high, and may be on average slightly higher than in patients with uncomplicated thyrotoxicosis (24). On the other hand, serum T₃ concentrations may be normal in patients who have been sick for more than a few days, due to the decrease in extrathyroidal conversion of T₄ to T₃ that occurs in many nonthyroidal illnesses (25,26) (see section on nonthyroidal illness in Chapter 11C).

In a patient with previously undiagnosed thyrotoxicosis, the most rapid confirmation of the diagnosis may be obtained by measuring thyroid radioiodine uptake 2 hours after administration of radioiodine or thyroid pertechnetate uptake 20 or 30 minutes after administration of pertechnetate (see Chapter 12). It should be possible to obtain the results of serum T₄ and thyrotropin (TSH) determinations in an hour or two on an emergency basis in many hospitals.