Hyperthyroidism and Pregnancy.[ref. 5]--Pregnancy may be adversely affected by poorly controlled hyperthyroidism, with an increased rate of fetal loss. The goal of treatment during pregnancy is to maintain euthyroidism, using the smallest doses of ATDs possible. Propylthiouracil is preferred in pregnancy because it crosses the placenta less than methimazole, but methimazole is not contraindicated, and is used successfully by some clinicians. Since pregnancy itself has an ameliorative effect on Graves' disease, low doses or even discontinuation of ATDs may be possible in the third trimester. Hyperthyroid pregnant patients should be seen at 4- to 6-week intervals (or more frequently as the situation dictates), with a collaborative effort between the treating physician and the obstetrician. Thyroid-stimulating immunoglobulin titers, obtained in the last trimester, may predict the likelihood of neonatal hyperthyroidism, but any newborn from a mother who has a history of hyperthyroidism should be observed for this possibility. Patients treated for hyperthyroidism during pregnancy should be reevaluated 6 weeks post partum, since there can be postpartum worsening of the disease. If surgery is felt to be necessary because of inability to adequately control hyperthyroidism with ATDs, it should preferably be performed when the chance for fetal survival is likely in the event of early delivery.

Graves' Ophthalmopathy.[ref. 6]--The minority of patients with Graves' disease have clinical eye involvement, which may even develop after the diagnosis and treatment of hyperthyroidism. Milder eye symptoms include excess tearing, photophobia, and a feeling of grittiness. More severe symptoms include proptosis, diplopia, eye pain, and a decrease in visual acuity. Physical findings may include eyelid retraction, conjunctival injection and suffusion (chemosis), proptosis (either unilateral or bilateral), periorbital edema, and ophthalmoplegia.

Exposure keratitis may occur when the patient is unable to close the eyelids completely. When eye disease occurs in patients with known hyperthyroidism, no specific laboratory tests are required to confirm the diagnosis. When ophthalmopathy occurs in patients who are biochemically euthyroid, autoimmune thyroid disease should be suspected, and the diagnosis can be confirmed by the finding of antimicrosomal (antithyroperoxidase [anti-TPO]) antibodies or thyroid-stimulating antibodies in the serum. In euthyroid patients, orbital computed tomography or magnetic resonance imaging may be indicated to exclude the diagnosis of other orbital diseases that can mimic thyroid ophthalmopathy. Therapy of Graves' eye disease is directed toward restoring thyroid function to normal, as well as treating the eye symptoms. Sunglasses (to decrease photophobia) and artificial tears (for lubrication) may be helpful. For periorbital edema, elevation of the head of the bed while sleeping, as well as the judicious use of diuretics, may be useful. Systemic glucocorticoids have been used by some physicians in patients with active ophthalmopathy, in an effort to prevent its progression, particularly after 131I therapy, but their efficacy is not fully established. Management of patients with more than mild symptoms and signs should be carried out in conjunction with an ophthalmologist.

Toxic Nodular Goiter.[ref. 7]--Toxic nodular goiter (TNG), or Plummer's disease, is more common than Graves' disease in elderly patients. The hyperthyroidism may be caused by multiple hyperfunctioning nodules or, less frequently, a single hyperfunctioning nodule. The disorder should be differentiated from Graves' disease. Ophthalmopathy is not present in patients with TNG.

Diagnostic approaches in a patient with suspected TNG include the thyroid function tests mentioned previously in the section on Graves' hyperthyroidism. The absence of thyroid autoantibodies may help to differentiate TNG from Graves' disease. The radioiodine uptake and thyroid scan may be useful in patients with TNG to determine whether a dominant nodule is hypofunctioning, suggesting the need for needle aspiration to rule out thyroid carcinoma. Although 131I is usually recommended for the treatment of TNG, surgery is appropriate for certain individuals who prefer surgery and are good operative risks, as well as for children, adolescents and young adults, and in those patients with large goiters, or if there is concern about thyroid malignancy.

As is the case with Graves' disease, elderly patients with TNG may be treated first with ATDs until they become euthyroid, followed by 131I therapy. Surgery may be indicated if there is a very large goiter or if symptoms of tracheal or esophageal compression are present. Patients with solitary hyperfunctioning thyroid nodules are usually treated with radioiodine, but surgery is equally appropriate for children and adolescents.

Thyroid Storm.[ref. 8]--Thyroid storm is a life-threatening, clinical syndrome characterized by exaggerated signs and symptoms of hyperthyroidism, fever, and altered mental status. While it usually occurs in individuals with Graves' disease, it has also been reported in patients with other causes of hyperthyroidism. Thyroid storm is usually precipitated by a concurrent illness or injury, but has been reported to occur spontaneously following withdrawal of ATDs or following radioactive iodine therapy for hyperthyroidism.

There are no specific laboratory findings distinguishing thyroid storm from uncomplicated hyperthyroidism. Thus, when the diagnosis is suspected clinically, therapy must be initiated immediately. Treatment should be initiated in the intensive care unit, and consists of providing supportive measures, treating the precipitating cause, and administering specific pharmacologic agents such as (1) drugs that inhibit thyroid hormone biosynthesis (propylthiouracil or methimazole); (2) drugs that inhibit release of thyroid hormone from the thyroid gland (eg, potassium iodide, lithium carbonate, ipodate); and (3) agents that decrease the peripheral effects of thyroid hormone (eg, propylthiouracil, corticosteroids, ipodate, iopanoic acid). The selection of drugs depends on the specific clinical situation. Because of the complexity of thyroid storm, it is recommended that an endocrinologist participate in the evaluation and management of such patients.