Case 537 -- An 11-year-old girl with symptoms of hyperthyroidism

Contributed by Anca V. Florea, MD and Mohamed A. Virji, MD, PhD


CASE HISTORY:

An 11-year-old female with no significant past medical history presented with symptoms suggestive of hyperthyroidism (weight loss, heat intolerance). She has also experienced a decline in grades at school. Family history is significant for thyroid disease in both grandmothers (both on thyroid replacement therapies). The clinician ordered thyroid function tests including Free T4, T3, TSH, anti-TSH receptor antibodies, antithyroglobulin and antithyroid peroxidase antibodies.

The results for the tests follow:

The laboratory findings confirmed the clinical impression and a diagnosis of Graves's disease (hyperthyroidism with thyrotoxicosis) was made.

The patient was started on methimazole right away but after approximately two weeks of treatment she developed severe adverse reaction to it with significant joint pain and swelling over her upper and lower extremities with hives; Methimazole was stopped immediately and she was started on Benadryl and Advil ; her symptoms improved after few days, although she did have some residual intermittent hives that were transient.

She has been given some brief course of Prednisone as well, and Atenolol 50 mg twice a day was also started.

After approximately two weeks, due to the fact that the medical management for hyperthyroidism failed, the patient was considered to have radioiodine ablation of her thyroid next day and for that she underwent a thyroid imaging with uptake showing enlarged thyroid gland, with homogeneous increased uptake, consistent with Graves disease with 24-hour uptake equaling 86%.

The patient underwent radio-iodine ablation as scheduled and she was stable on Atenolol 50 mg twice a day. She was discharged home.

At her next follow-up appointment in 2 weeks her thyroid functions tests lab values were as follows:

DISCUSSION:

"Thyrotoxicosis in a Pre-adolescent Patient with Averted Thyroid Storm Following Radio-pharmaceutically Induced Therapeutic Lysis of Thyroid Gland"

Laboratory evaluation of thyroid function in various clinical situations. Adapted from The Merck Manuals, Online Medical Library, Endocrine and Metabolic Disorder, November 2005 revision

Graves' disease is the most common cause of thyrotoxicosis in children. The disorder is rare before the age of 3 and increases progressively with age thereafter. Hyperthyroidism accounts for 10- 15% of all pediatric thyroid disorders and children constitute 1-5% of all Graves' disease patients. In Graves' disease, autoantibodies stimulate the thyrotropin receptor and lead to excess thyroid hormone production.

Thyroid storm is a potentially fatal, though uncommon condition that affects 1% of individuals with thyrotoxicosis (1), and accounts for between 1 and 10% of patients hospitalized for thyrotoxicosis (2,3). It is an exaggerated state of thyrotoxicosis involving decompensation of one or more organ systems and carries a mortality rate of between 20 and 30% (2).

CAUSES OF THYROID STORM:

Besides thyroid surgery, thyroid storm is triggered by radioactive iodine therapy, uncontrolled diabetes, emotional stress, abrupt withdrawal of antithyroid medication, excessive palpation of the thyroid gland in hyperthyroid patients, thyroid hormone overdose, pulmonary thromboembolism, toxemia of pregnancy, labor, trauma, acute infection, severe drug reaction or myocardial infection (Basic & Clinical Endocrinology, 3rd Edition, 1991, Greenspan, Francis p. 260-272).

SYMPTOMS:

The clinical manifestations of thyroid storm are those consistent with marked hypermetabolism. Patients in thyroid storm may complain of chest pain, palpitations, shortness of breath, tremor, nervousness, increased sweating, disorientation, fatigue and fever. Usually there is marked tachycardia, often with atrial fibrillation and high pulse pressure. On rare occasions symptoms may progress to heart failure. Central nervous system symptoms include marked agitation, restlessness, delirium, psychosis, and coma. Gastrointestinal symptoms include nausea, vomiting, diarrhea and jaundice. Fatal outcomes, which usually occur in the elderly, are associated with heart failure and shock.

BIOCHEMICAL CHANGES:

Previously it was thought that the release of stored thyroid hormone is responsible for thyroid storm. Nowadays it is known that the blood levels of thyroid hormone are no different from thyrotoxic patients who are free of thyroid storm symptoms. Evidence suggests that in thyroid storm the number of binding sites for catecholamines (epinephrine, norepinephrine, etc.) increases. Therefore, the heart and nervous tissue have increased sensitivity to circulating catecholamines. (Greenspan, 1991, p. 252).

Also, there is decreased binding to TBG, the protein which normally binds with thyroid hormone. Thus there is more available thyroid hormone in the circulation. The combined effect of excess free thyroid hormone along with increased catecholamine receptors causes an exaggerated response to illness, infection or surgical stress that precipitates the acute symptoms seen in thyroid storm.

RADIOACTIVE IODINE (RAI) therapy and withdrawal of antithyroid medications are two well described causes of thyroid storm (4). Thyroid storm following RAI therapy has generally been attributed to increased thyroid hormone release from degenerating follicles. Brooks et al. (5, 6) showed that patients with thyroid storm and uncomplicated thyrotoxicosis had comparable T4 and T3 levels, but that free T4 was significantly higher in the patients with thyroid storm. Studies have shown that after RAI therapy patients pretreated with antithyroid medications have lower serum T4 and T3 levels than non pretreated patients (7, 8). These studies also show that serum T4 and T3 levels increase significantly after withdrawal of antithyroid medication in preparation for RAI therapy. Retrospective studies have shown a lower success rate of RAI therapy in patients pretreated with PTU, but not methimazole (9 -11). In addition, studies have also demonstrated lower RAI efficacy in patients treated with PTU and methimazole after RAI therapy (9, 12). Treatment with methimazole before RAI therapy is beneficial because it does not affect the overall efficacy of RAI and pretreated patients have lower thyroid hormone levels than patients treated with RAI alone. Allahabadia et al. (13) determined that male gender and younger age of onset of Graves' disease are associated with a higher failure rate of treatment with antithyroid medication. They also found that male gender, independent of radioiodine dose and treatment with antithyroid medication before and after RAI, is associated with a higher failure rate after a single dose of RAI therapy.

The dose of 131I is calculated by a standard formula that uses the estimated weight of the thyroid gland and the 24-h RAI uptake to determine the dose required for the delivery of 50-200 mCi 131I/g thyroid tissue (14). Hamburger's (15) retrospective study showed that within 6 months of receiving a single dose of 200 mCi 131I/g thyroid tissue, 88% of the children were euthyroid or hypothyroid. Rivkees et al. (16) recommend that a single dose of 150-200 mCi 131I/g thyroid tissue will cure 85-90% of pediatric hyperthyroidism.

DIAGNOSIS AND TREATMENT


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