Pediatric Hyperthyroidism Workup

Absence of goiter, asymmetric goiter, or atypical laboratory test results should raise the suspicion for other causes of hyperthyroidism besides Graves disease.

Although thyroid is quite rare in children and because no specific laboratory findings define this condition, any suspicion that a patient has life-threatening condition should result in immediate referral to a pediatric intensive care unit and consultation with a pediatric endocrinologist.

Hyperthyroidism can be confirmed simply and quickly with measurements of T₄, T₃, T₃ resin uptake (T3RU), and thyroid-stimulating hormone (TSH). Patients with Graves disease have elevated levels of T₄, T₃, and T₃ RU and low or undetectable levels of TSH.

T4 levels

The T₄ level measures the total concentration of T₄ in serum (ie, free and bound). Patients who are clinically euthyroid but have elevated levels of T₄ may have increased plasma proteins, primarily T₄ -binding globulin (TBG). Biochemically, these patients can be distinguished easily from truly hyperthyroid patients by measuring either free T₄, which is normal, or T₃ RU, which is decreased.

Free T4 and T3RU levels

Free T₄ can be measured directly by means of immunoassay. Alternatively, T3RU levels can be obtained. T3RU levels correlate inversely with the available binding sites on TBG. Conditions that cause elevated TBG levels (eg, pregnancy) increase the number TBG binding sites for T₄ and T₃ and decrease the T₃ RU level. In contrast, conditions causing hyperthyroidism decrease the number of free TBG binding sites and, therefore, increase T₃ RU. The number derived from multiplication of the total T₄ and the T3RU, variably called the free T₄ index, T₇, or T₁₂, has been used as a surrogate for measured free T₄.

T₃ RU is no longer commonly used and is being replaced by better and more sensitive thyroid hormone testing (such as free T₄ by equilibrium dialysis).

TSH and TSI levels

An elevated TSH level in a patient with thyrotoxicosis is extremely unusual and indicates altered regulation at the level of the pituitary gland. Patients may potentially have either a TSH-secreting pituitary adenoma or isolated pituitary resistance to thyroid hormone.

Measurement of TSH receptor–stimulating autoantibodies (ie, thyroid-stimulating immunoglobulins [TSI]) is rarely necessary for diagnosis of Graves disease. TSI titers are high in Graves disease. This test has 95% sensitivity and 96% specificity for Graves disease; however, the test is also labor intensive, expensive, and not widely available. TSI levels are suggested to correlate with remission of Graves disease; however, this has not been confirmed in clinical studies.

Graves disease vs hashitoxicosis

Markedly elevated antithyroglobulin and antithyroid peroxidase antibodies without TSI may help to distinguish the hyperthyroid phase of chronic lymphocytic thyroiditis (hashitoxicosis) from Graves disease.

A more reliable method to distinguish the 2 conditions is a thyroid iodine-123 (¹²³ I) uptake and scan. In Graves disease, the uptake is elevated and diffuse, whereas in Hashimoto thyroiditis, the uptake is generally low and patchy in distribution.

A newer, rapid, fully automated electrochemiluminescent immunoassay reportedly provides the same or better results as existing commercial products for levels of thyrotropin receptor autoantibodies and shortens the measuring time.^[4]

Obtaining a complete blood cell (CBC) count before the initiation of antithyroid medications may be valuable for separating patients with underlying leukopenia or thrombocytopenia from patients who develop drug toxicity.

Mild leukopenia can be observed in many patients with Graves disease, whereas agranulocytopenia is a rare side effect of antithyroid medications. Because the onset of agranulocytosis is unpredictable and idiosyncratic, routine blood counts during follow-up do not aid in the treatment of patients with hyperthyroidism. However, if a patient on propylthiouracil (PTU) or methimazole develops fever or ulcerations in the mouth, a prompt CBC count is necessary.

In general, diagnostic radioiodine I-131 (¹³¹ I) uptake is rarely performed. Either technetium 99m (^99m Tc) or¹²³ I scan may be useful if the gland does not have a uniform consistency. Functioning nodules trap radioactive iodine and technetium, yielding a hot area of increased uptake on the scintiscan. If the patient is hyperthyroid from such a hot nodule, the remaining thyroid does not take up iodine because of the suppression of thyroid stimulating hormone (TSH) and the absence of thyroid-stimulating immunoglobulins (TSIs).