Radioactive iodine uptake is an indirect estimate of thyroid hormone production based on the need of the thyroid for iodine to make thyroid hormone, which, in turn, depends on the rate of thyroid hormone synthesis. A small dose of radioactive iodine is given, and a radiation detector measures the amount present in the gland at some standard time (usually 24 hours after the dose). The radioactive iodine uptake (RAIU) measurement is one of the oldest currently used thyroid function tests, but it has several drawbacks:

Thyroid Function Tests*

I. Thyroid uptake of iodine
A. RAIU
II. Thyroxine tests
A. “Direct” measurement
1. T4 by RIA or EIA
2. Free T4assay
B. “Indirect” measurement
1. THBR (T3 uptake, or T3U)
2. Free T4 index
III. Triiodothyronine tests
A. T3-RIA
IV. Pituitary and hypothalamic function tests
A. TSH assay
B. TRH assay
V. Other
A. Stimulation and suppression tests
B. Thyroid scan
C. Thyroid autoantibody assay

*RAIU = radioactive iodine uptake; = radioimmunoassay; EIA = enzyme immunoassay; THBR = thyroid hormone–binding ratio; TRH = thyrotropin-releasing hormone.

1. The RAIU result is falsely normal in 50%-70% (literature range, 20%-80%) of patients with hyperthyroidism due to toxic nodules.
2. The RAIU results are affected by a considerable number of medications (see Table 36-24) and may be elevated during the last trimester of pregnancy.
3. Any condition that alters thyroid requirements for iodine will affect the RAIU response. Iodine deficiency goiter elevates RAIU results, and some reports indicate that elevation for similar reasons occurs in 25%-50% of patients with cirrhosis. Excess iodine in the blood contained in certain medicines (inorganic iodide) or in x-ray contrast media (organic iodine) competes with radioactive iodine for thyroid uptake, thereby preventing uptake of some radioactive iodine and falsely decreasing test results.
4. The standard 24-hour uptake requires two patient visits and 2 days.
5. Normal values are uncertain due to increasing environmental and foodstuff iodine content. Before 1960 the average 24-hour RAIU reference range was 15%-40%. Reports from 1960-1970 suggest a decrease of the range to 8%-30%. There have been little recent data on this subject, and most nuclear medicine departments are unable to obtain reference values for their own locality.
6. Occasionally patients with hyperthyroidism have unusually fast synthesis and release (turnover) of T4 and T3. The RAIU measurement depends not only on uptake of radioactive iodine but also on retention of the radioactive iodine (incorporated into hormone) within the gland until the amount of radioactivity within the gland is measured. By 24 hours a significant amount of newly formed hormone may already be released, providing falsely lower thyroid radioactivity values compared with earlier (2-6 hours) uptake measurements.
7. The RAIU provides relatively poor separation of normal from hypothyroid persons. Before 1960, approximate sensitivity of the RAIU was 90% for hyperthyroidism and 85% for hypothyroidism. Current RAIU sensitivity in thyroid disease is difficult to determine because of reference range problems. However, sensitivity is probably about 80% for hyperthyroidism and about 50%-60% for hypothyroidism. One study found that patients over age 65 may have a higher incidence of normal 24-hour RAIU than younger persons. The 24-hour RAIU was normal in 15% of hyperthyroid patients under age 65 and 41% of those over age 65. Various factors can decrease the RAIU besides severe destruction of thyroid tissue (see the box).
8. The patient receives a certain small amount of radiation (especially if a scan is done), whereas thyroid hormone assays, even those using radioisotopes, are performed outside the patient’s body and therefore do not deliver any radiation to the patient.

Etiologies of Decreased Radioactive Iodine Uptake Values

Hypothyroidism, primary or secondary
Technical error
Excess organic iodine or inorganic iodide with euthyroidism
Subacute thyroiditis
Painless (silent) thyroiditis
Postpartum transient toxicosis
Chronic (Hashimoto’s) thyroiditis (some patients)
Amiodarone-induced hyerthyroidism
Self-administered (factitious) thyroid hormone intake
Iodide-induced (Jod-Basedow) hyperthyroidism
Struma ovarii

These difficulties have precluded use of the RAIU measurement for screening purposes. However, RAIU in conjunction with the thyroid scan has definite value in patients when there is laboratory evidence of hyperthyroidism. As will be discussed later, the RAIU can help differentiate between primary hyperthyroidism and hyperthyroidism secondary to thyroiditis or self-administration of thyroid hormone; and the thyroid scan can differentiate Graves’ disease from Plummer’s disease.