Changing Trend in Diagnostic Methods for Graves' Disease: Is an Immunological Diagnosis Preferred?

The diagnosis of Graves’ disease (GD) is traditionally based on the clinical features of persisting hyperthyroidism, enlarged thyroid gland, and often the presence of ophthalmopathy. However, when the clinical presentation of thyrotoxicosis is not diagnostic of GD, the 2011 American Thyroid Association guideline recommends “a radioactive iodine uptake scan should be performed” (1). Although it is long recognised that Thyrotropin (TSH) receptor antibody (TRAb) is the pathogenic agent of thyrotoxicosis, measurement of TRAb for diagnostic purpose is only recommended “when the thyroid scan and uptake are unavailable or contraindicated.” With the availability of highly sensitive TRAb assays, we performed an audit on the Royal Prince Alfred Hospital (RPAH) Thyroid Clinic encounters between years 2000 to 2012, examining the diagnostic utility of TRAb versus thyroid scan in confirming GD.

Thyroid scans were performed using technetium-99m sodium pertechnetate isotope. Positive thyroid scan was defined as diffuse thyroid uptake of the tracer and thyroid activity not being low. TRAb were analysed within the first 3 months of hyperthyroidism and the analysis were performed on newer generation TRAb assays (BRAHMS TRAK human RIA & Roche Elecsys Anti-TSHR assay). TRAb was considered positive if the antibody was above the upper limit of the population reference range.

Our audit showed 231 patients diagnosed with GD were seen in our clinic from 2000 – 2012; 183 had both clinical and biochemical hyperthyroidism during their contact with our service. Among the 183 patients, mean age was 37.2 and median was 35; 81.4% were female; 47% had East/South East Asian ancestry while 41% had European ancestry; 61.2% had a family history of thyroid disorders. Seventy nine out of 183 had both a thyroid scan and TRAb to confirm GD. All 79 thyroid scans were positive; 76 out of 79 cases were TRAb positive, making TRAb 96% sensitive against the thyroid scan. Of the total cohort of 183, 178 were TRAb positive. With the year by year audit of GD clinic management, TRAb was increasingly used as a first line confirmatory test over the last decade. Correspondingly, thyroid scan utilisation rate dropped from 55% in the early 2000 to only 31% in 2012 (P = 0.02).

From the cost effectiveness perspective, RPAH TRAb assay report time is within 5 working days and is one sixth the direct cost of the Thyroid scan (2). Furthermore, whilst technetium-99m sodium pertechnetate exposes the thyroid gland to less radiation than Iodine-123, it is twice the general background radiation dose (3).

In conclusion, considering the economic rationalisation required in health care delivery and increasing awareness of radiation exposure associated with nuclear medicine imaging, as well as the high sensitivity of TRAb in GD diagnosis, we suggest use of the TRAb assay as the first line confirmatory test for GD, and to reserve the use of thyroid scan for equivocal cases only.