The thyroid defect in PS was first associated with abnormal iodide processing by Morgans and Trotter, approximately 60 years after Pendred's original description.  This led to the development of a diagnostic test, the perchlorate discharge test, outlined below.  

    The response of the thyroid following perchlorate administration has been extensively studied.  Initially it was believed that leakage of radiolabeled iodine from the thyroid reflected failure of peroxidase to catalyze organification.  However, it was then demonstrated that peroxidase levels and function in persons with PS are not statistically different from normal controls (Ljunggren et al 1973).  This finding was supported by another group with who showed that there is no defect in any part of the organification reaction (Niepomniszcze 1978).  Other experiments indicated that in PS, radiolabeled iodine is sequestered from the normal processing pathway and that iodide turnover is particularly fast, signifying that only a small amount of the iodide taken into the follicle actually is used for hormone synthesis (Medeiros-Neto et al 1968).  We now know that perchlorate inhibits the sodium/iodide symporter allowing cytoplasmic iodide to leak back into the bloodstream in persons with SLC26A4.  

Basic Outline of the Perchlorate Test

1. Radiolabeled iodine is administered

2. Emittance of radioactivity is measured over the thyroid

3. Potassium perchlorate (a competitive inhibitor of iodide transport into the thyroid) is administered

4. Emittance of radioactivity is measured over the thyroid and compared to initial result.

Interpreting Results of the Perchlorate Test

• In unaffected individuals, the amount of radiolabeled iodine in the thyroid remains relatively stable.  This is due to the rapid oxidation of iodide to iodine and its subsequent incorporation into thyroglobulin.

• In affected individuals the transport of iodine into the follicle (and therefore its incorporation into thyroglobulin) is delayed, resulting in the leakage of iodide into the bloodstream.  This leakage is demonstrated by a decrease in radiolabeled iodine in the thyroid, which drops more than 10%.  No correlation has been noted between gland size and the amount of iodide released.

• The perchlorate test is not consistently positive in affected individuals.  This is illustrated by a study by Yong et al in which only three of six individuals with confirmed PS had  >10% iodide washout.  In addition, Reardon et al have reported a 2.9% false negative rate for this test.

References:

Genuth 1998
Morgans and Trotter 1958
Illum et al 1972
Yong et al 2001
Reardon et al 1997