Disseminated thyroid autonomy or Graves' disease: Reevaluation by a secondgeneration TSH receptor antibody assay

The clinical diagnosis of disseminated autonomy (DISA) can only be establis hed by exclusion of Graves' disease (GD). Both hyperthyroid conditions shar e the same scintigraphic appearance and can only be distinguished from each other clinically either by the presence or absence of endocrine ophthalmop athy (EO) or thyrotropin (TSH) binding inhibiting immunoglobulins (TBIIs). The purpose of this study was the reevaluation of thyroid autonomies origin ally classified as DISAs by a second-generation radioreceptor antibody assa y (RAA) (DYNOtest(R) TRAKhuman) (B.R.A.H.M.S. Diagnostika, Berlin, Germany) . The analysis included 32 patients (female: n = 25, male: n = 7; mean age: 46 +/- 18 years) who were initially diagnosed with DISA. All patients were TSH receptor (TSHR) antibody (TRAb) negative by a conventional radioimmuno assay (RIA) (TSH-REZAK(R) RIA) (Medipan Diagnostica, Selchow, Germany) duri ng their first evaluation. The presence of EO was excluded by clinical sign s in all patients. Surgery had been performed prior to our evaluation in 5 patients and after our survey in 1 patient. Four patients had been treated previously with I-131. Ten patients were treated with thionamides during ou r evaluation, and 13 had not been treated before. One hundred three patient s who had either healthy thyroids, nontoxic goiters, or focal autonomies se rved as controls and were evaluated both by the TSH-REZAK(R) assay and the DYNOtest(R) TRAKhuman assay. Seven of thirty-two (22%) patients originally classified as DISA were TRAb positive in the second-generation assay. In th is group, 5 of 7 patients had a total thyroid volume (TTV) <30 mt (positive predictive value [PPW] for TRAb positivity 71%), and 5 of 7 patients had a diffuse goiter (PPW for TRAb-positivity 71%). Six of seven patients were a nti-thyroperoxidase (TPO) positive (PPW for TRAb positivity 85%). A hypoech oid pattern on ultrasound was present by visual analysis in 3 of 7 patients (PPW for TRAb positivity 43%). A 100% PPW for TRAb positivity could be obt ained if a goiter <30 mi was combined with anti-TPO positivity, but this co mbination was present in only 4 of 7 (57%) patients. With the second-genera tion assay, one false positive test result was observed in the control grou p. Surgery was performed in 6 patients who were TRAb negative in both assay s. In all these cases, the histologic findings were compatible with autonom ous transformation of the thyroid. Our study demonstrates that a significan t number (22%) of patients formerly classified as DISA may actually have GD . However, DISA still exists as a clinical entity, and its pathophysiologic al link to multifocal and unifocal autonomy should be further investigated.