In vitro generation of NADPH as an index of thyroid stimulating immunoglobulins (TGI) in goitrous disease.

A quantitative cytochemical assay for the measurement of total NADPH formation in guinea pig thyroid tissue following incubation with thyroid stimulators was validated and applied to the measurement of such stimulators in IgG concentrates prepared from human plasma. Pentose shunt enzyme activity was not uniformly distributed in thyroid tissue but this could be overcome and NADPH generation in such tissue used to assess accurately thyroid stimulators if a sufficient number of thyroid cells were measured. Specificity studies showed that antiserum to human IgG significantly diminished the NADPH generating capacity of IgG concentrates prepared in plasma from goitrous patients while antiserum to h-TSH had no such effect. The measurement of thyroid growth stimulating immunoglobulins (TGI) depended not only on the amount of NADPH generated but also on the IgG concentration at which maximum responses occurred. TGI present in goitrous Graves' disease were 10 times more potent than those present in euthyroid goitre, while such stimulators when present in toxic nodular goitre appeared to possess an intermediate potency. This finding, when taken together with the demonstration that TSH stimulation decreased intercellular differences in pentose shunt activity, provides experimental evidence for the hypothesis that an acute intense growth stimulus affecting all thyroid cells produces the diffuse hyperplasia characteristic of Graves' disease. In contrast, the weaker stimulus observed in nodular goitre may, over a period of time, result in the asymmetric hyperplasia commonly observed in this condition.