Topographical Heterogeneity of Basal and Thyrotropin-Stimulated Adenosine 3′,5′-Monophosphate in Human Nodular Goiter*

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Abstract
Thyroid tissue from three different sites of 12 surgically removed human multinodular goiters was cut into 12– 16 very small slices. Half of the slices were incubated for 10 min with 10 mU/ml TSH and the other half were incubated without TSH in the presence of 10 mM theophylline, for measuring cAMP content. In addition, DNA was measured in all samples. Five pig thyroids, processed in the same way, were taken as normal controls. In samples adjacent to those used for cAMP and DNA determinations, we also measured thyroglobulin (Tgb) concentrations, iodination of Tgb, and, sometimes, 131I uptake. In another series of experiments, DNA, thyroglobulin, and iodine were measured in 6–10 different areas of 6 goiters and 6 morphologically normal human thyroids obtained post mortem. There was a much larger variability of Tgb per mg DNA, DNA per mg tissue, and, although less marked, I per mg Tgb in different areas of single goiters than in normal human or pig thyroids. In pig thyroids, both the basal level of cAMP and its response to TSH were remarkably homogeneous in all three samples of a single gland. In sharp contrast, basal cAMP levels varied by a factor of up to 100 between samples taken from different human goiters and by a factor of up to 15 between samples from different areas of the same gland. No correlation whatsoever existed between the resting cAMP level of a given sample and its subsequent response to TSH. We conclude that the pathogenesis of human nodular goiters involves a metabolic disorder at the level of the follicular cells. The biochemical alterations variably affect different follicles. This may be a factor in the development of morphological and functional heterogeneity.