To characterize the relationship of the TSH receptor-adenylate cyclase system to differentiation in human thyroid cancers, adenylate cyclase and TSH binding were studied in membranes from primary and metastatis thyroid carcinomas of varying histological types (n = 33) and normal thyroids (n = 12). Membranes from differentiated carcinomas (n = 23) exhibit wide patient to patient variability; some membranes show entirely normal adenylate cyclase and TSH-binding characteristics, and other membranes exhibit decreased TSH stimulation of adenylate cyclase which is accompanied by either a normal or decrease TSH-binding site concentration. With respect to the TSH-binding site concentration and TSH stimulation of the adenylat cyclase, the well differentiated carcinomas are not significantly different from normal thyroids, whereas the moderately differentiated and the papillary carcinomas are significantly different (P < 0.001 and P < 0.001, respectively). Membranes from undifferentiated carcinomas (n = 5) and those from medullary carcinomas (n = 5) are characterized by an absence of both TSH binding and TSH stimulation of the adenylate cyclase. In conclusion, while a general relationship exists between the impairment of TSH responsiveness and the dedifferentiation process, no pattern of membrane alteration is specific for any histological type.

Thyroid iodoproteins and hormone synthesis have been studied in vivo and in organ culture in 44 cases of thyroid cancer. In a few cases, Tg1) (17–19 S) is virtually absent; a portion of the light fractions (3–8 S), which seems to represent some precursors of Tg, incorporated in culture the 14C-amino acids. In most of the cases, the solubility profiles, sedimentation patterns as well as electrophoretic migration of proteins were normal. The content of Tg and the concentration of stable iodine (127I) in Tg are less than that of "normal" tissues, and the deficiency in iodination appears to be more pronounced than the depression of the Tg synthesis. Most frequently the radioiodine uptake is very low and most of the iodine remains in the gland as iodide and MIT. In those tissues which organify radioiodine, it is incorporated into tyrosine molecules and is metabolized to the stage of iodothyronines (T4 + T3); there must then be little or no defect in coupling reactions. There is a linear relation between the concentration of stable iodine in Tg and the level of hormone synthesis, as we have found in "normal" gland and benign thyroid diseases. These results suggest that the overall disorder seen in thyroid cancer tissues appears to involve one of the initial steps of hormone synthesis. The very low mean iodination of Tg in these tissues suggests a great heterogeneity in the functional activity throughout the tumour. TSH has a very variable effect on thyroid cancer tissues maintained in organ culture: in 46 % of the cases the hormone has no effect. In some instances TSH may significantly increase the incorporation of radioiodine into soluble iodoproteins, Tg as well as the albumin fraction.