Intrinsic abnormality of thyroid cells from a patient with a Brobdingnagian goiter

Thyrocytes from normal and goitrous portions of the thyroid gland from a patient with an enormous (635 gm) goiter were cultured in media, and their relative abilities to uptake thymidine, synthesize DNA, and secrete Tg and T4 were assessed. Tg, T4 and the ratio Tg/T4 in media at 72 h were 120 micrograms/dl, 1.6 micrograms/dl and 75 for normal cells, and 410 micrograms/dl and 273 for goitrous cells. DNA synthesis was 30-100% greater in goitrous than normal cells over a period of 72 h indicating abnormally high rates of cell division and growth, but their thymidine uptake was only 20% of that in normal cells. TSH elicited stimulation of thymidine uptake and DNA synthesis both in goitrous and in normal cells, but to a lesser extent in goitrous cells. No evidence of growth stimulating autoantibody activity was detected in the patient's serum. These data indicate that although the ability of goitrous cells to uptake thymidine was impaired, their DNA synthesis was more active than normal thyroid, which may have led to disordered cell growth as evidenced by the enormous goiter size in this patient. Although goitrous cells secreted more than three times as much Tg into media compared to normal, media T4 levels were similar, indicating an increased synthesis yet low iodination of Tg in goitrous cells. There does not appear to be any support for TGSI mediation of the goiter in this patient, but rather, the goiter may have been due to an intrinsic alteration in DNA synthesis resulting in vigorous cell growth.