LOSS OF VARIABILITY IN GRAVES-DISEASE - STIMULATORY TSH-RECEPTOR ANTIBODIES BIND TO THE TSH-RECEPTOR IN A CONTINUED, NONPULSATILE AND NONCHAOTIC FASHION

Thyroid-stimulating hormone (TSH) regulates thyroid growth and differe ntiated function by binding to the TSH-receptor (TSH-R). In Graves' di sease, hyperthyroidism and goiter growth are thought to be mediated by prolonged, continued activation of the TSH-R by TSH receptor-stimulat ing antibodies (TSAb). However, continuous experimental stimulation of the TSH-R with TSH or TSAb leads to a desensitization of the thyrocyt e with a decrease of thyroid function in vitro and in vivo. In order t o clarify this discrepancy we determined serum levels of TSH-binding-i nhibiting immunoglobulins (TBII) in 10 patients with GD every 10 minut es over 6h (patients 1 to 5, group A) and over 24h (patients 6 to 10, group B) using a commercially available radio ligand receptor assay (T RAK, Henning Berlin, FRG). Visual and computer analysis revealed some variation of TBII serum levels but no obvious pattern indicative of ci rcadian variation nor major secretory peaks could be distinguished. Va riation of TBII serum levels were within or only slightly above intraa ssay CV. Data were tested in order to decide whether the observed fluc tuations are of chaotic (deterministic) or of stochastic (random) orig in. In none of these tests did we find evidence for chaos in the data suggesting that the observed fluctuations reflect other sources of noi se such as sampling errors or intraassay variation. We conclude that i n Graves' disease, patients are rendered hyperthyroid by continued, no n-pulsatile and non-chaotic binding of stimulatory antibodies to the T SH binding site of the TSH-R.