Loss of variability in Graves' disease: stimulatory TSH-receptor antibodies bind to the TSH-receptor in a continued, non-pulsatile and non-chaotic fashion.

Thyroid-stimulating hormone (TSH) regulates thyroid growth and differentiated function by binding to the TSH-receptor (TSH-R). In Graves' disease, hyperthyroidism and goiter growth are thought to be mediated by prolonged, continued activation of the TSH-R by TSH receptor-stimulating antibodies (TSAb). However, continuous experimental stimulation of the TSH-R with TSH or TSAb leads to a desensitization of the thyrocyte with a decrease of thyroid function in vitro and in vivo. In order to clarify this discrepancy we determined serum levels of TSH-binding-inhibiting immunoglobulins (TBII) in 10 patients with GD every 10 minutes 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 (TRAK, Henning Berlin, FRG). Visual and computer analysis revealed some variation of TBII serum levels but no obvious pattern indicative of circadian variation nor major secretory peaks could be distinguished. Variation of TBII serum levels were within or only slightly above intraassay CV. Data were tested in order to decide whether the observed fluctuations are of chaotic (deterministic) or of stochastic (random) origin. In none of these tests did we find evidence for chaos in the data suggesting that the observed fluctuations reflect other sources of noise such as sampling errors or intraassay variation. We conclude that in Graves' disease, patients are rendered hyperthyroid by continued, non-pulsatile and non-chaotic binding of stimulatory antibodies to the TSH binding site of the TSH-R.