TSH regulation dynamics in central and extreme primary hypothyroidism.
BACKGROUND
Thyrotropin (TSH) changes in extreme primary hypothyroidism include increased secretion, slowed degradation, and diminished or absent TSH circadian rhythms. Diminished rhythms are also observed in central hypothyroid patients and have been speculated to be a cause of central hypothyroidism. We examined whether TSH secretion saturation, previously suggested in extreme primary hypothyroidism, might explain diminished circadian rhythms in both disorders.


METHODS
We augmented and extended the range of our published feedback control system model to reflect nonlinear changes in extreme primary hypothyroidism, including putative TSH secretion saturation, and quantified and validated it using multiple clinical datasets ranging from euthyroid to extreme hypothyroid (postthyroidectomy). We simulated central hypothyroidism by reducing overall TSH secretion and also simulated normal TSH secretion without circadian oscillation, maintaining plasma TSH at constant normal levels. We also utilized the validated model to explore thyroid hormone withdrawal protocols used to prepare remnant ablation in thyroid cancer patients postthyroidectomy.


RESULTS
Both central and extreme primary hypothyroidism simulations yielded low thyroid hormone levels and reduced circadian rhythms, with simulated daytime TSH levels low-to-normal for central hypothyroidism and increased in primary hypothyroidism. Simulated plasma TSH showed a rapid rise immediately following triiodothyronine (T(3)) withdrawal postthyroidectomy, compared with a slower rise after thyroxine withdrawal or postthyroidectomy without replacement.


CONCLUSIONS
Diminished circadian rhythms in central and extreme primary hypothyroidism can both be explained by pituitary TSH secretion reaching maximum capacity. In simulated remnant ablation protocols using the extended model, TSH shows a more rapid rise after T(3) withdrawal than after thyroxine withdrawal postthyroidectomy, supporting the use of replacement with T(3) prior to (131)I treatment.
Biocybernetics Laboratory, Department of Computer Science, University of California, Los Angeles, California, USA. meisenberg@mbi.osu.edu
Marisa C
MC
Eisenberg
Ferruccio
F
Santini
Alessandro
A
Marsili
Aldo
A
Pinchera
Joseph J
JJ
DiStefano
D002277:Carcinoma / Q000378:metabolism / Q000601:surgery; D002940:Circadian Rhythm / Q000502:physiology; D003198:Computer Simulation; D005246:Feedback / Q000187:drug effects; D006801:Humans; D007037:Hypothyroidism / Q000188:drug therapy / Q000378:metabolism*; D007457:Iodine Radioisotopes / Q000627:therapeutic use; D008954:Models, Biological; D013961:Thyroid Gland / Q000378:metabolism*; D013964:Thyroid Neoplasms / Q000378:metabolism / Q000601:surgery; D013965:Thyroidectomy; D013972:Thyrotropin / Q000097:blood / Q000378:metabolism*; D013974:Thyroxine / Q000097:blood / Q000378:metabolism / Q000627:therapeutic use; D014284:Triiodothyronine / Q000097:blood / Q000378:metabolism / Q000627:therapeutic use
D007457:Iodine Radioisotopes; D014284:Triiodothyronine; D013972:Thyrotropin; D013974:Thyroxine