Thyrotropin Secretion in Mild and Severe Primary Hypothyroidism Is Distinguished by Amplified Burst Mass and Basal Secretion with Increased Spikiness and Approximate Entropy

Context: Twenty-four-hour TSH secretion profiles in primary hypothyroidism have been analyzed with methods no longer in use. The insights afforded by earlier methods are limited. Objective: We studied TSH secretion in patients with primary hypothyroidism (eight patients with severe and eight patients with mild hypothyroidism) with up-to-date analytical tools and compared the results with outcomes in 38 healthy controls. Design and Methods: Patients and controls underwent a 24-h study with 10-min blood sampling. TSH data were analyzed with a newly developed automated deconvolution program, approximate entropy, spikiness assessment, and cosinor regression. Results: Both basal and pulsatile TSH secretion rates were increased in hypothyroid patients, the latter by increased burst mass with unchanged frequency. Secretory regularity (approximate entropy) was diminished, and spikiness was increased only in patients with severe hypothyroidism. A diurnal TSH rhythm was present in all but two patients, although with an earlier acrophase in severe hypothyroidism. The estimated slow component of the TSH half-life was shortened in all patients. Conclusion: Increased TSH concentrations in hypothyroidism are mediated by amplification of basal secretion and burst size. Secretory abnormalities quantitated by approximate entropy and spikiness were only present in patients with severe disease and thus are possibly related to the increased thyrotrope cell mass. (J Clin Endocrinol Metab 95: 928-934, 2010)