SERUM THYROTROPIN (TSH) HETEROGENEITY IN EUTHYROID SUBJECTS AND PATIENTS WITH SUBCLINICAL HYPOTHYROIDISM - THE CORE FUCOSE CONTENT OF TSH-RELEASING HORMONE-RELEASED TSH IS ALTERED, BUT NOT THE NET CHARGE OF TSH

The aims of the present study were to determine the influence of brief subclinical hypothyroidism on the isoforms of serum thyrotropin (TSH) and to examine the net charge of TSH in different metabolic states. S era were obtained from euthyroid subjects (n=7) and from patients with subclinical hypothyroidism (n=8) before and 30 min after the intraven ous administration of 200 mu g thyrotropin-releasing hormone (TRH). Th e TSH from human pituitary extracts (TRP 68/38), basal and TRH-stimula ted serum TSH was immunoconcentrated and further analysed by isoelectr ic focusing (IEF) and lentil lectin affinity chromatography. TSH immun oreactivity was determined in each specimen or fraction with an automa ted highly sensitive chemiluminometric TSH assay. We found that basal TSH in subclinical hypothyroidism, and TRH-released TSH in euthyroidis m and in subclinical hypothyroidism is distributed in a similar neutra l to acidic pattern, which significantly differs from the more alkalin e to neutral isoform pattern of intrapituitary TSH (P<0.05). IEF analy sis of pituitary standard TSH revealed 3 major peaks (pI values 7.5; 6 .6; 5.8) whereas in most euthyroid or subclinically hypothyroid subjec ts 5 peaks were found. Lentil lectin affinity chromatography revealed that TRH-released TSH in euthyroid subjects has more core fucose resid ues than TSH from patients with subclinical hypothyroidism (64.6 +/- 6 .7 vs 12.5 +/- 2.7%, P<0.0001). Thus pituitary standard TSH seems to b e less mature material than circulating TSH. Perhaps no alteration in the IEF pattern of TSH was detected during early hypothyroidism becaus e sialylation of TSH was increasing as sulfatation was decreasing. Nev ertheless, a change in the core fucose content of TSH was detectable b y lentil analysis.