Circulating thyrotropin bioactivity in sporadic central hypothyroidism

The etiopathogenesis of sporadic central hypothyroidism (CH) involves pitui tary and hypothalamic lesions. Pituitary CH (pCH) implies a diminished numb er of functioning thyrotropes, accounting for the quantitative impairment o f TSH secretion. Hypothalamic CH (hCH) is characterized by normal or even i ncreased TSH concentrations and qualitative abnormalities of TSH secretion, including a decreased bioactivity of circulating TSH. However, controversy still exists about the actual occurrence of bioinactive TSH among CH patie nts, and no data are available in pCH. Therefore, we studied 41 CH patients with different hypothalamic-pituitary disorders. Immunoreactive TSH (TSH-I ) ranged from 0.08-11.1 mU/L (normal, 0.24-4.0), free T-4 (FT4) ranged hom 0.6-8.8 pmol/L (normal, 9-18), and FT, ranged from 1.2-5.4 pmol/L (normal, 4-8). A blunted TSH response to TRH (<4 mU/L), indicating prevalent pCH, wa s found in 56% of the patients, and a net TSH-I increment greater than or e qual to 4 mU/L, indicating prevalent hCH, was found in the remaining 44%. N et TSH-I increments showed significant correlation with basal FT4 (P < 0.02 ), indicating the relevance of pituitary TSH reserve in the pathogenesis of CH. Circulating TSH was immunoconcentrated and tested in bioassay and in r icin affinity chromatography. The ratio between biological (B) and immunolo gical (1) activities of circulating TSH was reduced (n = 25; TSH B/I, 0.38 +/- 0.19) compared to the values recorded in normal subjects (n = 26; TSH B /I, 1.53 +/- 0.54; P < 0.001) and primary hypothyroid patients (n = 24; TSH B/I, 0.74 +/- 0.31; P < 0.001), but no difference between pCH (n = 9; 0.36 +/- 0.16) and hCH (n = 16; 0.39 +/- 0.20) was seen. TSH B/I values in CH p atients showed a limited overlap with normal values (20%) and a highly sign ificant correlation with the FT, response to endogenous TRH-stimulated TSH (P < 0.005). The elevated sialylation degree of TSH molecules may explain p art of these findings. In conclusion, the secretion of TSH molecules with reduced bioactivity is a common alteration in the patients with hypothalamic-pituitary lesions, con tributing along with the impairment of pituitary TSH reserve to the pathoge nesis of CH.