Discordant Elevation of the Common a-Subunit of the Glycoprotein Hormones Compared to β-Subunits in Serum of Uremic Patients*

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Abstract
Levels of α-subunit, LHβ, FSHβ, TSHβ, CGβ LH, FSH, TSH, testosterone, T3 and T4 were measured in preand posthemodialysis sera from 91 uremic patients on chronic hemodialysis and compared with values from 357 appropriately matched control subjects. Nonparametric statistical methods were used to establish sex-specific 5th, 50th, and 95th percentile cutoff values for each assay in the major diagnostic subgroups. Before hemodialysis, α-subunit levels were significantly higher in uremic men (n = 52) and uremic premenopausal (n = 11) and postmenopausal women (n = 28) than in healthy subjects and patients with primary hypothyroidism. Subunit values from uremic patients were compared with those from control subjects with similar levels of LH and FSH, or TSH. Levels of α-subunit exceeded the 95th psrcentiles of controls and were as high as 25.5 and 93 ng/ml in 96% and 73%, respectively, of patients with normal LH and FSH and elevated LH and/or FSH. Similar α-subunit elevations occurred in 100% and 71% of patients with normal and elevated TSH, respectively. In 8 of 91 (9%) patients, serum α-subunit exceeded 50 ng/ml. In contrast, LHβ and FSHβ were elevated (slightly) in only 19% and 14%, respectively, of the hypergonadotropinemic patients, while TSHβ was minimally elevated in just a single patient (1%) with a normal TSH level. CGβ elevations as high as 3.1 and 8.6 ng/ml occurred in 22% and 30% of patients with normal and elevated gonadotropins, respectively, and were not due to cross-reactivity with LH, FSH, or α-subunits. Molar ratios of α-subunit to LH and FSH and α-subunit to TSH were 6.6- and 30.4-fold higher in, uremic patients than in controls with normal LH and FSH or TSH levels, respectively, and were 4.7- and 70-fold greater in patients with elevated LH and/or FSH, or TSH, respectively. There were significant correlations (P < 0.001) between α-subunit and LH, FSH, LHβ, FSHβ, and CGβ, but not (P = 0.1) between α-subunit and TSH, TSHβ, T3, T4, testosterone, or creatinine. After hemodialysis, serum α-subunit rose slightly but significantly, apparently unrelated to hemoconcentration. The immunochemical and gel chromatographic properties of uremic serum α-subunit were similar to those of other secreted forms of α-subunit, suggesting that uremic serum α-subunit was normally glycosyl-ated. Serum testosterone was decreased in 14% of uremic men, while LH and FSH were elevated in 78% and 31%, respectively. Serum T3 and T4 were each decreased in 22% of uremic patients, while TSH was increased in 8% and decreased in 29%. There were significant correlations (P < 0.05) between TSH and both T3 and T4, but not (P = 0.05) between testosterone and either LH or FSH. Since in normal subjects, MCRs of α-subunit and TSHβ are similar, it seems more likely that the disproportionate excess of α- vs. β-subunits in uremic sera is due to an unbalanced overproduction of α-subunits, rather than to a selective decrease in the MCR of α-subunit. However, direct studies of α- and β-subunit MCRs and production rates in uremia will be required ;to distinguish between these two possibilities.