Hypersecretion of the α-subunit in clinically non-functioning pituitary adenomas: Diagnostic accuracy is improved by adding α-subunit/gonadotropin ratio to levels of α-subunit

Background: In vitro, the majority of clinically non-functioning pituitary adenomas (NFPAs) produce gonadotropins or their α-subunit; however, in vivo, measurements of α-subunit levels may not accurately detect the hypersecretion of the α-subunit. Aim: We wanted to estimate the reference intervals and decision limits for gonadotropin α-subunit, LH and FSH levels, and aratio (α-subunit/LH+FSH), especially taking into consideration patient gender and menstrual status. Furthermore, we wanted to examine if the diagnostic utility of α-subunit hypersecretion was improved when the α-ratios, rather than simply the α-subunit levels, were measured in patients with NFPAs. Material and Methods: Reference intervals for gonadotropin α-subunit serum levels and α-ratios were established in 231 healthy adults. The estimated cut-off limits were applied to 37 patients with NFPAs. Gonadotropin α-subunit, LH and FSH levels were measured and α-ratios were calculated. Results: In healthy adults, the cut-offs for α-subunit levels were significantly different between men and pre- and postmenopausal women: the cut-offs were 1.10, 0.48 and 3.76 IU/l, respectively. Using these estimated cut-offs, increased α-subunit levels were identified in 10 out of 37 (27%) patients with NFPAs. By adding α-ratio, in combination with α-subunit levels, 23 patients out of 37 (62%) were identified as having elevated α-subunit hypersecretion, and 22 out of these 23 patients (96%) had increased α-ratios. One premenopausal patient out of 23 had elevated α-subunit level but a normal α-ratio. Conclusion: Our data suggest that adding the simple calculation of α-ratio improves the ability of detecting gonadotropin α-subunit hypersecretion and thereby indentifying patients with NFPAs