Hypersecretion of the alpha-subunit in clinically non-functioning pituitary adenomas: Diagnostic accuracy is improved by adding alpha-subunit/gonadotropin ratio to levels of alpha-subunit.
BACKGROUND
In vitro, the majority of clinically non-functioning pituitary adenomas (NFPAs) produce gonadotropins or their alpha-subunit; however, in vivo, measurements of alpha-subunit levels may not accurately detect the hypersecretion of the alpha-subunit.


OBJECTIVE
We wanted to estimate the reference intervals and decision limits for gonadotropin alpha-subunit, LH and FSH levels, and aratio (alpha-subunit/LH+FSH), especially taking into consideration patient gender and menstrual status. Furthermore, we wanted to examine if the diagnostic utility of alpha-subunit hypersecretion was improved when the alpha-ratios, rather than simply the alpha-subunit levels, were measured in patients with NFPAs.


METHODS
Reference intervals for gonadotropin alpha-subunit serum levels and alpha-ratios were established in 231 healthy adults. The estimated cut-off limits were applied to 37 patients with NFPAs. Gonadotropin alpha-subunit, LH and FSH levels were measured and alpha-ratios were calculated.


RESULTS
In healthy adults, the cut-offs for alpha-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 alpha-subunit levels were identified in 10 out of 37 (27%) patients with NFPAs. By adding alpha-ratio, in combination with alpha-subunit levels, 23 patients out of 37 (62%) were identified as having elevated alpha-subunit hypersecretion, and 22 out of these 23 patients (96%) had increased alpha-ratios. One premenopausal patient out of 23 had elevated alpha-subunit level but a normal alpha-ratio.


CONCLUSIONS
Our data suggest that adding the simple calculation of alpha-ratio improves the ability of detecting gonadotropin alpha-subunit hypersecretion and thereby indentifying patients with NFPAs.
Department of Endocrinology, Odense University Hospital, Odense, Denmark. Marianne.Andersen@ouh.regionsyddanmark.dk
Marianne
M
Andersen
Joanna
J
Ganc-Petersen
Jens O L
JO
Jørgensen
Søren
S
Mellemkjaer
Per H
PH
Petersen
Ole
O
Blaabjerg
Claus
C
Hagen
D000328:Adult; D000368:Aged; D005260:Female; D005640:Follicle Stimulating Hormone / Q000097:blood; D015292:Glycoprotein Hormones, alpha Subunit / Q000097:blood*; D006062:Gonadotropins / Q000097:blood*; D006801:Humans; D007986:Luteinizing Hormone / Q000097:blood; D008297:Male; D008875:Middle Aged; D010911:Pituitary Neoplasms / Q000097:blood* / Q000175:diagnosis*; D055815:Young Adult
D015292:Glycoprotein Hormones, alpha Subunit; D006062:Gonadotropins; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone