Isolated follicle-stimulating hormone (FSH) deficiency in a young man with normal virilization who did not have mutations in the FSHbeta gene.
OBJECTIVE
To determine the cause of isolated FSH deficiency in a young infertile man.


METHODS
Case report.


METHODS
Clinical and genetic studies in an academic research environment.


METHODS
A 19-year-old man with normal virilization, azoospermia, and isolated FSH deficiency.


METHODS
Pituitary and gonadal functions were evaluated at baseline and after repeated GnRH stimulation. FSH was tested with both immunological and biological methods. The FSHbeta gene was sequenced in the patient and in a series of 50 controls.


METHODS
Clinical, endocrine, and genetic characterization of an infertile patient with isolated FSH deficiency.


RESULTS
LH and T secretions were normal. No interference in FSH measurement was detected, and serum FSH concentrations were very low and completely unresponsive to repeated GnRH stimulation. No circulating FSH-like bioactivity was detected by means of rat Sertoli cell bioassay. Other pituitary functions were unaffected, and no lesions were seen at pituitary nuclear magnetic resonance (NMR). Inhibin B and activin levels were normal, but a progressive decrease of activin concentrations was seen during GnRH stimulation. The coding sequence of the FSHbeta gene was normal, but the patient was homozygous for a novel G/T substitution in the promoter region within a P response element. This substitution was present in heterozygosity in eight out of 50 controls and in homozygosity in one man with normal FSH levels.


CONCLUSIONS
We report an infertile male with isolated FSH deficiency but no evidence of mutations in the FSHbeta gene. The G/T substitution in the FSHbeta promoter represents a novel silent polymorphism, indicating that other defects in factors involved in FSH-specific expression should be taken into account.
Mantovani
Giovanna
G
Institute of Endocrine Sciences, University of Milan, Ospedale Maggiore IRCCS, Italy.
Borgato
Stefano
S
Beck-Peccoz
Paolo
P
Romoli
Roberto
R
Borretta
Giorgio
G
Persani
Luca
L
D000328:Adult; D005640:Follicle Stimulating Hormone / Q000097:blood / Q000172:deficiency*; D037201:Follicle Stimulating Hormone, beta Subunit / Q000235:genetics*; D006801:Humans; D008297:Male; D009845:Oligospermia / Q000209:etiology* / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D012016:Reference Values
D037201:Follicle Stimulating Hormone, beta Subunit; D005640:Follicle Stimulating Hormone