Analysis of serum FSH bioactivity in a patient with an FSH-secreting pituitary microadenoma and multicystic ovaries: A case report

FSH-secreting pituitary adenoma (FSHoma) is often associated with increased levels of serum FSH and ovarian hyperstimulation syndrome (OHSS). The OHSS has historically been attributed to elevated FSH production by the FSHoma; however, some FSHoma patients with OHSS have normal serum FSH levels. OHSS may result not from increased FSH levels, but also from increased bioactivity of the FSH derived from the adenoma. To address this, we measured the FSH bioactivity in the serum of a 40-year-old woman with an FSHoma and OHSS, whose FSH levels were normal. Chinese hamster ovary cells stably expressing FSH receptors were prepared and transfected with a cAMP-responsive element-driven luciferase reporter plasmid. Cells were then treated with recombinant human FSH (rhFSH), the patient's sera, or sera from controls, collected at different time points, and subjected to a luciferase assay. Luciferase activity was increased in response to rhFSH in a dose-dependent manner. The responsiveness was further augmented by co-addition of a 3-methyl isobutylxanthine, which improved the sensitivity of our assay. Unexpectedly, the serum FSH bioactivity/immunoactivity ratio of the patient was mostly equal to that of normal subjects. This was confirmed with a granulosa cell aromatase assay. This case report suggests that alternate explanations may exist for the OHSS phenotype seen in some FSHoma patients.