Co-occurrence of congenital isolated FSH deficiency and androgen-secreting steroid cell tumour in a Chinese female - Intermittent menses in a patient with primary amenorrhoea

Background: Congenital isolated FSH deficiency is a rare autosomal recessive disorder characterized by primary amenorrhoea, absent or partial breast development, infertility, undetectable serum FSH, and pathogenic variant detected in FSHB gene. Ovarian steroid cell tumour is another rare disease entity that can present in the young, with features of androgenic, estrogenic, or cortisol excess. To date, there have been no reports of the two disease entities occurring in a single patient. Case report: A Chinese female presented with primary amenorrhoea and undetectable serum FSH at the age of 16. She developed spontaneous menses intriguingly at the age of 19, with elevated serum testosterone, leading to subsequent diagnosis of right ovarian steroid cell tumour, not otherwise specified (NOS). After surgical resection, the patient redeveloped amenorrhoea, along with normalized testosterone and undetectable estradiol. Sequencing of FSHB gene revealed homozygosity of a novel variant c.366C > A p.(Cys122*), which is predicted to disrupt FSH heterodimer formation. Literature review and discussion: Literature and case reports on congenital isolated FSH deficiency and steroid cell tumours published in English language were reviewed. The common involvement of gonadotropins and sex steroids by the two pathologies raises the suspicion of possible disease linkage. Conclusion: We herein report the first case of steroid cell tumour identified in a Chinese female with isolated FSH deficiency. The unique presentation of primary amenorrhoea, spontaneous menses, and secondary amenorrhoea post-surgery highlights the role of peripheral aromatization in FSH deficiency. Co-occurrence of the two rare disease entities may help uncover the role of FSH, inhibin, and LH in ovarian tumorigenesis.