Endocrine Abstracts

Background: Gonadal dysgenesis (GD) is a congenital disorder of sex development resulting in gonadal dysfunction caused by a variety of underlying genetic aberrations. Psychiatric morbidity is more common in women with GD in comparison to the general population but whether this is the result of a hormonal disbalance is unknown. However, psychotic symptoms due to abrupt changes in blood estrogen levels have been commonly reported. The aim is to report the first case of a psychotic episode due to hormone replacement treatment (HRT) discontinuation in a patient with 46, XY GD.

Case presentation: A 20-year-old Caucasian female presented with isolation, suspiciousness, avoidance of communication and insomnia during the last 2 months. The patient displayed paranoia and a lack of insight in her illness. A slow stream of thought process with increased latency and paranoid delusions in thought content were observed. The Minnesota Multiphasic Personality Inventory-2 showed a positive Goldberg Index, indicating psychotic functioning, with paranoia and schizophrenia in the patient profile basis. Soon after birth, the patient has been diagnosed with GD and has been under HRT, which she quit taking 2 months prior because of her fear of developing breast cancer. Estradiol was re-introduced into the treatment, which alleviated symptoms. Cytogenetic analysis revealed a male 46, XY karyotype. Next-generation sequencing of 25 genes related to GD revealed a heterozygous variant of uncertain significance (VUS) in the luteinizing hormone choriogonadotropin receptor gene and a hemizygous VUS on chromosome X in the androgen receptor gene. Both variants were not previously reported in major databases of population genetic variation.

Conclusions: Our findings identify a potential link between discontinuation of estrogen replacement therapy and acute psychosis in the context of GD and stress the importance of proper maintenance of hormonal balance for both the physical and mental health of these patients.