Endocrine Abstracts

Introduction: Endocrine late effects can manifest in hemopoietic stem cell transplantation survivors who were exposed to myelosuppressive conditioning treatment. These include dysfunction of the hypothalamic/pituitary, thyroid, and gonads leading to premature ovarian insufficiency and primary amenorrhoea. In addition, metabolic dysregulation and increased risk of diabetes have been observed in these patients. The investigation for primary amenorrhoea in this condition can rarely be complicated by an abnormal karyotype of 46XY in females who received HSCT from male donors leading to a misdiagnosis of disorder of sex development (DSD). To the best of our knowledge, only a handful of cases of misdiagnosed 46, XY DSD following bone marrow transplantation have been reported worldwide.

Case history: A 17-year-old female was referred to our endocrine clinic for the management of primary amenorrhoea as she was newly relocated to the UK. She was diagnosed with Beta Thalassemia Intermedia at age of 2 and had allogeneic hemopoietic stem cell transplantation from her brother at age of 2.5 with complete recovery. She had chemotherapy including Cyclophosphamide and Busulfan for myelosuppression in preparation for HSCT. Later, she consulted an endocrinologist abroad at the age of 16 due to delayed puberty. Her blood test showed a picture of hypergonadotrophic hypogonadism. Further investigations revealed a hypoplastic uterus. Genetic studies performed on a peripheral blood lymphocyte showed karyotype of 46XY which led to the suspicion of DSD. This usually necessitates surgical removal of gonads due to the risk of gonadoblastoma. However, as the clinical manifestations were not entirely consistent with the diagnosis given the presence of gonads and some secondary sexual characteristics, the diagnosis was revisited. A repeat chromosomal analysis on skin fibroblasts was arranged this time and demonstrated a karyotype of 46XX. This led to a diagnosis of premature ovarian insufficiency likely due to childhood chemotherapy. She was started on conjugate oestrogen and achieved pubertal changes in line with Tanner stage III. The oestrogen dose was incrementally built up, and her sexual development improved to Tanner stage IV. Her repeat ultrasound pelvis in Dec 2022 showed a small left ovary and an unidentified right ovary with a normal uterus.

Conclusion: Chromosomal analysis could be misleading following gender mismatched bone marrow transplant. This can lead that the patient to undergo unnecessary and potentially life changing invasive procedures. Pre- and post-treatment chromosomal analysis is essential in such cases.