Endocrine Abstracts

Case Report: A 16.4 year-old patient presented with a history of headaches and maternal concerns that these may be hormone-related due to primary amenorrhoea. There was also a history of low mood and self-harm, known to a private counsellor. The patient was a competitive swimmer at national level and had attributed amenorrhoea and lack of breast development to this, and viewed it positively. Examination revealed androgenised features, clitoromegaly and absence of typical female pubertal progression with pubertal development B1 P4 A3. Investigations showed normal baseline bloods, normal 17-OHP, low oestradiol, high androstenedione and borderline high testosterone. Pelvic ultrasound indicated the absence of Müllerian structures, with inguinal structures suggesting undescended testes. Genetic karyotyping confirmed 46XY genotype. Urine steroid profiling revealed excess adrenal androgens relative to cortisol metabolites, excluding alpha reductase and 17-alpha hydroxylase deficiency. These results were available to the team at the local joint endocrine clinic, but a considered decision was made not to share them at this stage given the significant psychological burden with background mental health concerns. When seen in the specialist MDT, further genetic results had confirmed 17-beta-hydroxysteroid dehydrogenase 3 (HSD17B3) deficiency. Management involved comprehensive counselling about the condition, its implications and treatment options. The MDT including endocrinologists, gynaecologists, and psychologists, played a crucial role in the patient’s care. The patient faced a challenging decision: continue with the current hormone imbalance or initiate hormone replacement therapy (HRT) with oestrogen to promote female secondary sex characteristics, while using GnRH analogues to suppress androgen production. The patient, despite initial reluctance due to potential impacts on swimming ability, opted for oestrogen HRT.

Discussion: HSD17B3 deficiency is a rare, autosomal recessive disorder of sex development (DSD). Clinical presentation at birth is variable, but children are often initially raised as girls then develop male secondary sex characteristics during puberty. There are numerous complexities in managing DSD, with nuances specific to individual patients. This patient’s journey illustrates that patient autonomy can be both empowering and daunting, feeling like a double-edged sword. It underscores the importance of a multidisciplinary approach in managing DSD, highlighting the need for clear yet sensitive communication with psychological support.