Diagnostic and therapeutic challenges in virilised female with learning difficulties
L Osborne1, A Balen3 & M Freeman2
Case: A 22-year-old lady was referred with marked hirsutism for 12 months and secondary amenorrhoea for 4 years. She has a complex medical background including persistent hyperinsulinaemic hypoglycaemia of infancy (PHII) necessitating subtotal pancreatectomy with subsequent diabetes. Perhaps a result of PHII, she also has learning difficulties and epilepsy. Other problems include myopathy and mild chronic thrombocytopaenia.
Medications: insulins glargine and aspart, valproate, losartan, budesonide and salbutamol inhalers.
Investigations: Testosterone 15.8 nmol/l (normal <2.8); adrenal androgens suppressed, 17- hydroxyprogesterone normal; imaging of adrenals and ovaries normal except 5 cm bilateral simple ovarian cysts.
Management/progress: Venous sampling would be poorly tolerated by this patient and a trial of gonadotrophinreleasing hormone agonist was initiated. After 3 months of goserelin her testosterone became undetectable but her platelets had fallen to 42. Leviteracetam was substituted for valproate but her platelets dropped further and her goserelin was discontinued. Testosterone remained normal for many months and her menstrual cycle and platelets normalised. A year after stopping the Goserelin, her hirsutism is once again increasing and her testosterone is 7.9 nmol/l. Her insulin requirements are inexplicably now increasing dramatically. She weighs 42 kg and is currently on 250 u with HbA1c of 9.4%. IGF-1 is awaited as is repeat CT pelvis to detect any changes in the ovarian cysts.
Discussion: Since testosterone remained normal for months after discontinuing the valproate and goserelin, the possibility that valproate could be implicated was considered. As her testosterone has risen again, this is unlikely and again she presents a diagnostic and therapeutic challenge. We are currently considering a further trial of goserelin or bilateral oophorectomy with hormone replacement given the remaining possibility of malignancy and fertility not being an issue.