Elevated Testosterone Levels With Unclear Etiology- the Need for Longer Follow up and Role of Dexamethasone Suppression Test as a Useful Tool to Distinguish Tumorous vs Non Tumorous Etiology

Background: Severe hirsutism in women in conjunction with elevated testosterone level raises concern for androgen secreting tumors. When initial investigations and radiological imaging do not identify a tumorous pathology, clinicians are faced with a dilemma on whether to investigate further or to consider a benign cause such as PCOS or ovarian hyperthecosis. There is inadequate evidence on how long these patients need to be followed up before considering a benign cause for their symptoms. Clinical Case: 57 years-old female, with pertinent history including primary hypothyroidism and eczema, was referred to endocrine clinic in September-2011 for work-up of severe hirsutism and elevated testosterone levels of 4.1 nmol /L (n: 0 - 2.5). All other tests including androstenedione, DHEAS, baseline pituitary profile and 24-hours urinary free cortisol levels were unremarkable. MRI of adrenal glands and ovaries was also unremarkable. Patient was presumptively diagnosed with ovarian hyperthecosis and commenced on spironolactone. There was improvement in hirsutism and patient was discharged from clinic in Feb 2012. Patient was re-referred to endocrine clinic 7 years later in September-2019 for worsening of hirsutism, male pattern baldness. At this stage, patient had testosterone levels of 17– 23 nmol/L (n: 0 - 2.5). Free androgen index 76.6% (n:0–7), SHBG (35 nmol/L, n: 18 – 114). Androstenedione (4 nmol, n: 1 – 8.5) DHEAS (2.3 umol/L, n: 0.3 – 12), 24-hours urine free cortisol level (< 13 nmol, n: < 165 nmol), 17-hydroxyprogesterone, serum ACTH, TSH, LH and FSH and estradiol levels were all normal. On examination patient had signs of virilization which had developed over previous six months. Patient had a low dose dexamethasone suppression test (0.5 mg of dexamethasone 6 hourly for 48 hours). The androgen profile obtained pre and post test showed no suppression in testosterone but well suppressed cortisol. Patient had repeat MRI of the adrenals and ovaries which revealed focal enhancing mass in right ovary (3.3 x 2.5 x 2.6 cm). Patient had an urgent bilateral oophorectomy and histology confirmed a rare steroid cell tumour of the right ovary. Following surgery there has been a significant improvement in her symptoms. Conclusion: Patients with elevated testosterone level and unclear etiology need longer follow up and review of investigations when symptoms worsen as yet undiscovered sinister etiology could be the likely reason. Dexamethasone suppression can be considered as a useful tool to distinguish tumorous vs non tumorous etiology in early stage of investigations as poor suppression of androgens with dexamethasone increases the likelihood of tumorous etiology(1)References: 1. Kaltsas GA, Isidori AM, Kola BP, et al. The Value of the Low-Dose Dexamethasone Suppression Test in the Differential Diagnosis of Hyperandrogenism in Women. The Journal of Clinical Endocrinology & Metabolism 2003; 88(6): 2634-43.