(CSEMP022) VERY HIGH DHEAS: A CASE OF STEROID SULFATASE DEFICIENCY IN A FEMALE PATIENT

Abstract:

Background: Steroid sulfatase deficiency (STSD) is an inherited disease which prevents the conversion of sulfatased steroids into their unconjugated forms, such as the conversion between dehydroepiandrosterone sulfate (DHEAS) and its biologically active counterpart, dehydroepiandrosterone (DHEA). The responsible gene is on the X-chromosome and males who inherit this disorder develop X-linked ichthyosis. Female carriers are asymptomatic and often remain undiagnosed.

Case Description: A previously healthy 27 year-old female was investigated for unilateral galactorrhea and change in menstrual pattern. She was not on any medications. Prolactin was found to be elevated at 165 ug/L (reference range < 24 ug/L). Screening investigations for other etiologies of menstrual dysregulation revealed very high DHEAS at >27.00 umol/L (reference range 2.68-9.23 umol/L). Patient had mild hirsutism with no other signs or symptoms of virilization. Menses occurred every 28-36 days. Additional investigations revealed: LH at 2.6 IU/L, FSH at 2 IU/L, 24h urine cortisol at 87 nmol/d, sex hormone binding globulin at 24 nmol/L, 17-Hydroxyprogesterone (17OHPreg) at 1.9 nmol/L and androstenedione (AnS) at 8.5 nmol/L, all within normal ranges. Total testosterone was elevated at 3.2 nmol/L (reference range < 2.0 nmol/L). Magnetic resonance imaging (MRI) of the abdomen noted unremarkable adrenals and ultrasound of ovaries was normal. MRI sella revealed a microadenoma consistent with prolactinoma and patient was started on cabergoline. Genetics assessment for STSD is pending.

Discussion: This patient’s significantly elevated DHEAS raised suspicion of possible ominous etiology such as adrenocortical carcinoma, which was fortunately excluded with normal imaging studies and benign clinical presentation. Other possible etiologies, such as congenital adrenal hyperplasia and polycystic ovarian syndrome, were also ruled out. A literature search revealed a similar case of female patient with DHEAS at 20.5 umol/L and otherwise unremarkable work up, and STSD was subsequently confirmed with genetic testing. Female carriers of STSD are rarely identified as they are asymptomatic. Our patient was only discovered incidentally, but a confirmed diagnosis may be useful for family planning. Male offspring can be affected with X-linked ichthyosis, which presents primarily with dark scaly skin, but can also be associated with corneal opacities and rarely cognitive deficits. Furthermore, placental STSD results in very low estradiol production which may hinder progression of labor. Today, this can be addressed with cesarean section but historically resulted in still birth at term. Overall, this condition is relatively benign but should be considered in the differential for elevated DHEAS.