Hyperandrogenism, Elevated 17-Hydroxyprogesterone and Its Urinary Metabolites in a Young Woman with Ovarian Steroid Cell Tumor, Not Otherwise Specified: Case Report and Review of the Literature

Abstract

We describe a case of a 24-year-old overweight woman who presented with hirsutism, secondary amenorrhea, clitoromegaly, and symptoms of diabetes mellitus (DM). While a diagnosis of polycystic ovary syndrome (PCOS) with its associated metabolic disturbances was initially considered, serum total testosterone, androstenedione, and 17-hydroxyprogesterone (17-OHP) measured by liquid chromatography tandem mass spectrometry (LC-MS/MS) were significantly increased. As 17-OHP did not increase upon ACTH (Synacthen) stimulation and the urinary steroid profile (USP) was compatible with an ovarian source of 17-OHP excess rather than adrenal, non classical congenital adrenal hyperplasia (NCCAH) was unlikely and an androgen-secreting tumor was suspected. Transabdominal ultrasound revealed the presence of an enlarged right ovary with a polycystic ovary morphology and no discrete mass. Transvaginal ultrasound and [18F]− fluorodeoxyglucose positron emission tomography–computed tomography (FDG PET–CT) enabled the localization of a right ovarian tumor. Laparoscopic right salpingo-oophorectomy was performed and a histological diagnosis of steroid cell tumor, not otherwise specified (SCT–NOS) was made. Hyperandrogenism and menstrual disturbances resolved postoperatively. A literature review revealed that 17-OHP-secreting SCT–NOS may uncommonly show positive responses to ACTH stimulation similar to 21-hydroxylase deficiency. Alternatively, USP might be useful in localizing the source of 17-OHP to the ovaries. Its diagnostic performance should be evaluated in further studies.

Ovarian Steroid Cell Tumor Masquerading as Steroid-Unresponsive Congenital Adrenal Hyperplasia

“…Wong et al 6 recently reviewed 21 case reports of SCTs, NOS, with 17-OHP concentrations reported and found a prevalence of 81% of elevated 17-OHP, similar to our patient. Yılmaz-Ağladıoğlu et al 7 reported a 13-year-old female who experienced a 6 year delay in diagnosis of SCT, NOS, by ultrasound due to presumed CAH.…”

“…SCTs NOS are of stromal cell origin with variable histological features. 6 The ovarian tumor from this case had abundant cytoplasm with fibrous bands of inflammation. Conversely, SCTs can also be classified as Leydig cell tumors with cytoplasmic crystals of Reinke, which the presented tumor lacked.…”

“…Rapid virilization with severe signs such as a deepening voice, male pattern baldness, and clitoromegaly are associated with ASN over CAH in females. 6 , 12 …”

“…While elevation in 17-hydroxyprogesterone (17-OHP) levels is suggestive of CAH 21-hydroxylase deficiency, there have been reports of steroid cell tumors (SCTs) presenting with hyperandrogenism and elevated 17-OHP. 1 , 2 , 3 , 4 , 5 , 6 , 7 Refractory cases of CAH to steroid therapy warrant further investigation into the cause of virilization, even in the presence of negative imaging. In this report, we describe the utility of selective venous sampling in the diagnosis of a female adolescent who presented with virilization secondary to an SCT masquerading as CAH.…”

Failure of multiple surgical procedures and adjuvant chemotherapy in early-stage steroid-cell ovarian tumor treatment: a case report and literature review

“… 5 , 6 More than half (56%–77%) of patients with an SCT-NOS show hyperandrogenic symptoms and signs of virilization, such as hirsutism, acne, deepened voice, clitoromegaly, amenorrhea, and infertility. 1 , 7 – 9 Additionally, it can present with estrogenic manifestations (6%–23%), such as menorrhagia or postmenopausal bleeding. Some patients also develop endometrial cancer.…”