Hyperandrogenism in post-menopausal women: a diagnosis challenge

A 79-year-old woman, presented with increased hair growth in the chin and the upper lip but no in other androgen-dependent areas of her body. Hormonal evaluation showed markedly elevated serum testosterone level (>1.7?ng/ml) and normal DHEA-S, androstenedione, 17-hydroxyprogesterone, cortisol and TSH levels. The diagnosis of probable pure testosterone secreting tumor was made. Transvaginal ultrasound and magnetic resonance image revealed a 16?mm?×?12?mm nodular formation indicative of an atypical adenoma in the left adrenal gland and a tube-shaped, fluid-filled, thin-walled image measuring 28?mm?×?14?mm suggestive of a hydrosalpinx in the right ovary. Differential diagnosis between the coexistence of an androgen-producing ovarian tumor (occult) associated with a finding of an adrenal image (Incidentaloma) or an adrenal tumor secreting testosterone only was done. Since cortisol levels went down, but total testosterone inhibition did not occur after suppression with dexamethasone. An ovarian androgen secreting tumour was suspected and surgery was performed. Histological examination showed a Leydig cells hyperplasia. After the operation testosterone returned to normal with regression of clinical symptoms.     

Virilising ovarian tumour: a case associating a Sertoli-Leydig cell tumour and a Brenner tumour

Ovarian Sertoli-Leydig cell tumours (SLCT), also termed arrhenoblastomas, are the most frequent virilising tumours in women of reproductive age. Very rare secretory Brenner tumours (BT) have been described, generally after the menopause. A 31-year-old woman sought medical advice for secondary amenorrhoea, progressive hirsutism and a 5-year history of virilisation syndrome with clitoromegaly. Testosterone was markedly high (285 ng/dl, N<85) with moderate elevation of delta 4-androstenedione (D4AD) (311 ng/dl, N <270), dehydroepiandrosterone sulfate (DHEAS) (366 μg/dl, N <340) and 17-hydroxyprogesterone (17OHP) (275 ng/dl). LH was 9 IU/l, FSH 4.3 IU/l, estradiol 60 pg/ml and progesterone 314 ng/100?ml. Cortisol was decreased (1.3 μg/dl) after the dexamethasone suppression test. Pelvic MRI showed a 5-cm right ovarian tumour with a 2.5?cm nodular component and cystic areas, and two nodules measuring 11?mm and 15?mm above the right and left ovaries. After right ovariectomy by laparoscopy, pathological examination concluded on a 3-cm SLCT and a 2-cm BT; the nodules above the ovaries were dysembryoplastic cysts. Postoperatively, testosterone level was normal after 24?h (26 ng/dl), estradiol and progesterone rapidly decreased, cyclic secretion then resumed and the patient menstruated at day 27. To our knowledge, this is the first report of an ovarian tumour associating a Sertoli-Leydig cell tumour and a Brenner tumour in a patient with virilisation syndrome which resolved after ovariectomy.     

Clinical,ultrasonographic, computed tomography and histopathological manifestations of ovarian steroid cell tumour,not otherwise specified: our experience of a rare case with female virilisation and review of the literature

Introduction.?Ovarian steroid cell tumours, not otherwise specified (NOS) are rare sex cord-stromal tumours of the ovary. These tumours should be considered a cause of isosexual precocious puberty in children and virilisation in adults.

Case.?We report a case of 40-year-old woman with mental handicap who presented with 3 years of amenorrhea and progressive virilisation. Pelvic ultrasonography identified a 6.19?×?6.15?cm well-defined echogenic-multilobular mass arising from the left ovary. Fluid in the cul-de-sac was noted. Colour Doppler examination with endovaginal ultrasonography showed high vascularity of the tumour with low resistance to flow. A computed tomography (CT) scan of the upper and lower abdomen showed a lobular mass with diaphragms in the left adnexal structure and fluid in the cul-de-sac; no adrenal gland enlargement or additional tumour was detected. Laboratory analysis revealed increased levels of serum total testosterone. Total abdominal hysterectomy with bilateral salpingo-oophorectomy was performed. Histological examination showed a benign steroid cell tumour, NOS without evidence of necrosis, haemorrhage or invasion. The immunohistochemical study showed that the tumour cells were positive for inhibin, CD 99, Melan A and vimentin and negative to CK AE1, CK AE3, progesterone and estrogen receptors.

Conclusion.?Careful medical history, physical examination, laboratory serum values and imaging studies are helpful in making the pre-operative diagnosis. Steroid cell tumours, NOS are usually benign, unilateral and characterised by the composition of two similar-appearing polygonal cell types. They differ from Leydig cell tumours in the lack of crystals of Reinke in their cytoplasm.     

Virilising Sertoli–Leydig cell tumour associated with thyroid papillary carcinoma: case report and general considerations

We present a case of a Sertoli–Leydig cell tumour manifested with progressive hirsutism, frontal alopecia and secondary amenorrhea in a 46-years-old female, evolving for 6 years until presentation. Serum testosterone level was 8.01 ng/ml and gonadotropic hormones were LH 8.57 mIU/ml and FSH 9.52 mIU/ml. Computed tomography revealed a dense, solid, heterogeneous mass of 3.5/2.8?cm in the right ovary. Bilateral ovariectomy and hysterectomy were performed. The histopathological report mentioned a Sertoli-Leydig cell tumor with intermediate grade of differentiation. Immunohistochemical stains showed positive reaction for α-inhibin, calretin and for progesterone receptor. The testosterone levels dramatically decreased after surgery (0.31 ng/ml) while levels of gonadotropes increased: LH 40.98 mIU/ml and FSH 50.41 mIU/ml. At 6 months follow-up the diagnosis of a left lobe thyroid nodule leaded to fine needle aspiration biopsy with suspicion of papillary carcinoma. Total thyroidectomy established the diagnosis of thyroid papillary carcinoma (2.17/2.18?cm) T2N0M0, stage II, followed by radioiodine administration. This is to our knowledge the first presented case of ovarian Sertoli–Leydig cell tumour associated with papillary thyroid carcinoma. This could suggest a common genetic background.     

Percutaneous administration of testosterone gel in postmenopausal women – a pharmacological study

We wished to investigate if a testosterone gel administered percutaneously to postmenopausal women could result in stable serum levels of the hormone and which dose was required to produce levels within the normal premenopausal range. Fifteen postmenopausal women, mean age 55.3 years (range 45–70 years), volunteered to participate in the study and were divided into three groups. They received 10, 20 or 30?mg of testosterone as a 1% testosterone hydroalcoholic gel at 09.00?hours daily for 14 days. The gel was applied in a thin layer on the outside of the thigh each morning, over an area of approximately 15?cm². Blood samples were collected hourly between 09.00 and 17.00?hours on days 1 and 14, and also at 08.00?hours on days 3, 5, 11, 12, 13 and finally day 16, i.e. 2 days after termination of treatment. The mean basal serum level of testosterone was 1.1?±?0.9?nmol/l and for 5α-dihydrotestosterone 208?±?143?pmol/l. There was a clear increase from the 10?mg to the 20?mg treatment (mean testosterone level during treatment 3.2 and 7.2?nmol/l, respectively) while serum testosterone values after 30?mg showed very little further increase (mean 7.5?nmol/l). Values for days 3–5 were quite similar to those for days 13–14. The present study suggests that adequate and acceptable serum levels of testosterone can be achieved with 10?mg testosterone applied transdermally.     

Ovarian steroid cell tumor as an example of severe hyperandrogenism in 45-year-old woman

Abstract

Approximately, 5% of ovarian tumors have hormonal activity. Steroid cell tumors (SCTs) represent about 0.1% of all ovarian tumors. They cause hyperandrogenism associated with typical virilization. In this case report, we present 45-year-old women with unmalignant ovarian SCT-producing androgens which cause severe virilization and secondary amenorrhea lasting two years. Transvaginal ultrasound, computed tomography of adrenal glands, magnetic resonance imaging of small pelvis, laboratory tests (including serum concentration of FSH, LH, testosterone (T), androstenedione (A), dehydroepiandrosterone sulfate (DHEA-S), as well as ROMA index) were performed. During hormonal evaluation, elevated concentrations of serum T – on admission 1.72?ng/ml and one month later 3.75?ng/ml (normal range 0.08–0.82?ng/ml) and A – 24.90?ng/ml (normal range 0.40–3.40?ng/ml) were found. The ROMA index was within the normal range. Enlargement of the left ovary by solid mass 56?×?43?mm was found during ultrasound examination. Based on small pelvis MRI scan and hormonal finding, patient was qualified for laparotomy. During this procedure, the left salpingo-oophorectomy with removal of the tumor was performed. The histopathological examination identified SCT. During follow-up examination, one day after surgery, we found serum testosterone levels within normal ranges – 0.74?ng/ml (normal range 0.08–0.82?ng/ml). This case shows that hormone-producing ovarian tumors are rare but very important clinical causes of severe hyperandrogenism.     

Clinical features and management of 33 patients with 46,XX pure gonadal dysgenesis

The objective of the study is to summarize the clinical characteristics of 33 patients’ cohort (46,XX pure gonadal dysgenesis, 46,XX PGD), discuss the management, and propose treatment suggestions. Patients’ information, medical history, and medical records were obtained. All patients were closely followed up. At the time of diagnosis, the patients presented 19.53?±?3.60 years old, 165?±?6.49?cm height, breast development of Tanner stage I, and infantile female genitalia. High level of follicle-stimulating hormone (87.41?±?21.50 mIU/mL) and LH (27.10?±?8.47 mIU/mL) and low level of E2 (8.85?±?6.13?pg/mL) were observed. Individualized hormone replacement therapy (HRT) was initiated after diagnosis. After 2 years of treatment, all patients had obvious breast development; the uterus showed (2.38?±?0.60)?×?(1.38?±?0.70)?×?(1.38?±?0.55) cm growth. The incidence of osteopenia changed from 69.70% to 22.22% and that of osteoporosis changed from 18.18% to 0. Dysgeminoma was found in one patient. We concluded that gonadal dysgenesis in 46,XX PGD causes secondary sexual characteristic absence, tendency of taller, osteoporosis, infertility, and sexual health problems. There is minor chance of tumor occurrence for the patients. Optimal care including HRT and close follow-up are required.     

Ovarian steroid cell tumor and a contralateral ovarian thecoma in a postmenopausal woman with severe hyperandrogenism.

A 49-year-old woman presented with rapidly progressing hirsutism, receding hairline, male-pattern baldness and deepening of voice, which had developed over the past 2 years. Hormonal evaluation showed a markedly elevated serum testosterone level (418 ng/dl) and no evidence of increased production of cortisol, dehydroepiandrosterone, dehydroepiadrosterone-sulfate, androstenedione, or 17-hydroxyprogesterone. Transvaginal ultrasound examination suggested the presence of a small mass within the left ovary, but all other radiological studies, including adrenal and ovarian computed tomography, magnetic resonance imaging, radio-labelled cholesterol scintigraphy and positron emission tomography, were negative. Subsequently, bilateral selective venous sampling showed a marked testosterone gradient in the right ovarian vein. Bilateral salpingo-oophorectomy was performed (the patient had had a previous vaginal hysterectomy), and histopathological examination revealed a 10-mm steroid cell tumor within the right ovary and a 15-mm thecal cell tumor within the left ovary. The postoperative serum testosterone level returned to normal and the patient showed a slow regression of clinical symptoms. The simultaneous occurrence of a virilizing ovarian steroid cell tumor and an apparently non-functioning thecoma within the contralateral ovary emphasizes the potential pitfalls that may exist in the preoperative evaluation of patients with markedly increased testosterone production.     

Ovarian steroid cell tumor and a contralateral ovarian thecoma in a postmenopausal woman with severe hyperandrogenism

A 49-year-old woman presented with rapidly progressing hirsutism, receding hairline, male-pattern baldness and deepening of voice, which had developed over the past 2 years. Hormonal evaluation showed a markedly elevated serum testosterone level (418 ng/dl) and no evidence of increased production of cortisol, dehydroepiandrosterone, dehydroepiandrosterone-sulfate, androstenedione, or 17-hydroxyprogesterone. Transvaginal ultrasound examination suggested the presence of a small mass within the left ovary, but all other radiological studies, including adrenal and ovarian computed tomography, magnetic resonance imaging, radio-labelled cholesterol scintigraphy and positron emission tomography, were negative. Subsequently, bilateral selective venous sampling showed a marked testosterone gradient in the right ovarian vein. Bilateral salpingo-oophorectomy was performed (the patient had had a previous vaginal hysterectomy), and histopathological examination revealed a 10-mm steroid cell tumor within the right ovary and a 15-mm thecal cell tumor within the left ovary. The postoperative serum testosterone level returned to normal and the patient showed a slow regression of clinical symptoms. The simultaneous occurrence of a virilizing ovarian steroid cell tumor and an apparently non-functioning thecoma within the contralateral ovary emphasizes the potential pitfalls that may exist in the preoperative evaluation of patients with markedly increased testosterone production.     

Erythrocytosis due to an erythropoietin-producing large uterine leiomyoma

BACKGROUND: Various etiologies of myomatous erythrocytosis syndrome (erythrocytosis associated with a uterine leiomyoma), one of which is altered production of erythropoietin, have been proposed. We report a case of erythrocytosis associated with a large uterine leiomyoma in which erythropoietin activity and immunostaining for erythropoietin in the leiomyoma were found. CASE: A 64-year-old woman, gravida 2, para 1, was referred to our department for treatment of a large uterine myoma and erythrocytosis with elevated levels of erythropoietin. Total abdominal hysterectomy with bilateral salpingo-oophorectomy was performed, and the results of the pathological examination confirmed the diagnosis of leiomyoma of the uterus, which weighed 920 g. The patient's postoperative course was satisfactory, and the levels of hemoglobin and erythropoietin were normalized and remained within normal ranges. The level of erythropoietin in the uterine leiomyoma measured by radioimmunoassay was elevated (372 mU/wet gram), and specific immunostaining for erythropoietin was found in the cytoplasm of leiomyoma cells. The levels of erythropoietin extracted from uterine leiomyomas of other patients who did not have erythrocytosis (control patients, n = 5) were lower (65 +/- 15.3 mU/wet gram), but specific immunostaining for erythropoietin was also found in the cytoplasm of leiomyoma cells from those patients. CONCLUSIONS: Our case was typical of myomatous erythrocytosis syndrome in which uterine leiomyoma was proved to produce erythropoietin. Our results also suggest that erythropoietin is produced in uterine leiomyomas of patients with and without erythrocytosis. Leiomyoma of the uterus may affect the production of erythropoietin and may develop into myomatous erythrocytosis syndrome when the level of erythropoietin exceeds the normal range.     

Inhibin A and inhibin B producing ovarian fibrothecoma revealed by suppression of follicle stimulating hormone (FSH) in a post-menopausal woman: report of the first case

In this report, we describe the first case ever reported in the literature, of an inhibin-A (INHA) and inhibin-B (INHB) producing fibrothecoma. A post-menopausal woman was referred to our unit because of follicle stimulating hormone (FSH) level below the reference interval for postmenopausal women. By contrast luteinizing hormone, hCG, and estradiol levels were within normal range. This discrepancy suggested the secretion of FSH inhibitory factors. INHB and INHA levels were markedly elevated for age, 475?pg/mL and 100?pg/mL, respectively. Ultrasonography and MRI showed a pelvic mass of indeterminate nature. Abnormal inhibin secretion is generally observed in granulosa cell tumors. In this case this etiology was unlikely because of low estradiol and AMH levels. Surgical exploration revealed a 10?cm mass of the left ovary proven histologically to be an ovarian fibrothecoma (OFT). After tumor removal, INHB and INHA levels decreased rapidly. Only three cases of OFT with an important secretion of INHB have been reported to date. INHA secretion has never been associated with OFT. There is a need to develop coupled hormone and imaging strategies to diagnose the source of INH secretion in case of FSH/LH discrepancy.     

Testosterone Levels Are Not Associated With Magnitude of Deformity in Men With Peyronie’s Disease

IntroductionThere are some data suggesting that there is a relationship between the magnitude of Peyronie’s disease (PD)–associated penile curvature and low serum testosterone.AimTo evaluate the relationship between PD associated penile deformity and total testosterone (TT) and free testosterone (FT) levels.MethodsWe identified patients diagnosed with PD who had early morning TT measurements. Because laboratories have different reference values, we analyzed testosterone values 2 ways, as raw values and as standardized values (TT and FT values converted into z-scores for each laboratory). Deformity assessment was conducted during an intracavernosal injection–induced rigid erection. The association between T levels and magnitude of penile curvature was analyzed in a number of ways. First, an independent measure t-test tested differences in curvature degree by TT groups (low T: <300 ng/dL; normal T: ≥300 ng/dL). Second, an association was sought between T levels based on quartiles of the normal range (<300, 300–450, 450–600, and >600 ng/dL). These analyses were conducted for both TT and FT levels and using both raw and standardized T values. Third, multivariable analysis using multiple linear regression was performed in an attempt to define predictors of the degree of penile curvature. Factors entered into the model included: TT level, FT level, patient age, race (white vs other), number of co-morbidities, body mass index, presence of erectile dysfunction, duration of PD, and prostatectomy (yes vs no).Main Outcome MeasuresThe relationship between T levels and the magnitude of penile curvature.Results184 subjects met all study criteria. Average age was 54 ± 12 years. Mean TT level was 425 ± 176 ng/dL, and mean curvature magnitude was 35° ± 19°. The percent of subjects in the first through fourth TT quartiles was 26%, 34%, 24%, and 16%. As a continuous variable, there was no association between TT levels (r = ?0.01, P = .95) or FT levels (r = ?0.08, P = .30) and the curvature magnitude. When examining TT groups, there was no difference in mean curvature between the low TT group and the normal TT group (35.4° ± 17° vs 34° ± 20°, P = .70). When analyzing the TT and FT levels standardized into z-scores, there was no association between degree of curvature and TT z-scores (r = ?0.003, P = .95) and FT z-scores (r = ?0.08, P = .43). There was also no association between testosterone levels and degree of curvature in the multivariable model.ConclusionsThere does not appear to be any association between testosterone levels and the magnitude of PD-associated penile deformity.Mulhall JP, Matsushita K, Nelson CJ. Testosterone Levels Are Not Associated With Magnitude of Deformity in Men With Peyronie’s Disease. J Sex Med 2019;16:1283–1289.     

Role of kisspeptin in polycystic ovary syndrome (PCOS)

Objective: Due to the complex relationship between kisspeptin and the hypothalamic-pituitary-gonadal axis, the study was planned to measure the kisspeptin levels in polycystic ovary syndrome (PCOS) and to analyze the correlations between kisspeptin and PCOS-related reproductive, metabolic changes.

Methods: The study was designed as a prospective study in Dokuz Eylul University between December 2011 and September 2013. A total of 285 PCOS cases and 162 controls were recruited. After the antropometric measeruments and physcial examination, blood samples were taken for biochemical analysis.

Results: PCOS group’s mean BMI was 24.32?±?3.40 and for the control group, BMI value was 23.44?kg/m²?±?4.08 (p?=?0.351). PCOS patients’ FSH level was 5.10?±?2.01 mIU/L, LH value was 7.75?±?4.31 mIU/mL, LH/FSH ratio was 1.70?±?1.28, DHEAS value was 221.84?±?105.02?mg/dl, total testosterone value was 50.51?±?27.93?ng/ml, free testosterone value was 2.52?±?1.05?pg/ml, SHBG was 63.74?±?45.62?nmol/L, LDL was 102.56?±?23.45?mg/dL, HDL value was 51.36?±?12.15?mg/dL, total cholesterol value was 214.85?±?39.27?mg/dL, triglyceride value was 112.95?±?46.88?mg/dL, Apo A1 value was 171.30?±?35.35?mg/dL, Apo B value was 71.08?±?19.07?mg/dL, Apo B/A1 ratio was 0.42?±?0.14, free androgen index was 13.77?±?14.15, fasting glucose value was 80.68?±?13.80?mg/dL, fasting insulin levels was 14.13?±?9.11 μiU/mL, HOMA-IR index was 2.76?±?2.34, AMH value was 5.93?±?3:33 in ng/ml, and found to be significantly higher (p?Conclusion: In this study, kisspeptin had a positive correlation with LH and leptin levels in PCOS. In fact, the serum levels of kisspeptin and leptin does not differ statistically between PCOS and healthy women. There are limited data in the literature with regard to changes in kisspeptin levels and its relation with metabolic and hormonal disturbances.     

Lipid cell tumor in an adolescent girl: a case report

BACKGROUND: Lipid cell tumors of the ovary are rare sex cord neoplasms and account for < 0.1% of ovarian tumors. CASE: A 16-year-old girl sought medical advice because of amenorrhea and virilization, manifested as facial hirsutism and temporal balding. Her total testosterone level was increased in comparison with normal values. Ultrasonography revealed an echogenic left adnexal tumor about 5.7 x 6.3 x 5.5 cm. The patient underwent laparoscopic ovarian cystectomy, and pathology showed a lipid cell tumor. Postoperatively, the serum testosterone level returned to normal. CONCLUSION: The tumor appeared to be the source of hyperandrogenism in this woman.     

CA125 Serum Levels and Secondary Laparotomy in Epithelial Ovarian Tumours

CA125 serum levels were assayed prior to 57 secondary laparotomies for ovarian epithelial tumours. Tumour was present in all 16 patients with an elevated level greater than 35 U/ml but the absence of tumour was incorrectly predicted in 15 of the 33 (45.5%) patients with CA125 levels less than 35 U/ml. For these patients the CA125 level was elevated in 14 of 20 (70%) with tumour greater than 1.5 cm, 1 of 7 (14.3%) with macroscopic tumour less than or equal to 1.5 cm and 1 of 4 (25%) with microscopic tumour. Tumour was resectable to less than or equal to 0.5 cm in 7 of 12 (58.3%) patients with CA125 less than 35 U/ml, 2 of 4 (50%) with CA125 in the range 35-100 U/ml and only 1 of 11 (9.1%) with CA125 greater than 100 U/ml (p less than .05). The CA125 level was elevated in 1 of 13 (7.7%) patients with less than 15 cm3 of tumour compared with 16 of 18 (88.9%) patients with 15 cm3 of tumour or more (p less than .0001). The correlation between the CA125 serum level and the tumour volume was almost statistically significant (r = +0.31, p = .053). The level of CA125 was normal in all 8 patients with mucinous tumours--4 of whom were found to have tumour at secondary surgery.(ABSTRACT TRUNCATED AT 250 WORDS)     

Virilizing oncocytic adrenocortical carcinoma: clinical and immunohistochemical studies

Context: Oncocytic tumors of the adrenal cortex are rare, mostly nonfunctioning and benign.

Setting: Report virilizing oncocytic adrenocortical carcinoma in a 50-year-old woman.

Patient: She presented a recent and progressive virilization syndrome, associated with high blood pressure. Hormonal evaluation showed elevated serum testosterone and delta-4-androstenedione levels, normal urinary free cortisol level and incomplete suppression of cortisol at the 1?mg dexamethasone suppression test. CT scan of the abdomen revealed a 35?mm left adrenal mass.

Intervention: The patient underwent a left adrenalectomy, and the histological study showed a 3?cm oncocytic adrenocortical carcinoma with signs of malignancy.

Results: Immunohistochemical study revealed that tumor cells expressed the steroidogenic enzymes involved into androgen synthesis (3βHSD and P450c17α), P450 aromatase and luteinizing hormone (LH) receptors. Post-operatively, signs of virilization improved rapidly, serum testosterone and delta-4-androstenedione levels returned to normal, as did the dexamethasone suppression test. During follow-up CT-scan and 18-FDG PET/CT showed a right ovary mass, corresponding to a follicular cyst associated with hyperthecosis. The patient is alive with no recurrence 48 months after adrenal surgery.

Conclusion: Oncocytic adrenocortical carcinomas, although extremely rare, should be considered in women with a virilization syndrome. In this woman immunohistochimical studies revealed the presence of steroidogenic enzymes involved into androgen synthesis and aromatization, and LH receptors could be implicated in this pathology.     

Hilus cell tumour of the ovary in a virilized, premenopausal woman. Case report and review of hyperandrogenism of ovarian origin

A 35 year-old woman presented with virilization and was found to have elevated serum testosterone levels. Investigation revealed an 11 mm hilus cell tumour in the left ovary. After unilateral oophorectomy, serum testosterone levels rapidly returned to normal levels. The various ovarian tumours and conditions causing virilization are described and a clinical approach to the investigation of virilization is outlined.     

Ovarian Leydig cell tumor in a peri-menopausal woman with severe hyperandrogenism and virilization.

The authors report a case of Leydig cell tumor in a 46-year-old woman who first presented with severe clinical hyperandrogenism and associated complex medical history. Investigations revealed markedly raised serum concentrations of testosterone (28.3 nmol/l) and free androgen index (54.4), whereas sex hormone binding globulin, random cortisol, androstenedione, 17-hydroxyprogesterone and dehydroepiandrosterone sulphate concentrations were all within the normal range. Transabdominal ultrasound and computed tomography scan of the pelvis and abdomen showed a slightly bulky right ovary, but no other abnormalities. An ovarian source of androgens was suspected and surgery was arranged. Following a three-year history of defaulting appointments due to agoraphobia, she underwent total abdominal hysterectomy with bilateral salpingo-oophorectomy and intraoperative selective ovarian venous sampling. Histopathological examination revealed a 2 cm Leydig cell tumor within the right ovary. Successful intraoperative ovarian venous sampling demonstrated significantly elevated testosterone levels (>260 nmol/l) from the right ovarian vein. Hyperandrogenaemia normalized post-operatively. The patient showed significant regression of clinical signs and symptoms, including the anxiety disorder. Clinical presentation, biochemistry and imaging modalities should allow to detect androgen-secreting ovarian tumors, while selective venous sampling should be reserved for patients whom uncertainty remains. The present case confirms that androgen-secreting ovarian tumors represent a diagnostic and therapeutic challenge. They have to be considered in the differential diagnosis of severe hyperandrogenism even in peri-menopausal women. Although selective venous sampling is of diagnostic value, however, its impact on future management should be considered on individual basis.     

Androgen-producing steroid cell ovarian tumor in a young woman and subsequent spontaneous pregnancy

Purpose

To describe the presentation and fertility sparing treatment of a young woman found to have a steroid cell tumor not otherwise specified (NOS) and her spontaneous pregnancy and delivery shortly after surgery.

Methods

A 20-year-old Hispanic female presented with hirsuitism, virilization, and elevated androgen levels (testosterone 328 ng/dL) and was wrongly diagnosed with polycystic ovarian syndrome. Four months later she sought a second opinion. Her androgens were as follows: testosterone level 485 ng/dL, androstenedione 1,738 ng/dL and DHEA 1,459 ng/dL. She had normal levels of progesterone, estradiol, and DHEA-SO4. On transvaginal ultrasound she had a solid-appearing right ovarian mass. She underwent fertility sparing surgery with a laparoscopic right oophorectomy.

Results

Gross and histological pathology confirmed a benign steroid cell tumor NOS. She had rapid normalization of all androgens 13 days after surgery. She had spontaneous resumption of menses 4 months later. She conceived despite using emergency contraception approximately 9 months following surgery and delivered a healthy boy at term without complication.

Conclusion

Prompt evaluation for an androgen producing tumor should be performed when testosterone levels are greater than 200 ng/dL. Pregnancy following removal of this rare tumor has not previously been reported.     

Pre-operative serum level of tumour-associated trypsin inhibitor and residual turnour size as prognostic indicators in Stage III epithelial ovarian cancer

Objective To evaluate the use of the pre-operative tumour-associated trypsin inhibitor (TATI) level and residual tumour size at primary surgery as a prognostic indicators for patients with Stage III epithelial ovarian cancer.
Design Retrospective cohort study.
Setting Department of Obstetrics and Gynaecology, University Hospital, Helsinki, Finland.
Participants Ninety-eight women with Stage III ovarian cancer.
Methods TATI was measured by radioimmunoassay from serum samples obtained within one week before surgery. A cutoff value of 22 μg/L was used. Multivariate analysis included pre-operative TATI level, age, histologic grade and histologic type. Mantel-Cox test was used for calculating statistical significance of differences in survival between groups.
Main outcome measures Cumulative five-year survival, pre-operative serum TATI level and residual tumour size.
Results Surgery was optimal (residual tumour size ≤ 2 cm) in 55 patients and suboptimal (residual tumour size > 2 cm) in 43. Pre-operative TATI level ≤ 22 μg/L predicted better prognosis both in patients with optimal and suboptimal surgery compared with patients with pre-operative TATI level > 22 μ/L. Patients with optimal surgery and a pre-operative TATI > 22 μg/L had a twofold relative risk of death compared with those with a pre-operative TATI ≤ 22 μg/L. The cumulative survival was less than three years for patients with suboptimal surgery and pre-operative TATI > 22 μg/L.
Conclusions Pre-operative serum TATI in combination with residual tumour size may be useful in stratifying patients with Stage III ovarian cancer into different categories in randomised treatment trials.