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All girls presenting with virilization (which signifies severe hyperandrogenism) warrant thorough investigation. Ovarian hyperthecosis (OHT) is a rare cause of virilization in premenopausal women. Here, we report the case of a previously healthy 12-year-old Chinese girl with signs of virilization at puberty. Her serum total testosterone was elevated at 5.1 nmol/L (146.97 ng/dL) (normal: <1.4 nmol/L, <40.35 ng/dL). Workup for Cushing syndrome, sex development disorders, congenital adrenal hyperplasia, and adrenal and ovarian androgen-secreting tumors was unrevealing. Ovarian and adrenal venous sampling demonstrated ovarian hyperandrogenism without lateralization. Ovarian biopsy revealed nests of theca cells in the stroma of the right ovary, substantiating the diagnosis of OHT. A single dose of a GnRH analog resulted in the complete suppression of serum testosterone, supporting the diagnosis of OHT. Medical treatment with hormonal replacement therapy normalized serum testosterone levels. Our case report illustrates the diagnostic approach to virilization among girls at puberty and the diagnosis of OHT as the underlying pathology. [ABSTRACT FROM AUTHOR]

Ovarian tumors are rare in children; however, their incidence increases with age. Of these ovarian tumors, Leydig cell tumors are some of the rarest, accounting for less than 0.1% of all ovarian tumors across all ages. Leydig cell tumors predominantly occur in postmenopausal women and are characterized by nodular proliferation of Leydig cells in the ovarian hilum with intracytoplasmic Reinke crystals. These tumors secrete androgens, which can disrupt ovarian function, clinically presenting with abnormal uterine bleeding and virilization. Although they are generally benign, current recommendations are for treatment with a unilateral salpingo-oophorectomy. In adolescents, hyperandrogenism is most commonly caused by polycystic ovarian syndrome (PCOS); however, the differential for hyperandrogenism is broad. We present a case of a 15-year-old girl with a history of primary amenorrhea who presented with a Leydig cell tumor associated with recurrent ovarian torsion and virilization. This case reviews the challenges with diagnosis, management, and future implications of a rare androgen-secreting tumor in young patients. [ABSTRACT FROM AUTHOR]

Background. NR5A1 [Steroidogenic factor 1 (SF1)] is a nuclear receptor that is essential for the development of gonads and adrenal glands as well as the establishment of steroidogenesis in these organs. The clinical findings of the mutations of NR5A1 gene in 46, XY individuals are variable. Virilization at puberty can be seen in some of the 46, XY children who have a female phenotype and are raised as female. A girl aged 13 years and 10 months old was brought by the family for deepening of her voice. On physical examination, her breast development was Tanner stage 2, axillary hair (+) and pubic hair was Tanner stage 4. She had labioscrotal fusion and 4.4 cm phallus (External Masculinisation Score was 6). Hypergonadotropic hypogonadism, low AMH and high testosterone levels were detected in laboratory tests. Uterus was not visualized in pelvic ultrasonography. Karyotype analysis was reported as 46, XY. Sequence analysis of the NR5A1 gene revealed a novel heterozygote c.1075_1089del (p.Leu359_Leu363del) variant. The patient was raised as a female and oestrogen replacement was started following gonadectomy. Conclusion. It should be kept in mind that virilization may develop at puberty in individuals with 46, XY disorder of sexual development due to NR5A1 mutation. [ABSTRACT FROM AUTHOR]

The article presents a case study of a 12-year-old assigned female at birth who presented with concerns about atypical genitalia, excess body hair, and voice deepening. The patient exhibited signs of virilization and underwent various examinations, laboratory tests, and genetic testing, revealing a diagnosis of 17-beta-hydroxysteroid dehydrogenase 3 deficiency.

Virilization of the 46,XX infant may be attributed to maternal or fetoplacental origin. Maternal sources may be endogenous, as with an androgen-producing tumor, or drug-related. Iatrogenic virilization by maternal drug exposure is rarely reported, with individual case reports and case series demonstrating the effects of progesterone and other medications affecting the pituitary-ovarian axis.1-3 The class of medications known as aromatase inhibitors are recognized as effective in treating hormone receptor-positive breast cancer by preventing the conversion of androgens into estrogens by aromatase. In fetal development, placental aromatase plays a critical role in preventing virilization of the XX fetus by maternal and fetal androgens during development. In the setting of placental aromatase deficiency, the XX fetus may be virilized. It is conceivable, therefore, that maternal exposure to aromatase inhibitors early in gestation may lead to in utero virilization, though there have been no known reports of this phenomenon to date. We present a case of virilization of a 46,XX infant attributed to pharmacologic aromatase inhibition. The infant's parents provided informed consent for the reporting of this case. [ABSTRACT FROM AUTHOR]

The Spanish artist, Jusepe de Ribera, painted a portrait of a virilized woman in 1631. He provided a brief clinical history on stone tablets, which indicates that the woman most likely harbored a benign, androgen-secreting ovarian tumor for 15 years. [ABSTRACT FROM AUTHOR]

Background: Elevated concentrations of circulating testosterone are present in hyperreactio luteinalis (HL), a pregnancy-specific, self-limited condition. HL is associated with maternal virilization in about 30% of cases. The correlation between testosterone levels and maternal virilization has not yet been quantified. Our aim was to identify a testosterone cut-off level which may allow to predict maternal virilization. Methods: A literature research was performed. Publications were chosen if serum testosterone concentrations and presence or absence of maternal virilization was mentioned. Additionally, we report serial levels of steroids analyzed by Liquid chromatography–tandem mass spectrometry (LC–MS/MS) in one case of HL managed at our institution. Results: In all, 31 cases fulfilled the search criteria. We found significant overlap between testosterone levels in asymptomatic women and women with signs of virilization (range 6.2–37.3 nmol/l and 13.7–197.5 nmol/l, respectively). The method applied for testosterone analysis was mentioned in three reports only. Peak serum testosterone concentration in our case was 120.3 nmol/l. Conclusion: From the available data, maternal virilization in HL cannot be predicted by the level of circulating testosterone. However, comparability of results is hampered by the analytical methods applied. LC–MS/MS should preferably be used for reporting concentrations of circulating testosterone. [ABSTRACT FROM AUTHOR]

Yolk sac tumors (YSTs) are rare malignancies that originate from germ cells and rarely present with endocrine symptoms. We report a case of a 13-year-old girl with a YST manifesting as virilization. A 13-year-old girl was diagnosed with a YST with endocrine symptoms because of Leydig cells in the stroma, which were identified using hematoxylin and eosin staining and immunohistochemistry. This case suggests that clinicians should consider the possibility of YST when encountering patients with symptoms of virilization. When a YST is found to have endocrine function, a functioning stroma could present. Immunohistochemistry is useful for identifying stromal cells and performing a differential diagnosis. [ABSTRACT FROM AUTHOR]

The diagnosis is made by peripheral blood tests for ovarian and adrenal hormones and imaging and, if possible, with adrenal and ovarian vein blood sampling. Although rare, an adrenal tumour was a remote possibility, but there was no adrenal abnormality on MRI (Table 1). In perimenopausal and especially postmenopausal women, rapidly progressing hirsutism and virilization could be a result of ovarian hyperthecosis or androgen-secreting ovarian tumour. [Extracted from the article]

Theca lutein cysts are rare, benign lesions responsible for gross cystic enlargement of both ovaries during pregnancy. This condition is also termed hyperreactio luteinalis. Elevated human chorionic gonadotropin (hCG) levels or states of hCG hypersensitivity seem to promote these changes, which in up to 30% of patients produce clinical signs of hyperandrogenism. Given the self-limiting course of theca lutein cysts, which are subject to spontaneous postpartum resolution, conservative treatment is the mainstay of patient management. Described herein is a rare case of theca lutein cysts with maternal virilization that failed to regress by 9 months after childbirth. Surgical intervention was eventually undertaken, necessitated by adnexal torsion. [ABSTRACT FROM AUTHOR]

Herein, we report two girls with a neonatal screening (NS)-negative 21-hydroxylase deficiency (21-OHD) requiring treatment with hydrocortisone due to virilization that developed in late childhood. Patient 1 was born prematurely on the 30th gestational week with normal external genitalia at birth. She passed the NS for 21-OHD. At 6 yr of age, she was referred to a hospital for evaluation of premature pubarche and clitoromegaly. Her diagnosis was central precocious puberty, and GnRH agonist was initiated. However, her symptoms did not improve despite treatment for over 4 years. She was then referred to our hospital where she was diagnosed with 21-OHD. Although she was started on hydrocortisone therapy, her adult height reached only 140 cm (-3.4 SD). Patient 2 was delivered at 37 weeks of gestation and passed the NS for 21-OHD. She was referred to a hospital because of premature pubarche at the age of 6 yr. She was diagnosed with 21-OHD, and hydrocortisone replacement therapy was initiated. Her present height at 13 yr of age is 148 cm (-1.3 SD). These cases reminded us that the possibility of 21-OHD should be considered when patients show premature pubarche or precocious puberty, even if they passed the NS test for 21-OHD. [ABSTRACT FROM AUTHOR]

Ovarian cystadenomas may present in a functional manner. Biochemical workup of seemingly benign ovarian lesions should be considered in the appropriate clinical context. [ABSTRACT FROM AUTHOR]

Background: Only 0.5% of all ovarian tumors are Leydig cell tumors and they are generally benign and unilateral. These androgen-secreting tumors lead to virilizing symptoms, most often in postmenopausal women. Because Leydig cell tumors are typically small, diagnosing them accurately can be challenging. Case Report: We report the case of a 77-year-old woman who was referred to our Endocrinology Clinic because of a 5-year history of hirsutism (Ferriman-Gallwey score of 11) with no discernible cause. The patient had high levels of serum testosterone and a normal level of dehydroepiandrosterone sulfate. Imaging, including transvaginal ultrasound and pelvic magnetic resonance, revealed a 16-mm uterine nodule, which was suspected to be a submucous leiomyoma, but no adrenal or ovarian lesions. Despite the lack of findings on imaging and because of the high suspicion for an androgen-secreting ovarian tumor, bilateral laparoscopic oophorectomy was performed. Histological examination of the specimen revealed a non-hilar Leydig cell tumor that measured 8 mm in its largest axis. After the surgery, the patient had significant clinical improvement and her laboratory test results normalized. Her sister had the same symptoms and laboratory findings at a similar age, which raised the suspicion of a possible familial genetic syndrome. No genetic testing was performed, however, because the patient's sister declined further diagnostic investigation. Conclusions: Leydig cell tumors are rare, and even when they are small, they can cause symptoms related to androgen excess. As a result, diagnosing them often is challenging. [ABSTRACT FROM AUTHOR]

We report a case of a 4-year-old girl with an ovarian steroid cell tumor, not otherwise specified (SCT-NOS). She was admitted to the hospital with progressing virilization and Cushing's syndrome, which included abnormality of the perineum, hirsutism, hypertrichosis, flushing of face, hoarseness, and weight gain. Blood testing showed a significantly increased testosterone level and slightly increased cortisol level. Computed tomography scan revealed an 8.0 × 5.0 × 5.0 cm tumor of the right ovary. The patient underwent right salpingo-oophorectomy, and pathological examination showed malignant potential. Three courses of bleomycin, etoposide, and cisplatin were administered as postoperative chemotherapy. After tumor resection, her testosterone decreased to undetectable levels. However, during the course of the treatment, the patient suffered from adrenal insufficiency resulting in the need for hydrocortisone replacement therapy. Although SCT-NOS in childhood are typically benign, pathological findings should be carefully observed for potential malignancy. In cases of cortisol-producing SCT-NOS, serum levels should be monitored, and hydrocortisone replacement therapy should be considered before resection. [ABSTRACT FROM AUTHOR]

Absent SRY gonadal dysgenesis (negative) is the set of clinical and biological manifestations linked to the lack of development of the testes in humans. Authors report the first case of gonadal dysgenesis SRY-negative 46, XX male with gynecomastia documented in Mali. Case observation: This is a 15 years old boy of a deaf-mute brother, no family consanguinity. He was referred to the hospital because of severe bilateral gynecomastia. Hypergonado-tropic hypogonadism condition was investigated by hormonal laboratory assessment and the result of cytogenetic analysis carried out in France revealed a karyotype SRY-negative 46, XX isch Yp11, 3. The patient received psychological assistance and substitutive treatment based on testosterone. Reconstructive surgery was also conducted to correct urogenital malformations. Conclusion: Diagnosis of 46, XX male syndrome is rare and need cytogenetic analysis. In Mali, cost and availability of this technique make diagnosis difficult and care inadequate for patients. [ABSTRACT FROM AUTHOR]

Leydig cell tumors are tumors of the steroids cells and represent less than 0.5% of ovarian tumors. They occur most often in postmenopausal women and present with virilization in half of the cases. We report the case of a 53-year-old woman with virilization history. Magnetic resonance imaging showed high serum testosterone levels and a 2-cm nodule in the right ovary. The patient underwent bilateral oophorectomy, and the pathological analysis confirmed the diagnosis of Leydig cell tumor in the right ovary. The day after surgery, serum testosterone level was normalized. In four months, the patient had normal serum testosterone level and partial regression of alopecia. In postmenopausal women with progressive virilization, ovarian neoplasms producing androgens should be investigated. [ABSTRACT FROM AUTHOR]

Androgen biosynthesis in the human fetus proceeds through the adrenal sex steroid precursor dehydroepiandrosterone, which is converted to testosterone in the gonads, followed by further activation to 5α-dihydrotestosterone in genital skin, thereby facilitating male external genital differentiation. Congenital adrenal hyperplasia due to P450 oxidoreductase deficiency results in disrupted dehydroepiandrosterone biosynthesis, explaining undervirilization in affected boys. However, many affected girls are born virilized, despite low circulating androgens. We hypothesized that this is due to a prenatally active, alternative androgen biosynthesis pathway from 17α-hydroxyprogesterone to 5α-dihydrotestosterone, which bypasses dehydroepiandrosterone and testosterone, with increased activity in congenital adrenal hyperplasia variants associated with 17α-hydroxyprogesterone accumulation. Here we employ explant cultures of human fetal organs (adrenals, gonads, genital skin) from the major period of sexual differentiation and show that alternative pathway androgen biosynthesis is active in the fetus, as assessed by liquid chromatography-tandem mass spectrometry. We found androgen receptor expression in male and female genital skin using immunohistochemistry and demonstrated that both 5α-dihydrotestosterone and adrenal explant culture supernatant induce nuclear translocation of the androgen receptor in female genital skin primary cultures. Analyzing urinary steroid excretion by gas chromatography-mass spectrometry, we show that neonates with P450 oxidoreductase deficiency produce androgens through the alternative androgen pathway during the first weeks of life. We provide quantitative in vitro evidence that the corresponding P450 oxidoreductase mutations predominantly support alternative pathway androgen biosynthesis. These results indicate a key role of alternative pathway androgen biosynthesis in the prenatal virilization of girls affected by congenital adrenal hyperplasia due to P450 oxidoreductase deficiency. [ABSTRACT FROM AUTHOR]

Mutations of CYP21A2 variably decrease 21-hydroxylase activity and result in a spectrum of disease expressions in patients with congenital adrenal hyperplasia (CAH). We examined the association between CYP21A2 mutations and virilization (Prader score) in females with CAH. The study population included 187 CAH females with fully characterized CYP21A2 mutations. One hundred fifty-eight patients were sorted into groups by expected enzyme activity (percent of normal activity) of the less severely affected allele: (A) null, 0%; (B) I2G, 1%; (C) I172N, 2%; and (D) V281L, >2%. We observed an inverse relationship between virilization and residual enzyme activity ( P < 0.001). Subjects in group A or B had a significantly higher likelihood (unadjusted odds ratio: 16; P < 0.001) of developing severe virilization compared with those in group C. Surprisingly, 24% of group D patients, whose mutation is usually associated with nonclassical (NC) CAH, had severe virilization. Among subjects with the NC P30L mutation, 66% expressed unexpected virilization. Virilization, usually leading to extensive reconstructive surgery, is highly likely in patients with null or I2G mutations; however, NC mutations (P30L/V281L) may also lead to unexpected virilization. These findings have implications for prenatal counseling and highlight the need for additional investigations into other factors that influence virilization in CAH. [ABSTRACT FROM AUTHOR]

Abstract: Background: Steroidogenic factor-1 (SF-1) gene (NR5A1) mutations cause disorders of sexual development due to gonadal dysgenesis, particularly in 46,XY individuals. In cases exhibiting this mutation, the phenotype is heterogeneous, and it may vary within a spectrum ranging from complete female appearance to an infertile male. Virilization observed in some cases in the pubertal age group may lead to diagnostic difficulties. Case: The present case report describes the clinical, histopathologic, and genetic characteristics of a 46,XY case, who was born with a female phenotype and raised as a girl, presented with findings of virilization in the pubertal period. She had no germ cells and very few Leydig cells with atrophic testis on biopsy and in whom a novel heterozygous mutation in the SF-1 gene (a heterozygous 7-bp deletion mutation in exon 7 [c.1308-1314del7bp] causing frameshift) was identified. Summary and Conclusion: Although the gonads are very dysgentic in patient with SF-1 mutations, sufficient androgen synthesis can cause severe virilization during puberty. [Copyright &y& Elsevier]

Ovarian steroid cell tumors are rare, life-threatening neoplasms that make about 0.1% of all primary ovarian tumors. They frequently present in premenopausal women with the manifestation of virilization. We report a 58-year-old postmenopausal woman that referred to our clinic with clinical manifestation of virilization. Laboratory findings showed markedly elevated serum testosterone level and ultrasound showed 2 follicles with 7 mm diameters in the left ovary. She treated by bilateral salpingo-oophorectomy and synchronous hysterectomy. Histological pathology confirmed a benign steroid cell tumor. The presentation of new-onset and rapid progressive hyperandrogenism is rare in postmenopausal women. In diagnosis, we must consider adrenal and ovarian malignancies. Stromal luteoma is a rare benign ovarian tumor, Which is treated with surgical treatment. [ABSTRACT FROM AUTHOR]

Background Aromatase deficiency is a rare autosomal recessive disorder that is caused by an impairment of androgen conversion to estrogens. Affected 46, XX individuals generally present with virilization of external genitalia at birth and mutations in CYP19A1 g ene. Objective This study described the clinical features and molecular basis of a Chinese 46, XX girl born with ambiguous genitalia and investigated the functional alteration of two novel mutations of the CYP19A1 gene. Methods and results Obvious prepartum virilization and remarkably elevated testosterone were observed in the mother, who was initially suspected to have a testosterone-producing ovarian tumor. Clinical phenotypes and hormone profiles of the patient and her mother were investigated. Genotyping analyses of the CYP19A1 gene were performed in the patient and her parents. Functional impairment of the mutations was explored using three-dimensional computer model and mutagenesises in vitro transfection assays. A compound heterozygous mutation of the CYP19A1 gene was revealed in the patient, with a G deletion in nucleotide 264 of exon 3 in one allele and a 23-bp insertion in exon 9 in another allele; both mutations resulted in reading frame-shifts that led to truncated proteins of 87 and 360 amino acids, respectively. Molecular modeling analysis suggested that the two renascent truncated proteins lacked crucial amino acids that were involved in substrate access and catalysis as well as heme-binding region. Functional studies in transfected HEK-293T cells exhibited a nearly complete abolishment of enzyme activity, which may underlie the phenotype and hormone profile. Conclusions Two novel CYP19A1 mutations were identified in a Chinese girl born with ambiguous genitalia and severe maternal virilization during pregnancy. Maternal virilization should prompt consideration of aromatase deficiency, preventing unnecessary interventions in pregnancy. This study broadens the spectrum of phenotype and genetic mutations of this rare disorder. [ABSTRACT FROM AUTHOR]

Background: In 21-hydroxylase deficiency (21-OHD), there is an influence of genotype on the severity of external genitalia virilization. However, females carrying mutations predicting a similar impairment of enzymatic activity present a wide variability of genital phenotypes. In such cases, interindividual variability in genes related to the sex steroid hormone pathway could play a role. Objective: To evaluate the influence of POR, HSD17B5 and SRD5A2 variants on the severity of external genitalia virilization in 21-OHD females. Design and Patients: Prader stages were evaluated in 178 females with 21-OHD from a multicenter study. The 21- OHD genotypes were divided into two groups according to their severity: severe and moderate. The influences of the POR p.A503V, HSD17B5 c.-71A>G, HSD17B5 c.-210A>C, and SRD5A2 p.A49T and p.V89L variants on the degree of external genitalia virilization were analyzed. Results: The POR p.A503V, HSD17B5 c.-71A>G, HSD17B5 c.-210A>C, and SRD5A2 p.A49T and p.V89L variants were found in 25, 33, 17, 1, and 31% of the alleles, respectively. In uni- and multilinear regression, HSD17B5 c.-210A>C has a significant influence on the degree of external genitalia virilization. This variant was also identified with a higher frequency in the most severely virilized females. Conclusion: We demonstrated that a variant in the promoter region of HSD17B5 related to fetal androgen synthesis influences the genital phenotype in 21-OHD females. [ABSTRACT FROM AUTHOR]

11-β hydroxylase deficiency (11 OHD) is the second most frequent type of congenital adrenal hyperplasia other than 21-hydroxylase deficiency. Both type of enzyme deficiencies may lead to complete virilization (prader stage 5) in 46,XX individuals. Majority of the cases with 11 OHD manifest hypertension which distinguish this disorder from the more common 21-hydroxylase deficiency. Herein we reported a 16-year old boy who presented to the pediatric endocrinology outpatient clinic with the complaint of short stature and was found to have hypertension, hyperpigmented skin, facial acne and nonpalpable gonads despite his male-appearing external genitalia. Based on these findings, further evaluation revealed the diagnosis of 11 OHD, resulting in complete virilization in a 46,XX patient. [ABSTRACT FROM AUTHOR]

Sclerosing stromal tumours are rare benign ovarian neoplasms of the sex cord stromal that occur predominantly in the second and third decades of life. To date, fewer than 200 cases have been described in the literature and most patients have menstrual irregularities and pelvic pain. Sclerosing stromal tumours were reported in which the inactive tumours did not represent endocrine clinical symptoms; however, currently according to several reports, it is the active tumour that produce hormones. Only a few cases of virilizing sclerosing stromal tumours of the ovary have been described in the literature and in this report first describes sclerosing stromal tumour of the ovary in a postmenopausal woman presenting with virilization. [ABSTRACT FROM AUTHOR]

Key Clinical Message Some testosterone-producing adrenal tumors can be successfully treated with long-acting Gn RH analogs and adrenal venous sampling can be useful to detect rare ectopic sex steroid-producing tumors or confirm bilateral adrenal androgen hyperproduction in female hyperandrogenism. [ABSTRACT FROM AUTHOR]

Virilizing ovarian dermoid cysts are very rare. The source of androgen in these cysts may be tumors such as Sertoli-Leydig cell tumor or Leydig cell hyperplasia. A 52-year-old postmenopausal female with virilization was found to have an ovarian dermoid cyst on ultrasound. Her serum testosterone levels were elevated. Leydig cell hyperplasia within the dermoid cyst was found to be the source of androgen in this patient. [ABSTRACT FROM AUTHOR]

Highlights: [•] Novel CYP19A1 mutation R192H causes 80% reduction in enzyme activity. [•] The R192H mutation in CYP19A1 caused 46,XX disorder of sex development. [•] There was no maternal virilization during pregnancy. [•] Healthy 46,XY brother with R192H had hypospadias and cryptorchidism. [•] Computational structure analysis shows R192H disrupts substrate access and binding. [ABSTRACT FROM AUTHOR]

Objective. To report an unusual case of ovarian Leydig cell hyperplasia resulting in virilization in a postmenopausal woman. Methods. Patient's medical history and pertinent literature were reviewed. Results. A 64-year-old woman presented with virilization with worsening hirsutism, deepening of her voice, male musculature, and male pattern alopecia. Her pertinent past medical history included type 1 diabetes, hyperlipidemia, and hypertension. Her pertinent past surgical history included hysterectomy due to fibroids. On further work-up, her serum total testosterone was 506 ng/dL (nl range: 2-45) and free testosterone was 40 pg/mL (nl range: 0.1-6.4). After ruling out adrenal causes, the patient underwent an empiric bilateral oophorectomy that showed Leydig cell hyperplasia on pathology. Six weeks postoperatively, serum testosterone was undetectable with significant clinical improvement. Conclusion. Postmenopausal hyperandrogenism can be the result of numerous etiologies ranging from normal physiologic changes to ovarian or rarely adrenal tumors. Our patient was found to have Leydig cell hyperplasia of her ovaries, a rarely reported cause of virilization. [ABSTRACT FROM AUTHOR]

The 21-hydroxylase deficiency ( 21OHD) is caused by CYP21A2 mutations resulting in severe or moderate enzymatic impairments. 21OHD females carrying similar genotypes present different degrees of external genitalia virilization, suggesting the influence of other genetic factors. Single nucleotide variants ( SNVs) in the CYP3A7 gene and in its transcription factors, related to fetal 19-carbon steroid metabolism, could modulate the genital phenotype. To evaluate the influence of the 21OHD genotypes and the CYP3A7, PXR and CAR SNVs on the genital phenotype in 21OHD females. Prader scores were evaluated in 183 patients. The CYP3A7, PXR and CAR SNVs were screened and the 21OHD genotypes were classified according to their severity: severe and moderate groups. Patients with severe genotype showed higher degree of genital virilization (Prader median III, IQR III-IV) than those with moderate genotype ( III, IQR II-III) (p < 0.001). However, a great overlap was observed between genotype groups. Among all the SNVs tested, only the CAR rs2307424 variant correlated with Prader scores ( r2 = 0.253; p = 0.023). The CYP21A2 genotypes influence the severity of genital virilization in 21OHD females. We also suggest that the CAR variant, which results in a poor metabolizer phenotype, could account for a higher degree of external genitalia virilization. [ABSTRACT FROM AUTHOR]

Ovarian hilus cell tumor is a rare cause of virilization. A 54-year-old female presented with new-onset facial and peri-areolar hair growth, alopecia, and progressive deepening of the voice. She was virilized with male pattern baldness, hirsutism, and clitoromegaly, and a markedly elevated total testosterone. Ultrasound and CT failed to show evidence of an adrenal or ovarian lesion. Other causes of hyperandrogenism were ruled out and the patient underwent a bilateral salpingo-oophorectomy. Pathology showed a well-circumscribed 0.8 x 0.6 x 0.75 cm mass in the left ovary composed of Leydig cells indicative of a hilus cell tumor. One month after surgery the total testosterone level was normal and there was gradual but complete resolution of masculinization. Ovarian hilus cell tumors are rare, difficult to localize, but cause dramatic virilization due to androgen overproduction. Oophorectomy and careful examination of the pathological specimen can confirm the diagnosis and is curative as well. [ABSTRACT FROM AUTHOR]

Background: Mature cystic teratomas are the most common form of ovarian tumor in children and adolescents. These tumors are mostly benign and non-secreting. Virilization from an ovarian teratoma is exceptionally rare in pediatrics. Equally rare is the association of ovarian teratomas with auto-immune encephalitis. Methods: We describe the case of a 15-year-old girl with menstrual abnormalities and virilization, who had a past medical history of encephalitis of an unknown etiology 16 months prior to presentation. Results: Endocrine evaluation revealed an elevated serum testosterone and 17-hydroxy progesterone. A large left ovarian tumor was seen on a CT scan. Surgical excision revealed a mature cystic teratoma containing 6 liters of clear fluid with high androgen levels. Antibodies to the N-methyl-D-aspartate receptor of the hippocampus were detected in pre-operatively archived serum, but undetectable 6 months postoperatively. Immunohistochemistry studies on the tumor sections revealed that the antibodies in the patient’s serum reacted with areas of the tumor expressing the N-methyl-D-aspartate receptor. Postoperatively, the patient’s menstrual cycles became regular and her behavioral problems resolved. Her testosterone levels fell precipitously as well. Conclusion: Both virilizing mature cystic teratomas and teratoma-associated encephalitis are extremely rare in the pediatric population. We report on the first instance of these 2 rare entities occurring in the same patient. Copyright © 2009 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Virilization in pregnancy due to borderline mucinous ovarian tumors is very rare. A case of a 28-year-old patient who was noted at 28 weeks' gestation to have marked virilization with raised serum androgens, ascites and a large complex right adnexal mass is presented. Delivery was carried out by cesarean section and at surgery a large tumor was noted in the right ovary. Histology revealed a borderline mucinous ovarian tumor with stromal luteinization, but there was no evidence of stromal invasion. Serum androgens returned to normal levels following surgery and the maternal virilization had resolved at the 6-week postnatal visit. Stromal changes in borderline mucinous ovarian tumors may result in virilization due to androgen production; surgical removal is associated with an excellent clinical outcome. [ABSTRACT FROM AUTHOR]

Introduction: In females, congenital adrenal hyperplasia (CAH), a spectrum of inherited genetic conditions related to the disruption of adrenal steroidogenesis, is among the most common conditions leading to inappropriate virilization. For adolescent and adult women, progression of hirsutism may have many psychological concerns. Objectives: To explore the psychological distress of a young Tunisian woman who sought medical help and psychological support at a late stage, after suffering from genital ambiguity and severe virilization. Methods: Harboring phenotypic male transformation at puberty, our patient attended genetic counselling for cytogenetics assessment. Clinical, biological, psychological and genetic explorations were thus carried out. Results: A 17-year-old female was born from first-degree consanguineous parents, and had healthy siblings (a sister and three brothers). After a single menstrual episode at puberty, she developed amenorrhea and an unexpected progressive virilization, including hirsutism with an inappropriate beard that she had to shave every day and a male voice. Clinical examination revealed a male morphotype with an enlarged clitoris that resemble a penis, male-type pubic hair, underdeveloped of breasts, abnormal cutaneous hyperpigmentation, and a short stature. Pelvic ultrasound revealed a small uterus, but with no visualized gonads. Genetic exploration showed a female 46,XX karyotype and the absence of Y chromosome sequences. Diagnosis of a non-classic CAH was confirmed. Psychological assessment found that the psychological development of the sexual identity corresponded to the assignment of the female sex. A severe psychological suffering due to the non-acceptance of her virile appearance impaired the quality of her daily personal and social life. Stigmata of a depressive syndrome were also revealed. Conclusions: Particular attention to the psychological assessment of patients with CAH is recommended, as changes in physical appearance have a detrimental impact on psychological and mental well-being. Disclosure of Interest: None Declared [ABSTRACT FROM AUTHOR]

Background. Ovarian neoplasms, other than sex cord–stromal tumors, are rare causes of hyperandrogenism. Only two cases of primary mucinous carcinomas associated with virilization have been reported.Case. A 50-year-old female was referred to our clinic with a large pelvic mass. On examination she had significant facial hirsutism, clitoromegaly, and male pattern pubic hair growth. Serum levels of testosterone and dihydroepiandrosterone sulfate were elevated. A 30-cm, multilocular, solid and cystic, left ovarian mass was resected. Histology revealed moderately to poorly differentiated mucinous cystadenocarcinoma. The ovarian stroma contained florid proliferation of luteinized cells. The right ovary showed cortical stromal hyperplasia. Abnormal hormone values normalized 10 days postoperatively.Conclusion. We report a rare case of mucinous cystadenocarcinoma with virilization, review the literature, and discuss the mechanisms of hormone production by these tumors. [Copyright &y& Elsevier]

A case is reported of yolk sac tumor occurring in the left ovary and complicated by pregnancy. The 22-year-old patient presented at 28 weeks gestation with virilization and elevated serum levels of testosterone and alpha-fetoprotein. The tumor showed the typical features of yolk sac tumor with a mixture of islands of Leydig cells. The accumulations of Leydig cells were well demarcated from the cellular components of the yolk sac tumor and were distributed throughout the tumor, although with predominant localization at the periphery. By immunohistochemistry the Leydig cells were intensely positive for vimentin and negative for cytokeratins, allowing clear distinction from the cell components of the yolk sac tumor, which were positive for cytokeratins and negative for vimentin. Testosterone was also identified in the cytoplasm of the Leydig cells. After tumor resection the testosterone and alpha-fetoprotein levels declined simultaneously; this, together with the immunohistochemical demonstration of testosterone, indicates that the Leydig cells were responsible for the endocrine manifestations. Furthermore, antibodies against inhibin alpha-subunit and calretinin could be used to detect the Leydig cells. The present case, a combination of yolk sac tumor and Leydig cells acting as a functioning stroma and causing virilization during pregnancy, is very rare. [ABSTRACT FROM AUTHOR]

Objective Congenital adrenal hyperplasia ( CAH) is an autosomal recessive inherited disorder in which the lack of 21-hydroxylase results in cortisol and aldosterone insufficiency and an overproduction of adrenal androgens. High levels of androgens in women may cause virilization of the larynx and a masculine voice. The purpose of the present study was to investigate subjective voice problems due to virilization in women with CAH. Design/Patients Participants were 42 women with CAH between 25 and 71 years of age, and 43 age-matched female healthy control subjects. All patients, but two, were in good disease control. Measurements A validated Swedish version of the Voice Handicap Index ( VHI) and questions related to voice virilization were used. Endocrine data were obtained from medical files. Results Patients scored significantly higher on VHI when the results were divided into no/mild, moderate and severe voice handicap as compared with the control subjects. They rated significantly higher for 'dark voice' and for 'being perceived as a man on the phone' compared with controls. Seven per cent of the women with CAH had voice problems clearly related to voice virilization. High ratings of dark voice were significantly associated with long periods of under-treatment with glucocorticoids and higher bone mineral density but not with severity of mutation. Conclusion Subjective voice problems due to voice virilization may occur in women with CAH. This further emphasizes the importance of avoiding long periods of increased androgen levels to prevent irreversible voice changes. For these patients, we recommend referral to voice assessment and treatment. [ABSTRACT FROM AUTHOR]

Background: Adenomas of the adrenal gland are rare causes of virilization in childhood. Case Report: A girl aged 2 years and 4 months presented with pubarche, distinct clitoral hypertrophy, tall stature, and increased height velocity. Plasma testosterone and dehydroepiandrosterone were elevated. Androgens remained unchanged after adrenocorticotropic hormone, and dexamethasone administrations. Ultrasound examination and magnetic resonance imaging indicated an extra-adrenal mass adjacent to the left adrenal gland, which was removed by endoscopic surgery. However, plasma androgens remained elevated and 131I-iodomethyl-norcholesterol scintigraphy revealed tracer enhancement in the right adrenal gland, which was consecutively removed. Virilization regressed after extirpation of the adenomas and height velocity normalized. Results: Histology revealed a circumscribed adenoma in the right adrenal gland and an epithelial mass with adrenal cortical cells in the left-sided ectopic tumor. In the ectopic tumor, melanocortin 2 receptor expression was augmented threefold compared to the control, indicating adrenal origin. Conclusions: In this young girl, virilization is due to concomitant ectopic and intra-adrenal adenomas of the adrenal cortex. By melanocortin 2 receptor expression, it was confirmed that the ectopic adenoma derived from the adrenal cortex. Specific scintigraphy, if available, assists in allocating the source of androgen hypersecretion. Copyright © 2013 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

ABSTRACT Introduction. Women with the classical form of congenital adrenal hyperplasia (CAH) are born with different degrees of virilization of the external genitalia. Feminizing surgery is often performed in childhood to change the appearance of the genitalia and to enable penile-vaginal intercourse later in life. There are suggestions that this affects sexual functioning. Aims. The aim is to study the anatomical, surgical, cosmetic, and psychosexual outcomes in women with CAH. Methods. Forty women with CAH, aged over 15 years, from two referral centers for management of Disorders of Sex Development in the Netherlands were included. Physical and functional status were assessed by a gynecological interview and examination. Sexual functioning was assessed with the Female Sexual Function Index and Female Sexual Distress Scale-Revised scales and compared with a reference group. Mean Outcome Measures. Surgery performed, anatomy, cosmetic score, sexual function and distress. Results. Thirty-six of the 40 women had undergone feminizing surgery; 25 women (69%) underwent more than one operation. Resurgery was performed in seven of the 13 (54%) women who had had a single-stage procedure. Anatomical assessment showed reasonable outcomes. Multiple linear regression showed that only level of confluence had a significant effect on cosmetic outcome, the impact depending on the number of surgeries performed. Cosmetic evaluations did not differ between the women and the gynecologists. Only 20 women had experience of intercourse. Eight women reported dyspareunia; seven women reported urinary incontinence. The women's perceived sexual functioning was less satisfactory than in the reference group, and they reported more sexual distress. Conclusion. The level of confluence was the major determinant for cosmetic outcome; the impact depended on the number of surgeries performed. Fifty-four percent of the women required resurgery after a single-stage procedure in childhood. Anatomical assessment showed reasonable outcomes. The women evaluated their sexual functioning and functional outcome less favorable than the reference group, and they experienced less often sexual intercourse. van der Zwan YG, Janssen EHCC, Callens N, Wolffenbuttel KP, Cohen-Kettenis PT, van den Berg M, Drop SLS, Dessens AB, Beerendonk C. Severity of virilization is associated with cosmetic appearance and sexual function in women with congenital adrenal hyperplasia : A cross-sectional study. J Sex Med 2013;10:866-875. [ABSTRACT FROM AUTHOR]

Context: Primary pigmented nodular adrenocortical disease (PPNAD) can lead to steroid hormone overproduction. Mutations in the cAMP protein kinase A regulatory subunit type 1A (PRKAR1A) are causative of PPNAD. Steroidogenesis in PPNAD can be modified through a local glucocorticoid feedforward loop. Objective: Investigation of regulation of steroidogenesis in a case of PPNAD with virilization. Materials and methods: A 33-year-old woman presented with primary infertility due to hyperandrogenism. Elevated levels of testosterone and subclinical ACTH-independent Cushing's syndrome led to the discovery of an adrenal tumor, which was diagnosed as PPNAD. In vivo evaluation of aberrantly expressed hormone receptors showed no steroid response to known stimuli. Genetic analysis revealed a PRKAR1A protein-truncating Q28X mutation. After adrenalectomy, steroid levels normalized. Tumor cells were cultured and steroidogenic responses to ACTH and dexamethasone were measured and compared with those in normal adrenal and adrenocortical carcinoma cells. Expression levels of 17β-hydroxysteroid dehydrogenase (17β-HSD) types 3 and 5 and steroid receptors were quantified in PPNAD, normal adrenal, and adrenal adenoma tissues. Results: Isolated PPNAD cells, analogous to normal adrenal cells, showed both increased steroidogenic enzyme expression and steroid secretion in response to ACTH. Dexamethasone did not affect steroid production in the investigated types of adrenal cells. 17β-HSD type 5 was expressed at a higher level in the PPNAD-associated adenoma compared with control adrenal tissue. Conclusion: PPNAD-associated adenomas can cause virilization and infertility by adrenal androgen overproduction. This may be due to steroidogenic control mechanisms that differ from those described for PPNAD without large adenomas. [ABSTRACT FROM AUTHOR]

Hyperandrogenism is characterized by hirsutism, acne, alopecia and oligo/amenorrhea, among its causes are polycystic ovaries and ovarian or adrenal tumors. We present the case of a patient with virilization secondary to a steroid cell tumor of the ovary that improved after resection. [ABSTRACT FROM AUTHOR]

Virilization caused by ovarian tumors with functioning stroma during pregnancy is extremely rare and has been reported to be due to different types of ovarian tumors. In mucinous cystadenomas with maternal virilization during pregnancy, the stromal cells responsible for hormone secretion resemble lutein or Leydig cells and have been referred to as luteinized stromal cells. Here we present a rare case of mucinous cystadenoma accompanied by virilization, whichwas also the cause of fetal intrauterine growth restriction during pregnancy and discuss the mechanisms of hormone production in these tumors in the light of the literature. [ABSTRACT FROM AUTHOR]

Context Prenatal treatment with dexamethasone to prevent virilization in pregnancies at risk for classical congenital adrenal hyperplasia (CAH) remains controversial. Objective To conduct a systematic review and meta-analyses of studies that evaluated the effects of dexamethasone administration during pregnancies at risk for classical CAH because of 21-hydroxylase deficiency (CYP21A2). Data Sources We searched MEDLINE, EMBASE, and Cochrane CENTRAL from inception through August 2009. Review of reference lists and contact with CAH experts further identified candidate studies. Study Selection Reviewers working independently and in duplicate determined trial eligibility. Eligible studies reported the effects on either foetal or maternal outcomes of dexamethasone administered during pregnancy compared to a control group that did not receive any treatment. Data Extraction Reviewers working independently and in duplicate determined the methodological quality of studies and collected data on patient characteristics, interventions, and outcomes. Data Synthesis We identified only four eligible observational studies (325 pregnancies treated with dexamethasone). The methodological quality of the included studies was overall low. Meta-analysis demonstrates a reduction in foetus virilization measured by Prader score in female foetuses treated with dexamethasone initiated early during pregnancy (weighted mean difference, −2·33, 95% CI, −3·38, −1·27). No deleterious effects of dexamethasone on stillbirths, spontaneous abortions, foetal malformations, neuropsychological or developmental outcomes were found although these data are quite sparse. There was increased oedema and striae in the mothers treated with dexamethasone. There were no data on long-term follow-up of physical and metabolic outcomes in children exposed to dexamethasone. Conclusions The observational nature of the available evidence and the overall small sample size of the whole body of the literature significantly weaken inferences about the benefits and harms of dexamethasone in this setting. Dexamethasone seems to be associated with reduction in foetus virilization without significant maternal or foetal adverse effects. However, this review underscores the current uncertainty and further investigation is clearly needed. The decision about initiating treatment should be based on patients' values and preferences and requires fully informed and consenting parents. [ABSTRACT FROM AUTHOR]

Background: Hyperandrogenism is a rare symptom of juvenile ovarian granulosa cell- tumors (JGCTO). This study aimed to determine whether hyperandrogenism was related to overexpression of SOX9, decreased expression of FOXL2 or absent aromatase expression in tumor with particular scheme of expression of P450scc and P450c17α. Methods: Through a nationwide study including the French Society of Pediatric Oncology, 6/30 patients with JGCTO presented with clinical hyperandrogenism and high plasma testosterone. Tumor specimens underwent immunofluorescence (SOX9, FOXL2) and immunochemistry (aromatase, P450scc, P450c17α). Results were compared with patients without hyperandrogenism. Results: SOX9 was expressed in the granulosa cell nucleus in 2/6 cases but also in 9/24 tumors without hyperandrogenism (p = n.s.). FOXL2 was absent or decreased in 3/6 cases of JGCTO with hyperandrogenism with no statistical difference from the group without this symptom. In 6/6 patients, the intratumoral expression of aromatase was absent (n = 5) or dramatically reduced (n = 1). In contrast, 15/24 patients without virilization exhibited conserved aromatase expression in their tumor (p < 0.05). A variable number of tumoral cells expressed P450scc while some interstitial cells were focally immunopositive for P450c17α. Conclusion: Unusual virilization in girls with JGCTO is not explained by a dysregulation in SOX9 or FOXL2 expression, but is related to a localized defect of aromatase expression in granulosa cells and to the ability of interstitial cells to produce testosterone. [ABSTRACT FROM AUTHOR]

Background Women with 21-hydroxylase deficiency present much variability in external genitalia virilization, even among those with similar impairments of 21-hydroxylase (21OH) activity. Objective To evaluate if the number of CAG (nCAG) repeats of the androgen receptor gene influences the degree of external genitalia virilization in women with CYP21A2 mutations, grouped according to impairment of 21OH activity. Patients The nCAG was determined in 106 congenital adrenal hyperplasia (CAH) patients and in 302 controls. The patients were divided, according to their CYP21A2 genotypes, into Groups A and B, which confer total and severe impairment of 21OH activity, respectively. Methods The inactivation pattern of the X-chromosome was studied through genomic DNA digestion with Hpa II. The CAG repeat region was amplified by polymerase chain reaction (PCR) and analysed by GeneScan. Results The nCAG and the frequency of severe skewed X-inactivation did not differ between normal women and patients. The nCAG median in genotype A was 20·7 (IQR 2·3) for Prader I + II, 22·5 (3·6) for Prader III and 21 (2·9) for Prader IV + V ( P < 0·05 for Prader III and Prader IV + V). The nCAG median in genotype B was 21·3 (1·1) for Prader I + II, 20·5 (2·9) for Prader III and 22 (2·8) for Prader IV + V ( P > 0·05). A significant difference was found regarding the nCAG median in patients presenting Prader III from genotypes A and B. Conclusions We observed great variability in the degree of external genitalia virilization in both CYP21A2 genotypes, and we showed that the CAG repeats of the androgen receptor gene influences this phenotypic variability. [ABSTRACT FROM AUTHOR]

The presence of testosterone and anti-Müllerian hormone in males cause the mesonephric ducts to develop into the seminal vesicles, epididymis, vas deferens, and efferent ducts of the testis and the paramesonephric ducts to regress into the appendix epididymis. There is only one prior report of epididymis-like virilization of mesonephric remnants, and it occurred in the left paratubal region of a 28-year-old female-to-male transgender patient treated with testosterone.[1] Our patient has no history of exogenous androgen use, hormone replacement therapy, or hormone-producing tumors, and the exact cause of the epididymis-like virilization is not known. [Extracted from the article]

Virilization in association with ovarian dermoid cyst is a rare occurrence. We report two cases of severe virilization and secondary amenorrhea caused by elevated serum testosterone levels associated with benign cystic teratoma of the ovary. After laparoscopic unilateral oophorectomy, serum testosterone levels rapidly returned to normal with gradual regression of virilization. (J GYNECOL SURG 21:181) [ABSTRACT FROM AUTHOR]

The external genitalia of the female spotted hyena are male in character, consistent with virilization by androgens during embryogenesis that results in the fusion of the vaginal labia to form a pseudo scrotum and enlargement of the clitoris to form a phallus. Explanations advanced to account for these anatomic differences have centered on the production or metabolism of androgens in utero or on abnormalities of the androgen receptor (such as a constitutively active AR). The structure of the spotted hyena AR was examined at the level of genomic DNA and cDNA. Southern analysis detected two Eco RI endonuclease cleavage fragments (4.4 and 4.7 kb) that encode the bulk of the AR hormone-binding domain. Isolation of the smaller fragment from a size fractionated genomic library revealed that it contained exons 6, 7 and 8. The remaining portions of the coding sequence were cloned by RT-PCR and RACE analyses. The spotted hyena cDNA sequence predicts protein 912 amino acids in length, which is most closely related to the sequence of the dog AR. Although a number of differences in the predicted amino acid sequence are identified, particularly within the amino terminus, only single amino acid substitutions are present in the DNA- and ligand-binding domains compared to the human AR. In transfection assays, the spotted hyena AR does not exhibit constitutive activity and responds normally to a range of androgenic and non-androgenic ligands. These findings suggest that the structural changes in the AR do not account for the abnormal virilization in the female spotted hyena. These results serve to focus attention on processes proximal (an abnormality of hormone formation in situ) or distal (activation by other mechanisms of processes normally regulated by androgen) to the AR as the cause of the virilization. [Copyright &y& Elsevier]

Summary objective In girls with congenital adrenal hyperplasia (CAH), genital ambiguity usually leads to a rapid neonatal diagnosis. Rarely, CAH causes complete virilization and male sex assignment with a delayed diagnosis. After being confronted with very specific problems in two of such patients, we collected data of patients with CAH and complete virilization in a nationwide study to delineate specific problems of these rare patients in order to improve their management. design and patients Through the German Working Group of Paediatric Endocrinology (Arbeitsgemeinschaft Pädiatrische Endokrinologie, APE), questionnaires were sent to all members caring for patients with CAH and complete virilization in their endocrine clinics. Data from 16 patients from 10 paediatric endocrine centres were assessed by questionnaire. results The following problems have been encountered. (1) Sex assignment/gender identity: initially all patients had a male sex assignment. Six patients were diagnosed during the first month of life. Five were reassigned to female sex immediately, one at the age of 19 months. Except in one girl demonstrating some tomboyish behaviour, gender role behaviour in these patients did not differ from unaffected girls. Ten patients were diagnosed late at 3·4–7 years of age. In seven patients with a late diagnosis, male sex assignment was maintained; one of them expressed some concerns about living as a male. In three patients late sex reversal was performed, gender identity is very poor in one and new sex assignment is currently under consideration. (2) Surgery: irrespective of the sex assigned, all patients had between one and three surgical procedures, including clitoris reduction and (repeated) vaginoplasties in patients with female sex assignment. Hysterectomy and ovarectomy were performed in patients with male sex assignment. (3) Short stature: patients with a late diagnosis of CAH had extremely advanced bone ages of +6·3 to... [ABSTRACT FROM AUTHOR]

Background: We present a 12-year-old girl with a 5-year history of progressive virilization. Results: Regarding elevated plasma levels of 17-hydroxyprogesterone (17-OHP) and androgens, normal ultrasound and CT scan of ovaries and adrenal glands, the nonclassic form of congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency was presumed the cause of virilization. As the glucocorticoid therapy did not normalize high levels of 17-OHP and androgens, and the DNA analysis did not demonstrate a mutation causing CAH, a laparotomy was performed. Near the right ovary a tumor was found and extirpated. Pathohistological studies determined it to be a rare steroid cell tumor, ‘not otherwise specified’. Within the next months the signs of virilization resolved and menarche occurred. Conclusions: Steroid cell tumor should be considered in differential diagnosis of virilization in childhood. Regarding the age of our patient and pathohistological findings of the tumor, her prognosis is favorable.Copyright © 2001 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

The article presents a case study of two sisters, with consanguineous parents, who have aromatase deficiency (AD), which is noted to be the cause of female fetal virilization. A novel generic mutation is reported as the cause of the disorder and outlines the characteristics of AD. The use of laparoscopy is mentioned.