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PubMed1987

Bilateral ovarian thecosis and virilization in pregnancy. A case report.

Virilization is usually associated with amenorrhea, infertility and ovarian stromal lesions. Paradoxically, however, it may also be seen in pregnancy; this type of virilization is rare and accompanies ovarian thecosis. Thecosis, also known as thecomatosis and stromal thecosis, is a complex assortment of types of ovarian stromal proliferation associated with various types and amounts of hormonal activity. A patient had progressive virilization that began about seven years after menarche. Nonetheless, she had six pregnancies and bore five normal living children. Her last child, a female, was not affected by the high maternal testosterone levels. The patient's virilization was associated with an ovarian stromal hyperplasia classified as combined thecosis. In this case, as in some others, there was reason to suspect a genetic basis for such progressive virilization with retained fertility; an analysis of it provides insight into the complex nature of ovarian stromal hyperplasia and hormonal activity.

Adult↗
PubMed1997

Steroid cell tumor of the ovary as a rare cause of virilization.

BACKGROUND: Virilization is associated with either ovarian causes, including polycystic ovary syndrome, hyperthecosis, and ovarian tumor, or with adrenal causes, including tumors and congenital adrenal hyperplasia. In establishing the diagnosis, levels of dehydroepiandresterone sulfate, testosterone, and 17 alpha-hydroxyprogesterone (17-OHP), with their response to dexamethasone treatment, should be assessed; and, where indicated, computerized tomography, ultrasound, and selective venous catheterization should be undertaken. CASE REPORT AND RESULTS: A 21-year-old woman presented with a 17-year history of early accelerated linear growth and virilization. During this time, a putative diagnosis of nonclassic congenital adrenal hyperplasia had been made, and she had been treated with glucocorticoids, with no regression in virilization, for 8 years. On presentation to our group, the failure of low- and high-dose dexamethasone suppression tests to decrease blood levels of testosterone and 17-OHP, combined with a relatively low blood level of corticotropin, led us to investigate an androgen-secreting tumor of ovarian origin. When ultrasonography and computerized tomography of the ovaries and adrenal glands displayed no abnormality, selective venous catheterization was performed, revealing an abnormal ovarian-peripheral gradient for testosterone, 17-OHP, estradiol, and androstenedione in the right ovarian vein. On exploratory laparotomy, a neoplasm adjacent to the right ovary was resected and was found to be a steroid cell tumor of the ovary not otherwise specified, one of the rarest tumors causing virilization in children. Symptomatic resolution followed tumor removal. CONCLUSION: Selective ovarian and adrenal venous catheterization for hormone assays is an efficient method of identification and localization of an androgen source in virilizing syndromes when noninvasive methods fail.

Adult↗
PubMedDate not supplied

Data on virilization and erotosexual behavior in male hypogonadotropic hypopituitarism during gonadotropin and androgen treatment.

The goal of this investigation was to assess whether or not gonadotropin therapy enhanced the degree of virilization and psychosexual behavior of men with hypogonadotropic hypopituitarism. Pre- and post-gonadotropin assessments of virilization in four men indicated that gonadotropin therapy was associated with dramatic improvements in the degree of virilization that each man previously obtained on androgen only. Retrospective interview data on erotosexual behavior indicated improved erotosexual function on gonadotropin as compared to the prior androgen treatment. These data suggest that complete virilization in these men was partially gonadotropin dependent. Whether or not the behavioral benefits reported by these men represented a direct or synergistic effect of gonadotropin in the expression of erotosexual behavior or an indirect effect of improved virilization can not be answered by these data.

20-alpha-Dihydroprogesterone↗
PubMed1993

Virilizing adrenocortical tumors in adult women. Report of 10 patients, 2 of whom each had a tumor secreting only testosterone.

BACKGROUND: Virilizing adrenocortical tumors are uncommon in adult women. These lesions generally secrete dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate (DHEAS), but not testosterone, which usually is produced by ovarian tumors. Exceptionally, adrenal growths may give off testosterone and no other assessable androgen. The detection of the site of excess testosterone yield is paramount for proper surgery. The true nature of the growth often is unpredictable, even at the time the pathologist examines the surgical specimen. METHODS: The workup in a virilized adult woman relies on biochemical tests such as 24-hour urinary 17-KS and 17-OHCS levels and plasma corticosteroid levels (testosterone, DHEA, DHEAS, and androstenedione), and on modern imaging studies such as ultrasonography, computed tomography, and digital angiography. RESULTS: Among a series of 190 adrenal tumors collected in the last 30-year period, only 10 virilizing growths (5.3%) were detected. Two cases of virilization mixed with cushingoid features were observed. In two other cases, reported in detail, the tumor secreted testosterone only, without other assessable androgens. Seven of the 10 tumors were malignant. CONCLUSIONS: In cases of tumors secreting testosterone only, high-resolution imaging has contributed significantly in pinpointing the site of the growth, whereas dynamic hormone testing, using selective stimulation or suppression studies, has been misleading. The malignant nature of the growth may be revealed only by the presence of metastases, because pleomorphism and capsular and vascular invasion have been detected histologically in clinically benign tumors. The prognosis for large tumors usually is dismal.

Adrenal Gland Neoplasms↗
PubMed2005

Maternal and female fetal virilization caused by pregnancy luteomas.

OBJECTIVE: To present the maternal and female fetal virilization caused by excessive androgen secretion of pregnancy luteomas. DESIGN: Case report. SETTING: University-based teaching hospital. PATIENT(S): A nulligravida woman suffering from bilateral hydronephrosis and recurrent acute pyelonephritis caused by bilateral solid ovarian tumors presented virilization during the third trimester. Without prompt surgical intervention, the maternal hyperandrogenemia returned to a normal level and regression of bilateral ovarian tumors occurred spontaneously after a female fetus with clitoral hypertrophy and temporal hyperandrogenemia was delivered. In spite of lacking histology, the clinical course is compared to that of pregnancy luteomas. INTERVENTION(S): Noninvasive imaging assessment. MAIN OUTCOME MEASURE(S): Maternal and female fetal virilization. RESULT(S): Regression of androgen-secreting pregnancy luteomas and hyperandrogenism during the puerperium but apparent female fetal clitoral hypertrophy. CONCLUSION(S): The maternal and female fetal virilization was caused by exaggerating androgen secretion of bilateral ovarian solid tumors. Spontaneous regression of ovarian tumors and hyperandrogenemia during the puerperium is the natural course of pregnancy luteomas, not true neoplasms.

Adult↗
PubMed2002

Complete virilization in congenital adrenal hyperplasia: clinical course, medical management and disease-related complications.

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 +9.5 years, leading to severely reduced final height of 137 to 150 cm in adult patients. Patients tended to follow height percentiles of genetic females. One pubertal patient was suicidal due to short stature. (4) Central precocious puberty (CPP): prolonged exposition to adrenal androgens led to CPP in one patient. He was treated with GnRH analogues until gonadectomy. CONCLUSIONS: Patients with CAH and complete virilization have a high risk of being diagnosed late. There are major problems and uncertainties of the patients' families and the treating physicians concerning gender assignment. Gender identity is disturbed in some patients. In addition, multiple surgical procedures are necessary and short stature as well as central precocious puberty might be important to avoid late sequelae. While some surgical interventions are probably unavoidable, most of these issues could be resolved with an early diagnosis. Thus, especially for these patients, a neonatal screening programme for CAH would be of paramount importance.

Adolescent↗
PubMed2000

Virilizing tumors of the ovary: imaging features.

AIM: Virilizing tumors of the ovary are an uncommon cause of a common clinical problem. The reported imaging features of these tumors are based on case reports. The purpose of this study was to determine the spectrum of imaging characteristics of these tumors based on a larger referral population. PATIENTS AND METHODS: Case records from the Armed Forces Institute of Pathology were searched for clinical evidence of virilization as a presentation of an excised sex cord-stromal and steroid cell ovarian tumor. Records and imaging studies on 14 patients with virilizing tumors were found. All available imaging studies (ultrasound studies of the pelvis (11 patients), CT scans of the pelvis (five patients), MRI examinations of the pelvis (two patients), and plain films of the pelvis (four patients) were reviewed by three radiologists independently for ascites, calcification, percent solid portion, echogenicity and attenuation. RESULTS: On CT and/or ultrasound most (69%) of the tumors appeared to be solid or mostly solid. The amount of solid tissue varied with the tumor type, granulosa cell tumors were predominantly cystic. The masses were isoechoic (82%) or hypoechoic (18%). Ascites was an infrequent (23%) finding. Only a minority of these tumors (14%) were calcified on imaging studies. Six tumors were 5.0 cm or less in mean size, and two less than 3.0 cm in size. All cases were stage I tumors at presentation. CONCLUSION: The majority of virilizing tumors of the ovary are typically solid, noncalcified, confined to the ovary at presentation, and not associated with ascites. Variability in appearance depends in part on tumor type. Many are small and may be difficult to recognize as a mass morphologically.

Adolescent↗
PubMed1989

Virilizing stromal thecosis of the ovary associated with multiple corpora atretica.

Virilism can be associated with a variety of ovarian lesions, including stromal hyperplasia. Focal luteinization, a thickened tunica albuginea, and multiple cystic follicles are histologic features that have been associated with stromal hyperplasia in virilized women. This report describes the case of a 57-year-old woman who presented with a four-year history of virilization. The testosterone level was 13.8 nmol/L (3,980 ng/L). At laparotomy, the ovaries were found to be enlarged, each measuring 4 cm in maximum dimension. Salient histologic findings included diffuse stromal hyperplasia interspersed with a marked increase in the number of corpora atretica. Focal luteinization, including in some corpora atretica, was seen. Electron microscopic study demonstrated cells with increased smooth endoplasmic reticulin and mitochondria with tubular cristae as well as other features consistent with theca cells; Reinke crystals were not seen. The testosterone level normalized after removal of the ovaries, and the signs of virilism gradually abated. These results are compatible with an abnormal stimulation of the ovaries as evidenced by an increased though abortive follicular development, stromal hyperplasia, and focal luteinization.

Female↗
PubMed1995

Recurrent maternal virilization during pregnancy associated with polycystic ovarian syndrome: a case report and review of the literature.

Maternal virilization in pregnancy is associated, in most benign cases, with luteoma of pregnancy and hyperreactio luteinalis. Only a few reports relate this phenomenon to hyperthecosis or polycystic ovarian syndrome (PCOS). A case of recurrent maternal virilization during two consecutive pregnancies in a patient with PCOS is presented. In both pregnancies, the deepening of her voice, facial hirsutism and scalp hair loss began at the end of the first trimester and regressed 3-4 months post-partum. The patient underwent ovarian venous catheterization, and androgen secretion from both ovaries was found to be markedly high but similar, therefore ruling out an ovarian androgen-secreting tumour. Reviewing the English literature of similar cases, we found reports of only seven cases of maternal virilization during pregnancy associated with PCOS. Here, we present a case of recurrent maternal virilization in pregnancy associated with PCOS.

Adult↗
PubMed1988

Large benign virilizing adrenal adenoma.

The young woman described sought evaluation for infertility and was found to have virilization due to a large left adrenal tumor. Further endocrine studies confirmed a syndrome of pure virilization with normal glucocorticoid function. Resection of this apparently benign tumor resulted in regression of virilization, as well as pregnancy. Pure virilization is an unusual manifestation of benign adrenocortical tumors, and adrenal tumors of this size are most frequently malignant.

Adenoma↗
PubMed2005

Evaluating the accuracy of Malformations Surveillance Program in detecting virilization due to congenital adrenal hyperplasia.

Malformations surveillance programs of newborn infants have been developed as a method for identifying serious and relatively common birth defects. The virilization of newborn infants with the classic 21-hydroxylase form of congenital adrenal hyperplasia must be identified early if the associated metabolic crisis in the perinatal period is to be prevented. We compared the detection of virilization associated with 21-hydroxylase congenital adrenal hyperplasia in infants by three methods: an 'active' malformations surveillance of medical records at a large urban hospital; routine medical care by examining physicians; and newborn biochemical screening of blood samples. The experience at a large maternity center in Boston, since 1972, showed that pediatricians often recognized affected females (6/6), but not males (0/2); the state newborn screening program, begun in 1990, identified correctly all affected males and females. The Active Malformations Surveillance Program was the least effective screening method, identifying four of six affected females and neither of the affected males. The low rate of detecting affected females by the Surveillance Program was attributed to a failure to sensitize the research assistants to the importance of physicians' notations regarding the signs and symptoms of virilization. The failure of examining physicians, and thereby, the malformations surveillance program, to detect virilized newborn males was due to the lack of consistent associated physical features. These comparisons between these three methods of detection can be used to design and improve malformations surveillance programs.

Adrenal Hyperplasia, Congenital↗
PubMed2001

Extraovarian steroid cell tumor 'not otherwise specified' as a rare cause of virilization in twelve-year-old girl.

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.

Child↗
PubMed2006

Role of the alternate pathway of dihydrotestosterone formation in virilization of the Wolffian ducts of the tammar wallaby, Macropus eugenii.

Dihydrotestosterone in androgen target tissues is formed under most circumstances by the 5alpha-reduction of testosterone, but an alternate pathway involves the oxidation of androstanediol to dihydrotestosterone. To investigate the mechanism by which androgens virilize the Wolffian ducts in the tammar wallaby, [(3)H]progesterone was incubated with testes from d 10 and 19 pouch young, and radioactivity was recovered in testosterone and androstanediol at both ages. Analysis of the intermediates indicates that androstanediol was formed both from testosterone via 5alpha-reduction and 3alpha-keto reduction and directly from 5alpha-reduced progestogens. 5alpha-Reductase activity was high in minces of mesonephros/epididymis from d 6-21 pouch young. When minces of urogenital tract tissues from d 19 pouch young were incubated with [(3)H]testosterone, [(3)H]dihydrotestosterone, and [(3)H]androstanediol, dihydrotestosterone was the principal androgen formed in the mesonephros/epididymis, urogenital sinus, and urogenital tubercle, whereas androstanediol was the principal androgen formed by the testis. In intact pouch young studied between d 10 and 34, administration of the 5alpha-reductase inhibitor, 17beta-(N,N-diethyl)carbamoyl-4-methyl-4-aza-5alpha-androstan-3-one, blocked virilization of the Wolffian ducts in males, and administration of androstanediol caused virilization of the Wolffian ducts in females. We conclude that dihydrotestosterone, largely formed in the tissue by the oxidation of androstanediol derived from the testes and also the 5alpha-reduction of testosterone, is responsible for Wolffian duct virilization in this species.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗
PubMed1978

Virilizing effect of testosterone and its metabolites on the urovaginal septum of female fetal rats.

A single injection of 50 microgram testosterone was given to fetal rats on day 17, 18, 19 or 20 of gestation. On day 21, the fetuses were removed from the mother under maternal ether anesthesia, and the length of the urovaginal septum was measured microscopically in female fetuses in order to assess the virilizing effect of testosterone. In fetuses treated with testosterone on day 17, the length of the urovaginal septum was comparable to that of oil-treated littermate controls. In fetuses treated on day 18, the length was significantly abridged compared with controls. In fetuses treated on day 19, the abridgment of the urovaginal septum was most marked. In fetuses treated on day 20, the length of the septum was again comparable to that of controls. The observations suggest that day 19 is the critical day for the virilizing effect of testosterone. Various amounts of testosterone and its metabolites including dihydrotestosterone, androstane-3 beta, 17beta-diol and androstane-3 alpha, 17beta-diol were injected into 19-day-old female fetuses, in order to test the dose relation to the virilizing effects of these steroids in terms of abridgment of the urovaginal septum. As a consequence, it was found that testosterone was the most effective for virilization.

Androstenedione↗
PubMed2005

Disappearance of a virilizing adrenal tumor following therapy with cyproterone acetate.

A 57-year-old woman presented with an apparently obvious diagnosis of iatrogenic virilization. At the age of 51, she began a 4-year treatment with prednisone or cyclosporine, which are known to promote hair growth, for Behçet disease. At the age of 56, osteoporosis was overtreated with the anabolic steroid nandrolone. Insignificant inhibition by dexamethasone of the extremely high serum concentrations of testosterone and less high concentrations of weak androgens prompted us to search for a virilizing tumor. Computed tomography showed a 2.3 x 1.5 cm nodule in the right adrenal gland. As the patient refused surgery, virilization was treated with the antiandrogen cyproterone acetate (CPA), but for only 4 months because clinical and hormone abnormalities reversed and the tumor was no longer visible. The patient remains symptom-free. This first report of a curative effect of CPA on a purely virilizing adrenal tumor opens new avenues in the management of such tumors.

Adrenal Gland Neoplasms↗
PubMed1986

Diagnostic considerations in virilization: iodomethyl-norcholesterol scanning in the localization of androgen secreting tumors.

Accurate localization of the source of androgen hypersecretion is critical to the appropriate surgical or medical management of women with virilization. Seven patients with virilization and hyperandrogenism of various causes were evaluated with the use of sequential studies: testosterone stimulation and suppression tests; computerized tomography (CT); selective venous catheterization; and 131I-iodomethyl-norcholesterol (NP-59) scintigraphy. Comparison of the diagnostic accuracies of these localization studies with the ultimate diagnoses in this group of virilized women showed that: endocrinologic suppression/stimulation studies are of limited value in tumor localization and helpful only in patients with steroidogenic enzyme deficiencies; both selective catheterization and CT scanning may provide spurious localization data; and NP-59 scintigraphy, by depicting both the anatomic localization and functional androgen hypersecretion, may provide the most significant localization data in the evaluation of patients with virilizing syndromes.

Adenoma↗
PubMed1993

[A case of virilizing adrenocortical carcinoma in adult].

A case of virilizing adrenocortical carcinoma is reported. A 35-year-old woman was referred to our clinic because of left adrenal mass detected incidentally by ultrasonography. At the time of admission, facial acne, systemic hirsutism, hypertrophied clitoris and amenorrhea for two months were observed. Serum testosterone showed obviously high level and urinary 17-KS and 17-OHCS showed slightly high level. A computed tomography revealed a heterogeneous mass with calcification in the left adrenal region. Selective angiography revealed hypervascularity. Under the preoperative diagnosis of virilizing left adrenal tumor, left adrenalectomy was performed. The tumor measured 8 x 6 x 7 cm, and weighed 194 g. A diagnosis of adrenocortical carcinoma was made by pathological examination. Virilizing adrenocortical carcinoma is very rare in adults. We reviewed and discussed 10 cases of virilizing adrenocortical carcinoma in adults, including our case, in the Japanese literature.

Adrenal Cortex Neoplasms↗
PubMed2002

Anabolic steroids, testosterone-precursors and virilizing androgens induce distinct activation profiles of androgen responsive promoter constructs.

Different androgens, e.g. virilizing androgens such as testosterone and its precursors as well as synthetic anabolic steroids, respectively, induce diverse biological effects. The molecular basis for this variety in biological actions, however, is not well understood. We hypothesized that this variability of actions may be due to steroid-specific target gene expression profiles following androgen receptor (AR)-activation. Therefore, we investigated androgen receptor dependent transactivation of three structurally different androgen responsive promoter constructs ((ARE)(2)TATA-luc, MMTV-luc, GRE-OCT-luc) in co-transfected Chinese hamster ovary (CHO)-cells as an artificial model simulating different natural target genes. Three virilizing androgens (dihydrotestosterone, testosterone, methyltrienolone), three anabolic steroids (oxandrolone, stanozolol, nandrolone) and two testosterone-precursors of gonadal and adrenal origin (dehydroepiandrosterone, androstenedione) were used as ligands (0.001-100 nM). All steroids proved to be potent activators of the AR. Remarkably, anabolic steroids and testosterone-precursors showed characteristic promoter activation profiles distinct from virilizing androgens with significantly lower (ARE)(2)TATA-luc activation. Hierarchical clustering based on similarity of activation profiles lead to a dendrogram with two major branches: first virilizing androgens, and second anabolics/testosterone-precursors. We conclude that steroid-specific differences in gene transcription profiles due to androgen receptor activation could contribute to differences in biological actions of androgens.

Adjuvants, Immunologic↗