1/263. Normal female infants born of mothers with classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency. women with congenital adrenal hyperplasia due to 21-hydroxylase deficiency, especially those patients with the salt-losing form, have decreased fertility rates. pregnancy experience in this population is limited. We report the pregnancy outcomes and serial measurements of maternal serum steroid levels in four women with classic 21-hydroxylase deficiency, three of whom were female pseudohermaphrodites with the salt-losing form. These glucocorticoid-treated women gave birth to four healthy female newborns with normal female external genitalia, none of whom were affected with 21-hydroxylase deficiency. In three women, circulating androgen levels increased during gestation, but remained within the normal range for pregnancy during glucocorticoid therapy. In the fourth patient, androgen levels were strikingly elevated during gestation despite increasing the dose of oral prednisone from 5 to 15 mg/day (two divided doses). Notwithstanding the high maternal serum concentration of androgens, however, placental aromatase activity was sufficient to prevent masculinization of the external genitalia of the female fetus and quite likely the fetal brain, consistent with the idea that placental aromatization of androgens to estrogens is the principal mechanism that protects the female fetus from the masculinizing effects of maternal hyperandrogenism. These four patients highlight key issues in the management of pregnancy in women with 21-hydroxylase deficiency, particularly the use of endocrine monitoring to assess adrenal androgen suppression in the mother, especially when the fetus is female. Recommendations for the management of pregnancy and delivery in these patients are discussed. ( info) |
2/263. 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. ( info) |
3/263. Virilizing ovarian dermoid cyst with peripheral steroid cells. A case study with immunohistochemical study of steroidogenesis. A case of virilizing ovarian dermoid cyst with peripheral steroid cells and virilization is reported in a 62-year-old woman. The level of testosterone dropped to normal after oophorectomy. The cyst wall was bordered by a discontinuous band of steroid cells focally accompanied by smooth muscle cells. Immunohistochemically, the steroid cells were enzymatically active and displayed a profile similar to the internal theca cells of ovarian follicles. These steroid cells were most probably modified stromal cells associated with smooth muscle metaplasia of the ovarian stroma. ( info) |
| The stromal leydig cell tumor is a very rare benign tumor originating from the ovarian stroma. Only seven cases have been reported, all in postmenopausal women, except for one in a 15-year-old girl. In the present case, masculinization developed over a few months in a 24-year-old woman. The serum concentration of testosterone was 4.7 ng/ml before operation. Left salpingo-oophorectomy and wedge resection of the right ovary were performed. The encapsulated left ovarian tumor was an ovarian stromal leydig cell tumor on microscopic examination. ( info) |
| We describe a rare androgen and desoxycorticosterone (DOC)-secreting adrenal tumor in a non-Cushingoid 14 year-old Haitian girl with secondary amenorrhea, hypertension and virilization. Her steroid pattern simulated an 11 beta-hydroxylation defect with notable elevation of adrenal androgens, 11-desoxycortisol (S), DOC, 17 alpha-hydroxyprogesterone and pregnenelone. Exogenous ACTH stimulated steroidogenesis. A CAT scan unfortunately failed to delineate an adrenal mass. dexamethasone (DEX) was administered, therefore, which partially suppressed androgen levels, reduced DOC and S by 80% and 82% respectively, and normalized blood pressure. Nevertheless, the response to glucocorticoid was incomplete and an MRI was obtained, which revealed a right adrenal tumor. Post surgery, the patient promptly resumed menses and became normotensive. This case illustrates that ACTH and DEX cannot reliably differentiate tumor from hyperplasia, whereas the simultaneous increase of delta 4 and delta 5 steroids, present here, may favor a tumor. This case also allows speculation that the hypersecretion of DOC may result from inhibition of 11 beta-hydroxylase activity by excess androgens. The importance of appropriate imaging for diagnosis is underscored. ( info) |
6/263. Severe virilization in a girl with a steroid cell tumor of the ovary. We report a 6-year-old girl with striking signs of virilization, as well as elevated concentrations of testosterone and 17-hydroxyprogesterone. Although the elevated 17-hydroxyprogesterone concentration initially suggested late-onset 21-hydroxylase deficiency, she was found to have an ovarian mass by sonography which at surgery proved to be a hilus cell subtype of steroid cell tumor. This intra-ovarian tumor appears to be the smallest tumor of its type ever reported. The testosterone concentration was normal three days after tumor resection and has remained so two years later. ( info) |
7/263. prenatal diagnosis and treatment of 11beta-hydroxylase deficiency congenital adrenal hyperplasia resulting in normal female genitalia. Congenital adrenal hyperplasia (CAH) consists of autosomal recessive disorders of cortisol biosynthesis, which in the majority of cases result from 21-hydroxylase deficiency. Another enzymatic defect causing CAH is 11beta-hydroxylase deficiency. In both forms, the resulting excessive androgen secretion causes genital virilization of the female fetus. For over 10 yr female fetuses affected with 21-hydroxylase deficiency have been safely and successfully prenatally treated with dexamethasone. We report here the first successful prenatal treatment with dexamethasone of an affected female with 11beta-hydroxylase deficiency CAH. The family had two girls affected with 1beta-hydroxylase deficiency born with severe ambiguous genitalia who were both homozygous for the T318M mutation in the CYP11B1 gene, which codes for the 11beta-hydroxylase enzyme. In the third pregnancy in this family, the female fetus was treated in utero by administering dexamethasone to the mother, starting at 5 weeks gestation. The treatment was successful, as the newborn was not virilized and had normal female external genitalia. A second family with two affected sons was also studied in preparation for a future pregnancy. We report a novel 1-bp deletion in codon 394 (R394delta1) in the CYP11B1 gene in this family. ( info) |
8/263. Masculinizing granulosa cell tumor of the ovary in a postmenopausal woman. A case report. BACKGROUND: A total of 32 cases of virilizing granulosa cell tumors of the ovary have been reported. The current case has some unique features not previously reported. CASE: A 78-year-old woman presented with symptoms and signs of masculinization. A large, painless abdominal mass was discovered. Exploration revealed the mass to be originating in the left ovary, and surgical resection resulted in prompt reversal of the clinical and biochemical hyperandrogenic manifestations. Morphologic studies demonstrated a homogeneous granulosa cell tumor. CONCLUSION: This is the oldest patient on record with a masculinizing granulosa cell tumor and also the only masculinizing tumor presenting with advanced, stage III disease. Such tumors, although rare, should be considered in the differential diagnosis in postmenopausal women presenting with masculinizing symptoms. ( info) |
9/263. Diffuse stromal Leydig cell hyperplasia: a unique cause of postmenopausal hyperandrogenism and virilization. A 60-year-old woman presented with diffuse scalp alopecia, hirsutism, and clitorimegaly, and the mean serum testosterone levels were greater than 200 ng/dL. Findings on computed tomography of both adrenal glands were normal. After bilateral oophorectomy, a unique histological picture consisting of diffuse stromal Leydig cell hyperplasia was found. Reinke crystals were present, but neither hilus cell hyperplasia nor stromal hyperthecosis was noted. Sequencing of the 11 exons of the gene for the luteinizing hormone receptor revealed no abnormality. Relevant data suggest that treatment of the postmenopausal woman with hyperandrogenism and virilization is bilateral laparoscopic oophorectomy if she has no pronounced ovarian enlargement or adrenal tumor on imaging. In this setting, an intensive endocrine evaluation or a search for metastatic disease seems to be unnecessary. ( info) |
10/263. Isodicentric y chromosome in an Ullrich-Turner patient without virilization. We report on a 17-year-old young woman with Ullrich-turner syndrome (UTS), who was found to have a karyotype 45,X/46,X,idic(Y)(q11). She had age-appropriate genitalia without virilization in spite of the presence of the Y-derived marker chromosome and SRY locus in 70% of her lymphocytes. Having reviewed the literature, we conclude that a possible explanation for the lack of virilization in these mosaic patients is most likely an uneven distribution of tissue mosaicism (gonadal mosaicism). ( info) |