1/15. Fluorescent PCR and automated fragment analysis in preimplantation genetic diagnosis for 21-hydroxylase deficiency in congenital adrenal hyperplasia.Congenital adrenal hyperplasia (CAH) is an autosomal recessive disease which is most often caused by a deficiency in steroid 21-hydroxylase. The disease is characterized by a range of impaired adrenal cortisol and aldosterone synthesis combined with an increased androgen synthesis. These metabolic abnormalities lead to an inability to conserve sodium and virilization of females. The most common mutation causing the severe form of CAH is a conversion of an A or C at nucleotide (nt) 656 to a G in the second intron of the steroid 21-hydroxylase gene (CYP21) causing aberrant splicing of mRNA. A couple was referred to our centre for preimplantation genetic diagnosis (PGD) for 21-hydroxylase deficiency in CAH. A PGD was set up to detect the nt656 A/C-->G mutation using fluorescent polymerase chain reaction (PCR) and subsequent restriction enzyme digestion and fragment analysis on an automated sequencer. Using dna or single cells from the father, the normal allele could not be amplified. Non-amplification of the normal allele has been previously described in asymptomatic carriers, therefore the PCR was further developed using heterozygous lymphoblasts from the mother. The PCR was shown to be highly efficient (96% amplification), accurate (0% contamination) and reliable (0% allelic drop-out). The couple started PGD treatment and the second PGD cycle resulted in a twin pregnancy. The genotype of the fetuses was determined in our laboratory using chorionic villus sampling material using the method described here. Both fetuses were shown to be heterozygous carriers of the mutation, and two healthy girls were born.- - - - - - - - - - ranking = 1keywords = cycle (Clic here for more details about this article) |
2/15. 21-hydroxylase deficiency and Turner's syndrome: a reason for diminished endometrial receptivity.OBJECTIVE: To report a case of cryptic 21-hydroxylase deficiency identified at the time of ovum donation in a patient with Turner's syndrome. DESIGN: Case report. SETTING: University IVF practice. PATIENT(S): A 28-year-old woman with Turner's syndrome who presented for ovum donation. INTERVENTION(S): Four cycles of donor IVF. MAIN OUTCOME MEASURE(S): pregnancy, endometrial appearance, progesterone, and 17-hydroxyprogesterone values. RESULT(S): The patient failed two fresh and two frozen ET cycles with donated oocytes. The appearance of the endometrium suggested elevated progesterone before progesterone supplementation. An elevated progesterone was detected but not suppressed by leuprolide acetate. progesterone was suppressed by adding dexamethasone. The diagnosis of cryptic 21-hydroxylase deficiency was confirmed biochemically. CONCLUSION(S): patients with Turner's syndrome reportedly have poorer outcomes with donor IVF than other women. They also have an increased incidence of carrying a defective 21-hydroxylase gene. We suggest that some of the poorer outcomes may be explained by the presence of elevated progesterone and recommend evaluation of possible congenital adrenal hyperplasia in patients with Turner's syndrome who want oocyte donation.- - - - - - - - - - ranking = 2keywords = cycle (Clic here for more details about this article) |
3/15. Mechanism for the development of ovarian cysts in patients with congenital lipoid adrenal hyperplasia.OBJECTIVE: Although ovarian cysts commonly occur in patients with congenital lipoid adrenal hyperplasia (CLAH), the mechanism of development remains to be determined. To clarify the pathogenesis of the ovarian cysts, endocrinological examinations were performed in patients with CLAH. methods: The subjects were three Japanese CLAH patients. Basal body temperature, serum and urinary gonadotropin levels, serum and/or urinary ovarian hormones and mutations of the steroidogenic acute regulatory protein (StAR) gene were examined. RESULTS: The basal body temperature was not biphasic in any patient. Basal LH levels were high in all CLAH patients and markedly responded to LH-releasing hormone in two patients. Urinary gonadotropin analysis revealed repetitive LH surges in the menstrual cycles of the CLAH patients. No increase in the urinary pregnanediol suggested anovulation in all patients, and bilateral ovarian cysts were found in two of the subjects. Examination of the StAR gene revealed a frameshift mutation 840delA at codon 238, a nonsense mutation Q258X at codon 258, a homozygotic mutation at Q258X, and a compound heterozygotic mutation with 251insG and Q258X. CONCLUSIONS: We concluded that the development of ovarian cysts may be derived from continued anovulation in CLAH patients. Elevated LH levels may be explained by increased sensitivity of the anterior pituitary to circulating estrogen.- - - - - - - - - - ranking = 84.430135926675keywords = menstrual cycle, cycle (Clic here for more details about this article) |
4/15. Induction of endometrial cycles and ovulation in a woman with combined 17alpha-hydroxylase/17,20-lyase deficiency due to compound heterozygous mutations on the p45017alpha gene.OBJECTIVE: To describe the case of a Japanese woman with combined 17alpha-hydroxylase/17,20-lyase deficiency (congenital adrenal hyperplasia type V) and to discuss possible therapeutic procedures in such patients. DESIGN: Case report. SETTING: University hospital. PATIENT(s): A 26-year-old woman with secondary amenorrhea and primary sterility. INTERVENTION(s): Nucleotide sequencing of the P45017alpha gene (CYP17), induction of endometrial maturation with steroid hormone replacement, and ovulation induction with gonadotropin. MAIN OUTCOME MEASURE(s): Nucleotide sequence of CYP17, endometrial thickness and follicle diameter measured by transvaginal ultrasonography, and histologic evaluation of the endometrium. RESULT(s): Two different mutations were detected on CYP17: One was a deletion of the phenylalanine codon (TTC) at either amino acid 53 or 54 in exon 1, and the other was a missense mutation with the substitution of histidine (CAC) by leucine (CTC) at position 373 in exon 6. Repeated histologic evaluations performed during treatment with P consistently revealed an unripe endometrium with glands of the early secretory phase and markedly scanty stroma. Ultrasound examination revealed follicular growth and ovulation after gonadotropin administration, but insufficient thickness of the endometrium. CONCLUSION(s): ovulation induction was possible in this patient with 17alpha-hydroxylase/17,20-lyase deficiency, but the endometrial response to steroid hormone replacement was extremely poor.- - - - - - - - - - ranking = 4keywords = cycle (Clic here for more details about this article) |
5/15. Fertility and body composition after laparoscopic bilateral adrenalectomy in a 30-year-old female with congenital adrenal hyperplasia.Congenital adrenal hyperplasia due to 21-hydroxylase deficiency is caused by an inborn defect in the 21-hydroxylase gene (CYP21), leading to virilization of female patients and causing ambiguous genitals in the majority of female infants. adult women may suffer from loss of libido, irregular or absent cycles, and reduced fertility, despite intensive medical treatment. These problems have stimulated the search for alternative treatment modalities. We present an adult female patient, who was difficult to treat medically and whose clinical situation markedly improved after laparoscopic bilateral adrenalectomy. The procedure was well tolerated and without side effects. Postoperatively the elevated serum progesterone and 17-hydroxyprogesterone levels, as well as the undetectable LH levels, normalized. The procedure resulted in marked clinical improvement. Within 12 months after surgery she lost 11 kg in weight. This weight loss consisted mainly of adipose tissue. Acne disappeared, and she had a regular 4-week menstrual cycle, with progesterone levels that are compatible with a luteal phase. The introduction of laparoscopic techniques may give an impulse to the application of surgical therapy at a larger scale in patients with 21-hydroxylase deficiency who are difficult to treat with adrenal suppression therapy.- - - - - - - - - - ranking = 85.430135926675keywords = menstrual cycle, cycle (Clic here for more details about this article) |
6/15. Genetic and endocrinological evaluations of three 46,XX patients with congenital lipoid adrenal hyperplasia previously reported as having presented spontaneous puberty.Congenital lipoid adrenal hyperplasia (CLAH) is an autosomal recessive disorder characterized by impaired synthesis of adrenal and gonadal steroids. It was demonstrated that loss-of-function mutations in the steroidogenic acute regulatory protein (StAR) gene cause CLAH and that 46,XX patients with CLAH develop spontaneous puberty. We had reported that three 46,XX patients with CLAH had presented spontaneous puberty and one of the patients had developed life-threatening ovarian cysts, before the etiology of CLAH had been clarified. In the present study, we analyzed their StAR gene and demonstrated mutations. Endocrinological examinations of the patients revealed that serum LH and FSH levels and their responses to the LHRH stimulation were not exaggerated before the onset of puberty. serum LH levels and its response to LHRH were increased during puberty, whereas serum FSH levels remained within the normal range. serum estradiol increased after the administration of human menopausal gonadotropins in the pubertal patient, suggesting that the ovary might have another system than StAR to facilitate cholesterol transport into the mitochondria. Although the patients had menstrual cycles, they remained anovulatory, and the resultant increased secretion of LH was speculated to be responsible for the development of ovarian cysts.- - - - - - - - - - ranking = 84.430135926675keywords = menstrual cycle, cycle (Clic here for more details about this article) |
7/15. adrenal cortex, tumor, and peripheral production of deoxycorticosterone.A method is reported for the measurement of the urine excretion rates of tetrahydro-11-deoxycorticosterone (3 alpha,5 beta-THDOC), an important metabolite of 11-deoxycorticosterone (DOC). Quantification using gas chromatography/mass spectrometry (GC/MS) was achieved by comparing the ion fragment response for the molecular ion (m/z 507) of the analyte (as methyloxime trimethylsilyl ether derivative) to that of a fixed amount of an isomer of THDOC added to urine as internal standard. To improve the specificity of measuring THDOC in clinical samples, an additional Sephadex LH-20 chromatography step was introduced to separate 11-deoxycortisol and some progesterone metabolites. In the luteal phase of the menstrual cycle, THDOC excretion was higher than in the follicular phase; it was also higher than in women taking oral contraceptives. The correlation of THDOC with progesterone production, independent of a constant cortisol output, supports an ovarian or peripheral conversion of progesterone to DOC. The assay proved useful (1) in monitoring for the recurrence of a mineralocorticoid-secreting tumor and (2) when adrenal production of DOC was not fully suppressed in congenital adrenal hyperplasia due to 11 beta-hydroxylase deficiency. Under the latter circumstances, the renin-angiotensin system seemed to be an important regulator of DOC production.- - - - - - - - - - ranking = 84.430135926675keywords = menstrual cycle, cycle (Clic here for more details about this article) |
8/15. Monitoring of menstrual cycles, ovulation, and adrenal suppression by saliva sampling in female patients with 21-hydroxylase deficiency.OBJECTIVE: To investigate the correlation between menstrual cycles, ovulation, and adrenal suppression in congenital adrenal hyperplasia. DESIGN: Prospective observational study. SETTING: An academic outpatient clinic. PATIENT(S): Five females with salt-wasting 21-hydroxylase deficiency, aged 15.5 to 22.9 years; one had amenorrhea, one had irregular bleeding, and three had regular bleeding. INTERVENTION(S): Daily morning saliva sampling for 40 to 280 days. MAIN OUTCOME MEASURE(S): Salivary levels of progesterone (P), 17-hydroxyprogesterone (17-OHP), and androstenedione. RESULT(S): In the amenorrheic patient, the elevated P and 17-OHP levels decreased when the glucocorticoid dose was increased, and subsequently menarche occurred. The androstenedione levels were normal. The correlations between P and 17-OHP levels before and after menarche suggest that adrenal progesterone had prevented menarche. The patient with irregular bleeding showed slightly elevated androstenedione levels and increased levels of 17-OHP and P in an irregular pattern, without correlation in time with vaginal bleeding. Three patients with regular cycles showed a biphasic pattern of P levels, indicating ovulation. CONCLUSION(S): These longitudinal data support the hypothesis that menstrual cycling in females with 21-hydroxylase deficiency can be prevented or disturbed by elevated progesterone levels of adrenal origin, in the absence of androgen excess. Increasing glucocorticoid dose could suppress adrenal progesterone production, resulting in menarche.- - - - - - - - - - ranking = 423.15067963338keywords = menstrual cycle, cycle (Clic here for more details about this article) |
9/15. A case of adrenogenital syndrome with aberrant 11beta-hydroxylation.A 17 year old female patient with hypertension, amenorrhoea and hirsutism was found to have subnormal levels of plasma and urinary cortisol, significant plasma levels of Reichstein's compound S and 21-deoxycortisol, high urinary levels of THS and pregnanetriolone as well as elevated levels of plasma and urinary testosterone. Treatment with 0.5 mg/day of dexamethasone or 25 mg/day cortisone reduced her hypertension and restored her menstrual cycles, but also resulted in the development of moon face, body striae and a gain in weight. Lower doses of cortisone were without effect. The deficient cortisol production coupled with the presence of unusual intermediates such as Reichstein's compound S and 21-deoxycortisol can be explained by a shift in the substrate specificity of 11beta-hydroxylase from C-21-hydroxylated substrates (i.e. compound S) to C-21-deoxy substrates (i.e. 17-hydroxyprogesterone).- - - - - - - - - - ranking = 84.430135926675keywords = menstrual cycle, cycle (Clic here for more details about this article) |
10/15. adult-onset familial adrenal 21-hydroxylase deficiency.Two sisters (28 and 30 years) were investigated for primary infertility and milk hirsutism. Both had normal puberty, were having regular menses and had normal female sexual characteristics. Studies revealed elevated urinary 17-ketosteroid levels (15.8, 18.8 mg/24 hours) and increased serum levels of 17-OH-progesterone (2,756, 1,121 ng/dl), 21-desoxycortisol (1,882, 1,090 ng/dl), progesterone (300, 346 ng/dl), dehydroepiandrosterone (DHA) (1,600, 1,700 ng/dl), and androstenedione (402, 366 ng/dl) and testosterone (100, 104 ng/dl), together with a slight increase in serum 11-desoxycortisol (1,180, 1,560 ng/dl). blood pressure, serum sodium/potassium plasma renin and serum aldosterone, corticosterone, 11-desoxycorticosterone and cortisol levels were normal. The administration of ACTH caused a further increase in 21-hydroxylase precursors; the administration of dexamethasone normalized hormone levels and produced ovulatory cycles. Similar studies in two siblings were normal. The affected sisters were HLA identical and did not share any hla antigens with their healthy siblings. The data suggest that these patients have a mild form of 21-hydroxylase deficiency which was insufficient to cause prenatal virilization. The gene for this disorder may be allelic with that for typical congenital adrenal hyperplasia.- - - - - - - - - - ranking = 1keywords = cycle (Clic here for more details about this article) |
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