Major hyperestrogenism in a feminizing adrenocortical adenoma despite a moderate overexpression of the aromatase enzyme.

A 30-year-old male was referred for the rapid development of gynecomastia, and dramatic hyperestrogenemia was assessed: plasma estrone, estradiol but also cortisol were not suppressed by high-dose dexamethasone, while gonadotropin pulsatility was completely abolished. A 60-mm right adrenal tumor was evidenced on computed tomography-scan, and the patient underwent adrenalectomy. The tumor was found to express a moderate increase in aromatase activity compared with adjacent non-neoplastic adrenal tissue. Quantitative RT-PCR also showed a weak and non-significant increase in total aromatase mRNA in the tumor compared with normal adrenal tissue. Aromatase transcripts were mainly promoter PII-derived, but different patterns of aromatase minor transcripts were found: promoter I.3- and I.6-derived transcripts were identified in the tumor, while only promoter I.4-derived transcripts were found in normal adrenal. This case report demonstrates that a sharp aromatase overexpression is not a prerequisite for clinical and biochemical hyperestrogenism, and further characterizes the aromatase promoter utilization in this feminizing adrenocortical tumor and in the normal adrenal cortex.

Fetuses with Down's Syndrome detected by prenatal screening are more likely to abort spontaneously than fetuses with Down's Syndrome not detected by prenatal screening.

OBJECTIVE: Pregnancy with Down's Syndrome is often terminated by miscarriage. We have investigated whether prenatal screening would lead preferentially to the identification of fetuses with Down's Syndrome prone to abort spontaneously. DESIGN: A comparison between the observed and the expected decrease in the prevalence of Down's Syndrome at term following extensive prenatal screening. SETTING: A study from 1990 to 1998 in a limited and well controlled area of western France (Basse Normandie), with a birth rate close to 20,000 a year. POPULATION: Women under 38 years of age among whom prenatal screening for Down's Syndrome using biochemical tests and ultrasound findings became progressively extensive in this era. METHODS: Our study was based on the registration of Down's Syndrome cases detected prenatally from screening, and live births with Down's Syndrome. Fetal loss rate in the population of prenatally detectable Down's Syndrome was evaluated by comparing the increase in detection of cases of Down's Syndrome following prenatal screening with the expected decrease in the number of cases of Down's Syndrome at birth. The results obtained were compared with published data on the rates of fetal losses postulated to occur among fetuses with Down's Syndrome. MAIN OUTCOME MEASURES: Comparison of the potential fetal loss rate in a population in whom Down's Syndrome was detected prenatally with the expected fetal loss rate of unselected ones. RESULTS: Prenatal screening resulted in a significant (42%) decrease (P < 0.001) in the prevalence at term of the disorder. Among the 53 fetuses with Down's Syndrome detected prenatally during the last three years of the study, about 50% would have aborted spontaneously if the pregnancy had been allowed to continue. This figure was significantly higher (P < 0.002) than expected on the basis of results from the literature, indicating that current estimates of miscarriage rates among fetuses with Down's Syndrome do not apply to the selected group of cases detectable from prenatal screening. CONCLUSIONS: Our results suggest that fetuses with Down's Syndrome detectable prenatally from screening are more likely to abort spontaneously than fetuses with Down's Syndrome which are not detected.