Prenatal diagnosis and treatment of adrenogenital syndrome. Prevent virilization of female fetuses

Congenital adrenal hyperplasia (CAH) is the common name of a constellation of diseases that impair cortisol synthesis in the adrenal cortex. As defects in each of three steroidogenic enzymes, 21-hydroxylase, 11 beta-hydroxylase, and 3 beta-hydroxysteroid dehydrogenase, promote overproduction of adrenal androgens, affected female fetuses may be virilised. The major cause of CAH is 21-hydroxylase deficiency, the incidence of which is 1:10,000 live births in the Swedish population. Of the 10-15 children born in Sweden each year with 21-hydroxylase deficiency, 3-5 will be virilised girls who must undergo traumatic surgery of the external genitalia. This can be prevented by administration of dexamethasone to the gravida during pregnancy. Prenatal treatment was introduced in Sweden in 1985, prenatal diagnosis being based in most cases on direct mutational analysis using allele-specific PCR on DNA from chorionic villus samples. In our experience, genotype corresponds well to phenotype, and we recommend that all children with 21-hydroxylase deficiency be genotyped in order to prepare the family for rapid and reliable prenatal diagnosis and possible treatment when the next child is awaited. Since 1985, 35 women have received prenatal treatment in Sweden, six of the 35 fetuses being found to be affected females and treated until term. As compared with their older sisters, all of these six girls were characterised by no signs, or only minor signs, of virilisation, and only one required surgery because of labial fusion and recurrent urinary tract infections. As a group, the 35 infants were characterised by normal birth weight and length, and normal growth during the first year of life. Passage of developmental milestones was normal though several adverse events, both in treated mothers and infants, have been reported. Approximately one fourth of the women treated throughout pregnancy reported some side-effect (e.g., excessive weight gain, severe cutaneous striae, mood fluctuations and irritability, acne and hirsutism, or oedema). One unaffected boy, treated for seven weeks, was born with severe hydrocephalus and agenesis of the corpus callosum; two affected sisters and one unaffected girl were characterised by failure to thrive during the first year of life, but later recovered (one of the affected sisters was later diagnosed as suffering from mitochondrial disease). Although in our experience prenatal treatment with dexamethasone is effective in preventing virilisation of girls with 21-hydroxylase deficiency, some adverse events have been noted in treated infants. As it remains unknown whether these events were attributable to the treatment, it must still be regarded as experimental, and its use should be centralised and meticulously monitored until more experience has been gained.     

Prenatal molecular genetic diagnosis and treatment of congenital adrenal hyperplasia due to 21-hydroxylase deficiency

Congenital adrenal hyperplasia due to 21-hydroxylase deficiency (21-OH), in its severe forms, produces virilization of the external genitalia of the affected female fetus. Early treatment with dexamethasone of the pregnant mother at risk of a fetus with 21-OH deficiency avoids the masculinization of the affected female fetus. We present a pregnant mother, where the prenatal diagnosis was established by DNA analysis of a chorionic villous sample obtained in the 9th week of gestation. Molecular analysis showed the female fetus to be affected of 21-OH deficiency. Maternal treatment with dexamethasone started on the 6th week of gestation has prevented the virilization of the affected baby. No significant side effects have been encountered. Prenatal diagnosis and treatment for 21-OH deficiency is effective and safe, as is described in the literature. This is the first case in Spain where both prenatal molecular diagnosis and treatment for 21-OH deficiency have been reported.     

Parasitological and clinical studies on human scabies in Cairo

This study is a parasitological and clinical study on human scabies. This study was carried out on 100 patients attending the Dermatology Outpatient Clinic at Ain Shams University Hospitals, including 54 males and 46 females. All patients were subjected to detailed history taking, complete dermatological examination including Skin Scraping Test and Burrow Ink Test. Younger patients attended the dermatology clinic earlier than older patients, who usually delayed their visits until complications occurred. Scratching, erythematous papules and secondary infected lesions were the commonest lesions. The hands, wrist and external genitalia were the most frequently affected sites while the feet, ankles, knees and back were the least affected. Burrows could only be detected in 40% of patients. The most frequent sites were the web spaces, external genitalia, and finger sides. Burrow Ink Test was positive among 85% of patients with burrows while mites could be identified by Skin Scraping Test in 55% of patients. The most frequent clinical manifestations in the parasitologically positive patients were itching, burrows, and papules, and the most frequent sites were the web spaces, and the finger sides. Multiple sites affection was the characteristic feature among the preschool age children who represented 14% of cases.     

Prenatal androgens and gender-typed behavior: A study of girls with mild and severe forms of congenital adrenal hyperplasia.

Gender-typed behaviors and interests were investigated in 26 girls, aged 2-10 years, affected with congenital adrenal hyperplasia (CAH) and in 26 unaffected girls matched for age. Girls with CAH were more interested in masculine toys and less interested in feminine toys and were more likely to report having male playmates and to wish for masculine careers. Parents of girls with CAH rated their daughters' behaviors as more boylike than did parents of unaffected girls. A relation was found between disease severity and behavior indicating that more severely affected CAH girls were more interested in masculine toys and careers. No parental influence could be demonstrated on play behavior, nor did the comparison of parents' ratings of wished for behavior versus perceived behavior in their daughters indicate an effect of parental expectations. The results are interpreted as supporting a biological contribution to differences in play behavior between girls with and without CAH. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Early hormonal influences on cognitive functioning in congenital adrenal hyperplasia.

Administered a cognitive test battery that emphasized spatial ability, verbal fluency, and perceptual speed and accuracy to 17 females (aged 12.7–23.2 yrs) and 8 males (aged 13–29.9 yrs) with congenital adrenal hyperplasia (CAH) and 13 normal female relatives (aged 11.4–31.1 yrs) and 14 unaffected male relatives (aged 12.5–28.8 yrs). In addition, 13 fathers and 15 mothers of CAH patients participated. Ss also completed the Progressive Matrices, a vocabulary test, and an early life activities questionnaire (ELAQ). Findings indicate that CAH females, as compared with normal females, showed significantly enhanced performance on hidden pattern, card rotation, and mental rotation tests of spatial ability. On the ELAQ, CAH females, relative to normal females, showed significantly lower frequencies of participation in activities involving verbal expression and a trend toward greater participation in spatial manipulation activities. However, differences between CAH females and normal females in early childhood activities did not account for observed differences in spatial ability, given the absence of a significant correlation between the spatial manipulation activity scale and spatial ability. There was an absence of reliable differences between male CAH patients and controls across spatial tasks. Results are consistent with an effect of pre- and perinatal androgenizing hormones on the development of spatial ability. (58 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Receptor-activated Ca2+ influx via human Trp3 stably expressed in human embryonic kidney (HEK)293 cells. Evidence for a non-capacitative Ca2+ entry

Gonadal differentiation involves a complex interplay of developmental pathways. The sex determining region Y (SRY) gene plays a key role in testis determination, but its interaction with other genes is less well understood. Abnormalities of gonadal differentiation result in a range of clinical problems. 46,XY complete gonadal dysgenesis is defined by an absence of testis determination. Subjects have female external genitalia and come to clinical attention because of delayed puberty. Individuals with 46,XY partial gonadal dysgenesis usually present in the newborn period for the valuation of ambiguous genitalia. Gonadal histology always shows an abnormality of seminiferous tubule formation. A diagnosis of 46,XY true hermaphroditism is made if the gonads contain well-formed testicular and ovarian elements. Despite the pivotal role of the SRY gene in testis development, mutations of SRY are unusual in subjects with a 46,XY karyotype and abnormal gonadal development. 46,XX maleness is defined by testis determination in an individual with a 46,XX karyotype. Most affected individuals have a phenotype similar to that of Klinefelter syndrome. In contrast, subjects with 46,XX true hermaphroditism usually present with ambiguous genitalia. The majority of subjects with 46,XX maleness have Y sequences including SRY in genomic DNA. However, only rare subjects with 46,XX true hermaphroditism have translocated sequences encoding SRY. Mosaicism and chimaerism involving the Y chromosome can also be associated with abnormal gonadal development. However, the vast majority of subjects with 45,X/46,XY mosaicism have normal testes and normal male external genitalia.     

Early androgen effects on aggression in children and adults with congenital adrenal hyperplasia

Males are more likely than females to show aggressive behavior across species, ages, and situations, and these differences may be partly influenced by early hormones. We studied aggression in three samples of subjects with congenital adrenal hyperplasia (CAH), who were exposed to high levels of androgen in the prenatal and early postnatal periods. Controls were siblings and first cousins similar in age. In Sample 1, adolescents and adults completed the Multidimensional Personality Questionnaire (MPQ), which includes an Aggression scale. In Sample 2, adolescents and adults completed the MPQ and a paper-and-pencil version of Reinisch's Aggression Inventory. In Sample 3, parents rated the aggression of children aged 3-12, using a modification of Reinisch's Inventory. In all three samples, control males had higher aggression scores than control females. Further, as predicted, females with CAH had higher aggression than control females, but the difference was significant only in adolescents and adults. These results suggest that early androgens contribute to variability in human aggression.     

Water balance of Dermatophagoides pteronyssinus (Acari: Pyroglyphidae) maintained by brief daily spells of elevated air humidity

OBJECTIVES: To review the urological abnormalities in conjoined twins, a rare congenital abnormality arising from an incomplete separation of a pair of monozygotic twins, and who can be joined from the head to the pelvis with varying degrees of union. PATIENTS AND METHODS: The records and urological anomalies of conjoined twins presenting from 1985 to 1995 were reviewed retrospectively and the management and surgical reconstruction described. RESULTS: Seven of 11 sets of conjoined twins underwent surgical exploration. Complex urological problems occurred in all twins with omphalo-ischiopagus. The urological anomalies were: Set 1; both twins had one lateral crossed fused renal ectopia with uncrossed ureters draining into a single bladder with one urethra. They had one set of genitalia. Each twin received one crossed fused ectopic kidney, half the bladder and genitalia, with one retaining the urethra and one a vesicostomy. Set 2; these twins had four kidneys (two lateral and two central that were fused), four ureters (two of which crossed) and these drained into two sagittal bladders that emptied by one urethra associated with a single set of external genitalia containing three corpora cavernosa. At separation, the crossed ureters were re-routed, each received a bladder and the genitalia were split. Set 3; there were four kidneys with two crossed ureters draining into two collateral bladders, there was a partial duplication of the urethra and a single hypospadiac penis. After separation, each had kidneys draining into a bladder, one received the urethra and external genitalia, and one a urostomy. CONCLUSION: Complex urological problems occur in conjoined twins, although restricted to those with pelvic fusion (ischiopagus). Assessment and treatment needs to be individualised and overseen by a surgeon with experience in complex urology.     

Hormonal modulation of genital reflexes in male and masculinized female dogs.

When testosterone propionate (TP) is administered to adult, neonatally castrated male dogs and to adult females with masculinized genitalia produced by prenatal and neonatal exposure to androgen, both types of animals are unsuccessful in their attempts to copulate with receptive females. In the present experiment, 6 neonatally castrated male and 10 genitally masculinized female beagles were tested before and after TP treatment for responses to manual stimulation of the genitalia. An additional experimental group consisted of 6 males castrated as adults, and there was a control group of 5 normal males. After a series of TP injections (5 mg/kg), neonatally castrated males, adult castrates, and genitally masculinized females exhibited complete and strong erectile and ejaculatory reflexes. Erect penis lengths of neonatally castrated males and masculinized females were significantly shorter than those of normal males or of males castrated as adults. It is suggested that the failure of males castrated at birth, and of genitally masculinized females, to insert and lock when mounting receptive females is due to incomplete penile development and not to incomplete "organization" of spinal reflex mechanisms. (12 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Wall effects observed in tissue-equivalent proportional counters from 1.05 GeV/nucleon iron-56 particles

A strong overlap between P-glycoprotein (Pgp) and cytochrome P450 3A (CYP3A) substrates and modulators has been reported. To test the hypothesis that CYP3A and Pgp are coordinately regulated, we examined the effects of known inducers of CYP3A (triacetyloleandomycin, rifampicin, dexamethasone, pregnenolone 16alpha-carbonitrile) on Pgp expression in rat liver. We also investigated the gender-specific expression of Pgp and compared its response to dexamethasone between male and female rats. In male rats, western blot analyses showed that rifampicin and dexamethasone caused 50% and 5-fold increases in Pgp levels, respectively. RNase protection assays using gene-specific probes for the three Pgp isoforms revealed a 3-fold increase in mdr2 mRNA levels after dexamethasone administration and a 2-fold increase following rifampicin treatment. Triacetyloleandomycin and pregnenolone 16alpha-carbonitrile had no effect on Pgp expression and mRNA levels. We also observed that the basal level of Pgp was 40% lower in male rats than in females and that mdr2 mRNA levels in male rats were one-half those in females. As opposed to the results in male rats, dexamethasone reduced Pgp expression by approximately 60% and caused a 30% decrease in mdr2 mRNA levels in female rats. Mdr1a was not affected and mdr1b was not detected in female or male rats. We conclude that, at the dosage regimen used, CYP3A and Pgp responses to CYP3A inducers are regulated independently in rat liver. In addition, this study shows that Pgp expression and regulation are gender specific.     

Posttraumatic syringomyelia. A report of an atypical case

Isolated congenital lymphoedema of the external genitalia in boys is extremely rare. It can have major physical and emotional consequences for the children. Three male patients with primary lymphoedema of the penis and scrotum are described. The first case presented with lymphoedema of the prepuce and the phallic skin that persisted after the age of 1 year. Circumcision and excision of the subcutaneous tissues of the phallic skin were successful in producing the appearance of a normal circumcised penis. The second case presented with oedema of both phallic and scrotal skin. At age 1 year only a pastous thickening of the prepuce remained, scrotal and phallic skin normalised spontaneously. Routine circumcision was successful with a 5-year follow up. The third case presented with persistent oedema of both the scrotum and the phallus. He suffered leakage of lymph requiring incontinence pads, with complicating skin infections recurring every 4-6 weeks at age 8 years. After complete peeling of the scrotal and phallic skin from subcutaneous tissue some leakage persisted, infections subsided. The cause of this disorder remains unknown, although hypoplasia of the lymphatic vessels is reported in most cases. In the literature, several congenital malformations have been associated with primary lymphoedema. These were not noted in our patients. Rarely, the lymphoedema regresses spontaneously. The treatment of persistent lymphoedema is surgical and consists of meticulous excision of all subcutaneous layers of the affected skin, combined with reconstruction of the penis and/or scrotum. CONCLUSION: Primary lymphoedema of the male external genitalia is an extremely rare malformation of the lymphatic vessels of unknown origin. If persistent, surgical treatment is necessary.     

Species-specific patterns of urine investigation and flehmen in Grant's gazelle (Gazella granti), Thomson's gazelle (G. thomsoni), impala (Aepyceros melampus), and eland (Taurotragus oryx).

During sexual encounters in most antelope species, males routinely investigate recently voided urine or the genitalia of females and often perform flehmen following such investigations. Quantitative data from field studies of gazelles and eland confirmed previous observations that the most common result of the female's urinating when being sexually pursued is to terminate the male's sexual pursuit, presumably by communicating the state of anestrus. Impala females do not urinate when being sexually pursued. This difference between impala and the other antelope was attributed to the ease with which impala females can escape sexual pursuit of males by dashing into the tightly clustered herd of females or losing the male in light woodland brush. Eland males direct 93% of all flehmen responses to genital contact or the urine stream of females they are pursuing, in contrast to gazelles, which devote less than 10% of flehmen responses to these stimuli. These species differences were related to differences between the multimale groups characterizing eland herds and the territorial, single-male social system characterizing gazelle. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Premenstrual syndromes

A splicing junction mutation at nucleotide 656 (A-> G substitution, I2G) in the steroid 21-hydroxylase gene (CYP21) is the most frequently detected mutation in patients with the salt-wasting and simple-virilizing forms of steroid 21-hydroxylase deficiency (approximately 60%). In this disease, prenatal diagnosis and treatment to minimize the effects of excess androgen in affected females has been advocated. Therefore, to detect the I2G mutation rapidly, accurately, and without the use of radioisotope, we developed a modified polymerase chain reaction (PCR) with a mismatched 3' nucleotide primer to introduce a new restriction site upon PCR amplification of the mutant allele. This allowed the mutant allele to be identified readily by restriction enzyme digestion of the PCR product, and subsequently this PCR product was subjected to restriction enzyme digestion for diagnosis. Chorionic villus biopsy samples (CVS) were obtained at 10 to 11 weeks gestation from two females carrying fetuses at risk for steroid 21-hydroxylase deficiency. Prenatal diagnosis was successful in both cases. One affected female was treated with dexamethasone to term. In the other case, treatment was withdrawn at an early stage when testing revealed a normal fetus. The results demonstrate the rapid and accurate detection of the I2G mutation by this method, thereby indicating the feasibility of for prenatal diagnosis of the I2G mutation.     

Consequences of perinatal hormone manipulation on the adult sexual behavior of female rats.

Compared male and female behavior of 46 female Sprague-Dawley albino rats treated with prenatal or prolonged postnatal testosterone propionate (TP) or cyproterone acetate (Cyp A), an antiandrogen, to 13 control females. Prenatal TP decreased quality and rate of lordotic responding while increasing incomplete and complete male copulatory rate. Postnatal TP also impaired female behavior but increased only complete male copulations. Results suggest that, in the rat, gonadal steroid levels present during prenatal as well as postnatal developmental stages determine the direction and degree of differentiation of adult sexual behavior. Prenatal Cyp A had no effect on female behavior or external genitalia but decreased both types of male copulatory responses, suggesting that male behavior in normal females is based on prenatal androgenic modification of the nervous system. (30 ref.) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Congenital adrenal hyperplasia (21-hydroxylase deficiency) without demonstrable genetic mutations

Congenital adrenal hyperplasia (CAH) owing to 21-hydroxylase deficiency (21-OHD) is the most common inherited defect of adrenal steroid biosynthesis. At least 36 mutations in the CYP21 gene, which is mapped to chromosome 6p21.3, have been described. We performed genetic analysis of the CYP21 gene in a patient with classic 21-OHD CAH and her family. The entire exonic coding regions and intronic regions, as well as the -1 kb 5' upstream promoter region, were thoroughly sequenced and analyzed. Despite extensive sequencing, no mutation was found in this 3.7 kb area. The 11beta-hydroxylase defect, closely mimicking the clinical and biochemical phenotype of classic 21-OHD, was excluded by directly sequencing 2.6 kb covering the entire coding of the CYP11B1 gene. Herein we describe a phenotypically and hormonally affected patient with classic simple virilizing 21-OHD CAH who lacks a mutation in the entire CYP21 gene and coding region of the CYP11B1 gene.     

Targeted disruption of StAR provides novel insights into congenital adrenal hyperplasia

To explore the function of StAR in a system that can be experimentally manipulated, and to develop a mouse model for the human disorder lipoid congenital adrenal hyperplasia (lipoid CAH), we used targeted gene disruption to produce a mouse line deficient in StAR protein. Initially, StAR knockout mice were indistinguishable from wildtype littermates, except that all had female external genitalia. After birth, they showed signs of either respiratory distress or volume depletion and eventually died. Hormone assays confirmed severe defects in adrenal steroids, whereas hormones constituting the gonadal axis did not differ significantly from levels in wildtype littermates. Histologically, the adrenal cortex of StAR knockout mice contained florid lipid deposits, as visualized with oil red O stain. Lesser lipid deposits were observed in the steroidogenic compartment of the testis and none in the ovary. The sex-specific differences in gonadal involvement provide evidence for a two-stage model of the pathogenesis of StAR deficiency, with trophic hormone stimulation causing progressive accumulation of lipids within the steroidogenic cells which ultimately kills them. These StAR knockout mice provide a novel system in which to study StAR's essential roles in adrenocortical and gonadal steroidogenesis.     

Congenital adrenal hyperplasia in pregnancy

The congenital adrenal hyperplasias (CAH) are a group of inherited enzymatic defects of adrenal steroid biosynthesis. Deficiencies of each enzyme required in the steroid biosynthesis pathway are known, and these deficiencies are all inherited as autosomal recessive disorders. During pregnancy, maternal and fetal problems are confined to women who have 21-hydroxylase deficiency (P450c21 deficiency), 11-hydroxylase deficiency (P450c11 deficiency), and 3 beta-hydroxysteroid dehydrogenase deficiency (3 beta HSD deficiency), because other adrenal enzyme deficiencies are not compatible with fertility. The interposition of the placenta on the hypothalamic-pituitary-adrenal axis and other endocrine changes during pregnancy impact considerably on the clinical evaluation of the congenital adrenal hyperplasias. Successful management of CAH in pregnancy requires a firm knowledge of normal adrenal anatomic and endocrine changes that occur during gestation. Women with severe forms of CAH have decreased fertility rates because of oligo-ovulation, and successful conception requires a combination of good therapeutic compliance, careful endocrine monitoring, and often ovulation induction. From a fetal and neonatal standpoint, accurate prenatal diagnosis of 21-hydroxylase deficiency and 11-hydroxylase deficiency is now possible, which allows for prenatal treatment in an attempt to minimize clinical problems in the neonates. Prevention of masculinization of affected female fetuses by corticosteroid suppression has been attempted in both 21-hydroxylase deficiency and 11beta-hydroxylase deficiency CAH, with variable degrees of success. This review provides an overview of the congenital adrenal hyperplasias and their management during pregnancy.     

Pustular psoriasis in childhood

The activity of tumor necrosis factor (TNF) in serum and in peripheral blood monocytes (PBMC) was determined in 8 patients with fulminating viral hepatitis (FVH), 10 patients with chronic active hepatitis (CAH) and 10 health controls. The activity was monitored in FVH patients before and after treatment with hepatocyte growth factor (HGF). It was found that TNF level was significantly higher in CAH patients than in controls (t = 3.56, P < 0.01) and also significantly higher in FVH than in CAH patients (t = 3.07, P < 0.01). The activity of TNF decreased gradually in FVH patients after HGF treatment and there was a positive correlation (r = 0.09, P < 0.01) between the activity of serum and PBMC TNF. It was found that in animal models of hepatic necrosis there was transient elevation of TNF activity with its peak occurring after 6 hours; the peak could be lowered with HGF treatment (t = 3.65, P < 0.05). The authors are of the opinion that TNF is an important mediator causing hepatic necrosis. The relationship between HGF and TNF was also discussed.     

Reduced tumorigenicity of cultured neuroblastoma cells after treatment in vitro with dexamethasone

The effect of dexamethasone on tumorigenicity of cultured neuroblastoma and on de novo synthesis of DNA and protein was determined. Within 12 hr dexamethasone caused a dose-dependent inhibition of [3H]-thymidine incorporation into DNA. Incorporation of [3H]-leucine into protein was not affected by dexamethasone. Neurite formation was interrupted by actinomycin D or cycloheximide. Cells treated with dexamethasone before inoculation into A/J mice produced fewer tumors with longer latent periods than controls. About 2.6 times as many neuroblastoma cells treated with 50 micrograms/ml dexamethasone for 4 days were required for tumor development in 50% of recipient animals as compared to controls. Reduced tumorigenicity was dependent upon the length of treatment and the concentration of dexamethasone used. Cortexolone did not mimic the effects of dexamethasone. If, instead of inoculation, cells were replated and grown without dexamethasone, cellular aggregations appeared among the cells cultured in the absence of dexamethasone. By autoradiography, replated cells previously treated with ethanol displayed uniform incorporation of [3H]-thymidine, whereas replated cells from dexamethasone-treated cultures exhibited no incorporation in differentiated cells. However, incorporation was noted among the clusters. We hypothesize that tumors arising after dexamethasone treatment may be due to the presence of an unresponsive subpopulation of cells.     

Congenital adrenal hyperplasia presenting as massive adrenal incidentalomas in the sixth decade of life: report of two patients with 21-hydroxylase deficiency

Divergent recommendations exist regarding the evaluation of adrenal incidentalomas. Recent data have indicated a prevalence of adrenal tumors of 71% in nonclassical congenital adrenal hyperplasia (CAH) and unmasked heterozygotes. These data expand the differential diagnosis of such incidental tumors and substantially modify the approach to their evaluation. We present two patients, female pseudohermaphrodites with the simple virilizing form of CAH and 21-hydroxylase deficiency, who functioned successfully as married phenotypic males. Both came to medical attention in the sixth decade by virtue of massive adrenal incidentalomas encountered in the evaluation of recurrent urinary tract infections. Each had a 46, XX karyotype, no palpable testes, and markedly elevated baseline levels of 17-hydroxyprogesterone (17-OH Prog) of 6086 ng/dL and 6750 ng/dL. Both responded appropriately to dexamethasone suppression with reduction of 17-OH Prog, androgens and, in the second patient, ACTH to normal or near normal levels. Histologic and autopsy examination of the first patient's tumor and computed tomographic characteristics of the second revealed a benign adenoma and myelolipoma respectively. We extend and confirm previous recommendations that CAH be included in the differential diagnosis of adrenal incidentaloma and that baseline 17-OH Prog. levels be obtained, with ACTH stimulation if necessary, to diagnose the presence of nonclassical CAH.