Frederico A.Q. Silva

Male pseudohermaphroditism due to steroid 5α-reductase 2 deficiency. Diagnosis, psychological evaluation, and management

Sixteen subjects (from 10 Brazilian families) with male pseudohermaphroditism due to steroid 5alpha-reductase 2 deficiency have been evaluated in 1 clinic. The diagnoses were made on the basis of normal plasma testosterone values, normal or low plasma dihydrotestosterone levels and high testosterone/dihydrotestosterone ratios in the basal state in postpubertal subjects or after treatment with either human chorionic gonadotropin or testosterone in prepubertal subjects. The analysis of the ratios of etiocholanolone to androsterone in urine confirmed the diagnosis in all subjects who were tested, and the molecular basis of the underlying mutations was established in 9 of the families. Fourteen of the individuals were evaluated by the same psychologist. All subjects but 1 were given a female sex assignment at birth. Three of the subjects (1 the sibling of an individual who has undergone female to male social behavior) maintain a female social sex; they have been gonadectomized and treated with exogenous estrogens. Ten of 13 subjects of postpubertal age underwent a change of social sex from female to male, had surgical correction of the hypospadias, and were treated with high-dose testosterone esters by parenteral injection and subsequently with dihydrotestosterone cream. These regimens brought serum dihydrotestosterone levels to the normal male range (or above) but resulted only in limited growth of the prostate and penis and, in some, increase in body and facial hair and enhancement of libido and sexual performance. Treatment of the prepubertal boys with testosterone and/or dihydrotestosterone resulted in a doubling of penis size.

Male pseudohermaphroditism due to 17 beta-hydroxysteroid dehydrogenase 3 deficiency. Diagnosis, psychological evaluation, and management.

Ten male pseudohermaphrodites with 17 beta-hydroxysteroid dehydrogenase 3 (17 beta-HSD3) deficiency were evaluated in 1 clinic with an average follow-up of 10.1 years. The diagnoses were made by demonstrating low to normal serum testosterone levels, high androstenedione levels, and high ratios of serum androstenedione to testosterone in the basal state or after treatment with human chorionic gonadotropin. The molecular features of the underlying mutations were identified in all 7 families. Two additional males in the same families are believed to be affected on the basis of history obtained from family members. All of the 46,XY individuals in these families were registered at birth and raised as females (despite the presence of ambiguous genitalia in all or most), and all virilized after the time of expected puberty due to a rise in serum testosterone to or toward the normal male range. The age at diagnosis varied from 4 to 37 years. Ten individuals were studied by the same psychologist, and change of gender role (social sex) from female to male occurred in 3 subjects and in the 2 presumed affected subjects not studied. The individual with the highest serum testosterone level maintained female sexual identity, and in 2 families some of the affected males changed gender role and others did not. Thus, while androgen action plays a role in the process, additional undefined psychological, social, and/or biologic factors must be determinants of gender identity/role behavior. Management of the 7 individuals who chose to maintain female sex roles included castration, clitoroplasty, vaginal enlargement procedures when appropriate, treatment of hirsutism, cricoid cartilage reduction, and estrogen replacement. Three of the 7 are married (2 twice), 1 is involved in a long-term heterosexual relationship, 1 is engaged to be married, and the other 2 are not married and not believed to be sexually active. The 3 subjects who changed gender role behavior to male underwent hypospadias repair, and 1 was given supplemental testosterone therapy. One of these men is divorced, and the other 2 (aged 29 and 35 years) are unmarried. The diagnosis in 8 of these subjects was made after the time of expected puberty; it is unclear whether the functional and social outcomes would have been different if the diagnosis had been made and therapy begun earlier in life.

Clinical, Hormonal and Pathological Findings in a Comparative Study of Adrenocortical Neoplasms in Childhood and Adulthood

PURPOSE We reviewed clinical and laboratory findings in 6 male and 32 female patients with functional adrenocortical neoplasms, and compared pediatric and adult data. MATERIALS AND METHODS Hormonal measurements were performed by radioimmunoassay, histological analysis was based on Weiss criteria and staging was done according to previously established guidelines. RESULTS Children had a higher incidence of virilization (72%), whereas in adults the predominant feature was Cushings syndrome (60%). A high testosterone level was the most common finding in adults and children with virilization followed by high dehydroepiandrosterone sulfate, androstenedione and dehydroepiandrosterone levels. High 11-deoxycortisol levels were frequently associated with tumor recurrence. Cortisol suppression after dexamethasone was altered in 93% of patients with virilization and no clinical features, suggesting autonomous cortisol secretion. CONCLUSIONS No statistically significant relation was noted between tumor weight and prognosis but there was a negative correlation between patient age and prognosis since children had a more favorable followup than adults. Mixed features in both groups resulted in the worst prognosis. A Weiss criteria grade IV or greater correlated well with a poor prognosis in adults but not children, while staging was more reliable in children.

Management of ambiguous genitalia in pseudohermaphrodites: new perspectives on vaginal dilation.

OBJECTIVE To evaluate vaginal size and sexual activity after different techniques of feminization of external genitalia in patients with pseudohermaphroditism. DESIGN Retrospective clinical study. SETTING Pseudohermaphrodite patients seen at our institution. PATIENT(S) Three female and 20 male pseudohermaphrodites raised as females. INTERVENTION(S) Bilateral orchidectomy, feminization of external genitalia (clitoridectomy or clitoroplasty, urogenital sinus enlargement), and/or neovaginoplasty or vaginal dilation with acrylic molds. MAIN OUTCOME MEASURE(S) Psychological evaluation, vaginal size, and quality of intercourse. RESULT(S) All patients referred sexual drive to men. Fifty percent of the patients who were submitted to neovaginoplasty referred pain or bleeding during sexual intercourse. On the other hand, 87% of the patients who were submitted to vaginal dilation with acrylic molds, after genitoplasty or not, referred satisfactory sexual intercourse. All patients who were submitted to clitoroplasty referred orgasm and 29% of the patients submitted to clitoridectomy referred no orgasm. Of three patients with congenital adrenal hyperplasia due to 21-hydroxylase deficiency, two became pregnant and delivered normal children through cesarian section. CONCLUSION(S) In pseudohermaphrodites with female social sex, surgical correction of external genitalia performed in childhood and vaginal dilation with acrylic molds performed when they wished to start having sexual intercourse resulted in best outcome.

Laparoscopic Diagnosis and Treatment of Nonpalpable Testis

INTRODUCTION Treatment of the cryptorchid testicle is justified due to the increased risk of infertility and malignancy as well as the risk of testicular trauma and psychological stigma on patients and their parents. Approximately 20% of cryptorchid testicles are nonpalpable. In these cases, the videolaparoscopic technique is a useful alternative method for diagnosis and treatment. MATERIALS AND METHODS We present data concerning 90 patients submitted to diagnostic laparoscopy for impalpable testicles. Forty-six patients (51.1%) had intra-abdominal gonads. In 25 testicles of 19 patients, we performed a two stage laparoscopic Fowler-Stephens orchiopexy. The other 27 patients underwent primary laparoscopic orchiopexy, in a total of 29 testicles. RESULTS We obtained an overall 88% success rate with the 2 stage Fowler-Stephens approach and only 33% rate success using one stage Fowler-Stephens surgery with primary vascular ligature. There was no intraoperative complication in our group of patients. In the laparoscopic procedures, the cosmetic aspect is remarkably more favorable as compared to open surgeries. Hospital stay and convalescence were brief. CONCLUSIONS In pediatric age group, the laparoscopic approach is safe and feasible. Furthermore, the laparoscopic orchiopexy presents excellent results in terms of diagnosis and therapy of the impalpable testis, which is why this technique has been routinely incorporated in our Department.

The laparoscopic management of intersex patients : the preferred approach

In the worlds largest series of patients with intersex treated by laparoscopy, authors from Sao Paulo found that this technique allowed easy identification and removal of gonads. They also found that other organs could be removed and genitoplasty performed.

Laparoscopic pyeloplasty in children: Is the outcome different in children under 2 years of age?

PURPOSE To report the outcomes of a series of children younger than 2 years with ureteropelvic junction obstruction (UPJO) who underwent laparoscopic pyeloplasty (LP), compared to children older than 2 years. PATIENTS AND METHODS Twenty-three children (18 male) with UPJO underwent 24 Anderson-Hynes transperitoneal LPs between March 2003 and July 2007. The diagnosis of UPJO was confirmed on renal sonography and diuretic renogram. Nine children were younger than 2 years (Group 1) and 14 were older (Group 2). One child had bilateral UPJO and underwent two non-simultaneous procedures. All children were investigated with postoperative diuretic renogram and renal sonography, and the results were statistically analysed. RESULTS LP was feasible without conversions or intraoperative complications in all 24 cases. Median age in Groups 1 and 2 was 11 months (4-24) and 74 months (27-204), respectively, (P<0.00001). No differences were found between the groups regarding median operative time, complications, technical difficulties, discharge home and follow-up. All patients in both groups experienced resolution of symptoms or obstruction. CONCLUSIONS The LP in children younger than 2 years is highly successful with a low-rate of complications, and has the same outcomes as in older children.

Tratamento da hiperplasia supra-renal congênita por deficiência da 21-hidroxilase

The purpose of the treatment for congenital adrenal hyperplasia due to 21-hydroxylase deficiency (CAH-21OH) is to replace gluco and mineralocorticoids, prevent virilization of the external genitalia, salt loss and hyperandrogenism and preserve gonadal function, fertility and final height. Our experience in the treatment of 96 patients with CAH-21OH is presented. Children have been treated with cortisone acetate (18-20 mg/m2/day) and adults with dexamethasone (0.25-0.75 mg/day). If necessary, mineralocorticoid replacement was accomplished with 9a-fludrocortisone, 50-250 µg/day, according to chronological age. Despite therapy with gluco and mineralocorticoids the end results for CAH-21OH is still inadequate, especially when growth is concerned; in most reports final height reaches between 1 to 2 SD bellow target height. New therapeutic approaches for CAH-21OH, such as the association of flutamide and testolactone to hydrocortisone and fludrocortisone, and even surgical or chemical adrenalectomy, are still experimental and long-term follow-up is necessary to evaluate their validity.