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.

Low frequency of CYP2B deletions in Brazilian patients with congenital adrenal hyperplasia due to 21-hydroxylas deficiency.

The frequency of large mutations was determined in 131 Brazilian patients with different clinical forms of 21-hydroxylase deficiency, belonging to 116 families. DNA samples were examined by Southern blotting hybridization with genomic CYP21 and C4cDNA probes after Taql and Bg/II restriction. Large gene conversions were found in 6.6% and CYP21B deletions in 4.4% of the alleles. The breakpoint in these hybrid genes occurred after exon 3 in 92% of the alleles. All rearrangements involving CYP21B gene occurred in the heterozygous form, except in a patient with simple virilizing form who presented homozygous CYP21B deletion. Our data showed that in these Brazilian patients, CYP21B deletions were less frequent than in most of the large series previously reported.

17Beta-hydroxysteroid dehydrogenase 3 deficiency in women.

In genetic males, mutation of the 17beta-hydroxysteroid dehydrogenase 3 (17HSD3)gene that is normally expressed in the testes impairs testosterone formation and causes development of male pseudohermaphroditism. We have ascertained seven women who are sisters of men with 17HSD3 deficiency and who are either homozygotes or compound heterozygotes for the same mutations as their affected brothers. Our findings confirm the concept that women with such mutations are asymptomatic.

Effect of acute and chronic oral zinc administration in hyperprolactinemic patients.

The inverse relationship between zinc (Zn(++)) and prolactin (PRL) was detected in in vitro studies, whereas in vivo results are contradictory. In order to evaluate this controversial subject we studied patients with hyperprolactinemia. Basal serum Zn(++) levels and serum PRL response to acute and chronic oral Zn(++) administration were evaluated in seven patients with prolactinomas and one with idiopathic hyperprolactinemia. Serum PRL levels did not change after acute oral Zn(++) administration (37.5 mg), although Zn(++) levels increased from 1.11+/-0.15 to 2.44+/-0.39 mug/mL (P<0.05). ZnZn(++) administration (47.7 mg daily) during 60 days increased serum Zn(++) levels from 1.11 +/- 0.15 to 1.59 +/- 0.58 mug/mL (p < 0.05) but caused no change in serum PRL levels. The TRH tolerance test (200 mug) was performed before and after 60 days of Zn(++) administration, and PRL response to TRH was unchangeable and similar in both tests. We concluded that acute or chronic Zn(++) administration does not inhibit PRL secretion in basal condition or by TRH effect in hyperprolactinemic patients.

Effect of zinc administration on thyrotropin releasing hormone-stimulated prolactinemia in healthy men.

Previous in vitro studies have demonstrated zinc (Zn++) inhibition of basal and of potassium (K+) or thyrotropin-releasing hormone (TRH)-stimulated prolactin (PRL) secretion, in a selective, reversible, and dose-dependent manner. Thus, Zn++ may regulate physiologically pituitary PRL secretion. Furthermore, studies with patients with uremia, cirrhosis or prolactinoma, have shown the coexistence of hypozincemia and hyperprolactinemia and zinc supplementation did not correct hyperprolactinemia in these patients. In normal individuals Zn++ administration produced controversial results on PRL secretion. Here, we investigated whether zinc administration affects TRH-stimulated PRL in healthy men. We found that Zn++ administration does not change the TRH-stimulated PRL. Therefore, in normal conditions, Zn++ does not inhibit TRH-stimulated prolactinemia. In addition, we found that acute increases of blood PRL and TRH do not alter blood Zn++ levels.

Serum inhibin levels before and after gonadotropin stimulation in cryptorchid boys under age 4 years.

We evaluated eleven cryptorchid boys under four years of age to determine the usefulness of serum inhibin as a marker of seminiferous tubule dysfunction. Serum testosterone, inhibin, LH and FSH concentrations were measured by RIA before and after 6 weeks of human chorionic gonadotropin plus human menopausal gonadotropin therapy, and bilateral testicular biopsies were performed at orchiopexy. Hormonal results from the cryptorchid group were compared to those from an age-matched control group. Basal LH and testosterone levels were similar in the two groups. Cryptorchid boys had lower basal inhibin and higher FSH levels than controls. After gonadotropin treatment the inhibin/FSH ratio was lower in cryptorchid than control children, suggesting the presence of seminiferous tubule damage (p = 0.002). Normal numbers of spermatogonia were seen in 6/9 scrotal and in 1/13 cryptorchid testes. The peak of inhibin was positively correlated to the number of spermatogonia (r = 0.68; p = 0.02). We conclude that basal and stimulated inhibin concentrations, as well as basal and stimulated inhibin/FSH ratio, provide additional information on seminiferous tubule function in cryptorchid boys and can be useful to evaluate Sertoli cell function in these patients.

Long-acting gonadotropin-releasing hormone agonists in the differential diagnosis of male precocious puberty.

Male sexual precocity is defined as the development of secondary sexual characteristics before 9 years of age. It can be classified as gonadotropin-dependent precocious puberty (GnDP) or gonadotropin-independent precocious puberty (GnIP) and sometimes the differential diagnosis between these entities is difficult. To determine whether long-acting GnRH agonists (GnRH-a) are effective in differential diagnosis of male precocious puberty, we measured gonadotropins and testosterone levels 30 days after a single administration of depot GnRH-a (triptorelin, gosereline or leuprolide) in 10 boys with sexual precocity of different etiologies. Testosterone levels 30 days after depot GnRH-a were in the prepubertal range in patients with GnDP but not in GnIP. We conclude that measurement of testosterone levels 30 days after long-acting GnRH-a is effective in the differential diagnosis of male sexual precocity.

[Pheochromocytoma of the urinary bladder, report of a case and review of the literature]. / Feocromocitoma vesical, relato de caso e revisão da literatura.

Pheochromocytoma is a rare neoplasm, found in 0.1% of all hypertensive patients. Extraadrenal pheochromocytomas occur in 18% of all cases and 1% accurate in the bladder. In this study, we report a case of a vesical pheochromocytoma in a 40-year-old male patient with typical clinical symptoms for 6 years. He related episodes of severe headaches and palpitation with increase of the blood pressure after micturition, which decreased within a few seconds and fatigue afterwards. The patient was evaluated through urinary catecholamine (NE: 263 ug/24 h; E: 14 ug/ 24 h; Dopa: 303 ug/24 h; normal range respectively < 80; < 20 and < 400) and plasma catecholamine level determinations before and after micturition (NE: 1.660-->34.790 pg/ml; E: 55-->231 pg/ml-normal range respectively < 268 and < 75). Magnetic resonance imaging, sonography and 131Iodine-methiliodobenzylguanidine scintigraphy were performed for diagnostic localization. In this case plasma catecholamine level determinations before and after voiding were important to confirm the diagnosis. All imaging techniques were able to disclose the tumor. Typical symptoms, diagnoses and therapy for vesical pheochromocytoma are described and compared to the reports found in the literature.

Male pseudohermaphroditism due to steroid 5alpha-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.