Tumor ovárico de células de Leydig en una niña de 7 años que se presentó como pubarquia precoz con elevación de 17 hidroxiprogesterona / Ovarian tumor of Leydig cells in a 7-year-old girl who presented as precocious pubarche with elevation of 17 hydroxyprogesterone

Clinical case: a girl of 7 ½ years who consulted for early pubarche without thelark, with a percentile size of 75 for a genetic target size in the 10th percentile, overweight with a 90th percentile BMI, and normal blood pressure. The biochemical study showed high levels of androgens: testosterone: 7.2 ng/dL, androstenedione of 5.1 ng / ml, 17OHP: 15 ng / dL with low normal DHEAS (0.26 ug/ml), Plasma Renin Activity normal low: 0.22 ng/mL/h. Initial imaging study showed a bone age of 10 years 6 months and normal abdominal and pelvic ultrasound. Molecular study showed no pathogenic variants in the CYP21A2 gene (21 Hydroxylase). With a probable diagnosis of non-classical congenital adrenal hyperplasia (HSRNC) and no known mutation, he started treatment with hydrocortisone (12 mg/m2). At 8.7 years, pubertal development begins and braking begins with LHRH analogues, which are administered for 18 months. Despite the treatment, signs of virilization and elevation of androgens (testosterone up to 130 ng/ml) are progressively accentuated, which do not diminish when trying different corticosteroid schemes. MRI of the abdomen and pelvis shows the normal adrenal glands and a solid nodular image of 2.1 x 1.6 cm in the right ovary (Figure 2), later demonstrated with pelvic ultrasound (Figure 2). Right laparoscopic oophorectomy was performed, whose biopsy demonstrated a Leydig cell tumor. One month after surgery, all androgenic levels were normalized, so the gradual suspension of corticosteroids began. Conclusion: Although HSRNC is the most frequent pathological cause of early pubarche, when it is associated with progressive clinical and biochemical hyperandrogenism despite adequate treatment and without pathogenic variants in the CYP21A2 gene, even with high levels of 17OHP, other causes should be considered, specifically, androgen producing tumors.

Caso clínico: niña de 7½ años que consulta por pubarquia precoz sin telarquia, con talla en percentil 75 para una talla objetivo genético en percentil 10, sobrepeso con IMC percentil 90 y presión arterial normal. El estudio bioquímico mostró niveles elevados de andrógenos: testosterona: 7,2 ng/dL, androstenediona de 5,1 ng/ml, 17OHP: 15 ng/dL con DHEAS normal baja (0,26 ug/ml), Actividad de Renina Plasmática normal baja: 0.22 ng/ mL/h. Estudio de imágenes inicial mostró una edad ósea de 10 años 6 meses y ecografía abdominal y pelviana normales. Estudio molecular no mostró variantes patogénicas en el gen CYP21A2 (21 Hidroxilasa). Con diagnosticó probable de hiperplasia suprarrenal congénita no clásica (HSRNC) y sin mutación conocida,inició el tratamiento con hidrocortisona (12 mg/m2). A los 8.7 años comienza desarrollo puberal y se inicia frenación con análogos de LHRH, los cuales se administran por 18 meses. A pesar del tratamiento se acentúan progresivamente los signos de virilización y hayelevación de los andrógenos (testosterona hasta 130 ng/ml), que no disminuyen intentando diferentes esquemas de corticoides. Se realiza RM de abdomen y pelvis que muestra las glándulas suprarrenales normales y una imagen nodular sólida de 2.1 x 1.6 cm en el ovario derecho (Figura 2), demostrada posteriormente con Ecografía pelviana (Figura 2). Se realiza ooforectomía derecha por vía laparoscópica, cuya biopsia demostró un tumor de células de Leydig. Un mes después de la cirugía, se normalizan todos los niveles androgénicos por lo que se inició la suspensión gradual de los corticoides. Conclusión: Aunque la HSRNC es la causa patológica más frecuente de la pubarquia precoz, cuando se asocia con un hiperandrogenismo clínico y bioquímico progresivo a pesar de un tratamiento adecuado y sin variantes patógenicas en el gen CYP21A2, incluso con niveles elevados de 17OHP, otras causas deben ser consideradas, específicamente tumores productores de andrógenos.

Effects of Adrenal Androgen Levels on Bone Age Advancement in Prepubertal Children: Using the Ewha Birth and Growth Cohort Study

Bone age (BA) advancement in prepubertal children may be associated with earlier onset of puberty and obesity. This study aimed to define the effects of adrenal androgen levels on the advancement of BA in prepubertal children, independent of obesity. During July and August 2011, we examined BA in 200 prepubertal children aged 7–9 years who were part of the Ewha Birth & Growth Cohort Study. BA was assessed by the Greulich-Pyle method. An index of BA advancement was calculated as the ratio of BA to chronological age (CA) (BA/CA), and this ratio was classified into 3 tertiles. We analyzed the relationship between BA advancement and anthropometric characteristics and adrenal hormone levels. The number of overweight children increased from the first group to the third group (P(Trend) = 0.03). The levels of adrenal androgens showed a significant positive correlation with the tertile groups after adjusting for age and sex (testosterone: r = 0.26, P < 0.001; dehydroepiandrosterone: r = 0.21, P < 0.001; androstenedione: r = 0.20, P < 0.001). Further, after controlling for body mass index (BMI), sex, and age, the BA/CA was found to be positively correlated with androstenedione (β = 0.04, R² = 3.7%) and testosterone levels (β = 0.05, R² = 4.7%). Based on our results, it is suggested that adrenal androgen levels are associated with BA advancement independent of BMI.

Repetitive ultrasonographic assessment of adrenal size and shape changes: a clue for an asymptomatic sex hormone-secreting adenoma

Diagnosis of an adrenal tumor without typical clinical signs related to hyperadrenocorticism and elevated alkaline phosphatase is challenging. This report describes a sex hormone-secreting adrenal tumor in a 10-year-old castrated male Shih Tzu evaluated through repetitive ultrasonographic examination. An adrenocorticotropic hormone stimulation test revealed elevated concentrations of androstenedione and 17-hydroxyprogesterone but a normal cortisol concentration. A mass was surgically excised and adenoma was diagnosed histopathologically. In the present case, adrenal tumor was strongly suspected based on a gradual increase in adrenal size and a change from peanut shape to an irregular mass on repetitive ultrasonography. Repetitive ultrasonographic examination of the adrenal gland is recommended when an abnormal ultrasonographic appearance of adrenal gland is identified, even in an asymptomatic dog.

novel mutation causing 17-beta-hydroxysteroid dehydrogenase type 3 deficiency in an Omani child: first case report and review of literature

This is the first case report in Oman and the Gulf region of a 17-beta-hydroxysteroid dehydrogenase type 3 [17-beta-HSD3] deficiency with a novel mutation in the HSD17B3 gene that has not been previously described in the medical literature. An Omani child was diagnosed with 17-beta-HSD3 deficiency and was followed up for 11 years at the Pediatric Endocrinology Clinic, Royal Hospital, Oman. He presented at the age of six weeks with ambiguous genitalia, stretched penile and bilateral undescended testes. Ultrasound showed no evidence of any uterine or ovarian structures with oval shaped solid structures in both inguinal regions that were confirmed by histology to be testicular tissues with immature seminiferous tubules only. The diagnosis was made by demonstrating low serum testosterone and high androstenedione, estrone, and androstenedione:testosterone ratio. Karyotyping confirmed 46,XY and the infant was raised as male. Testosterone injections [25 mg once monthly] were given at two and six months and then three months before his surgeries at five and seven years of age when he underwent multiple operations for orchidopexy and hypospadias correction. At the age of 10 years he developed bilateral gynecomastia [stage 4]. Laboratory investigations showed raised follicle-stimulating hormone, luteinizing hormone, androstenedione, and estrone with low-normal testosterone and low androstendiol glucurunide. Testosterone injections [50 mg once monthly for six months] were given that resulted in significant reduction in his gynecomastia. Molecular analysis revealed a previously unreported homozygous variant in exon eight of the HSD17B3 gene [NM_000197.1:c.576G>A.Trp192*]. This variant creates a premature stop codon, which is very likely to result in a truncated protein or loss of protein production. This is the first report in the medical literature of this novel HSD17B3 gene mutation. A literature review was conducted to identify the previous studies related to this disorder

Accumulation of 9α-hydroxy-4-androstene-3,17-dione by co-expressing kshA and kshB encoding component of 3-ketosteroid-9α-hydroxylase in Mycobacterium sp. NRRL B-3805 / 生物工程学报

9α-hydroxy-4-androstene-3,17-dione (9-OH-AD) is an important intermediate in the steroidal drugs production. 3-ketosteroid-9α-hydroxylase (KSH), a two protein system of KshA and KshB, is a key-enzyme in the microbial steroid ring B-opening pathway. KSH catalyzes the transformation of 4-androstene-3,17-dione (AD) into 9-OH-AD specifically. In the present study, the putative KshA and KshB genes were cloned from Mycobacterium smegmatis mc(2)155 and Gordonia neofelifaecis NRRL B-59395 respectively, and were inserted into the expression vector pNIT, the co-expression plasmids of kshA-kshB were obtained and electroporated into Mycobacterium sp. NRRL B-3805 cells. The recombinants were used to transform steroids, the main product was characterized as 9α-hydroxy-4-androstene-3,17-dione (9-OH-AD), showing that kshA and kshB were expressed successfully. Different from the original strain Mycobacterium sp. NRRL B-3805 that accumulates 4-androstene-3,17-dione, the recombinants accumulates 9α-hydroxy-4-androstene-3,17-dione as the main product. This results indicates that the putative genes kshA, kshB encode active KshA and KshB, respectively. The process of biotransformation was investigated and the results show that phytosterol is the most suitable substrate for biotransformation, kshA and kshB from M. smegmatis mc(2)155 seemed to exhibit high activity, because the resultant recombinant of them catalyzed the biotransformation of phytosterol to 9-OH-AD in a percent conversion of 90%, which was much higher than that of G. neofelifaecis NRRL B-59395. This study on the manipulation of the ksh genes in Mycobacterium sp. NRRL B-3805 provides a new pathway for producing steroid medicines.

Ovarian Leydig cell tumor in a post-menopausal patient with severe hyperandrogenism / Tumor ovariano de células de Leydig em paciente em pós-menopausa com hiperandrogenismo grave

Leydig cell tumors are rare ovarian steroid cell neoplasms. More than 75% of patients show signs of virilization due to overproduction of testosterone. We report a case of an 8-year-old woman with progressive signs of virilization, and presenting vaginal bleeding. Clinical analyses revealed high levels of serum testosterone, delta 4-androstenedione and estradiol, and also inappropriate low levels of gonadotrophins for a post-menopausal woman. Transvaginal ultrasound showed no evidence of ovarian tumor, but pelvic and abdominal computerized axial tomography imaging revealed a left ovarian solid nodule, and no evidence of alteration in the adrenal glands. Total hysterectomy and bilateral salpingoophorectomy were performed. Histopathology and immunohistochemistry confirmed the diagnosis of Leydig cell tumor. After surgery, androgen levels returned to normal, and there was regression of the signs of virilization.

Tumores ovarianos de células de Leydig são neoplasias raras de células ovarianas esteroidogênicas. Mais de 75% dos pacientes apresentam sinais de virilização devido à produção excessiva de testosterona. Relatamos aqui o caso de uma mulher de 81 anos de idade com sinais progressivos de virilização e ocorrência de sangramento vaginal. As análises clínicas mostraram altos níveis de testosterona sérica, delta 4-androstenediona e estradiol, além de níveis inadequadamente baixos de gonadotrofinas para uma mulher em pós-menopausa. O ultrassom transvaginal não apresentou evidências de tumor ovariano, mas a tomografia axial computadorizada da região pélvico-abdominal mostrou um nódulo sólido no ovário esquerdo e nenhuma evidência de alteração nas adrenais. Foi feita uma histerectomia total e salpingooforectomia bilateral. Os exames histopatológicos e a imuno-histoquímica confirmaram o diagnóstico de tumor de células de Leydig. Após a cirurgia, os níveis de androgênios voltaram ao normal, e os sinais de virilização regrediram.

A novel homozygous mutation p.E25X in the HSD3B2 gene causing salt wasting 3β-hydroxysteroid dehydrogenases deficiency in a Chinese pubertal girl: a delayed diagnosis until recurrent ovary cysts / 中华儿科杂志

<p><b>OBJECTIVE</b>3β- hydroxysteroid dehydrogenase deficiency (3βHSD), a rare form of congenital adrenal hyperplasia (CAH) resulted from mutations in the HSD3B2 gene that impair steroidogenesis in both adrenals and gonads. We report clinical features and the results of HSD3B2 gene analysis of a Chinese pubertal girl with salt wasting 3βHSD deficiency.</p><p><b>METHOD</b>We retrospectively reviewed clinical presentations and steroid profiles of the patient diagnosed in Guangzhou Women and Children's Medical Center in 2013. PCR and direct sequencing were used to identify any mutation in the HSD3B2 gene.</p><p><b>RESULT</b>A 13-year-old girl was diagnosed as CAH after birth because of salt-wasting with mild clitorimegaly and then was treated with glucocorticoid replacement. Breast and pubic hair development were normal, and menarche occurred at 12 yr, followed by menstrual bleeding about every 45 days. In the last one year laparoscopic operation and ovariocentesis were performed one after another for recurrent ovary cysts. Under corticoid acetate therapy, ACTH 17.10 pmol/L (normal 0-10.12), testosterone 1.31 nmol/L (normal <0.7), dehydroepiandrosterone sulfate 13.30 µmol/L (normal 0.95 - 11.67), cortisol 720 nmol/L (normal 130-772.8), androstenedione, 17-hydroxyprogesterone and progesterone were normal. Estradiol 461 pmol/L, follicle-stimulating hormone 3.04 IU/L, luteinizing hormone 8.52 IU/L in follicular phase. A pelvic ultrasound showed lateral ovaries cysts (58 mm × 50 mm × 35 mm) and a midcycle-type endometrium. A novel nonsense mutation c.73G >T (p.E25X) was identified in HSD3B2 gene. The girl was homozygous and her mother was heterozygous, while her father was not identified with this mutation.</p><p><b>CONCLUSION</b>A classic 3βHSD deficiency is characterized by salt wasting and mild virilization in female. Ovary cysts may be the one of features of gonad phenotype indicating ovary 3βHSD deficiency. A novel homozygous mutation c.73G >T(p.E25X) was related to the classical phenotype.</p>

16β-hydroxylation of 4-androstene-3,17-dione by Aspergillus niger / 生物工程学报

In order to discover the steroid biotransformation ability of filamentous fungus Aspergillus niger TCCC41650, we studied the fermentation of 4-androstene-3,17-dione with A. niger TCCC41650. The transformation product was purified, crystallized and determined as 16β-hydroxy-androst-4-ene-3,17-dione by X-ray single crystal diffraction method. The best fermentation condition was found to be pH 6.0, ethanol amount 2% with a substrate concentration of 1 per thousand, the transformation rate is 85.81% after 72 h. Based on the best of our knowledge, 16β-hydroxylation rarely occurs in microbial transformations of steroid. This study laid the foundation for the research of 16β-hydroxylation steroids

Anti-mullerian and androgens hormones in women with polycystic ovary syndrome undergoing IVF/ICSI

Despite its frequency, the polycystic ovary syndrome [PCOS] is still a difficult diagnosis in endocrinology, gynecology, and reproductive medicine. The Rotterdam consensus conference proposed to include the ultrasonographic follicle count as a new diagnostic criterion. Unfortunately, its assessment does not offer sufficient reliability worldwide. To explore the possible roles of altered circulating androgens and anti-mullerian hormone among PCOS women regarding their body mass index and their outcomes after IVF. In this cross sectional study, 195 women with PCO were included, they were divided according to their body mass index [BMI <27 kg/m[2]] as obese PCOS [n=91] and overweight PCOS [BMI >/= 27 kg/m[2]] [n=104]. Serum levels of androgens [dehydroepiandrosterone sulfate [DHEAS], testosterone and androstenedione [A4]], and anti-mullerian hormone [AMH] were assessed and compared with the endocrine profile and cycles outcomes. AMH, A4, FSH, and TSH concentrations were significantly higher in obese than in overweight women [p<0.001]. Contrary, LH: FSH ratio values, E[2], PRL and DAHE-S levels were significantly lower in obese than in overweight women [p<0.0001]. Total oocyte retrieved, mature and fertilized oocyte were significantly higher in obese than in overweight women. Among pregnant obese PCOS women both AMH and A4 were significantly increased and DAHE-S was significantly decreased compared to pregnant overweight PCOS women. Obese PCOS women have a higher chance of getting pregnant over those categorized as overweight PCOS. Also, androgens and AMH levels recommended to be considered in IVF attributes among obese and overweight PCOS women

Advances in the study of steroidal inhibitors of cytochrome P45017alpha / 药学学报

The steroidal enzyme cytochrome P45017alpha catalyzes the conversion of progesterone and pregnenolone into androgens, androstenedione and dehydroepiandrosterone, respectively, the direct precursors of estrogens and testosterone. Dihydrotestosterone is the principal active androgen in the prostate, testosterone is also an active stimulant of the growth of prostatic cancer tissue. Inhibition of this enzyme as a mechanism for inhibiting androgen biosynthesis could be a worthwhile therapeutic strategy for the treatment of PCA. In this paper, four categories of steroidal inhibitors of cytochrome P45017alpha will be reviewed, a diverse range of steroidal inhibitors had been synthesized and shown to be potent inhibitors of P45017alpha.

Modulation of Cx43 and gap junctional intercellular communication by androstenedione in rat polycystic ovary and granulosa cells in vitro

Gap-junctional intercellular communication [GJIC] is implicated in physicological processes and it is vitally important for granulosa cell [GC] differentiation and oocyte growth. We investigated the expression of connexin 43 [Cx43], a gap junctional protein, in normal and androstenedione-induced polycystic ovary [PCO], the effects of androstenedione on Cx43 expression, GJIC and progesterone production in granulosa cells in vitro. Isolated GCs from rat ovary were supplemented with FSH and dripped with EHS-matrix [EHS-drip] in culture media, were treated with physiological [10-7 M] or pathological [10-5 M] androstenedione concentrations to induce differentiation. Cx43 protein levels were assessed by Western blotting. Immunohistochemistry was also used to determine the localization of Cx43 in GCs and corpus luteum [CL] of controls and PCOs. Differentiation of GCs was determined by progesterone assay and Lucifer yellow dye transfer for GJIC status. The degree of significance of variations between the results was analyzed by ANOVA using SPSS [version 11.5; 2002]. Cx43 localized in the GC layer of both the control and PCOs. Its protein levels were upregulated in PCO rat ovaries. GCs in culture with or without androstenedione had a punctate membranous distribution of Cx43. However, androstenedione increased GJIC and upregulated progesterone and Cx43 protein levels. Inhibiting GJIC by 18-? GA in androstenedione-treated GCs caused partial inhibition of progesterone production, suggesting a possible role of GJIC in mediating the action of androstenedione on GC differentiation. This study presented a suitable culture model for polycystic ovary syndrome and showed that Cx43 and GJIC might contribute to the pathogenesis of polycystic ovary syndrome

Progress in study of the structure, catalytic mechanism and inhibitors of aromatase / 药学学报

Aromatase is a key enzyme responsible for in vivo estrogen biosynthesis. Inhibition of the activity of the aromatase has become an alterative way for treatment of breast cancer. In this review, the structure and catalytic mechanism of the aromatase is briefly introduced followed by thorough review of the progress in the study of the steroidal and non-steroidal aromatase inhibitors. This review is focused on the natural compounds that exhibit the aromatase inhibition, which include flavonoids, xanthones, coumarins, and sesquiterpenes. The structure-activity relationship of these compounds is also discussed.

Determination of serum steroids in monitoring therapy of congenital adrenal hyperplasia / 中华儿科杂志

<p><b>OBJECTIVE</b>To assess the utility of serum steroids measurement in monitoring the treatment of children with congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency (21OHD).</p><p><b>METHOD</b>Nineteen Patients with CAH 21OHD aged (3.67±1.54) years treated with hydrocortisone and fluorocortisone replacement were followed up at an intervals of 0.33 - 1.0 years over a period of (1.47±0.7) years. At each visit, roentgenograms of the hands and wrists were taken, fasting peripheral blood were collected to test serum dehydroepiandrosterone sulfate, progesterone, 17-hydroxyprogesterone (17-OHP), androstenedione (Δ4-A), testosterone, free testosterone, estrone, and estradiol concentrations at 8 AM in the morning before the first dose of glucocorticoid. Then the patients were classified as being in "Good Control" or in "Poor Control" based on clinical criteria including signs of androgen excess, growth velocity and bone age increment at each interval. Comparisons were carried out between the serum steroid concentrations of the two groups. The receiver operating characteristic (ROC) curves were used to determine the cut-off values for diagnosing "Poor Control".</p><p><b>RESULT</b>Both of serum Δ4-A and 17-OHP concentrations were higher in "Poor Control" group than those in "Good Control" group [5.95 (2.23-11.2) nmol/L versus 1.05 (1.05-9.89) nmol/L, t=2.19; 13.85 (6.06-20) µg/L versus 3.67 (0.42-21.1) µg/L, t=2.17; P<0.05, respectively]. The ROC curves for serum Δ4-A concentrations, serum 17-OHP concentrations, serum Δ4-A in combination with 17-OHP concentrations were constructed with areas under the ROC curves (95%CI) of 0.76 (0.62, 0.90), 0.75 (0.62, 0.88), 0.69 (0.54, 0.84), P<0.05, respectively. Serum Δ4-A of 3.9 nmol/L had 0.78 of sensitivity and 0.75 of specificity in diagnosing "Poor Control". Serum 17-OHP of 7.1 µg/L has 0.67 of sensitivity and 0.71 of specificity in diagnosing "Poor Control".</p><p><b>CONCLUSION</b>Each of serum 17-OHP or/and Δ4-A concentration was of significance in diagnosing "Poor Control" during the glucocorticoid replacement treatment of CAH 21OHD, with the diagnostic efficacy being serum Δ4-A concentration, serum 17-OHP concentration and serum Δ4-A in combination with 17-OHP concentration in descending order. Serum Δ4-A and 17-OHP concentrations may be used as the biochemical indicators to monitor the therapy of CAH 21OHD.</p>

Hiperplasia sebácea cutânea: estudo piloto para a correlação da doença com hormônios androgênios / Sebaceous hyperplasia: a pilot study to correlate this skin disease with circulating androgen levels

FUNDAMENTOS: As glândulas sebáceas são suscetíveis à ação dos hormônios androgênios e apresentam proliferação benigna com a idade, ou seja, hiperplasia. OBJETIVOS: Estudo piloto para verificar se há correlação entre a taxa de hormônios masculinos circulantes e o aumento da incidência da hiperplasia das glândulas sebáceas. MÉTODOS: 16 pacientes do sexo feminino, com diagnóstico de hiperplasia sebácea cutânea, foram comparados a um grupo-controle de mesmo gênero e idades semelhantes, sem a doença. Ambos os grupos foram submetidos a testes de dosagem sanguínea para avaliação das taxas de hormônios androgênios circulantes (testosterona livre e total, androstenediona). Os resultados foram tabulados e analisados estatisticamente. RESULTADOS: Os dados demonstraram não haver mudanças nos níveis de hormônios masculinos circulantes dos pacientes com hiperplasia sebácea cutânea, quando comparados ao grupo-controle. CONCLUSÃO: Os dados sugerem que não há alterações estatisticamente significantes nas taxas dos hormônios circulantes (testosterona livre e total, androstenediona, deidroepiandrosterona, sulfato de deidroepiandrosterona) dos pacientes com hiperplasia sebácea cutânea.

BACKGROUND: The sebaceous glands are susceptible to the effects of androgens. A benign proliferation of these hormones, i.e. hyperplasia, occurs with age. OBJECTIVES: This was a pilot study to demonstrate whether any correlation exists between circulating androgen levels and an increase in the incidence of sebaceous hyperplasia. METHODS: Sixteen female patients with a diagnosis of sebaceous hyperplasia were compared to a control group of females of a similar age without the disease. Blood tests were performed on participants of both groups to measure circulating androgen levels (free and total testosterone and androstenedione levels). Results were tabulated for statistical analysis. RESULTS: These data showed no statistically significant differences in circulating androgen levels between the patients with sebaceous hyperplasia and the control group. CONCLUSION: These data suggest that no significant changes occur in circulating androgen levels [free and total testosterone, androstenedione, dehydroepiandrosterone (DHEA) and DHEA sulfate] in patients with sebaceous hyperplasia.

Relationships of Basal Level of Serum 17-Hydroxyprogesterone with that of Serum Androstenedione and Their Stimulated Responses to a Low Dose of ACTH in Young Adult Patients with Congenital Adrenal Hyperplasia due to 21-Hydroxylase Deficiency

A single measurement of serum 17alpha-hydroxyprogesterone (17OHP) level can be unreliable because of its marked diurnal variation. We investigated the relationship of serum level of 17OHP with that of androstenedione (AD), which shows a smaller diurnal variation. And we tested whether the responses of these two hormones to low-dose ACTH stimulation are correlated in patients with 21-hydroxylase deficiency. Baseline serum 17OHP and AD levels were measured in 87 patients and a low-dose ACTH stimulation test was performed in 41 patients. The basal 17OHP level correlated positively with the basal AD level independently of sex, type of 21-hydroxylase deficiency, and the time of day of blood sampling (n = 87, R2 = 0.75, P < 0.001). The area under the curve of 17OHP and AD correlated positively with their respective basal levels. The fold-change increase in 17OHP after ACTH injection correlated negatively with the basal 17OHP level, but that of AD did not correlate with the basal AD level. The random serum 17OHP level, used in the clinic, is a reliable guide and a low-dose ACTH stimulation test provides no extra benefit for assessing the treatment adequacy in patients with 21-hydroxylase deficiency.

Concentração dos hormônios esteroides no fluido folicular de folículos ovarianos maduros e imaturos de pacientes com síndrome dos ovários policísticos submetidas à fertilização in vitro / Concentration of steroid hormones in the follicular fluid of mature and immature ovarian follicles of patients with polycystic ovary syndrome submitted to in vitro fertilization

OBJETIVO: avaliar a concentração dos hormônios esteroides no fluido folicular (FF) de folículos pequenos (10-14 mm) e grandes (> 18 mm) de mulheres com síndrome dos ovários policísticos (SOP) submetidas à hiperestimulação ovariana controlada (HOC) e ciclos de fertilização in vitro (FIV). MÉTODOS: estudo caso-controle foi conduzido em 13 mulheres inférteis com SOP (17 ciclos) e 31 mulheres inférteis por fator masculino - Grupo Controle (31 ciclos). Os FF foram aspirados individualmente e dividos em 4 grupos: G1 (FF pequeno do Grupo Controle), G2 (FF pequeno do grupo SOP), G3 (FF grande do Grupo Controle) e G4 (FF grande do grupo SOP). A metodologia utilizada para as dosagens de estradiol, progesterona e β-hCG foi a quimioluminescência, e de testosterona e androstenediona o radioimunoensaio. Para a análise das dosagens hormonais no FF entre os grupos SOP e Controle utilizou-se o teste t não-pareado, e para a comparação entre os quatro grupos, o ANOVA. Para a taxa de gravidez, foi utilizado o teste exato de Fisher. RESULTADOS: os folículos pequenos dos dois grupos tiveram valores menores de progesterona (8.435±3.305 ng/mL) comparados aos grandes (10.280±3.475 ng/mL), com valor de p<0,01. Os níveis de progesterona de todos os folículos do grupo SOP (8.095±4.151 ng/mL) foram inferiores ao Controle (9.824±3.128 ng/mL), com valor de p=0,03. Os níveis de testosterona diferiram entre G1 (326,6±124,4 ng/dL) e G3 (205,8±98,91 ng/dL), com valor de p<0,001, e entre G3 (205,8±98,91 ng/dL) e G4 (351,10±122,1 ng/dL), com valor de p<0,001. Os folículos pequenos (508,9±266 ng/dL) apresentaram valores superiores de testosterona comparados aos grandes (245,10±123 ng/dL), com valor de p<0,0001. As taxas de gravidez não diferiram entre os grupos SOP (5/13, 38,5 por cento) e Controle (9/31, 40,9 por cento), com valor de p=072. CONCLUSÕES: mulheres com SOP apresentam altas concentrações de testosterona no FF, independentemente do estágio de desenvolvimento folicular, e níveis de progesterona diminuídos, sugerindo que fatores parácrinos podem inibir sua secreção pelas células foliculares. As taxas de gravidez mostraram que o tratamento de HOC e FIV é uma boa opção para mulheres com infertilidade secundária à SOP.

PURPOSE: to evaluate the concentration of steroid hormones in follicular fluid (FF) of small (10-14 mm) and large (> 18 mm) follicles of women with polycystic ovary syndrome (PCOS) submitted to controlled ovarian hyperstimulation (COH) and in vitro fertilization (IVF) cycles. METHODS: a case-control study was conducted on 13 infertile women with PCOS (17 cycles) and 31 infertile women due to male factor - Control Group (31 cycles). FF was aspirated individually and divided into four groups: G1 (FF of small follicles of the Control Group), G2 (FF of small follicles of the PCOS group), G3 (FF of large follicles of the Control Group) and G4 (FF of large follicles of the PCOS group). Estrogen, progesterone and β-hCG were determined by chemiluminescence, and testosterone and androstenedione by radioimmunoassay. The unpaired t-test was used to compare the hormone determinations in the FF of the PCOS and Control Groups, and the four groups were compared by ANOVA. Fisher's exact test was used to compare the pregnancy rates. RESULTS: the small follicles of the two groups had lower progesterone levels (8,435±3,305 ng/mL) than large follicles (10,280±3,475 ng/mL), p-value <0.01. The progesterone levels of all follicles of group PCOS (8,095±4,151 ng/mL) were lower than Control (9,824±3,128 ng/mL), p-value =0.03. Testosterone differed between G1 (326.6±124.4 ng/dL) and G3 (205.8±98.91 ng/dL), p-value <0.001, and between G3 (205.8±98.91 ng/dL) and G4 (351.10±122.1ng/dL), p-value <0.001. Small follicles had higher testosterone levels (508.9±266 ng/dL) than large follicles (245.10±123 ng/dL), p-value <0.0001. The pregnancy rates did not differ between the PCOS (5/13, 38.5 percent) and the Control groups (9/31, 40.9 percent), p-value =072. CONCLUSIONS: women with PCOS had high testosterone concentrations in the FF, regardless of the stage of follicle development, and reduced progesterone levels, suggesting that paracrine factors may inhibit the secretion of the latter by follicular cells. The pregnancy rates showed that treatment with COH and IVF is a good option for women with infertility secondary to PCOS.

Infantile and early childhood masturbation: sex hormones and clinical profile

Few studies have explored the hormonal triggers for masturbation in infants and young children. Thus, we aimed to study the sex hormones and clinical profiles of masturbating infants and young children. This case-control study involved infants and young children who masturbate and were referred to three pediatric neurology clinics between September 2004 and 2006 [n=13], and a similar control group. All children underwent basic laboratory investigations prior to referral. Other tests included electroencephalography [n=8] and brain neuroimaging [n=9]. We measured dehydroepiandrosterone sulfate, 17-hydroxyprogesterone, free testosterone, estradiol, dehydroepiandrosterone, sex hormone-binding globulin [SHBG], and androstenedione in all participants. The median age at the first incident was 19.5 months [range, 4-36 months]; the median masturbation frequency, 4 times/day; and the median duration of each event, 3.9 min. The subjects masturbated in both prone [n=10] and supine positions [n=3]; two subjects used the knee-chest position. All subjects showed facial flushing; 6, friction between the thighs; 5, sweating; 9, sleeping after the event; and 12, disturbance on interruption. EEG was abnormal in one of eight subjects tested, and neuroimages were normal in all of nine subjects examined. The case and control groups had comparable levels of all sex hormones, except estradiol, which showed significantly lower levels in the case group [P=.02]. Masturbation in children seems to be associated with reduced estradiol levels, but not with other sex hormones. Further studies are needed to confirm our findings

Controlling effect of berberine on in vitro synthesis and metabolism of steroid hormones in insulin resistant ovary / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To investigate the functional and metabolic alterations in cultured insulin resistant ovary model in vitro, and to observe the effect of berberine (Ber, a Chinese medical monomer) in improving insulin resistance (IR).</p><p><b>METHODS</b>Ovary of mouse was cultured in vitro and treated by dexamethasone (Dex) to induce IR for establishing IR model ovary. The functional alteration in model ovary was assessed through detecting glucose and hormone levels in medium using RT-PCR, meanwhile, the expression of key molecules in insulin signal and steroid synthetic pathway were detected, and condition of IR improved by berberine was evaluated also.</p><p><b>RESULTS</b>(1) The model ovary was made by Dex in dose- and acting time-dependent manner. After being treated by 300 nmol/L Dex for 48 h, the glucose uptake of ovary reduced from 9.05 +/- 0.75 mg/g to 2.48 +/- 0.29 mg/g (P < 0.05); it further decreased (from 9.59 +/- 1.74 mg/g to 1.94 +/- 0.19 mg/g, P < 0.01) under the stimulation of insulin, which proved that the IR model ovary was made successfully. Berberine significantly increased the glucose uptake of model ovaries (1.89 +/- 0.33 mg/g to 13.95 +/- 3.30 mg/g, P < 0.05). (2) As compared with control group, levels of testosterone (T) and androstenedione (A2) were higher, and levels of progesterone (P) and 17-hydroxyprogesterone (17-OHP) were lower significantly in the model. Berberine reversed the alternations of T, A2 and 17-OHP levels, but did not influence the level of P. (3) RT-PCR showed that the mRNA expressions of cytochrome 17-hydroxylase (CYP17) and mini-chromosome maintenance protein-2 (MCM-2) elevated, but extracellular regulated protein-1 (ERK-1), protein kinase B (AKT-2) and glycogen synthase kinase-3 (GSK-3beta) lowered in the medium after Dex inducing. Berberine treatment restored these molecular index obviously.</p><p><b>CONCLUSIONS</b>(1) Dex could induce IR in mouse ovary, which might enhance the androgenic synthesis. (2) Berberine could alleviate the degree of IR and the androgen synthesis, indicating that the Chinese sensitizing agents has favorable therapeutic effect for the treatment of polycystic ovaries.</p>

Green tea polyphenols inhibit testosterone production in rat Leydig cells / 亚洲男科学杂志(英文版)

This study investigated the acute effects of green tea extract (GTE) and its polyphenol constituents, (-)-epigallocatechin-3-gallate (EGCG) and (-)-epicatechin (EC), on basal and stimulated testosterone production by rat Leydig cells in vitro. Leydig cells purified in a Percoll gradient were incubated for 3 h with GTE, EGCG or EC and the testosterone precursor androstenedione, in the presence or absence of either protein kinase A (PKA) or protein kinase C (PKC) activators. The reversibility of the effect was studied by pretreating cells for 15 min with GTE or EGCG, allowing them to recover for 1 h and challenging them for 2 h with human chorionic gonadotropin (hCG), luteinizing hormone releasing hormone (LHRH), 22(R)-hydroxycholesterol or androstenedione. GTE and EGCG, but not EC, inhibited both basal and kinase-stimulated testosterone production. Under the pretreatment conditions, the inhibitory effect of the higher concentration of GTE/EGCG on hCG/LHRH-stimulated or 22(R)-hydroxycholesterol-induced testosterone production was maintained, whereas androstenedione-supported testosterone production returned to control levels. At the lower concentration of GTE/EGCG, the inhibitory effect of these polyphenols on 22(R)-hydroxycholesterol-supported testosterone production was reversed. The inhibitory effects of GTE may be explained by the action of its principal component, EGCG, and the presence of a gallate group in its structure seems important for its high efficacy in inhibiting testosterone production. The mechanisms underlying the effects of GTE and EGCG involve the inhibition of the PKA/PKC signalling pathways, as well as the inhibition of P450 side-chain cleavage enzyme and 17beta-hydroxysteroid dehydrogenase function.

Serum androgen levels and their relationship to pattern and severity of hair growth in hirsute women presenting at private centre in Hyderabad

To determine the frequency of raised serum androgen levels in hirsute women and their relationship to the pattern and severity of hair growth in patients presenting at private cosmetic center at Hyderabad. In this cross-sectional study, conducted in a private cosmetic and aesthetic centre, Hyderabad, from January, 2007 to December, 2007, 65 consecutive patients of hirsutism attending the centre were enrolled. Twenty normal women of similar ages [mean age 23.60 +/- 2.90 years] without signs of hirsutism and with normal menstrual cycle were also included as control group. Informed consent was obtained from all patients. Duration, pattern, and severity of hair growth [Ferriman-Gallwey score], weight, body mass index, acne and sebhorrhea were also evaluated. Serum testosterone, serum androstenedione and dehydroepiandrosterone sulphate levels were assessed in all patients and controls. Correlation between serum androgen levels and pattern and severity of hair growth was determined. Chisquare test was applied to determine p value. A total of 65 patients were enrolled in study. Their ages ranged from 16 to 45 years [mean age 24.49 +/- 6.44 years]. Thirty nine [60%] patients had normal androgen levels without evidence of significant endocrine abnormality. These were assigned idiopathic category. 26 [40%] patients had modest elevations of serum androgens. Among them, 21 had polycystic ovaries. Patients having modest to greatly elevated androgen levels [serum testosterone] had severe hirsutism with Ferriman-Gallwey scores [F-G score] >/= 8. [p