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.

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.

Determinação dos ritmos circadianos e circanuais nas concentrações plasmáticas de testosterona e androstenediona em machos ovinos / Circadian and circannual rhythms determination in testosterone and androstenedione plasma concentrations in ovine males / Determinación de los ritmos circadianos y circanuales en las consentraciones plasmáticas de testotesrona y androstenediona en machos ovinos

Estudou-se a estacionalidade reprodutiva de machos ovinos no Estado de São Paulo para estabelecer os ritmos endócrinos circadianos e circanuais, de cinco carneiros Ideal-Polwarth. O sangue foi colhido por venopunção jugular, em um período de 24 horas, sendo as colheitas realizadas de duas em duas horas, a cada dois meses (seis momentos de colheita em um ano), para a obtenção do plasma e avaliação dos níveis de testosterona e androstenediona por radioimunoensaio. As concentrações plasmáticas de androstenediona e testosterona não permitiram a definição de um ritmo circadiano em suas respectivas secreções, porém, demonstraram ritmos circanuais, com níveis mais baixos de junho a outubro e mais elevados de dezembro a abril.

The reproductive seasonality of ovine males in Sao Paulo State was studied to establish the circadian and circannual endocrine rhythms of 5 Ideal-Polwarth rams. Blood was collected by puncturing the jugular vein for 24 hours with 2-hour intervals every 2 months (6 collections throughout the year) in order to obtain plasma and evaluate testosterone and the androstenedione levels by radioimmunoassay. The Testosterone and androstenedione plasma concentrations did not demonstrate a circadian rhythm in their respective secretions; however, they showed lower levels of circannual rhythms from June to October and higher from December to April.

Se estudió la estacionalidad reproductiva en machos ovinos en el Estado de São Paulo para determinar los ritmos endocrinos circadianos y circanuales, de cinco moruecos Ideal-Polwarth. La sangre se recogió por venopunción yugular, en un período de 24 horas, con las colectas de dos en dos horas, a cada dos meses (seis colectas en un año), para la obtención del plasma y evaluación de los niveles de la testosterona y androstenediona por el radioimunoensayo. Las concentraciones de la testosterona y androstenediona no permitieron la definición de un ritmo circadiano en sus secreciones, pero demostraron ritmos circanuales, con niveles más bajos de junio hasta octubre y más elevados de diciembre hasta abril.

Concentrações hormonais e desenvolvimento folicular de vacas leiteiras em hipertermia sazonal e aguda / Hormone concentration and follicular development in dairy cows under seasonal and acute hyperthermia

Avaliaram-se as concentrações hormonais e os parâmetros de desenvolvimento folicular de vacas leiteiras expostas ao calor sazonal e agudo. Dividiram-se os animais em quatro grupos: verão (n=5), outono (n=5), inverno com hipertermia aguda (grupo câmara climática, (CC), n=5) e inverno (n=9). Os animais foram abatidos no sétimo dia após a ovulação, e os parâmetros de desenvolvimento folicular avaliados. O líquido folicular do maior folículo foi aspirado e armazenado para posterior análise de hormônios esteróides e inibina. O número de células da granulosa vivas no verão e no outono foi 40 e 45 por cento respectivamente, menor que no inverno (P<0,05). A concentração de estradiol (E2) no inverno foi 62 por cento maior que no outono (P<0,05) e 34 por cento superior ao grupo verão (P<0,06). Houve um aumento na quantidade de androstenediona no verão em relação aos grupos inverno (P<0,08) e outono (P<0,05). A concentração de inibina foi maior no inverno do que no verão e CC (P<0,05). A exposição ao calor sazonal e agudo modificou os parâmetros de desenvolvimento do folículo e as concentrações hormonais no líquido folicular, podendo explicar em parte a queda nas taxas de concepção no verão.

The present study evaluated the seasonal and acute heat stress on follicular development and steroid and inhibin concentrations in follicular fluid, in bovine dominant follicle. Cows were distributed into four treatments: summer (n=5), autumn (n=5), animals heat stressed during the winter (n=5) and winter (n=9). On day 7 of the estrous cycle, animals were slaughtered and parameters related to follicle development were evaluated. The follicular fluid (FF) was aspirated and stored for further hormonal analysis. During the summer, the number of viable granulosa cells was 40 percent lower than during the winter, and there was a 45 percent decrease in this parameter during the autumn (P<0.05). In the winter, estradiol concentration was 62 percent higher than during the autumn (P<0.05) and 42 percent higher than during the summer (P<0.06). There was an increase in androstenedione concentration in summer group, when compared to winter (P<0.08) and autumn (P<0.05) groups. Inhibin concentration was higher in winter groups than summer and winter heat stressed groups (P<0.05). Seasonal and acute heat stress altered developmental parameters in dominant follicle and hormonal concentration in follicular fluid, those effects can partially explain the decrease in conception rates during summer.

Estradiol and testosterone concentrations in follicular fluid as criteria to discriminate between mature and immature oocytes

The objective of the present study was to examine the association between follicular fluid (FF) steroid concentration and oocyte maturity and fertilization rates. Seventeen infertile patients were submitted to ovulation induction with urinary human follicle-stimulating hormone, human menopausal gonadotropin and human chorionic gonadotropin (hCG). A total of 107 follicles were aspirated after hCG administration, the oocytes were analyzed for maturity and 81 of them were incubated and inseminated in vitro. Progesterone, estradiol (E2), estrone, androstenedione, and testosterone were measured in the FF. E2 and testosterone levels were significantly higher in FF containing immature oocytes (median = 618.2 and 16 ng/ml, respectively) than in FF containing mature oocytes (median = 368 and 5.7 ng/ml, respectively; P < 0.05). Progesterone, androstenedione and estrone levels were not significantly different between mature and immature oocytes. The application of the receiver-operating characteristic curve statistical approach to determine the best cut-off point for the discrimination between mature and immature oocytes indicated levels of 505.8 ng/ml for E2 (81.0 percent sensitivity and 81.8 percent specificity) and of 10.4 ng/ml for testosterone (90.9 percent sensitivity and 82.4 percent specificity). Follicular diameter was associated negatively with E2 and testosterone levels in FF. There was a significant increase in progesterone/testosterone, progesterone/E2 and E2/testosterone ratios in FF containing mature oocytes, suggesting a reduction in conversion of C21 to C19, but not in aromatase activity. The overall fertility rate was 61 percent but there was no correlation between the steroid levels or their ratios and the fertilization rates. E2 and testosterone levels in FF may be used as a predictive parameter of oocyte maturity, but not for the in vitro fertilization rate.

Diagnóstico pré-natal da hiperplasia congênita de supra-renal / Pre-natal diagnosis of congenital adrenal hyperplasia

Os autores utilizam a dosagem da 17-OH-Progesterona e delta-4-androstenediona no líquido amniótico para rastrear a ocorrência de hiperplasia congênita da supra-renal em cinco fetos com risco da doença. Os casos foram estudados no pós-natal e confirmaram o acerto do diagnóstico pré-natal em todos os casos, caracterizando o teste como adequado no rastreamento da doença.