OBJECTIVES: We aimed to investigate whether glucocorticoid receptor gene polymorphisms are associated with clinical and metabolic profiles in patients with polycystic ovary syndrome. Polycystic ovary syndrome is a complex endocrine disease that affects 5-8% of women and may be associated with metabolic syndrome, which is a risk factor for cardiovascular disease. Cortisol action and dysregulation account for metabolic syndrome development in the general population. As glucocorticoid receptor gene (NR3C1) polymorphisms regulate cortisol sensitivity, we hypothesized that variants of this gene may be involved in the adverse metabolic profiles of patients with polycystic ovary syndrome. METHOD: Clinical, metabolic and hormonal profiles were evaluated in 97 patients with polycystic ovary syndrome who were diagnosed according to the Rotterdam criteria. The alleles of the glucocorticoid gene were genotyped. Association analyses were performed using the appropriate statistical tests. RESULTS: Obesity and metabolic syndrome were observed in 42.3% and 26.8% of patients, respectively. Body mass index was positively correlated with blood pressure, triglyceride, LDL-c, total cholesterol, glucose and insulin levels as well as HOMA-IR values and inversely correlated with HDL-c and SHBG levels. The BclI and A3669G variants were found in 24.7% and 13.4% of alleles, respectively. BclI carriers presented a lower frequency of insulin resistance compared with wild-type subjects. CONCLUSION: The BclI variant is associated with a lower frequency of insulin resistance in women with polycystic ovary syndrome. Glucocorticoid gene polymorphism screening during treatment of the syndrome may be useful for identifying subgroups of at-risk patients who would benefit the most from personalized treatment.

Os incidentalomas adrenais não são infreqüentes e podem ser encontrados em pacientes com hirsutismo. Nesse relato, apresentamos o caso de coexistência de um incidentaloma adrenal com hipertecose de ovário, em uma mulher com 54 anos de idade com amenorréia e hirsutismo de início abrupto e sinais leves de virilização. As testosteronas total e livre basal foram de 191 ng/dL e 179 pmol/L, respectivamente. O ultra-som pélvico demonstrou o ovário direito com 10,3 cc e ovário esquerdo com 9,8 cc, sem nódulos ou cistos e a tomografia computadorizada de abdome demonstrou adrenal direita adrenal e nódulo sólido de 0,8 cm na adrenal esquerda. Após a administração de análogo de GnRH, as testosteronas total e livre foram de 23 ng/dL e 17 pmol/L, respectivamente. Considerando a supressão da concentração de testosterona pelo análogo de GnRH, a paciente foi submetida a histeroooforectomia por via laparoscópica. O diagnóstico histológico foi de hipertecose, com focos de células estromais luteinizadas. Somente folículos atréticos foram visualizados. Não se detectou hiperplasia de células hilares. Em conclusão, a presença de massa adrenal em uma paciente com hirsutismo pode levar ao diagnóstico errado. Neste caso, o teste de supressão com análogo de GnRH foi fundamental para se determinar a origem da hiperandrogenemia.

Adrenal incidentaloma is not infrequent and can be found in hirsute women. We report a case of a 54-year-old woman with amenorrhea and hirsutism of abrupt onset and mild signs of virilization that had an adrenal incidentaloma coexisting with ovarian hyperthecosis. Basal total and free testosterone were 191 ng/dL and 179 pmol/L. Pelvic ultrasonography disclosed a right ovary with 10.3 cc and a left ovary with 9.8 cc without nodules or cysts, and computerized tomography of the abdomen disclosed a normal right adrenal gland. On the left adrenal gland a solid nodule with 0.8 cm was seen. After GnRHa administration, total testosterone was 23 ng/dL and free testosterone was 17 pmol/L. In view of a suppression of testosterone by GnRHa, the patient was submitted to a hystero-oophorectomy by laparoscopy. Symmetrically enlarged ovaries were seen. No tumor was apparent. Histology showed hyperthecosis, with foci of luteinized stromal cells. Only atretic follicles were detected. No hilar cell hyperplasia was seen. In conclusion, the presence of an adrenal mass in a hirsute woman can lead to a wrong diagnosis. In this case the suppression GnRHa test was fundamental to determine the origin of hyperandrogenemia.

Como há controvérsia sobre a prevalência de hipertensão arterial em pacientes com a síndrome dos ovários policísticos (SOP) e, até o momento, nenhum estudo avaliou o impacto do índice de massa corporal (IMC) sobre a pressão arterial (PA), foram estudados retrospectivamente 69 pacientes com a SOP, com IMC de 29,0 ± 6,7 kg/m² e idade de 25,6 ± 5,6 anos, subdivididos em 3 grupos de acordo com o IMC (normal, sobrepeso e obesos) e avaliados com relação à PA, perfil hormonal basal, glicemia de jejum e sensibilidade à insulina (HOMA-IR). As médias das pressões arteriais sistólica (PAS) e diastólica (PAD) foram normais (118,1 ± 17,0 e 74,7 ± 11,5 mmHg, respectivamente), com uma prevalência de hipertensão de 20,3%. Das pacientes hipertensas, 78,6% eram obesas e 21,4% apresentavam sobrepeso. Quando os grupos, subdivididos de acordo com o IMC, foram comparados, aumento significativo da PAS e PAD foi observado (PAS maior nas pacientes com sobrepeso e obesas e PAD maior nas pacientes obesas), assim como um aumento progressivo da glicemia, insulina e HOMA-IR, e um decréscimo significante e progressivo de LH. Quando as pacientes foram subdivididas em normotensas e hipertensas, diferença significativa foi observada somente para IMC (28,2 ± 6,1 e 34,7 ± 8,6 kg/m², respectivamente; p = 0,007). Em conclusão, observamos um impacto significativo e progressivo do IMC sobre os níveis pressóricos em nossas pacientes com a síndrome dos ovários policísticos.

As there is controversy about the prevalence of hypertension in patients with polycystic ovary syndrome (PCOS) and, up to the present moment, no studies have evaluated the impact of body mass index (BMI) on blood pressure levels (BP) in these patients, we studied retrospectively sixty-nine patients with PCOS, with BMI of 29.0 ± 6.7 kg/m² and aged 25.6 ± 5.6 yr, subdivided into three groups according to BMI (normal, overweight and obese) and evaluated regarding BP (mercury sphygmomanometer), basal hormonal profile, fasting glucose, and insulin sensitivity (HOMA-IR). Mean systolic blood pressure (SBP) and diastolic blood pressure (DBP) were normal (118.1 ± 17.0 and 74.7 ± 11.5 mmHg, respectively), with a hypertension prevalence of 20.3%. Of these patients, 78.6% were obese and 21.4% were overweight. When the groups were compared according to BMI, a significant increase in SBP and DBP was observed (higher in overweight and obese patients for SBP and higher in obese for DBP), as well as a significant progressive increase in glucose, insulin, homeostatic model assessment, and a significant progressive decline in LH levels. When the patients were subdivided as normotensive or hypertensive, a significant difference was observed only for BMI (28.2 ± 6.1 and 34.7 ± 8.6 kg/m², respectively; p = 0.007). In conclusion, we observed a significant and progressive impact of BMI on blood pressure levels in our patients with polycystic ovary syndrome.

O objetivo deste estudo foi o de determinar a prevalência, características e preditores da síndrome metabólica em mulheres com a síndrome dos ovários policísticos. Setenta e três mulheres, com índice de massa corporal de 30,4 ± 7,8 kg/m² e 25,0 ± 6,0 anos de idade, subdivididas de acordo com o índice de massa corporal, foram estudadas retrospectivamente. Não se observou diferença significativa de idade entre os grupos (p = 0,228). A prevalência da síndrome metabólica foi de 38,4%, estando ausente nas mulheres com índice de massa corporal normal (n = 18) e presente em 23,8% das com sobrepeso (n = 17), 62,9% das obesas (n = 28) e 85,5% das obesas mórbidas (n = 7). Quando comparadas, as mulheres com síndrome metabólica apresentaram uma idade mais avançada (27,3 ± 5,3 vs. 24,2 ± 4,6 anos; p = 0,031) e um índice de massa corporal maior (36,3 ± 7,7 vs. 26,9 ± 5,4; p < 0,001) que as mulheres sem a síndrome, não havendo diferença significativa com relação ao grau de hirsutismo (p = 0,593) e padrão menstrual (p = 0,119). Com relação aos parâmetros laboratoriais, a concentração de DHEAS foi menor (1.646 ± 1.007 vs. 2.594 ± 1.563; p = 0,007) e o valor do HOMA-IR foi maior (9,9 ± 9,7 vs. 4,6 ± 4,7; p = 0,004) nas pacientes com a síndrome metabólica. Os melhores preditores para a presença da síndrome metabólica foram a circunferência abdominal > 88 cm, HDL-colesterol < 50 mg/dL e triglicérides > 150 mg/dL.

The aim of this study was to determine the prevalence of metabolic syndrome in women with polycystic ovary syndrome, as well as its characteristics and predictors. Seventh-three women, with body mass index of 30.4 ± 7.8 kg/m² and 25.0 ± 6.0 years old, subdivided according to body mass index, were studied retrospectively. There was no significant mean age difference among body mass index groups (p = 0.228). Prevalence of metabolic syndrome was 38.4%, with a null prevalence for normal (n = 18), 23.8% for overweight (n = 17), 62.9% for obese (n = 28), and 85.5% for morbidly obese women (n = 7). Women with metabolic syndrome were older than women without metabolic syndrome (27.3 ± 5.3 vs. 24.2 ± 4.6 vs. years old; p = 0.031) and presented a higher body mass index (36.3 ± 7.7 vs. 26.9 ± 5.4; p < 0.001). There was no difference for degree of hirsutism and menstrual patterns between women with and without metabolic syndrome (p = 0.593 and p = 0.119, respectively). Regarding laboratory parameters, DHEAS was lower (1,646 ± 1,007 vs. 2,594 ± 1,563; p = 0.007) and HOMA-IR were higher (9.9 ± 9.7 vs. 4.6 ± 4.7; p = 0.004) in women with metabolic syndrome (p = 0.031 and p < 0.001, respectively). The best predictors of metabolic syndrome were waist circumference > 88 cm, HDL-cholesterol < 50 mg/dL and triglycerides > 150 mg/dL.

Pacientes com a síndrome dos ovários policísticos (SOP) têm um risco maior para desenvolver anormalidades do metabolismo da glicose (AMG). Para avaliarmos a prevalência dessas anormalidades na nossa população, submetemos 85 pacientes, com índice de massa corporal (IMC) de 28,5 ± 6,6 kg/m² e média etária de 25,5 ± 5,4 anos, a teste de tolerância oral à glicose (TTOG). Os estados de tolerância à glicose foram classificados considerando a glicemia de jejum (GJ; American Diabetes Association - ADA) e glicemia aos 120 minutos (G120; Organização Mundial de Saúde - OMS). De acordo com a ADA, 83,5% das pacientes foram normais e 16,5% com AMG, com 15,3% apresentando glicemia de jejum imprópria e 1,2% diabetes mellitus (DM). De acordo com a OMS, 68,2% foram normais e 31,8% com AMG, com 27,0% apresentando intolerância à glicose (IG) e 4,8% DM. Observamos que 73% das pacientes com IG pelos critérios da OMS apresentavam GJ normal pelos critérios da ADA. A prevalência de AMG para ambos os critérios foi maior entre as pacientes com IMC mais elevado. Conclusão: encontramos maior prevalência de AMG nas pacientes com a SOP do que na população geral, sendo mais elevada entre as pacientes obesas. Além disso, a G120 no TTOG identificou maior número de pacientes com AMG do que a GJ. Assim, recomendamos avaliação de AMG através do TTOG para todas as pacientes portadoras da SOP.

Patients with polycystic ovary syndrome (PCOS) present a higher risk for abnormalities of glucose metabolism (AGM). For to study this in our population, we submitted 85 patients, with body mass index (BMI) of 28.5 ± 6.6 kg/m² and aged 25.5 ± 5.4 years old, to an oral glucose tolerance test (OGTT), and assessed the impact of BMI on the prevalence of impaired glucose tolerance (IGT) and of diabetes mellitus (DM). The states of glucose tolerance were classified considering fasting plasma glucose (FPG) according to the American Diabetes Association (ADA) criterion and plasma glucose at 120 minutes according to the Word Health Organization (WHO) criterion. According to the ADA criteria, 83.5% classified as normal and 16.5% as with AGM, with 15.3% presenting impaired fasting glucose and 1.2% DM, while according to the WHO criteria, 68.2% were classified as normal and 31.8% as with AGM, with 27.0% of them presenting IGT and 4.8% DM. Seventy-three percent of PCOS patients with IGT by WHO criterion had normal FPG by ADA criterion. The prevalence of AGM for both criteria increased with the body mass index. In conclusion, we found a higher prevalence of AGM in PCOS patients than that found in the general population, being the highest in obese patients. Glycemia at 120 minutes on the OGTT identified more patients with AGM than fasting glycemia. We recommended that the assessment of AGM must be done by the OGTT in all patients with PCOS.

A resposta da 17-hidroxiprogesterona (17OHP) ao estímulo agudo com um análogo do hormônio liberador de gonadotrofinas (GnRHa) e sua relação com a sensibilidade à insulina (SI) foi avaliada em 8 mulheres voluntárias normais e obesas (grupo N), com idades entre 24 e 40 anos (mediana de 29) e índice de massa corpóreo (IMC) entre 32,0 e 46,5kg/m² (mediana de 35,7) e 8 pacientes portadoras da síndrome dos ovários policísticos (grupo SOP) com idades entre 19 e 28 anos (mediana de 26) e IMC entre 30,1 e 40,1kg/m² (mediana de 35,8), submetidas a estímulo agudo com acetato de leuprolide, 10µg/kg SC e a teste de tolerância oral à glicose (TTOG). Observou-se aumento significativo da concentração de 17OHP, tanto no grupo N (1,5 vs. 2,9ng/mL; p= 0,023) quanto no grupo SOP (0,8 vs. 3,1ng/mL; p= 0,007), não havendo diferença significativa entre os grupos. A SI foi avaliada através da área sob a curva de insulina (ASCI) no TTOG. O grupo N apresentou ASCI significativamente menor que o grupo SOP (14.384 vs. 22.800µUI/mL/min, p= 0,04). Não houve correlação entre a concentração de 17OHP após estímulo e a ASCI.

The response of 17-hydroxyprogesterone (17OHP) to gonadotropin-releasing hormone analogue (GnRHa) acute stimulation and its relationship to insulin sensitivity (IS) were evaluated in 8 normal obese voluntary women (group N), aged 24 to 40 years (median 29) and body mass index (BMI) of 32.0 to 46.5kg/m² (median of 35.7), and 8 patients with polycystic ovary syndrome (group PCOS) aged 19 to 28 years (median of 26) and BMI of 30.1 to 40.1kg/m² (median of 35.8), submitted to an acute stimulation with leuprolide acetate 10µg/kg and to am oral glucose tolerance test. We observed a significant increase of 17OHP levels in group N (1.5 vs. 2.9ng/mL; p= 0.023) as well as in group PCOS (0.8 vs. 3.1ng/mL; p = 0.007), with no significant difference between both groups. The area under the curve of insulin (AUCI) was significantly less in the group N (14,384 vs. 22,800mUI/mL/min, p= 0,04). There was no correlation between 17OHP and the AUCI.