Determinants of intensive insulin therapeutic regimens in patients with type 1 diabetes: data from a nationwide multicenter survey in Brazil.

BACKGROUND: To evaluate the determinants of intensive insulin regimens (ITs) in patients with type 1 diabetes (T1D). METHODS: This multicenter study was conducted between December 2008 and December 2010 in 28 public clinics in 20 Brazilian cities. Data were obtained from 3,591 patients (56.0% female, 57.1% Caucasian). Insulin regimens were classified as follows: group 1, conventional therapy (CT) (intermediate human insulin, one to two injections daily); group 2 (three or more insulin injections of intermediate plus regular human insulin); group 3 (three or more insulin injections of intermediate human insulin plus short-acting insulin analogues); group 4, basal-bolus (one or two insulin injections of long-acting plus short-acting insulin analogues or regular insulin); and group 5, basal-bolus with continuous subcutaneous insulin infusion (CSII). Groups 2 to 5 were considered IT groups. RESULTS: We obtained complete data from 2,961 patients. Combined intermediate plus regular human insulin was the most used therapeutic regimen. CSII was used by 37 (1.2%) patients and IT by 2,669 (90.2%) patients. More patients on IT performed self-monitoring of blood glucose and were treated at the tertiary care level compared to CT patients (p < 0.001). The majority of patients from all groups had HbA1c levels above the target. Overweight or obesity was not associated with insulin regimen. Logistic regression analysis showed that economic status, age, ethnicity, and level of care were associated with IT (p < 0.001). CONCLUSIONS: Given the prevalence of intensive treatment for T1D in Brazil, more effective therapeutic strategies are needed for long term-health benefits.

Relationship between adherence to diet, glycemic control and cardiovascular risk factors in patients with type 1 diabetes: a nationwide survey in Brazil.

BACKGROUND: To determine the relationship between adherence to the diet reported by patients with type 1 diabetes under routine clinical care in Brazil, and demographic, socioeconomic status, glycemic control and cardiovascular risk factors. METHODS: This was a cross-sectional, multicenter study conducted between December 2008 and December 2010 in 28 public clinics in 20 Brazilian cities. The data was obtained from 3,180 patients, aged 22 ± 11.8 years (56.3% females, 57.4% Caucasians and 43.6% non-Caucasians). The mean time since diabetes diagnosis was 11.7 ± 8.1 years. RESULTS: Overall, 1,722 (54.2%) of the patients reported to be adherent to the diet without difference in gender, duration of diabetes and socioeconomic status. Patients who reported adherence to the diet had lower BMI, HbA1c, triglycerides, LDL-cholesterol, non HDL-cholesterol and diastolic blood pressure and had more HbA1c at goal, performed more frequently self-monitoring of blood glucose (p < 0.001), and reported less difficulties to follow specific schedules of diet plans (p < 0.001). Less patients who reported to be adherent were obese or overweight (p = 0.005). The quantity of food and time schedule of the meals were the most frequent complaints. Logistic regression analysis showed that ethnicity, (Caucasians, (OR 1.26 [1.09-1.47]), number of medical clinical visits in the last year (OR 1.10 [1.06-1.15]), carbohydrate counting, (OR 2.22 [1.49-3.30]) and diets recommended by diabetes societies', (OR 1.57 [1.02-2.41]) were related to greater patients' adherence (p < 0.05) and age, [adolescents (OR 0.60 [0.50-0.72]), high BMI (OR 0.58 [0.94-0.98]) and smoking (OR 0.58 [0.41-0.84]) with poor patients' adherence (p < 0.01). CONCLUSIONS: Our results suggest that it is necessary to rethink medical nutrition therapy in order to help patients to overcome barriers that impair an optimized adherence to the diet.

Heterogeneous behavior of lipids according to HbA1c levels undermines the plausibility of metabolic syndrome in type 1 diabetes: data from a nationwide multicenter survey.

BACKGROUND: Cardiovascular risk factors (CVRF) may cluster in type 1 diabetes, analogously to the metabolic syndrome described in type 2 diabetes. The threshold of HbA1c above which lipid variables start changing behavior is unclear. This study aims to 1) assess the behavior of dyslipidemia according to HbA1c values; 2) detect a threshold of HbA1c beyond which lipids start to change and 3) compare the clustering of lipids and other non-lipid CVRF among strata of HbA1c individuals with type 1 diabetes. METHODS: Effects of HbA1c quintiles (1st: ≤7.4%; 2nd: 7.5-8.5%; 3rd: 8.6-9.6%; 4th: 9.7-11.3%; and 5th: >11.5%) and covariates (gender, BMI, blood pressure, insulin daily dose, lipids, statin use, diabetes duration) on dyslipidemia were studied in 1275 individuals from the Brazilian multi-centre type 1 diabetes study and 171 normal controls. RESULTS: Body size and blood pressure were not correlated to lipids and glycemic control. OR (99% CI) for high-LDL were 2.07 (1.21-3.54) and 2.51 (1.46-4.31), in the 4th and 5th HbA1c quintiles, respectively. Hypertriglyceridemia increased in the 5th quintile of HbA1c, OR 2.76 (1.20-6.37). OR of low-HDL-cholesterol were 0.48 (0.24-0.98) and 0.41 (0.19-0.85) in the 3rd and 4th HbA1c quintiles, respectively. HDL-cholesterol correlated positively (0.437) with HbA1c in the 3rd quintile. HDL-cholesterol and insulin dose correlated inversely in all levels of glycemic control. CONCLUSIONS: Correlation of serum lipids with HbA1c is heterogeneous across the spectrum of glycemic control in type 1 diabetes individuals. LDL-cholesterol and triglycerides worsened alongside HbA1c with distinct thresholds. Association of lower HDL-cholesterol with higher daily insulin dose is consistent and it points out to a role of exogenous hyperinsulinemia in the pathophysiology of the CVRF clustering. These data suggest diverse pathophysiological processes depending on HbA1c, refuting a unified explanation for cardiovascular risk in type 1 diabetes.

Regional differences in clinical care among patients with type 1 diabetes in Brazil: Brazilian Type 1 Diabetes Study Group.

BACKGROUND: To determine the characteristics of clinical care offered to type 1 diabetic patients across the four distinct regions of Brazil, with geographic and contrasting socioeconomic differences. Glycemic control, prevalence of cardiovascular risk factors, screening for chronic complications and the frequency that the recommended treatment goals were met using the American Diabetes Association guidelines were evaluated. METHODS: This was a cross-sectional, multicenter study conducted from December 2008 to December 2010 in 28 secondary and tertiary care public clinics in 20 Brazilian cities in north/northeast, mid-west, southeast and south regions. The data were obtained from 3,591 patients (56.0% females and 57.1% Caucasians) aged 21.2 ± 11.7 years with a disease duration of 9.6 ± 8.1 years (<1 to 50 years). RESULTS: Overall, 18.4% patients had HbA1c levels <7.0%, and 47.5% patients had HbA1c levels ≥ 9%. HbA1c levels were associated with lower economic status, female gender, age and the daily frequency of self-blood glucose monitoring (SBGM) but not with insulin regimen and geographic region. Hypertension was more frequent in the mid-west (32%) and north/northeast (25%) than in the southeast (19%) and south (17%) regions (p<0.001). More patients from the southeast region achieved LDL cholesterol goals and were treated with statins (p<0.001). Fewer patients from the north/northeast and mid-west regions were screened for retinopathy and nephropathy, compared with patients from the south and southeast. Patients from the south/southeast regions had more intensive insulin regimens than patients from the north/northeast and mid-west regions (p<0.001). The most common insulin therapy combination was intermediate-acting with regular human insulin, mainly in the north/northeast region (p<0.001). The combination of insulin glargine with lispro and glulisine was more frequently used in the mid-west region (p<0.001). Patients from the north/northeast region were younger, non-Caucasian, from lower economic status, used less continuous subcutaneous insulin infusion, performed less SBGM and were less overweight/obese (p<0.001). CONCLUSIONS: A majority of patients, mainly in the north/northeast and mid-west regions, did not meet metabolic control goals and were not screened for diabetes-related chronic complications. These results should guide governmental health policy decisions, specific to each geographic region, to improve diabetes care and decrease the negative impact diabetes has on the public health system.

Analysis of vitamin D receptor gene (VDR) polymorphisms in Turner syndrome patients.

Individuals with Turner syndrome (TS) have increased risk for autoimmune diseases, especially thyroid abnormalities. The function of the vitamin D receptor (VDR) gene is influenced by several genetic polymorphisms which are associated with a susceptibility to a range of autoimmune diseases. Thus, we have hypothesized a possible relationship between thyroid abnormalities and VDR polymorphisms (ApaI/G1025-49T, TaqI/T1056C, FokI/T2C and BsmI G1024 + 283A) in TS patients. A case-control study was performed comprising 101 Brazilian women with TS and a control group consisting of 133 healthy fertile women without a history of autoimmune diseases. In TS group, 21.8% had Hashimoto's thyroiditis. Detection of VDR polymorphisms was performed using TaqMan system by real-time PCR. The χ(2) was used to compare allele and genotype frequencies between groups. Combined genotypes of VDR gene polymorphisms were assessed by the haplotype analysis. A p value <0.05 was considered statistically significant. Relatively similar VDR polymorphisms genotype and allelic frequencies in cases and controls were found, even when only considering the patients with thyroid abnormalities. Haplotype analysis showed that none of the VDR haplotypes were associated to thyroid diseases in TS patients. In conclusion, the results showed no association between VDR gene polymorphisms and thyroid abnormalities in Brazilian TS patients tested.

A specific bioelectrical impedance equation to predict body composition in Turner's syndrome.

INTRODUCTION: Cardiovascular disease is one of the main causes for Turner syndrome (TS) mortality and the evaluation of its risk factors such as excess body fat and its distribution is considered one of the major aspects of the adult patient care. OBJECTIVE: To develop and validate a specific bioelectrical impedance analysis (BIA) equation to predict body composition in TS patients. SUBJECTS AND METHODS: Clinical and anthropometric data, dual-energy X-ray absorptiometry (DXA) for total fat-free mass (FFM) and BIA for resistance and reactance were obtained from 50 adult TS patients. Linear regression analysis was performed with multiple clinical and BIA data to obtain a predicting equation. RESULTS: The equation developed to estimate FFM in adult TS patients showed great consistency with DXA, elevated correlation (r = 0.974) and determination (r(2) = 0.948) coefficients and an adequate standard error estimate (SEE = 1.52 kg). CONCLUSIONS: The specific equation developed here allowed making an adequate FFM estimate in adult TS patients.

OCT4 gonadal gene expression related to the presence of Y-chromosome sequences in Turner syndrome.

To show that in the dysgenetic gonads of 104 Turner syndrome patients no significant difference was found regarding the expression of the genes DAX1, FOG2, GATA4, OCT4, SF1, SRY, TSPY, WT1, and STRA8 compared with controls, except for genes OCT4, SRY, and TSPY in both gonads of a patient whose chromosomal constitution was 45,X/45,X,add(15)(p11). The expression analysis of genes OCT4, SRY, and TSPY in the dysgenetic gonads of Turner syndrome patients may allow introducing modifications in the microenvironment that could contributed to a malignant transformation process.

A specific bioelectrical impedance equation to predict body composition in Turner's syndrome / Uma equação de bioimpedanciometria específica para predição de composição corporal na síndrome de Turner

INTRODUCTION: Cardiovascular disease is one of the main causes for Turner syndrome (TS) mortality and the evaluation of its risk factors such as excess body fat and its distribution is considered one of the major aspects of the adult patient care. OBJECTIVE: To develop and validate a specific bioelectrical impedance analysis (BIA) equation to predict body composition in TS patients. SUBJECTS AND METHODS: Clinical and anthropometric data, dual-energy X-ray absorptiometry (DXA) for total fat-free mass (FFM) and BIA for resistance and reactance were obtained from 50 adult TS patients. Linear regression analysis was performed with multiple clinical and BIA data to obtain a predicting equation. RESULTS: The equation developed to estimate FFM in adult TS patients showed great consistency with DXA, elevated correlation (r = 0. 974) and determination (r² = 0. 948) coefficients and an adequate standard error estimate (SEE = 1.52 kg). CONCLUSIONS: The specific equation developed here allowed making an adequate FFM estimate in adult TS patients.

INTRODUÇÃO: A doença cardiovascular é uma das principais causas de mortalidade na síndrome de Turner (ST) e a avaliação de seus fatores de risco, como excesso e distribuição de gordura corporal, é considerada uma das principais metas da assistência às pacientes adultas. OBJETIVO: Desenvolver e validar uma equação de análise por bioimpedanciometria específica para estimar massa magra na ST. SUJEITOS E MÉTODOS: Foram obtidos dados clínicos, antropométricos, densitometria para massa magra total e bioimpedanciometria para resistência e reactância de 50 mulheres adultas com ST. Para obter uma equação preditora, foi realizada análise de regressão linear com múltiplos dados clínicos e da bioimpedanciometria. RESULTADOS: A equação desenvolvida para estimar massa magra na ST demonstrou grande concordância com a densitometria, elevados coeficientes de correlação (r = 0,974) e determinação (r² = 0,948) e um adequado erro padrão da estimativa (SEE = 1,52 kg). CONCLUSÕES: A equação desenvolvida possibilitou uma adequada estimativa da massa magra em adultas com ST.

PTPN22 C1858T polymorphism in women with endometriosis.

PROBLEM: Endometriosis has been suggested to be an autoimmune disease and recently, an allelic variation of the PTPN22 (C1858T) gene was revealed to be associated with the development of autoimmunity. The aim of the study was to determine the frequency of the PTPN22 (C1858T) polymorphism in Brazilian women with endometriosis as compared with controls. METHOD OF STUDY: Case-control study included 140 women with endometriosis and a control group consisting of 180 healthy fertile women without a history of endometriosis and/or autoimmune diseases from the ABC School of Medicine. The PTPN22 (C1858T) polymorphism was studied by restriction fragment length polymorphism polymerase chain reaction (RFLP-PCR). RESULTS: Genotypes CC, CT and TT of PTPN22 polymorphism presented frequencies of 67.9, 30.0 and 2.1% in the women with endometriosis (P = 0.008); 76.2, 19.0 and 4.8% in women with minimal/mild endometriosis (P = 0.173); 61.0, 39.0 and 0.0% in women with moderate/severe endometriosis (P < or = 0.001) and 82.8, 16.1 and 1.1% in control group. Allele C and T were present in 82.9 and 17.1%; 85.7 and 14.3%; 80.5 and 19.5%; and 90.8 and 9.2% respectively, in women with endometriosis (P = 0.004), women with minimal/mild endometriosis (P = 0.148), women with moderate/severe endometriosis (P = 0.002) and control group. CONCLUSION: The data suggest that in Brazilian women polymorphism PTPN22 (C1858T) may be an important genetic predisposing factor for endometriosis, especially, in advanced disease.

Obesity and its association with other cardiovascular risk factors in school children in Itapetininga, Brazil.

BACKGROUND: Paucity of data on childhood obesity and cardiovascular risk in Brazil. OBJECTIVE: To determine the prevalence of hypertension, dyslipidemia, obesity and their correlations in a sample of school children in Itapetininga, State of Sao Paulo, Brazil. METHODS: Cross-sectional study with systematic collection of anthropometric data (weight, height, waist circumference, BMI and blood pressure levels) and determination of glucose, total cholesterol, LDL, HDL, uric acid, and apolipoproteins A and B in a random sample representative of school children from the public education system in Itapetininga, State of Sao Paulo. For data analysis, we used population parameters from the NCHS curves (2000), blood pressure categories from NHBPEP (2004), and the serum cholesterol levels proposed by the AHA for children and adolescents (2003). RESULTS: A total of 494 children and adolescents participated in the study. Of these, 11.7% had HBP, 51% increased total cholesterol, 40.5% increased LDL-cholesterol, 8.5% increased triglycerides, and 6.1% low HDL-cholesterol levels. Mean (+/- standard deviation) TC, HDL-cholesterol, LDL-cholesterol and triglycerides were 172.1(27.9), 48.1(10.0), 105.7(23.1) and 90.9(43.8), respectively. Obesity and overweight were detected in 12.8% and 9.7% of the sample, respectively. Individuals of the obese group had a greater chance of presenting with dyslipidemia and hypertension in comparison with those of the other groups. CONCLUSION: This study supports the hypothesis of different prevalences of excess weight among school children from the public education system of the northeastern and southeastern regions of Brazil, with higher rates in the latter. Additionally, it demonstrates an association of obesity with dyslipidemia and hypertension in that group. In light of the paucity of Brazilian data on this issue, our study provides important data for further comparisons.

A obesidade e sua associação com os demais fatores de risco cardiovascular em escolares de Itapetininga, Brasil / La obesidad y su asociación con los demás factores de riesgo cardiovascular en escolares de Itapetininga, Brasil / Obesity and its association with other cardiovascular risk factors in school children in Itapetininga, Brazil

FUNDAMENTO: A escassez de dados sobre a obesidade infantil e o risco cardiovascular no Brasil. OBJETIVO: Determinar a prevalência de hipertensão, dislipidemia, obesidade e suas correlações em uma amostra de escolares de Itapetininga-SP. MÉTODOS: Corte transversal com coleta sistematizada de dados antropométricos (peso, altura, cintura, índice de massa corporal e níveis pressóricos) e dosagens de glicose, colesterol (total e frações), ácido úrico e apolipoproteina A e B, em uma amostra aleatória, representativa de escolares da rede pública de Itapetininga-SP. Análise dos dados utilizando parâmetros populacionais das curvas do NCHS(2000), categorias de pressão arterial do NHBPEP(2004) e categorias dos níveis séricos de colesterol propostos pela AHA para crianças e adolescentes(2003). RESULTADOS: Um total de 494 crianças e adolescentes participaram do estudo. Dos participantes, 11,7 por cento apresentaram HAS, 51 por cento apresentaram aumento do colesterol total, 40,5 por cento apresentaram aumento do LDL-colesterol, 8,5 por cento apresentaram aumento dos triglicérides e 6,1 por cento tiveram valores baixos de HDL-colesterol. As médias (±desvio padrão) do CT, HDL-colesterol, LDL-colesterol e triglicérides foram respectivamente 172,1(27,9), 48,1(10,0), 105,7(23,1) e 90,9(43,8). A obesidade e o sobrepeso foram detectados em 12,8 por cento e 9,7 por cento da amostra, sendo que a obesidade determinou uma maior chance de se detectar a dislipidemia e a hipertensão quando comparada com os demais grupos. CONCLUSÃO: Este estudo fornece subsídios para a hipótese de uma distinta prevalência de excesso de peso entre escolares da rede pública das regiões nordeste e sudeste, maior nesta última. Adicionalmente, demonstra uma associação da obesidade com a dislipidemia e a hipertensão naquele grupo. Diante da incipiência de dados no Brasil sobre a questão estudada, o nosso trabalho fornece dados importantes para futuras comparações.

BACKGROUND: Paucity of data on childhood obesity and cardiovascular risk in Brazil. OBJECTIVE: To determine the prevalence of hypertension, dyslipidemia, obesity and their correlations in a sample of school children in Itapetininga, State of Sao Paulo, Brazil. METHODS: Cross-sectional study with systematic collection of anthropometric data (weight, height, waist circumference, BMI and blood pressure levels) and determination of glucose, total cholesterol, LDL, HDL, uric acid, and apolipoproteins A and B in a random sample representative of school children from the public education system in Itapetininga, State of Sao Paulo. For data analysis, we used population parameters from the NCHS curves (2000), blood pressure categories from NHBPEP (2004), and the serum cholesterol levels proposed by the AHA for children and adolescents (2003). RESULTS: A total of 494 children and adolescents participated in the study. Of these, 11.7 percent had HBP, 51 percent increased total cholesterol, 40.5 percent increased LDL-cholesterol, 8.5 percent increased triglycerides, and 6.1 percent low HDL-cholesterol levels. Mean (± standard deviation) TC, HDL-cholesterol, LDL-cholesterol and triglycerides were 172.1(27.9), 48.1(10.0), 105.7(23.1) and 90.9(43.8), respectively. Obesity and overweight were detected in 12.8 percent and 9.7 percent of the sample, respectively. Individuals of the obese group had a greater chance of presenting with dyslipidemia and hypertension in comparison with those of the other groups. CONCLUSION: This study supports the hypothesis of different prevalences of excess weight among school children from the public education system of the northeastern and southeastern regions of Brazil, with higher rates in the latter. Additionally, it demonstrates an association of obesity with dyslipidemia and hypertension in that group. In light of the paucity of Brazilian data on this issue, our study provides important data for further comparisons.

FUNDAMENTO: La escasez de datos sobre la obesidad infantil y el riesgo cardiovascular en Brasil. OBJETIVO: Determinar la prevalencia de hipertensión, dislipidemia, obesidad y sus correlaciones en una muestra de escolares de Itapetininga-SP. MÉTODOS: Corte transversal con recolección sistematizada de datos antropométricos (peso, altura, cintura, índice de masa corporal y niveles de presión) y dosificaciones de glucosa, colesterol (total y fracciones), ácido úrico y apolipoproteína A y B, en una muestra aleatoria, representativa de escolares del sistema público de Itapetininga-SP. Análisis de los datos utilizando parámetros poblacionales de las curvas del NCHS (2000), categorías de presión arterial del NHBPEP(2004) y categorías de los niveles séricos de colesterol propuestos por la AHA para niños y adolescentes (2003). RESULTADOS: Un total de 494 niños y adolescentes participaron en el estudio. De los participantes, el 11,7 por ciento presentó HAS, el 51 por ciento presentó aumento del colesterol total, el 40,5 por ciento presentó aumento del LDL-colesterol, el 8,5 por ciento presentó aumento de los triglicéridos y el 6,1 por ciento tuvieron valores bajos de HDL-colesterol. Los promedios (+desviación estándar) del CT, HDL-colesterol, LDL-colesterol y triglicéridos fueron respectivamente 172,1 (27,9), 48,1 (10,0), 105,7 (23,1) y 90,9 (43,8). La obesidad y el sobrepeso se detectaron en el 12,8 por ciento y el 9,7 por ciento de la muestra, teniendo en cuenta que la obesidad determinó una mayor probabilidad de detectarse la dislipidemia y la hipertensión cuando comparada con los demás grupos. CONCLUSIÓN: Este estudio suministra los argumentos a la hipótesis de una distinta prevalencia de exceso de peso entre escolares del sistema público de las regiones nordeste y sudeste, hallándose mayor en ésta última. Adicionalmente, demuestra una asociación de la obesidad con la dislipidemia y la hipertensión en aquel grupo. Ante la condición incipiente ...

[Growth hormone treatment inTurner syndrome: data and reflections]. / O hormônio de crescimento na síndrome de Turner: dados e reflexões.

Short stature is the major characteristic of Turner syndrome. The statural appeal is premature and become evident in the puberty. Haploinsufficiency of SHOX gene has been related as main factor on final height of these patients. Despite the majority of the patients are not growth hormone deficient, the GHr therapy improves the final height. Recently, a great number of publications have described the association between GH and cancer. The cancer risk, in these patients, is mainly associated with the presence of Y chromosome sequences that can lead to the gonadoblastoma development. In conclusion, the GHr therapy in ST patients deserves caution. The investigation of Y chromosome sequences should be performed as well as the prophylactic gonadectomy in the positive cases conferring confidence to the treatment.

O hormônio de crescimento na síndrome de Turner: dados e reflexões: [revisão] / Growth hormone treatment inTurner syndrome: data and reflections: [review]

A baixa estatura é a principal característica na síndrome de Turner (ST). O agravo estatural na ST é precoce e torna-se mais evidente na puberdade. A haploinsuficiência do gene SHOX tem sido implicada como principal fator na definição da estatura de mulheres, no entanto, ainda que a maioria das pacientes não tenha deficiência do hormônio de crescimento, a terapia com GHr melhora a altura final. Recentemente, tem-se chamado a atenção para a associação entre GH e câncer. O risco de câncer nessas pacientes está associado à presença de fragmentos do cromossomo Y que pode levar ao desenvolvimento de gonadoblastoma. Dessa forma, a administração de GHr na ST deve ser feita com cautela. A investigação de seqüências do cromossomo Y deve ser realizada, bem como a gonadectomia profilática nos casos positivos, conferindo maior segurança ao tratamento.

Short stature is the major characteristic of Turner syndrome. The statural appeal is premature and become evident in the puberty. Haploinsuficiency of SHOX gene has been related as main factor on final height of these patients. Despite the majority of the patients are not growth hormone deficient, the GHr therapy improves the final height. Recently, a great number of publications have described the association between GH and cancer. The cancer risk, in these patients, is mainly associated with the presence of Y chromosome sequences that can lead to the gonadoblastoma development. In conclusion, the GHr therapy in ST patients deserves caution. The investigation of Y chromosome sequences should be performed as well as the prophylactic gonadectomy in the positive cases conferring confidence to the treatment.

Determination of the sexual phenotype in a child with 45,X/46,X,Idic(Yp) mosaicism: importance of the relative proportion of the 45,X line in gonadal tissue.

We report on a girl who, despite her 45,X/46,X,der(Y) karyotype, showed no signs of virilization or physical signs of the Ullrich-Turner syndrome (UTS), except for a reduced growth rate. After prophylactic gonadectomy due to the risk of developing gonadoblastoma, the gonads and peripheral blood samples were analyzed by fluorescence in situ hybridization (FISH) and polymerase chain reaction (PCR) to detect Y-specific sequences. These analyses allowed us to characterize the Y-derived chromosome as being an isodicentric Yp chromosome (idic(Yp)) and showed a pronounced difference in the distribution of the 45,X/46,X,idic(Yp) mosaicism between the two analyzed tissues. It was shown that, although in peripheral blood almost all cells (97.5%) belonged to the idic(Yp) line with a duplicated SRY gene, this did not determine any degree of male sexual differentiation in the patient, as in the gonads the predominant cell line was 45,X (60%).