Seis novos casos confirmam o perfil clínico molecular de deficiência combinada de 17 alfa-hidroxilase/17,20-liase no Brasil

In 2004, Costa-Santos and cols. reported 24 patients from 19 Brazilian families with 17&#945;-hydroxylase deficiency and showed that p.W406R and p.R362C corresponded to 50% and 32% of CYP17A1 mutant alleles, respectively. The present report describes clinical and molecular data of six patients from three inbred Brazilian families with 17&#945;-hydroxlyse deficiency. All patients had hypogonadism, amenorrhea and hypertension at diagnosis. Two sisters were found to be 46,XY with both gonads palpable in the inguinal region. All patients presented hypergonadotrophic hypogonadism, with high levels of ACTH (&gt; 104 ng/mL), suppressed plasmatic renin activity, low levels of potassium (< 2.8 mEq/L) and elevated progesterone levels (&gt; 4.4 ng/mL). Three of them, including two sisters, were homozygous for p.W406R mutation and the other three (two sisters and one cousin) were homozygous for p.R362C. The finding of p.W406R and p.R362C in the CYP17A1 gene here reported in additional families, confirms them as the most frequent mutations causing complete combined 17&#945;-hydroxylase/17,20-lyase deficiency in Brazilian patients.Em 2004, segundo Costa-Santos e cols., p.W406R e p.R362C correspondiam a 50% e 32% dos alelos mutantes do gene CYP17A1, respectivamente, em 24 pacientes de 19 famílias brasileiras com deficiência da 17&#945;-hidroxilase. Apresentamos os dados cl&#957;nicos e moleculares de seis pacientes de três famílias consanguíneas brasileiras com deficiência da 17&#945;-hidroxilase. Todas as pacientes apresentavam hipogonadismo, amenorreia e hipertensão ao diagnóstico. Duas irmãs tinham cariótipo 46,XY, ambas com gônadas palpáveis na região inguinal. Todas tinham hipogonadismo hipergonadotrófico, com nível aumentado de ACTH (&gt; 104 ng/mL), atividade de renina plasmática suprimida, baixos níveis de potássio (< 2,8 mEq/L) e progesterona aumentada (&gt; 4,4 ng/mL). Três delas, incluindo duas irmãs, apresentaram homozigose para a mutação p.W406R e as outras três (duas irmãs e uma prima) foram homozigotas para a mutação p.R362C. A recorrência das mutações p.W406R e p.R362C no gene CYP17A1 aqui relatada em famílias adicionais confirma que essas são as mais frequentes causadoras do fenótipo completo da deficiência combinada de 17&#945;-hidroxilase/17,20-liase em pacientes brasileiros.71171

Six New Cases Confirm The Clinical Molecular Profile Of Complete Combined 17α-hydroxylase/ 17,20-lyase Deficiency In Brazil.

In 2004, Costa-Santos and cols. reported 24 patients from 19 Brazilian families with 17α-hydroxylase deficiency and showed that p.W406R and p.R362C corresponded to 50% and 32% of CYP17A1 mutant alleles, respectively. The present report describes clinical and molecular data of six patients from three inbred Brazilian families with 17α-hydroxlyse deficiency. All patients had hypogonadism, amenorrhea and hypertension at diagnosis. Two sisters were found to be 46,XY with both gonads palpable in the inguinal region. All patients presented hypergonadotrophic hypogonadism, with high levels of ACTH (> 104 ng/mL), suppressed plasmatic renin activity, low levels of potassium ( 4.4 ng/mL). Three of them, including two sisters, were homozygous for p.W406R mutation and the other three (two sisters and one cousin) were homozygous for p.R362C. The finding of p.W406R and p.R362C in the CYP17A1 gene here reported in additional families, confirms them as the most frequent mutations causing complete combined 17α-hydroxylase/17,20-lyase deficiency in Brazilian patients.54711-

Long-term Follow-up Of An 8-year-old Boy With Insulinoma As The First Manifestation Of A Familial Form Of Multiple Endocrine Neoplasia Type 1.

Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant hereditary cancer syndrome characterized mostly by parathyroid, enteropancreatic, and anterior pituitary tumors. We present a case of an 8-year-old boy referred because of hypoglycemic attacks. His diagnosis was pancreatic insulinoma. Paternal grandmother died due to repeated gastroduodenal ulcerations and a paternal aunt presented similar manifestations. At a first evaluation, the father presented only gastric ulceration but subsequently developed hyperparathyroidism and lung carcinoid tumor. During almost 15 years of follow-up, three brothers and the index case presented hyperparathyroidism and hyperprolactinemia. Molecular study showed a G to A substitution in intron 4, at nine nucleotides upstream of the splicing acceptor site, causing a splicing mutation. All affected members of the family have the same mutation. Paternal grandmother and aunt were not studied and the mother does not carry any mutation. MEN1 is a rare condition that requires permanent medical assistance. Early clinical and genetic identification of affected individuals is essential for their own surveillance and also for genetic counseling.54754-6

Higher Body Fat but Similar Phase Angle Values in Patients with the Classical Form of Congenital Adrenal Hyperplasia in Comparison to a Control Group

This study aimed to compare phase angle (PhA) and bioelectrical impedance vector analysis (BIVA) values between adult patients with congenital adrenal hyperplasia caused by 21-hydroxylase deficiency (CAH21OHD) and a control group. A total of 22 patients (15 women, 22.9 ± 3.7 years) were compared with 17 controls (11 women, 27.0 ± 2.5 years). Body composition was determined by dual-energy X-ray absorptiometry. Bioelectrical impedance was used to calculate PhA, and BIVA was performed using specific software. Student’s t-test and analysis of covariance were used to compare groups. Hedges’ G and partial n2 were calculated for the effect estimates. Hotelling’s t2 test was used to compare the mean impedance vectors between the groups. The Mahalanobis test was used to determine the distance between confidence ellipses. Patients with CAH21OHD had a higher fat mass percentage than that of the control group (both sexes). There was no significant difference in PhA values between groups (CAH21OHD vs. control) in females (6.9° vs. 6.3°, p = 0.092) and males (8.2° vs. 8.1°, p = 0.849), after adjusting for covariates (age and height). BIVA analysis showed a significant difference in the mean impedance vectors between the female groups (T2 = 15.9, D = 1.58, p = 0.003) owing to the higher reactance/height (Δ = 8.5; p < 0.001) of the patients. The PhA did not significantly differ between the groups. Female patients had significantly higher reactance values. However, further studies are needed to determine the usefulness of bioimpedance parameters in evaluating the hydration status and cellular integrity of patients with CAH21OHD

A pituitary adenoma secreting follicle-stimulating hormone with ovarian hyperstimulation: treatment using a gonadotropin-releasing hormone antagonist

Objective: To describe the management of a patient with a pituitary adenoma secreting follicle-stimulating hormone (FSH) associated with ovarian hyperstimulation who was treated with a gonadotropin-releasing hormone (GnRH) antagonist. Design: Case report. Setting: University teaching hospital. Patient(s): A woman of reproductive age with secondary amenorrhea and ovarian hyperstimulation due to a pituitary adenoma secreting FSH, which persisted after transsphenoidal surgery. Intervention(s): Clinical treatment with a GnRH antagonist. Main Outcome Measure(s): A decrease in serum estradiol levels. Result(s): During the treatment period, ovarian hyperstimulation decreased as shown by a reduction in estradiol levels and an improvement in the patient's clinical condition and in the ultrasonography parameters. Conclusion(s): The GnRH antagonist was found to be effective for the short-term treatment of ovarian hyperstimulation secondary to a pituitary adenoma secreting FSH, thus representing a therapeutic option that should be taken into consideration in such cases. (Fertil Steril (R) 2012;97:231-4. (C) 2012 by American Society for Reproductive Medicine.)97123123