Diagnosis of 5alpha-reductase type 2 deficiency: contribution of anti-Müllerian hormone evaluation.

AIM: To evaluate anti-Müllerian hormone (AMH) levels in patients with clinical and molecular diagnosis of 5alpha-reductase 2 deficiency. PATIENTS AND METHODS: Data from 14 patients whose age ranged from 21 days to 29 years were analyzed according to age and pubertal stage. Sexual ambiguity was rated as Prader III in 11 patients. LH, FSH, testosterone (T), dihydrotestosterone (DHT) and AMH serum levels were measured in all but two patients, who had been previously submitted to gonadectomy; T and DHT were also measured in 20 age-matched controls. RESULTS: Gonadotropin levels were normal in all but one patient who retained gonads (six of whom had reached puberty) and T/DHT ratio was elevated in all patients when compared to controls. All prepubertal patients had AMH levels < -1 SD for age, while most pubertal patients had AMH levels compatible with pubertal stage. CONCLUSIONS: Prepubertal patients with 5alpha-reductase 2 deficiency have AMH values in the lower part of the normal range. These data indicate that T does not need to be converted to DHT to inhibit AMH secretion by Sertoli cells.

[5alpha-reductase type 2 deficiency: experiences from Campinas (SP) and Salvador (BA)]. / Deficiência de 5alfa-redutase tipo 2: experiências de Campinas (SP) e Salvador (BA).

OBJECTIVE: To report the experience regarding patients with steroid 5alpha-reductase type 2 deficiency from three different clinical services in Brazil. CASUISTIC AND METHODS: Twenty five patients with clinical and hormonal features of 5alpha-reductase deficiency from 23 families (15 from Bahia, 7 from São Paulo and 1 from Minas Gerais) were included in this study. Clinical, hormonal and molecular data were evaluated. The molecular analysis of the five exons of the SRD5A2 gene was done by automatic or manual sequencing of PCR products. RESULTS: In ten families, SRD5A2 mutations were found in homozygosis (5 with G183S, 2 with R246W, 1 with G196S, 1 with del642T, 1 with 217_218insC), in three in compound heterozygosis (1 with Q126R/IVS3+1G>A, 1 with Q126R/del418T, 1 with Q126R/G158R) while other three were heterozygous, with only one deleterious mutation (1 with G196S, 1 with A207D, and 1 with R246W). In seven cases, no sequencing abnormalities were detected. The G183S substitution was the most frequently found among miscegenated patients (Afro-Euro-Brazilians) from Bahia. Hormonal and clinical findings did not differ between patients with or without mutations, exception made to a higher frequency of consanguinity and greater severity of genital ambiguity in the first group. CONCLUSION: Our results reinforce the importance of molecular investigation for the diagnosis of this disease and point out to the finding of a very frequent mutation (G183S) in our series, especially in patients with mixed ethnic background from Bahia, and the description of mutations that have only been reported in Brazilian patients so far.

[Elevated levels of leptin and LDL-cholesterol in patients with well controlled congenital adrenal hyperplasia]. / Valores elevados de leptina e LDL-colesterol em pacientes com hiperplasia adrenal congênita bem controlados.

OBJECTIVE: The objective of this study was to evaluate patients with classic CAH before and after treatment with glucocorticoids/mineralocorticoid and compare the metabolic profile of the well controlled (WC) and poorly controlled (PC) group. SUBJECTS AND METHODS: We selected newly diagnosed patients and patients monitored for CAH, classical form, regularly using or not glucocorticoids/mineralocorticoid in the Genetics Service Hupes-UFBA, seen from March/2004 to May/2006. All patients underwent detailed clinical evaluation and laboratory tests (glucose, sodium and potassium; total cholesterol, HDL, LDL, triglycerides and uric acid; leptin, 17-hydroxyprogesterone, total testosterone, C peptide, and insulin). Patients with normal androgens were classified as well controlled (WC), and those with high levels of androgens either using or not glucocorticoids/mineralocorticoids were classified as poorly controlled (PC). RESULTS: We studied 41 patients with CAH: 11 in the WC group and 30 in PC group. Leptin and LDL cholesterol levels were higher in WC than in the PC group (p < 0.05). Uric acid values were lower in WC compared with the PC group (p < 0.05). CONCLUSION: Adequate control of CAH with steroids seems safe, as it is associated with only mild changes in lipid profile and leptin values. No other metabolic abnormality was associated with glucocorticoid use. The reason for lower uric acid levels found in WC CAH patients is unknown and should be further studied.

Valores elevados de leptina e LDL-colesterol em pacientes com hiperplasia adrenal congênita bem controlados / Elevated levels of leptin and LDL-cholesterol in patients with well controlled congenital adrenal hyperplasia

OBJETIVO: O objetivo deste estudo foi avaliar pacientes com HAC clássica antes e após tratamento com glicocorticoides e/ou mineralocorticoides e comparar o perfil metabólico entre o grupo bem controlado (BC) e mal controlado (MC). SUJEITOS E MÉTODOS: Foram selecionados pacientes recém-diagnosticados e pacientes em acompanhamento por HAC, forma clássica, em uso regular ou não de glicocorticoides/mineralocorticoides do Serviço de Genética do Hupes-UFBA, atendidos de março/2004 a maio/2006. Todos os pacientes foram submetidos a avaliação clínica detalhada e exames laboratoriais (glicemia, sódio e potássio, colesterol total, HDL, LDL, triglicerídeos, ácido úrico, leptina, 17-hidroxiprogesterona, testosterona total, peptídeo C e insulina). Os pacientes com valores normais de andrógenos foram classificados como bem controlados (BC) e os com valores elevados de andrógenos em uso ou não de glicocorticoides/mineralocorticoides foram classificados como mal controlados (MC). RESULTADOS: Foram estudados 41 pacientes com HAC: 11 no grupo BC e 30 no grupo MC. Leptina e LDL colesterol estavam mais elevados no grupo BC que no MC (p < 0,05). Valores de ácido úrico eram menores no grupo BC quando comparados com MC (p < 0,05). CONCLUSÃO: O controle adequado da HAC com glicocorticoides parece seguro, pois está associado a alterações discretas no perfil lipídico e da leptina. Não observamos outras alterações metabólicas associadas ao uso de glicocorticoides. O motivo para o menor valor de ácido úrico encontrado nos pacientes com HAC bem controlada não é conhecido e deve ser mais bem estudado.

OBJECTIVE: The objective of this study was to evaluate patients with classic CAH before and after treatment with glucocorticoids/mineralocorticoid and compare the metabolic profile of the well controlled (WC) and poorly controlled (PC) group. SUBJECTS AND METHODS: We selected newly diagnosed patients and patients monitored for CAH, classical form, regularly using or not glucocorticoids/mineralocorticoid in the Genetics Service Hupes-UFBA, seen from March/2004 to May/2006. All patients underwent detailed clinical evaluation and laboratory tests (glucose, sodium and potassium; total cholesterol, HDL, LDL, triglycerides and uric acid; leptin, 17-hydroxyprogesterone, total testosterone, C peptide, and insulin). Patients with normal androgens were classified as well controlled (WC), and those with high levels of androgens either using or not glucocorticoids/mineralocorticoids were classified as poorly controlled (PC). RESULTS: We studied 41 patients with CAH: 11 in the WC group and 30 in PC group. Leptin and LDL cholesterol levels were higher in WC than in the PC group (p < 0.05). Uric acid values ​​were lower in WC compared with the PC group (p < 0.05). CONCLUSION: Adequate control of CAH with steroids seems safe, as it is associated with only mild changes in lipid profile and leptin values. No other metabolic abnormality was associated with glucocorticoid use. The reason for lower uric acid levels found in WC CAH patients is unknown and should be further studied.

Deficiência de 5alfa-redutase tipo 2: experiências de Campinas (SP) e Salvador (BA) / 5alpha-reductase type 2 deficiency: experiences from Campinas (SP) and Salvador (BA)

OBJETIVO: Apresentar a experiência relativa a pacientes com deficiência da enzima 5alfa-redutase tipo 2 provenientes de três serviços distintos no Brasil. CASUíSTICA E MÉTODOS: Foram incluídos 25 pacientes com sinais clínicos e hormonais de deficiência da 5alfa-redutase 2 pertencentes a 23 famílias, 15 oriundas da Bahia, 7 de São Paulo e 1 de Minas Gerais. Foram avaliados dados clínicos, hormonais e moleculares. A análise molecular dos 5 éxons do gene SRD5A2 foi feita por meio da técnica de PCR, seguida de seqüenciamento automático ou manual. RESULTADOS: Em 10 famílias havia mutações no gene SRD5A2 em homozigose (5 com G183S, 2 com R246W, 1 com G196S, 1 com del642T, 1 com 217_218insC) e em 3 em heterozigose composta (1 com Q126R/IVS3+1G>A, 1 com Q126R/del418T e 1 com Q126R/G158R); em 3 casos os afetados eram heterozigotos, apresentando apenas uma mutação deletéria (1 com G196S, 1 com A207D e 1 com R246W). Em 7 casos não foram detectadas anormalidades ao seqüenciamento. Observou-se maior freqüência da G183S em pacientes miscigenados (Afro-Euro-Brasileiros) oriundos da Bahia. Os achados clínicos e hormonais não diferiram entre os casos com e sem mutação, à exceção da freqüência de consangüinidade e da maior gravidade da ambigüidade genital nos primeiros. CONCLUSÕES: Os resultados encontrados salientam a importância da investigação molecular para o diagnóstico dessa doença, ressaltando o achado de uma mutação bastante freqüente em nosso meio (G183S), especialmente em pacientes miscigenados oriundos da Bahia, e a descrição de mutações que até o momento só foram relatadas em pacientes brasileiros.