Testicular Adrenal-Like Tissue in a Patient with 17&amp;alpha;-Hydroxylase Deficiency

García‐Mayor, Ricardo V.; Sopeña, Bridget C.; Flutters, E.; Páramo, C.; Martín, Fernández; Galofré, Juan Carlos; Olivié, Andrade

doi:10.1159/000182551

Cited by 9 publications

(3 citation statements)

References 13 publications

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“…A total of 122 different CYP17A1 mutations have been described [Stenson et al, 2014]. To our knowledge, only 1 Spanish patient with a homozygous splice site mutation has been described to date [Perales Martínez et al, 2015], but others have been reported clinically [Garcia-Mayor et al, 1992]. It is possible that pediatric and adult patients can remain undiagnosed if the clinical and biochemical phenotypes are not adequately analyzed by experienced professionals.…”

Section: Discussionmentioning

confidence: 99%

Discordant Genotypic Sex and Phenotype Variations in Two Spanish Siblings with 17α-Hydroxylase/17,20-Lyase Deficiency Carrying the Most Prevalent Mutated CYP17A1 Alleles of Brazilian Patients

Fernández‐Cancio¹,

García-García²,

González-Cejudo

et al. 2017

Sex Dev

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17α-hydroxylase/17,20-lyase deficiency is a rare form of congenital adrenal hyperplasia caused by mutations in CYP17A1. Two phenotypic female sisters, aged 17 and 15 years and with 46,XY and 46,XX karyotypes, respectively, presented with primary amenorrhea and absent secondary sexual characteristics. The elder sib also presented with high blood pressure. Both patients had elevated levels of ACTH, gonadotropins, progesterone, corticosterone, and deoxycorticosterone, and reduced levels of estradiol, testosterone, androstenedione, 17-OH-P, DHEA-S, cortisol, aldosterone, and renin activity. The CYP17A1 gene was sequenced, and polymorphic haplotypes were further analyzed in the Spanish family and in Brazilian patients. The 2 sisters were compound heterozygous for p.Arg362Cys and p.Trp406Arg mutations, previously described as the most prevalent mutations in Brazilian families of Spanish (p.Trp406Arg) or Portuguese (p.Arg362Cys) origin. Analysis of polymorphisms in CYP17A1 suggested that the paternal allele with p.Arg362Cys may share a common origin with the Brazilian carriers, while the maternal allele with p.Trp406Arg did not. Hydrocortisone and sex hormone replacement therapy was initiated in both patients. In conclusion, one CYP17A1 mutation (p.Arg362Cys) may share a common ancestry in Brazilian and our present Spanish patients, while p.Trp406Arg may have arisen separately. The elder patient (46,XY) developed a more severe phenotype and a poorer response to estradiol replacement therapy.

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Section: Discussionmentioning

confidence: 99%

Discordant Genotypic Sex and Phenotype Variations in Two Spanish Siblings with 17α-Hydroxylase/17,20-Lyase Deficiency Carrying the Most Prevalent Mutated CYP17A1 Alleles of Brazilian Patients

Fernández‐Cancio¹,

García-García²,

González-Cejudo

et al. 2017

Sex Dev

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“…A deficiência dos esteróides gonadais, por sua vez, determina a ausência de desenvolvimento dos caracteres sexuais secundários no paciente 46XX ou presença de pseudohemafroditismo masculino. Alguns aspectos relacionados à fisiopatologia da HAC por D17OH ainda não estão totalmente elucidados, como: 1) níveis elevados de aldosterona em alguns pacientes japoneses (76); 2) os possíveis casos de deficiência parcial da enzima, com genitália ambígua, menarca, níveis pressóricos ou de potássio dentro da normalidade; 3) definição clínica e laboratorial da deficiência isolada de 17,20 liase (77); e 4) a associação de achados fortuitos como restos de tecido adrenal em testículo (78), mielolipoma (79), adenoma adrenal (80), gônadas disgenéticas e desenvolvimento incompleto de ductos müllerianos (81).…”

Section: Hiperplasia Adrenal Congênita Por Deficiência De 17-hidroxilunclassified

Bases Moleculares da Hiperplasia Adrenal Congênita

Mello

Bachega

Costa-Santos

et al. 2002

Arq Bras Endocrinol Metab

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RESUMOHiperplasia adrenal congênita (HAC) é uma doença autossômica recessiva decorrente da alteração de enzimas que participam da síntese do cortisol. As manifestações podem ser causadas pela deficiência do cortisol e, em alguns casos, aldosterona e pelo acúmulo de precursores. O objetivo desta revisão é apresentar os mecanismos moleculares dos principais defeitos enzimáticos envolvidos na etiopatogênese da HAC. A deficiência da 21-hidroxilase (21OH) ocorre em 95% dos casos de HAC. Existem dois genes que codificam o P450c21: um ativo, CYP21, e um pseudogene CYP21P. Ambos são altamente homólogos (98%), o que favorece o emparelhamento desigual dos cromossomos homólogos durante a meiose, levando a duplicações e/ou deleções ou conversões desses genes. Adicionalmente, foram também descritas mutações de ponto, muitas delas presentes no pseudogene sugerindo microconversões. Mutações no gene CYP11B1 causam HAC por deficiência da 11β-hidroxilase, forma esta que corresponde a 5% dos casos. Algumas mutações são recorrentes, situando-se principalmente entre os exons 6-8 que representaria uma área hot-spot no gene CYP11B1. A deficiência de 17-hidroxilase é causada por mutações no gene CYP17, que codificam uma proteína alterada, levando a deficiência total ou parcial de 17-hidroxilação e 17,20-liase ou deficiência isolada de 17,20-liase. Finalmente, deficiência de 3β-HSD é causada por mutações no gene HSD3B2, que codifica a enzima 3β-HSD tipo II e estas mutações têm sido associadas tanto com a forma clássica como com a forma não clássica da deficiência da 3β-HSD. Congenital adrenal hiperplasia (CAH) is a recessive autossomic disease caused by inherited defects in cortisol biosynthesis. The manifestations are caused both by the deficient synthesis of cortisol, and sometimes of aldosterone, and by accumulation of the precursor steroids. The objective of this review is to present the molecular mechanisms of the main enzymatic defects involved in the etiopathogenesis of CAH. Deficiency of 21-hydroxylase (21OH) accounts for more than 95% of all cases of CAH. The human genome contains two CYP genes: one active, CYP21, and a pseudogene, CYP21P. Both are highly homologous (98%), facilitating recombination events during meiosis, leading to duplication and/or deletion or conversion of these genes. Additionally, point mutations have also been described. Deficiency of 11β-hydroxylase (11βOH) is caused by mutations in the CYP11B1 gene, and accounts for 5% of all cases. Some mutations are recurrent, and mainly located on exons 6-8, which is considered a hot-spot area in CYP11B1 gene. Deficiency of 17α-hydroxylase (17OH) is caused by mutations in the CYP17 gene, producing a truncated or impaired protein. These mutations have been described in patients with combined defi-

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“…Discrimination between cell types would not only be of great importance in dogs, but could also be helpful for the correct diagnosis of testicular tumours in man. For example, it can be difficult to distinguish histologically testicular adrenal rest tumours from Leydig cell tumours in patients that have congenital adrenal hyperplasia (Solish et al, 1989;Garcia-Mayor et al, 1992;Jódar-Gimeno et al, 1997). Furthermore, different areas of testicular stromal tumours may show an admixture of Leydig and Sertoli cells (Mostofi and Price, 1973) that could be recognized more easily using immunohistochemical markers.…”

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confidence: 99%

Use of antibodies against LH receptor, 3beta-hydroxysteroid dehydrogenase and vimentin to characterize different types of testicular tumour in dogs

Peters¹

2001

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Testicular Adrenal-Like Tissue in a Patient with 17α-Hydroxylase Deficiency

Cited by 9 publications

References 13 publications

Discordant Genotypic Sex and Phenotype Variations in Two Spanish Siblings with 17α-Hydroxylase/17,20-Lyase Deficiency Carrying the Most Prevalent Mutated<b><i> CYP17A1</i></b> Alleles of Brazilian Patients

Discordant Genotypic Sex and Phenotype Variations in Two Spanish Siblings with 17α-Hydroxylase/17,20-Lyase Deficiency Carrying the Most Prevalent Mutated<b><i> CYP17A1</i></b> Alleles of Brazilian Patients

Bases Moleculares da Hiperplasia Adrenal Congênita

Use of antibodies against LH receptor, 3beta-hydroxysteroid dehydrogenase and vimentin to characterize different types of testicular tumour in dogs

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