A New Male Pseudohermaphroditism Associated with Hypertension due to a Block of 17α-Hydroxylation

Bricaire, H; Luton, J P; Laudat, P; Legrand, J.; Turpin, G; Corvol, P; Lemmer, Miriam

doi:10.1210/jcem-35-1-67

Cited by 55 publications

(12 citation statements)

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“…Subsequent reports identified 17OHD as a cause not only of incomplete male pseudohermaphroditism (14), but also sexual infantilism in 46,XY subjects (15). The lack of adrenal 17␣-hydroxylase activity drives massive overproduction of the 17-deoxysteroids 11-deoxycorticosterone (DOC) and corticosterone (B), which are the mineralocorticoids that cause hypertension and hypokalemia in 17OHD (4).…”

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confidence: 99%

Two PrevalentCYP17Mutations and Genotype-Phenotype Correlations in 24 Brazilian Patients with 17-Hydroxylase Deficiency

Costa-Santos¹,

Kater²,

Auchus³

2004

The Journal of Clinical Endocrinology & Metabolism

203

146

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We performed molecular genetic analysis of 24 subjects from 19 families with 17-hydroxylase deficiency in Brazil. Of 7 novel CYP17 mutations, 2 (W406R and R362C) account for 50% and 32% of the mutant alleles, respectively. Both mutations were completely inactive when studied in COS-7 cells and yeast microsomes; however, phenotypic features varied among subjects. Some 46,XY individuals with these genotypes had ambiguous genitalia, and other subjects had normal blood pressure and/or serum potassium. We found mutations W406R and R362C principally in families with Spanish and Portuguese ancestry, respectively, suggesting that two independent founder effects contribute to the increased prevalence of 17-hydroxylase deficiency in Brazil. Mutations Y329D and P428L retained a trace of activity, yet the two individuals with these mutations had severe hypertension and hypokalemia. The 46,XX female with mutation Y329D reached Tanner stage 5, whereas the 46,XY subject with mutation P428L remained sexually infantile. The severity of hypertension, hypokalemia, 17-deoxysteroid excess, and sex steroid deficiency varied, even among patients with completely inactive CYP17 protein(s). Spontaneous sexual development occurred only in 46,XX females with partial deficiencies. We conclude that other factors, in addition to CYP17 genotype, contribute to the phenotype of individual patients with 17-hydroxylase deficiency.

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confidence: 99%

Two PrevalentCYP17Mutations and Genotype-Phenotype Correlations in 24 Brazilian Patients with 17-Hydroxylase Deficiency

Costa-Santos¹,

Kater²,

Auchus³

2004

The Journal of Clinical Endocrinology & Metabolism

203

146

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“…This block also seems to be reversible by glucocorticoid hor¬ mone therapy through the suppression of ACTH, DOC and B, and the subsequent increase of renin, angiotensin II and serum potassium levels. The return of aldosterone to normal values may be achieved within few days of suppressive therapy (Goldsmith et al 1967;Mills & Wilson 1967;New 1970;Feit et al 1978;Rovner et al 1979), but treatment often requires at least one year to pro¬ duce this change (Biglieri et al 1966;Bricaire et al 1972;de Lange et al 1977). In our patient, aldo¬ sterone remained low 4 months after the onset of glucocorticoid therapy.…”

Section: Resultsmentioning

confidence: 61%

“…However, the urinary metabolites of 18-OHB have been found to be increased in some patients with 17-OHDS (Bricaire et al 1972;Rovner et al 1979), suggesting an 18-dehydrogenase (or me¬ thyl-oxidase type II) defect. Biglieri & Schambelan ( 1979) stressed the crucial role of potassium dele¬ tion in establishing a functional impairment in the final dehydrogenation of 18-OHB since there is a negative correlation between changes in K+ concentration and the 18-OHB:aldosterone ratio.…”

Section: Resultsmentioning

confidence: 99%

“…This was due to urinary mineralocorticoid excess, responsible for a Zimmermann-like chromagen (Goldsmith et al 1967;Rovner et al 1979). The main gonadal secretion is therefore progesterone, which, in consequence, has a double origin : the gonads and the adrenals (Goldsmith et al 1967 (New 1970;Bricaire et al 1972;de Lange et al 1977;Waldhäusl et al 1978). In female patients, decreased oestrogens will result in primary amenorrhoea and absence of sexual maturation.…”

Section: Resultsmentioning

confidence: 99%

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17α-Hydroxylase deficiency syndrome associated with bilateral streak gonads and impaired development of Müllerian ducts derivatives

Gennes¹,

Jambart²,

Turpin³

et al. 1982

Acta Endocrinologica

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We report severe 17\g=a\-hydroxylase deficiency in a 17 year-old black girl with 46,XX genotype. The diagnosis was suspected because of primary amenorrhoea, absence of sexual maturation, hypertension and hypokalaemia with renal potassium wasting. Endocrine investigation revealed low basal levels of all steroid hormones which require 17\g=a\-hydroxylation for biosynthesis (i.e. glucocorticoids, androgens and oestrogens). No increase in their basal levels was seen following adrenal stimulation, indicating a severe block. Plasma concentrations of ACTH, FSH and LH were elevated as were progesterone, 11-deoxycorticosterone and corticosterone. Plasma renin activity was suppressed and aldosterone levels were very low. After 4 months of glucocorticoid replacement therapy, aldosterone was still low, even though the suppression was otherwise effective. Our case is unusual because bilateral streak gonads and impaired development of M\l=u"\llerianducts derivatives were also present. To our knowledge, a similar case has never been reported before. Steroid 17a-hydroxylation is an obligatory step in the biosynthesis of glucocorticoids, androgens and oestrogens ( Table 1). The 17a-hydroxylase defi¬ ciency syndrome (17-OHDS) is a very rare entity, first described by Biglieri et al. (1966) in a female patient and by New (1970) in a male patient. To date, no more than 25 patients have been reported. We report a female patient presenting typical signs of severe 17cx-hydroxylase deficiency, associated with bilateral streak gonads and impaired develop¬ ment of Müllerian duct derivatives. Case ReportThe patient was first seen at the age of 17 years because of primary amenorrhoea and complete lack of secondary sex development. She had been born after a normal pregnancy and delivery, and her infancy and childhood were uneventful. Her parents are not related and no family history of endocrine disease was found.Physical examination showed a black girl, 162 cm in height and 55 kg in weight. Breasts were undeveloped and no pubic or axillary hair was present. There was no webbing of the neck nor cubitus valgus. External geni¬ talia were those of an immature female. The vagina was short. On rectal examination, the uterus and the internal genitalia were not detected. The blood pressure was 170/120 mmHg in both arms and remained unchanged in the upright position. This hypertension was well tolerated.The bone age was determined to be 12 years. Films of the skull were normal. Films of the chest revealed a posteroinferior mediastinal ovoid mass. This mass showed a cystic appearance on CT-scan. The sodium was 143 mmol/1, potassium 3.2 mmol/1, chloride 103 mmol/1, bicarbonate 28 mmol/1, creatinine 62 u.mol/1, glucose 3.88 mmol/1, calcium 2.34 mmol/1, phosphorus 1.67 mmol/1 and alkaline phosphatase 191 IU/1. The urinary daily 1 To whom requests for reprints should be addressed. Service d'Endocrinologie Métabolisme, Hôpital de la Pitié, 83 boulevard de l'Hôpital, 75013 Paris

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“…4 The lack of sex hormones causes sexual infantilism in untreated females and pseudohermaphroditism in males.5 Secondary sexual characteristics in males may range from apparently normal female genitalia and a blind vaginal pouch to hypospadias and a small phallus.6-8 In the few reported cases of male pseudohermaphrodites, persistence of Mullerian ducts has not been described. [6][7][8] We report the occurrence of 17m-hydroxylase deficiency in a Chinese patient with a male genotype. The unusual finding was the persistence of Mullerian duct structures.…”

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confidence: 92%

17α-Hydroxylase deficiency with persistence of müllerian ducts in a genotypic male and paradoxical aldosterone secretion

Panesar

Yeung

Chan

et al. 1993

Postgraduate Medical Journal

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We report a case of congenital adrenal hyperplasia due to 17 alpha-hydroxylase deficiency in a Chinese genotypic male patient. Despite the male genotype, normal female external genitalia were present and with the introduction of cyclical oestrogen therapy withdrawal bleeding occurred, confirming the presence of functional endometrial tissue. We believe this to be the first report of persistent Mullerian duct structures in a genotypic male with 17 alpha-hydroxylase deficiency. It could be explained by either impaired secretion or impaired action of anti-Mullerian hormone. Further, contrary to the usual finding of suppressed aldosterone secretion, this patient had measurable levels of plasma aldosterone.

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A New Male Pseudohermaphroditism Associated with Hypertension due to a Block of 17α-Hydroxylation

Cited by 55 publications

References 0 publications

Two PrevalentCYP17Mutations and Genotype-Phenotype Correlations in 24 Brazilian Patients with 17-Hydroxylase Deficiency

Two PrevalentCYP17Mutations and Genotype-Phenotype Correlations in 24 Brazilian Patients with 17-Hydroxylase Deficiency

17α-Hydroxylase deficiency syndrome associated with bilateral streak gonads and impaired development of Müllerian ducts derivatives

17α-Hydroxylase deficiency with persistence of müllerian ducts in a genotypic male and paradoxical aldosterone secretion

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