Pseudohermaphroditism, female

Mendonca BB, Leite MV, de Castro M, et al. (2002) Female pseudohermaphroditism caused by a novel homozygous missense mutation of the GR gene. J Clin Endocrinol Metab. 87, 1805-1809. 

Steroid Ilfi-Hydroxylase (EC 1.14.15.4). Decreased cortisol synthesis induces increased ACl H secretion with resulting overproduction of deoxycorticosterone (a potent salt-retaining hormone). Iririlization in both sexes and female pseudohermaphroditism. Not all patients show hypertension... 

Steroid 17a-hydroxyiase (EC 1.14.99.9). Decreased secretion of glucocorticoids and sex steroids Excessive secretion of mineralocorticoids Hyperkalemia and hypertension. Sexual infantism in females. Pseudohermaphroditism in males. 

Fig. 29.4. Diagnosis of steroidogenic defects. For initial screening of intersexuality see Fig. 26.3. Other female pseudohermaphroditism. 180H-B 18-hydroxycorticosterone. Male pseudohermaphroditism.

The more severe cases of proximal hypospadias often show a narrowing of the urethra with signs of urinary outflow obstruction and are commonly associated with cloacal anomalies and female pseudohermaphroditism (Knight et al.l995). 

In most instances 46, XX disorders with ambiguous genitalia (former female pseudohermaphroditism) result from either exposure of a female fetus to excessive androgens or sex chromosome disorders. 

Evidence that BPH could be hormone related came from studies of a population of pseudohermaphrodites in the Dominican Republic. These individuals are genetically male, but do not display normal male genitalia until the onset of puberty. They are therefore raised as females until puberty. Studies revealed that these pseudohermaphrodites are deficient in an isoform of the enzyme steroid 5a-reductase, which is responsible for catalyzing the conversion of testosterone to dihydrotestosterone (DHT). In addition to the overt sexual manifestations of this condition, affected individuals show no incident of male pattern baldness, mild or no acne, and underdevelopment of the prostate. These observations led researchers to postulate that a selective inhibitor of steroid 5a-reductase would be an effective treatment for BPH. 

Mendonca BB, Russell AJ, Vasconcelos-Leite M, Arnhold IJ, Bloise W, Wajchenberg BL, Nico-lau W, Sutcliffe RG, Wallace AM (1994) Mutation in 3/1-hydroxysteroid dehydrogenase type II associated with pseudohermaphroditism in males and premature pubarche or cryptic expression in females. J Mol Endocrinol 12 119-122... 

A deficiency of ll -hydroxylase is the second most common form of CAH, with an incidence of 1 per 100,000 births, and is associated with manifestations of virilization, elevated concentrations of plasma androstenedione and DHEA-S, and hypertension. The mineralocorticoid-induced hypertension is caused by an elevation of DOC 11-deoxycortisol concentrations are markedly raised in subjects with this enzyme defect,The major distinguishing characteristic of this disorder from 21-hydroxylase deficiency, besides the elevated plasma concentrations of 11-deoxycortisol, is hypertension elicited by the salt retention caused by increased concentrations of DOC, A deficiency of 3 -hydroxysteroid dehydrogenase-isomerase has been reported and leads to an elevation in the ratio of 17a-hydroxypregnenolone to that of 17a-hydroxyprogesterone and to an increased ratio of DHEA to androstenedione. In severe forms of this rare disorder, female infants have pseudohermaphroditism, and male infants present with incomplete masculinization. Patients with this disorder usually present in early infancy with complete adrenal insufficiency including salt wasting. A late-onset form has also been reported in patients with premature pubarche with hirsutism, acne, and menstrual irregularities. The... 

Endocrine disruptors are exogenous chemicals (for example, PCBs) that enter the body and act like hormones. They can dismpt physiology, sometimes with devastating consequences. Startling evidence from animal studies shows that male fish in detergent-contaminated water express female characteristics, turtles are sex-reversed by PCBs, male frogs exposed to a common herbicide form multiple ovaries, pseudohermaphroditic offspring are produced by polar bears found in contaminated waters, and seals in contaminated water have an excess of uterine fibroids.46... 

The accumulation of 17-ketosteroids with androgen activity is responsible for partial virilization of the female, leading to pseudohermaphroditism. In males, the disease is not associated with sexual precocity, but with incomplete development of the genital organ manifested by hypospadias and cryptorchidism. 

In the absence of cortisone, the negative feedback on the anterior hypophysis does not operate. Consequently, the hypophysis is induced to secrete ACTH. The high level of ACTH stimulates proliferation of the adrenal cortex, and androgens are secreted in excess. In the female, cortical hyperplasia at birth leads to enlargement of the clitoris, and possibly to a urogenital sinus and an imperforated vagina. Thus, the newborn female is often taken for a male. The victim is a pseudohermaphrodite. Precocious growth of sexual hair, irreducible amenorrhea, and ovarian atrophy will occur in these patients. 

This is an inherited condition in which there is a deficiency of one of the enzymes of cortisol biosynthesis. The resulting low plasma cortisol levels result in high levels of ACTH production because of the absence of feedback control. This in turn results in the accumulation of androgens and cortisol precursors. The consequences of this are pseudohermaphroditism in the female child and virilization in the male child. Deficiencies of 3 -dehydrogenase, 21 -hydroxylase and 1 IjS-hydroxylase have been described. The most common is 21 -hydroxylase deficiency, in which there is abnormal sodium loss (the salt-losing syndrome), due to impaired aldosterone production. 11 -Hydroxylase deficiency results in the excess secretion of 11-deoxycorticosterone and since this is an active mineralocor-ticoid, salt and water retention and hypertension result. 

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