A syndrome characterized by hypogonadism as a result
of a defect in androgen receptor. Often described as the male
pseudohermaphrodism, presenting with hypospadias, gynecomastia, normal XY
karyotype, and a pattern X-linked recessive inheritance.
Partial Androgen Insensitivity; Gynecomastia-Hypospadias
Syndrome; Hereditary Familial Hypogonadism; Male Pseudohermaphroditism.
Two types have been suggested: Type I refers to the
familial incomplete male pseudohermaphrodism and Type II is the autosomal
Undetermined; however, it is certainly common because of its
often mild and variable features.
Underlying defect is the partial deficiency of
androgen receptors (AR), causing partial androgen resistance, and not
because of a lack of androgen synthesis.
Clinical features (hypogonadism); family history;
elevated plasma luteinizing hormone and testosterone levels; oligospermia or
azoospermia; testis biopsy show normal Leydig and Sertoli cells but immature
germinal cells and no spermatozoa; cultured fibroblast from genital skin
show reduced levels of androgen receptor present with decreased cytoplasmic
dihydrotestosterone binding capacity. The normal chromosomal study (46,XY) and
normal testosterone conversion enzyme study (particularly 5-reductase level)
exclude other causes of androgen resistance.
The phenotype is quite variable as a consequence
of the partial sensitivity of the androgen receptors. In its mildest form,
the man is infertile but otherwise normal. In its most severe form, the male
pseudohermaphrodite may have hypospadias, cryptorchism, bifid scrotum,
microphallus, atrophic ectopic testes, pseudovagina, gynecomastia, and
absent vas deferens. Axillary and pubic hair is usually normal but chest and
facial hair are minimal. Temporal recession of hairline is minimal and the
voice is prepubertal in character. Azoospermia is common and occasionally
accompanied by hypoplasia of vas deferens. Most have a male psychological
development. Germ cell malignancies can occur.
There are no reported consideration for
this disorder. However, supplemental steroid administration perioperatively
might be indicated.
17-Beta Hydroxysteroid Dehydrogenase Deficiency (17-Ketosteroid
Reductase Deficiency; 17-Beta HSD) presents clinically as male
pseudohermaphroditism associated with significant enlargement of the adrenal
glands and production of steroids impaired. It is inherited as either
autosomal recessive or X-linked recessive.
17-Alpha Hydroxylase Deficiency presents in adolescence
because of failure of the adrenal gland and testes to produce androgens.
Because males are not exposed to androgens during fetal development they are
born with female external genitalia. Failure to menstruate or to develop
secondary sexual traits such as breasts or body hair, hypertension, and
hypokalemia are characteristic.
3-Beta Hydroxysteroid Dehydrogenase Deficiency (3-Beta-HSD) is present at
birth and leads to death within the first few hours. Glucocorticoids and
mineralocorticoids are not produced. Boys are born with female or ambiguous external
genitalia. A few patients with incomplete forms of this disorder may only be detected
later in childhood or adulthood. Menstruation may occur between the ages of 4 and 8, the
clitoris is enlarged, acne and advanced maturation of the skeleton may be seen in
young children as well as hirsutism.