sex hormones abnormalities by lanyuehua


									 Sex Hormones
     Dr. Amal Baalash
         Steroid Hormones
   Are made from cholesterol, are lipophilic & can
    enter target cell
   Are immediately released from cell after
   Interact with cytoplasmic or nuclear receptors
   Activate DNA for protein synthesis
    Are slower acting and have longer half-life than
    peptide hormones
   Examples: cortisol, estrogen & testosterone
Steroid Hormones: Action

           Figure 7-7: Steroid hormone action
      Some Genetic Abnormalities of Gonadal
Many things can go wrong with sexual development
in both males and females; fortunately rarely. Only
at a few that clearly result from the inheritance of
single-gene mutations.
Inherited mutations in both copies of the gene
encoding the GnRH receptor result in failure to
develop at puberty.
Mutations in the gene encoding the LH receptor
prevent normal sexual development in both sexes.
   Genetic Abnormalities of Gonadal Function

Mutations in the gene encoding the FSH receptor
block development of the gonads in both males and
Mutations in any of the genes encoding the
enzymes for synthesis and metabolism of
testosterone interfere with normal sexual function
in males.
A similar spectrum of disorders in males can be
caused by mutations in the genes encoding the
androgen receptor.
Congenital Adrenal
   Congenital adrenal hyperplasia is a group of
    autosomal recessive disorders resulting from
    the deficiency of one of the five enzymes
    required for the synthesis of cortisol in the
    adrenal cortex.
   The most frequent is steroid 21-hydroxylase
    deficiency, accounting for more than 90
    percent of cases.
   Steroid 21-hydroxylase (CYP21, also termed
    CYP21A2 and P450c21) is a cytochrome P-450
    enzyme located in the endoplasmic reticulum.
   It catalyzes the conversion of 17-
    hydroxyprogesterone to 11-deoxycortisol, a
    precursor of cortisol, and the conversion of
    progesterone to deoxycorticosterone, a precursor
    of aldosterone.
   Owing to this loss of enzyme function, patients with
    21-hydroxylase deficiency cannot synthesize cortisol
    efficiently, and as a result, the adrenal cortex is
    stimulated by corticotropin and overproduces cortisol
   Some of these overproduced
    precursors are diverted to the
    biosynthesis of sex hormones,
    which may cause signs of
    androgen excess, including
    ambiguous genitalia in newborn
    girls and rapid postnatal growth in
    both sexes.
   Concomitant aldosterone
    deficiency may lead to salt
    wasting with consequent failure to
    thrive, hypovolemia, and shock.
   Mutations in the CYP21(CYP21A2) gene.
   CYP21 mutations can be grouped into three
    categories according to the level of enzymatic
   The first group consists of mutations such as deletions or
    nonsense mutations that totally ablate enzyme activity;
    these are most often associated with salt-wasting
   The second group of mutations, consisting mainly of the
    missense mutation, yields enzymes with 1 to 2 percent
    of normal activity.
   The final group includes mutations such as Val281Leu
    (V281L) and Pro30Leu (P30L) that produce enzymes
    retaining 20 to 60 percent of normal activity; these
    mutations are associated with the nonclassic disorder.
Clinical Picture:
Early appearance of male characteristics.
In a newborn girl with this disorder, the clitoris is
enlarged with the urethral opening at the base
(ambiguous genitalia, often appearing more male-like
than female). The internal structures of the
reproductive tract (ovaries, uterus, and fallopian tubes)
are normal. As she grows older, masculinization of some
features takes place, such as deepening of the voice, the
appearance of facial hair, and failure to menstruate at
In a newborn boy no obvious abnormality is present,
but long before puberty normally occurs, the child
becomes increasingly muscular, the penis enlarges,
pubic hair appears, and the voice deepens. Affected
males may appear to enter puberty as early as 2-3 years
of age.
At puberty, the testes are small.
Some forms of congenital adrenal hyperplasia
are more severe and cause adrenal crisis in the
newborn due to salt wasting. In this salt-losing
form of congenital adrenal hyperplasia,
newborns develop symptoms shortly after birth.
These include vomiting, dehydration, electrolyte
changes, and cardiac arrhythmias. Untreated,
this condition can lead to death within 1-6 weeks
after birth.
About 1 in 10,000 to 18,000 children are born
with congenital adrenal hyperplasia.
Androgen insensitivity
   A person who is genetically male (has one X
    and one Y chromosome) is resistant to male
    hormones (androgens). As a result, the
    person has some or all of the physical
    characteristics of a woman, despite having
    the genetic makeup of a man.
   Causes
   Androgen insensitivity syndrome (AIS) is
    caused by various genetic defects on the X
    chromosome that make the body unable to
    respond to the hormones responsible for
    the male appearance.
   The syndrome is divided into two main
   Complete AIS
   Incomplete AIS
   Complete androgen insensitivity prevents
    the development of the penis and other
    male body parts. The child born appears to
    be a girl. The complete form of the
    syndrome occurs in as many as 1 in 20,000
    live births.
   Symptoms
   A person with complete AIS appears to
    be female but has no uterus, and has
    very little armpit and pubic hair. At
    puberty, female secondary sex
    characteristics (such as breasts)
    develop, but menstruation and fertility do
   There may be:
   A vagina but no cervix or uterus
   Inguinal hernia with a testis that can be
    felt during a physical exam
   Normal female breast development
   Testes in the abdomen or other unusual
    places in the body
   Persons with incomplete AIS may
    have both male and female physical
    characteristics. Many have partial
    closing of the outer vaginal lips, an
    enlarged clitoris, and a short vagina.
   The degree of sexual ambiguity
    varies widely in persons with
    incomplete AIS.
   eg breast development in men,
    failure of one or both testes fail to
    descend into the scrotum after birth,
    and hypospadias, a condition where
    the opening of the urethra is on the
    underside, rather than at the tip, of
    the penis.
   Also included in the broad category
    of incomplete AIS is infertile male
    syndrome, which is sometimes due
    to an androgen receptor disorder.
   Exams and Tests
   Complete AIS is rarely discovered during childhood, unless a
    mass is felt in the abdomen or groin that turns out to be a testicle
    when it is explored surgically. Most people with this condition are
    not diagnosed until they fail to menstruate or have difficulties
    becoming pregnant.
   Incomplete AIS, however, is often discovered during childhood
    because the person may have both male and female physical
   Tests used to diagnose this condition may include:
   Blood work to check levels of testosterone, luteinizing hormone
    (LH), and follicle-stimulating hormone (FSH)
   Genetic testing (karyotyping)
   Pelvic ultrasound
   Other blood tests may be done to help tell the difference between
    AIS and androgen deficiency.
Klinefelter syndrome
   Alternative Names
   47 X-X-Y syndrome
   Definition of Klinefelter syndrome:
   Klinefelter syndrome is the presence of an extra X chromosome
    in a male. Klinefelter syndrome is one of a group of sex
    chromosome problems. It results in males who have at least one
    extra X chromosome. Usually, this occurs due to one extra X
    (written as XXY).
   Klinefelter syndrome is the most common disorder of sex
    chromosomes in humans found in about 1 out of every 500 -
    1,000 newborn males. Women who have pregnancies after age
    35 are slightly more likely to have a boy with this syndrome than
    younger women.
   Clinical Picture
47,XXY males may present with hypospadias, small phallus or
   cryptorchidism, developmental delay ... language delay,
   learning disabilities, or behavioral problems ... delayed or
   incomplete pubertal development, gynecomastia, and small
Adults are often evaluated for infertility or breast malignancy ...
replacement therapy should begin at puberty, around age 12
   years ... Affected individuals have longer arms and legs ...
   Testicular volume is typically less than 10 ml in postpubertal
   47,XXY individuals ... most patients with Klinefelter
   syndrome are infertile ... few patients with reports of
   pregnancy without assisted medical technology ...
wide range of intelligence quotient (IQ) has been noted ...
   breast carcinoma in 47,XXY is relatively increased ...
   Associated endocrine complications include diabetes
   mellitus, hypothyroidism, and hypoparathyrodism ... lupus
   erythematosus, Sjogren syndrome, and rheumatoid arthritis,
   are more common
 patients will often have a low serum testosterone level but
   high serum follicle-stimulating hormone (FSH) and
   luteinizing hormone (LH) levels.
                   Turner syndrome
A disorder in women caused by a chromosomal defect.
This disorder inhibits sexual development and causes
Causes, incidence, and risk factors:
Turner syndrome is usually caused by a missing X
chromosome. It affects 1 out of 3,000 live births. It is
usually sporadic meaning that it is not inherited from
a parent.
Rarely, a parent silently carries rearranged
chromosomes that can result in Turner syndrome in a
daughter; this is the only situation in which Turner
syndrome is inherited.
            Turner syndrome
There are many manifestations of this
syndrome, but the main features are short
stature, webbing of the skin of the neck,
absent or retarded development of secondary
sexual characteristics, absence of
menstruation, coarctation (narrowing) of the
aorta, and abnormalities of the eyes and
The condition is either diagnosed at birth
because of the associated anomalies, or at
puberty when there is absent or delayed
menses and delayed development of normal
secondary sexual characteristics.
       Turner’s syndrome

(Classic 45-XO)   Mosaic (46-XX / 45-XO)
Exams and Tests
   Turner syndrome can be diagnosed at any stage of
    life. It may be diagnosed before birth if chromosome
    analysis is done during prenatal testing.
   Physical exam shows signs of underdevelopment.
    Infants with Turner syndrome often have swollen
    hands and feet.
   The following tests may be performed:
   Blood hormone levels (luteinizing hormone and
    follicle stimulating hormone)
   Echocardiogram
   Karyotyping
   MRI of the chest
   Ultrasound of reproductive organs and kidneys
   Pelvic exam
   Turner syndrome may also alter various estrogen
    levels in the blood and urine.

To top