Adrenogenital syndrome (AGS)

is the name for a group of genetic disorders with autosomal recessive

inheritance, in which production of certain endogenous steroid hormones in the
adrenal cortex is disrupted. In AGS, inherent genetic modifications cause a
reduction in the production of cortisol and aldosterone and, at the same time, an
increase in the production of male hormones. The term AGS covers several
diseases, which are named according to the genetically modified enzyme
involved, by far the commonest form being 21-hydroxylase deficiency. Both boys
and girls can suffer from AGS but each gender manifests different gender-
specific symptoms.

If a form of AGS is present, conversion of cholesterol into the hormones cortisol

and aldosterone is inhibited. These hormones are therefore no longer produced
in sufficient quantity. Since the body attempts to offset this deficiency by
producing more hormones, the adrenal cortex is overstimulated.   However, since
this is impossible due to the enzyme defect (e.g. 21-hydroxylase), the body
produces a surplus of hormone precursors and these are then converted into
androgens (i.e. male hormones) in other metabolic processes. AGS is therefore
characterised by a deficiency of cortisol and aldosterone and a surplus of male
hormones.

The clinically severe form is known as "classical AGS". This form of the disease
can produce life-threatening symptoms right from birth, which could bring about
a salt wasting crisis in both genders or masculinisation of the external sexual
characteristics in girls. The latter range from enlargement of the clitoris right
through to formation of a pseudo-penis, despite the presence of internal female
genitalia.  Both genders experience rapid growth during childhood causing false
precocious puberty with development of pubic hair and breaking of the voice. A
rapidly growing penis in boys and the absence of periods in girls are then further
signs of "classical AGS", as is excessive body hair and acne. A new-born
screening programme also conducted in Austria includes checking for AGS, to
prevent life-threatening salt wasting crises and initiate substitution therapy as
soon as possible.
A milder form is "non-classical AGS", where symptoms do not occur until later in
life, often not being diagnosed until after puberty. These patients have a "milder
genetic defect" in the corresponding enzyme, so that the adrenal cortex can still
produce a certain amount of cortisol and aldosterone.

Before puberty, affected children are often taller than their contemporaries but,
without treatment, they will be small as adults. "Non-classical AGS" can even be
so minimal that, although there is a biochemical disruption in the hormone
balance, no marked clinical symptoms are exhibited, so that often AGS is only
diagnosed when sufferers fail to conceive children.

Doctor of sexual and internal medicine Michaela Bayerle-Eder and biochemist

Sabina Baumgartner-Parzer from the Division of Endocrinology & Metabolism of
the Department of Medicine III are looking at the extent to which prenatal
androgenisation due to AGS can potentially influence the sexual identity of
female patients. The aim of this Europe-wide research project is to clarify to what
extent AGS patients with severe and mild forms also suffer from sexual
dysfunction and what differences exist in their gender roles and sexual
preferences.

Based on their sexual history and various specific parameters, it was found that
AGS patients suffer more from sexual dysfunction and sexual stress than women
from the general population. No significant differences were found between the
group with classical and the group with non-classical AGS. There is an overall
tendency to greater restriction of sexual function and greater psychological
stress in patients with non-classical AGS and patients with classical AGS are
more likely to be orgasmic. A large proportion of all volunteers state their gender
role as mannish/masculine. As regards sexual orientation, women with classical
AGS displayed a greater homosexual preference. Prenatal hyperandrogenaemia
therefore seems to influence gender role and sexual preference."

In summary, it seems that patients with non-classical AGS, with less obvious
symptoms and mild genetic defects, suffer more due to the late diagnosis, since
they have had longer without any explanation of their "otherness" and have not
received any treatment.
Says Bayerle-Eder, who is also President of the Austrian Society for Sexual
Medicine and Sexual Health: "For women with signs of masculinisation (such as
acne and increased body hair), menstrual problems, the inability to conceive and
sexual dysfunction, it is therefore important to also consider non-classical AGS
when making a diagnosis and to order genetic tests where appropriate.