Chapter 050. Hirsutism and Virilization (Part 2) docx

Chapter 050. Hirsutism and
Virilization
(Part 2)

Hair Follicle Growth and Differentiation
Hair can be categorized as either vellus (fine, soft, and not pigmented) or
terminal (long, coarse, and pigmented). The number of hair follicles does not
change over an individual's lifetime, but the follicle size and type of hair can
change in response to numerous factors, particularly androgens. Androgens are
necessary for terminal hair and sebaceous gland development and mediate
differentiation of pilosebaceous units (PSUs) into either a terminal hair follicle or
a sebaceous gland. In the former case, androgens transform the vellus hair into a
terminal hair; in the latter, the sebaceous component proliferates and the hair
remains vellus.
There are three phases in the cycle of hair growth: (1) anagen (growth
phase), (2) catagen (involution phase), and (3) telogen (rest phase). Depending on
the body site, hormonal regulation may play an important role in the hair growth
cycle. For example, the eyebrows, eyelashes, and vellus hairs are androgen-
insensitive, whereas the axillary and pubic areas are sensitive to low levels of
androgens. Hair growth on the face, chest, upper abdomen, and back requires
greater levels of androgens and is therefore more characteristic of the pattern
typically seen in men. Androgen excess in women leads to increased hair growth
in most androgen-sensitive sites except in the scalp region, where hair loss occurs
because androgens cause scalp hairs to spend less time in the anagen phase.
Although androgen excess underlies most cases of hirsutism, there is only a
modest correlation between androgen levels and the quantity of hair growth. This
is due to the fact that hair growth from the follicle also depends on local growth
factors, and there is variability in end-organ sensitivity. Genetic factors and ethnic
background also influence hair growth. In general, dark-haired individuals tend to
be more hirsute than blonde or fair individuals. Asians and Native Americans have
relatively sparse hair in regions sensitive to high androgen levels, whereas people

of Mediterranean descent are more hirsute.
Clinical Assessment
Historic elements relevant to the assessment of hirsutism include the age of
onset and rate of progression of hair growth and associated symptoms or signs
(e.g., acne). Depending on the cause, excess hair growth is typically first noted
during the second and third decades. The growth is usually slow but progressive.
Sudden development and rapid progression of hirsutism suggest the possibility of
an androgen-secreting neoplasm, in which case virilization also may be present.
The age of onset of menstrual cycles (menarche) and the pattern of the
menstrual cycle should be ascertained; irregular cycles from the time of menarche
onward are more likely to result from ovarian rather than adrenal androgen excess.
Associated symptoms such as galactorrhea should prompt evaluation for
hyperprolactinemia (Chap. 333) and possibly hypothyroidism (Chap. 335).
Hypertension, striae, easy bruising, centripetal weight gain, and weakness suggest
hypercortisolism (Cushing's syndrome; Chap. 336). Rarely, patients with growth
hormone excess (i.e., acromegaly) will present with hirsutism. Use of medications
such as phenytoin, minoxidil, or cyclosporine may be associated with androgen-
independent excess hair growth (i.e., hypertrichosis). A family history of infertility
and/or hirsutism may indicate disorders such as nonclassic CAH (Chap. 336).
Physical examination should include measurement of height, weight, and
calculation of body mass index (BMI). A BMI >25 kg/m
2
is indicative of excess
weight for height, and values >30 kg/m
2
are often seen in association with
hirsutism. Notation should be made of blood pressure, as adrenal causes may be
associated with hypertension. Cutaneous signs sometimes associated with
androgen excess and insulin resistance include acanthosis nigricans and skin tags.
An objective clinical assessment of hair distribution and quantity is central

to the evaluation in any woman presenting with hirsutism. This assessment
permits the distinction between hirsutism and hypertrichosis and provides a
baseline reference point to gauge the response to treatment. A simple and
commonly used method to grade hair growth is the modified scale of Ferriman
and Gallwey (Fig. 50-1), where each of nine androgen-sensitive sites is graded
from 0 to 4. Approximately 95% of Caucasian women have a score below 8 on
this scale; thus, it is normal for most women to have some hair growth in
androgen-sensitive sites. Scores above 8 suggest excess androgen-mediated hair
growth, a finding that should be assessed further by hormonal evaluation (see
below). In racial/ethnic groups that are less likely to manifest hirsutism (e.g.,
Asian women), additional cutaneous evidence of androgen excess should be
sought, including pustular acne or thinning hair.
Figure 50-1