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 individuals 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 aterminal hair; in the latter, the sebaceous component proliferates and...
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Chapter 050. Hirsutism and Virilization (Part 2) Chapter 050. Hirsutism and Virilization (Part 2) Hair Follicle Growth and Differentiation Hair can be categorized as either vellus (fine, soft, and not pigmented) orterminal (long, coarse, and pigmented). The number of hair follicles does notchange over an individuals lifetime, but the follicle size and type of hair canchange in response to numerous factors, particularly androgens. Androgens arenecessary for terminal hair and sebaceous gland development and mediatedifferentiation of pilosebaceous units (PSUs) into either a terminal hair follicle ora sebaceous gland. In the former case, androgens transform the vellus hair into aterminal hair; in the latter, the sebaceous component proliferates and the hairremains vellus. There are three phases in the cycle of hair growth: (1) anagen (growthphase), (2) catagen (involution phase), and (3) telogen (rest phase). Depending onthe body site, hormonal regulation may play an important role in the hair growthcycle. For example, the eyebrows, eyelashes, and vellus hairs are androgen-insensitive, whereas the axillary and pubic areas are sensitive to low levels ofandrogens. Hair growth on the face, chest, upper abdomen, and back requiresgreater levels of androgens and is therefore more characteristic of the patterntypically seen in men. Androgen excess in women leads to increased hair growthin most androgen-sensitive sites except in the scalp region, where hair loss occursbecause androgens cause scalp hairs to spend less time in the anagen phase. Although androgen excess underlies most cases of hirsutism, there is only amodest correlation between androgen levels and the quantity of hair growth. Thisis due to the fact that hair growth from the follicle also depends on local growthfactors, and there is variability in end-organ sensitivity. Genetic factors and ethnicbackground also influence hair growth. In general, dark-haired individuals tend tobe more hirsute than blonde or fair individuals. Asians and Native Americans haverelatively sparse hair in regions sensitive to high androgen levels, whereas peopleof Mediterranean descent are more hirsute. Clinical Assessment Historic elements relevant to the assessment of hirsutism include the age ofonset 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 notedduring the second and third decades. The growth is usually slow but progressive.Sudden development and rapid progression of hirsutism suggest the possibility ofan androgen-secreting neoplasm, in which case virilization also may be present. The age of onset of menstrual cycles (menarche) and the pattern of themenstrual cycle should be ascertained; irregular cycles from the time of menarcheonward are more likely to result from ovarian rather than adrenal androgen excess.Associated symptoms such as galactorrhea should prompt evaluation forhyperprolactinemia (Chap. 333) and possibly hypothyroidism (Chap. 335).Hypertension, striae, easy bruising, centripetal weight gain, and weakness suggesthypercortisolism (Cushings syndrome; Chap. 336). Rarely, patients with growthhormone excess (i.e., acromegaly) will present with hirsutism. Use of medicationssuch as phenytoin, minoxidil, or cyclosporine may be associated with androgen-independent excess hair growth (i.e., hypertrichosis). A family history of infertilityand/or hirsutism may indicate disorders such as nonclassic CAH (Chap. 336). Physical examination should include measurement of height, weight, andcalculation of body mass index (BMI). A BMI >25 kg/m2 is indicative of excessweight for height, and values >30 kg/m2 are often seen in association withhirsutism. Notation should be made of blood pressure, as adrenal causes may beassociated with hypertension. Cutaneous signs sometimes associated withandrogen excess and insulin resistance include acanthosis nigricans and skin tags. An objective clinical assessment of hair distribution and quantity is centralto the evaluation in any woman presenting with hirsutism. This assessmentpermits the distinction between hirsutism and hypertrichosis and provides abaseline reference point to gauge the response to treatment. A simple andcommonly used method to grade hair growth is the modified scale of Ferrimanand Gallwey (Fig. 50-1), where each of nine androgen-sensitive sites is gradedfrom 0 to 4. Approximately 95% of Caucasian women have a score below 8 onthis scale; thus, it is normal for most women to have some hair growth inandrogen-sensitive sites. Scores above 8 suggest excess androgen-mediated hairgrowth, a finding that should be assessed further b ...