A family history should be obtained to disclose evidence of idiopathic hirsutism, PCOS, congenital or adult onset adrenal hyperplasia (CAH or AOAH), diabetes mellitus, and cardiovascular disease. A history of drug use should be obtained. In addition to drugs that commonly cause hypertrichosis, anabolic steroids and testosterone derivatives may cause hirsutism and even virilization. During the physical examination, attention should be directed to obesity, hypertension, galactorrhea, male-pattern baldness, acne (face and back), and hyperpigmentation. With virilization, the presence of an androgen-producing ovarian neoplasm or Cushing syndrome must be considered. In many cases of Cushing syndrome, the patient’s presenting symptom is hirsutism. This devastating disorder may masquerade as other disorders such as AOAH and PCOS. Before making these diagnoses, the physician should search for the physical signs of the syndrome such as “moon face,” plethora, purple striae, dorsocervical and supraclavicular fat pads, and proximal muscle weakness. A moon-shaped face, upper body obesity, muscle weakness, and the development of a pad of fat between the shoulder blades are particularly notable to both patients and diagnosticians considering the diagnosis of Cushing syndrome.
Figure 31.1 Ferriman-Gallwey hirsutism scoring system. Each of the nine body areas most sensitive to androgen is assigned a score from 0 (no hair) to 4 (frankly virile), and these separate scores are summed to provide a hormonal hirsutism score. (Reproduced from Hatch R, Rosefield RL, Kim MH, et al. Hirsutism: implications, etiology, and management. Am J Obstet Gynecol 1981;140:815–830. c Elsevier.) and luteinizing hormone (LH), respectively (Fig. 31.2). Biosynthesis begins with the rate-limiting conversion of cholesterol to pregnenolone by side-chain cleavage enzyme. Thereafter, pregnenolone undergoes a two-step conversion to the 17-ketosteroid DHEA along the -5 steroid pathway. This conversion is accomplished by CYP17, an enzyme with both 17αhydroxylase and 17,20-lyase activities. In a parallel fashion, progesterone undergoes transformation to androstenedione in the -4 steroid pathway. The metabolism of -5 to -4 intermediates is accomplished via a -5-isomerase, 3β-hydroxysteroid dehydrogenase (3β-HSD).
Secretion of adrenal 17-ketosteroids increases prepubertally and independently of pubertal maturation of the hypothalamic–pituitary–ovarian axis. This alteration in adrenal steroid secretion is termed adrenarche and is characterized by a dramatic change in the response of the adrenal cortex to ACTH and with preferential secretion of -5 steroids, including 17hydroxypronenolone, DHEA, and dehydroepiandrosterone sulfate (DHEAS). The basis for this action is related to the increase in the zona reticularis and in the increased activity of the 17hydroxylase and the 17,20-lyase enzymes. Independent of the increase in ovarian androgen secretion accompanying puberty, the increase in adrenal androgens owing to adrenarche can account for significant increases in pubic and axillary hair and sweat production by the axillary pilosebaceous units.
Approximately half of a woman’s serum testosterone is derived from peripheral conversion of secreted androstenedione and the other half is derived from direct glandular (ovarian and adrenal) secretion. The ovaries and adrenal glands contribute almost equally to testosterone production in women. The contribution of the adrenals is achieved primarily through secretion of androstenedione.