The most common cause of heterosexual development at the expected age of puberty is PCOS (Fig. 29.21). Because the syndrome is heterogeneous and poorly defined, clinical difficulties result in diagnosis and management (90). For the sake of simplicity, PCOS may be defined as LH-dependent hyperandrogenism (91). The Rotterdam criteria are commonly used to identify individuals with PCOS and require the presence of at least two of the following: oligoor anovulation, clinical and/or biochemical signs of hyperandrogenism, and polycystic ovaries, with exclusion of other etiologies (CAH, androgen-secreting tumors, Cushing syndrome) (92). Polycystic ovaries ultrasonically are defined as the presence of 12 or more follicles in each ovary measuring 2 to 9 mm in diameter and/or increased ovarian volume (>10 mL). Most clinical manifestations arise as a consequence of the hyperandrogenism and often include hirsutism beginning at or near puberty and irregular menses from the age of menarche because of oligoovulation or anovulation. Clinical manifestations are as follows: 1.
Affected girls may be but are not necessarily somewhat overweight.
2.
In rare instances, menarche may be delayed, and primary amenorrhea may occur.
3.
Basal levels of LH tend to be elevated in most affected individuals, and androgen production is invariably increased, even though circulating levels of androgens may be near the upper limits of the normal range in many affected women.
Figure 29.21 Typical facial hirsutism in three women with polycystic ovarian syndrome. A: 25-year-old.
4.
In anovulatory women, estrone levels are typically greater than estradiol levels.
5.
Because circulating levels of estrogens are not diminished in PCOS and androgen levels are only mildly elevated, affected girls become both feminized and masculinized at puberty. This is an important feature because girls with classic forms of CAH who do not experience precocious puberty (and even those who do) only become masculinized at puberty (i.e., they do not develop breasts).
6.
Some degree of insulin resistance may be present, even in the absence of overt glucose intolerance (93).
7.
Polycystic ovaries are frequently, but not always present in ultrasound exami nation.
Distinguishing PCOS from the nonclassic forms of CAH is problematic and controversial (94,95). The evaluation is as follows: 1.
Some clinicians advocate measurement of 17α-hydroxyprogesterone in all women who develop hirsutism. Although values of 17α-hydroxyprogesterone are commonly elevated more than 100-fold in individuals with classic 21-hydroxylase deficiency, they may or may not be elevated in nonclassic late-onset forms of the disorder.
2.
Measurement of 17α-hydroxyprogesterone can identify women with various forms of 11-hydroxylase deficiency.
3.
Basal levels of DHEAS and 17α-hydroxyprogesterone may be moderately elevated in patients with PCOS, making the diagnosis even more difficult.
4.
To screen for CAH, 17α-hydroxyprogesterone should be measured in early morning.
5.
In women with regular cyclic menses, it is important to measure 17αhydroxyprogesterone only in the follicular phase because basal levels increase at midcycle and in the luteal phase.
Figure 29.21 (Continued ) B: 21-year-old C: 17-year-old.