Hirsutism and virilization

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CHAPTER 48

Hirsutism and virilization

1. Define hirsutism.

2. Define virilization.

3. Where are androgens produced?

4. What causes hirsutism?

5. List the conditions that result in hirsutism

6. Describe the pathophysiology of PCOS.

7. How does PCOS manifest?

PCOS affects 5% to 10% of premenopausal women and is the most common cause of hirsutism. The hirsutism is gradually progressive, usually beginning at puberty, and most patients have irregular menses from the onset of menarche. However, in a study of hirsute patients with regular menses, 50% had polycystic ovaries. PCOS patients also frequently have insulin resistance and hyperinsulinemia. Because insulin decreases SHBG and increases the ovarian androgen response to LH stimulation, the hyperinsulinemia contributes to the elevated free androgen levels in PCOS. Thus, PCOS presents as a spectrum: some patients have minimal findings, whereas others have the entire constellation of hirsutism, acne, obesity, infertility, amenorrhea or oligomenorrhea, male pattern alopecia, acanthosis nigricans, hyperinsulinemia, and hyperlipidemia. The hyperandrogenism-insulin resistance-acanthosis nigricans (HAIR-AN) syndrome is a subtype of PCOS with marked hyperinsulinemia and androgen excess frequently associated with insulin receptor defects.

8. Describe the pathophysiology of the hyperandrogenism in CAH.

CAH results from a deficiency of one of the key enzymes in the cortisol biosynthesis pathway; it often manifests with precocious puberty and childhood hirsutism. Partial or late-onset CAH, resulting from milder deficiencies of the same enzymes, may cause postpubertal hirsutism. Ninety percent of CAH is secondary to 21-hydroxylase deficiency, which causes a defect in the conversion of 17-hydroxyprogesterone (17-OHP) to 11-deoxycortisol and of progesterone to desoxycorticosterone (DOC). The resulting low cortisol production rate leads to hypersecretion of pituitary adrenocorticotropic hormone (ACTH), which stimulates overproduction of 17-OHP and progesterone, as well as adrenal androgens, particularly androstenedione (Fig. 48-2). Hirsutism results from the androgen excess.

9. Do any other causes of CAH result in hirsutism?

Deficiency of 11-beta-hydroxylase decreases the conversion of 11-deoxycortisol to cortisol and of DOC to corticosterone. This stimulates hypersecretion of ACTH, with consequent overproduction of 11-deoxycortisol, DOC, and androstenedione. Patients also frequently develop hypertension from the mineralocorticoid DOC. Deficiency of 3-beta-hydroxysteroid dehydrogenase (3β HSD) decreases the conversion of pregnenolone to progesterone and 17-hydroxypregnenolone to 17-OHP. This defect increases pregnenolone, 17-hydroxypregnenolone, and the androgens DHEA, DHEA sulfate (DHEAS), and androstenediol, which promote the development of hirsutism. Deficiency of 17-ketosteroid reductase decreases the conversion of androstenedione to testosterone, DHEA to androstenediol, and estrone to estradiol. Affected patients have elevated basal levels of androstenedione, DHEA, and estrone (see Fig. 48-2).

10. Describe the pathophysiology of idiopathic and familial hirsutism.

11. How do Cushing syndrome, prolactinomas, hypothyroidism, and acromegaly cause hirsutism?

All causes of Cushing syndrome may result in hypertrichosis because of increased vellus hair on the face, forehead, limbs, and trunk secondary to cortisol hypersecretion. Cushing syndrome resulting from an adrenal tumor also may produce hirsutism and virilization from increased secretion of androgens with cortisol.

Hyperprolactinemia suppresses GnRH activity, which diminishes pulsatile LH secretion from the pituitary gland and results in decreased ovarian estrogen production and amenorrhea. Prolactin also increases the adrenal androgens, DHEA and DHEAS. Hypothyroidism decreases SHBG and thereby leads to an increase in free testosterone. Acromegaly is frequently associated with PCOS, and the hirsutism may result from the PCOS in conjunction with excessive insulin-like growth factor-I (IGF-I), growth hormone, and insulin resistance.

12. Which medications can cause hirsutism?

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