Medical brain notes 42

  Hirsutism and Virilization Hirsutism  is excess terminal hair in a male pattern of H  distribution. It is manifested initially by the appear-ance of midline terminal hair. Terminal hair is darker, coarser, and kinkier than vellus hair, which is soft, downy, and fine. Care must be taken to evaluate the pos-sibility that excess terminal hair is familial, not patholog-ical, in origin. A scale used for the evaluation of hirsutism is shown in Figure 36.1. When a woman is exposed to excess androgens, terminal hair first appears on the lower abdomen and around the nipples, next around the chin and upper lip, and finally between the breasts and on the lower back. Usually, a woman with hirsutism also has acne. For women in Western cultures, terminal hair on the abdomen, breasts, and face is considered unsightly and presents a cosmetic problem. As a result, at the first sign of hirsutism, women often consult their physician to seek a cause for the excess hair growth and seek trea...

  ANDROGEN PRODUCTION AND ANDROGEN ACTION   In women,  androgens  are produced in the adrenal glands, the ovaries, and adipose tissue, where there is extraglan-dular production of testosterone from androstenedione. The following three androgens may be measured when evaluating a woman with hirsutism and virilization.   ·       Dehydroepiandrosterone  (DHEA): a weak androgensecreted principally by the adrenal glands. (This is gen-erally measured as dehydroepiandrosterone sulfate [DHEA-S] because of its longer half-life, making it a more reliable measure.) ·       Androstenedione:  a weak androgen secreted in equalamounts by the adrenal glands and ovaries. ·       Testosterone:  a potent androgen secreted by theadrenal glands and ovaries and produced in adipose tis-sue from the conversion of androstenedione.   The sites of androgen production and proportions pro-duced are...

  POLYCYSTIC OVARY SYNDROME Polycystic ovary syndrome (PCOS)  is the most commoncause of androgen excess and hirsutism.   The etiology of this disorder is unknown. Some cases appear to result from a genetic predisposition, whereas others seem to result from obesity or other causes of LH excess.   Symptoms of PCOS include oligomenorrhea or amenorrhea, acne, hirsutism, and infertility.  The disorder is characterizedby chronic anovulation or extended periods of infrequent ovulation (oligo-ovulation). It is a syndrome primarily defined by excess androgen. The definition of PCOS has varied in the past, resulting in the National Institutes of Health (NIH)-convening consensus conferences in 1990 and 2000. In 2003 the Rotterdam consensus workshop developed a more encompassing definition of PCOS. To establish the diagnosis, the patient should have two of the following criteria:   Oligo-ovulation or anovulation usually marked by irreg-ular menstrual cyclesBiochemical...

  OVARIAN NEOPLASMS   Several androgen-secreting ovarian tumors can cause hir-sutism and virilization, including Sertoli-Leydig cell tumors and three rare neoplasms.   Sertoli–Leydig Cell Tumors   Sertoli–Leydig cell tumors  (also called androblastoma andarrhenoblastoma) are ovarian neoplasms that secrete testosterone.  These tumors constitute <0.4% of ovarian tumors and usu-ally occur in women between the ages of 20 and 40.  Thetumor is most often unilateral (95% of cases) and may reach a size of 7 to 10 cm in diameter.   The history and physical examination give critical clues in diagnosing subjects who present with hirsutism and testosterone-secreting ovarian tumors.    Testosterone-  secreting tumors usually have a more rapid onset and more severe hirsutism with virilizing signs.  Women with aSertoli–Leydig cell tumor have a rapid onset of acne, hirsutism (75% of patients), amenorrhea (30% of patients), and viriliza-tion...

  ADRENAL ANDROGEN EXCESS DISORDERS   Adrenal disorders that cause an increase in androgen pro-duction can lead to hirsutism and virilization; the most common are congenital adrenal hyperplasia, Cushing syn-drome, and adrenal neoplasms. Congenital Adrenal Hyperplasia   Congenital adrenal hyperplasia  (CAH) is caused byenzyme deficiencies that result in precursor (substrate) excess, thus resulting in androgen excess. DHEA is a pre-cursor for androstenedione and testosterone. The most common cause of increased adrenal androgen pro-duction is adrenal hyperplasia as a result of  21-hydroxylasedeficiency;  21-hydroxylase catalyzes the conversion of pro-gesterone and 17 α -hydroxyprogesterone to desoxycortico-sterone and compound S. When 21-hydroxylase is deficient, there is an accumu-lation of progesterone and 17 α -hydroxyprogesterone, which are metabolized subsequently to DHEA. This dis-order affects approximately 2% of the population and is caused by an alter...

  CONSTITUTIONAL HIRSUTISM   Occasionally after a diagnostic evaluation for hirsutism, there is no explanation for the cause of the disorder. By exclusion, this condition is often called  constitutional hir-sutism.  Data support the hypothesis that women with con-stitutional hirsutism have greater activity of 5 α -reductase than do unaffected women.   Treatment of constitutional hirsutism is primarily androgen blockade and mechanical removal of the excess hair. Spironolactone 100 mg/day is the most commonly used androgen blocker. Spironolactone also inhibits testos-terone production by the ovary and reduces 5 α -reductase activity. Other androgen blockers include flutamide and cyproterone acetate. The activity of 5 α -reductase can also be inhibited directly through the use of drugs such as finas-teride (5 mg orally daily). Eflornithine hydrochloride 13.9% is an irreversible inhibitor of L-ornithine decarboxy-lase, which slows and shrinks hair. This cream has be...

  IATROGENIC ANDROGEN EXCESS   Some drugs with androgen activity have been implicated in hirsutism and virilization, including danazol and progestin-containing oral contraceptives. Danazol   Danazol is an attenuated androgen used for the suppression of pelvic endometriosis.  It has androgenic properties, and somewomen develop hirsutism, acne, and deepening of the voice while taking the drug. If these symptoms occur, the value of the danazol should be weighed against the side effects before continuing therapy. Symptoms of voice changes may be irreversible upon discontinuation of treatment. Pregnancy should be ruled out before initiating a course of danazol therapy, because it can produce virilization of the female fetus. Oral Contraceptives   The progestins in oral contraceptives are impeded andro-gens. Rarely, a woman taking oral contraceptives develops acne and even hirsutism. If this occurs, another product with a less-androgenic progestin should be selected, ...