Endocrine

Hirsutism

Modified_Ferriman-Gallwey-score.png
https://en.wikipedia.org/wiki/Ferriman%E2%80%93Gallwey_score

 

Definition

Excessive male-pattern hair growth in the female

  • Affects between 5-10% of reproductive-age women
  • Areas of increased hair growth include above the lip, chin, chest, back and buttock
  • Can also be seen with increased acne or male pattern baldness

 

Pathogenesis

  • A result of the relationship bewteen androgen levels and hair follicle response to androgen.
    • Hirsutism can be caused by either increased levels of androgens or by increased sensitivity to the androgens
    • Increased androgen activity causes increased hair growth in androgen sensitive areas and increased hair follicle size, hair fiber diameter, and the proportion of time terminal hairs spend in the anagen phase
      • Cosmetically, this results in increase in coarse, dark hair in a typically male distribution
  • ​Hormones that can be in excess include:
    • Testosterone: generally of ovarian origin
    • Dehydroepiandrosterone sulfate (DHEA-S): generally of adrenal origin
    • Androstenedione: can be either of adrenal or ovarian origin
  • ​SHBG (sex hormone binding globulin) levels can also dictate the level of active androgen
    • ​SHBG can be suppressed in the setting of hyperinsulinemia or hypothyroidism
  • ​ Virilization occurs when androgen levels cause hirsutism plus additional symptoms such as voice changes, increased musculature, clitoromegaly, etc.
  • Note: though often of non-serious etiology, hirsutism can cause mental anguish and emotional trauma for patients and can be a serious cosmetic problem

 

Differential Diagnosis

  1. Hypertrichosis: hair would be distributed in a generalized, non-sexual pattern
    • Often due to the use of medications such as phenytoin, glucocorticoids, minoxidil, or cyclosporine.
  2. Idiopathic (familial trait, more common in some ethnic groups)
  3. Various causes of hyperandrogenism
    1. PCOS (most common cause of hirsutism)
      1. Insulin resistance leads to increased insulin levels; insulin stimulates ovarian theca cells to produce more androgens
    2. Congenital adrenal hyperplasia (Non-Classical)
    3. Androgen-secreting tumors
      1. Would see a rapid rate of hair growth a, evidence of virilzation (clitoromegaly, increased muscularity)
    4. Cushing's syndrome
    5. Hyperthecosis
      1. Increased production of testosterone from theca cells of the ovaries
    6. Hyperprolactinemia
    7. Acromegaly
    8. Thyroid Dysfunction
    9. Obesity or insulin resistance
    10. Idiopathic Hyperandrogenism
      1. Idiopathic production of androgen precursors leads to increased androgen levels

 

Criteria for Assessing Hirsutism

Ferriman-Gallwey Scoring System

  • Speed of onset
    • ​Fast onset suggestive of androgen producing neoplasm
    • Slow onset suggestive of functional causes of androgen excess
  • Age of onset
    •  Pre-pubescent onset: suggestive of androgen producing neoplasm or CAH
    • Pubescent or post-pubescent onset: consider other etiologies of hirsutism

  • Ferriman-Gallwey Scoring System

Diagnosis

When To Conduct Laboratory Tests:

  • Hirsutism is moderate or severe (FG score greater than 15)
  • Presence of virilization
  • When a secondary cause is possible

When NOT to Conduct Laboratory Tests:

  • Hirsutism is mild (FG score of 8-15), AND
  • Patient is having a regular period, AND
  • Secondary cause (such as ovarian tumor) is unlikely - most likely idiopathic

 

Laboratory Tests

Random Testosterone Level

  • If normal, supports idiopathic hirsutism
  • If elevated, need to order a plasma free testosterone level

Plasma free testosterone level

  • If elevated, refer to an endocrinologist
    • If due to free testosterone, related to LOW levels of SHBG (sex-hormone binding globulin) – total testosterone could be normal but low binding levels mean free testosterone is elevated
  • Test 50% more sensitive than total testosterone
  • Testosterone excess usually due to ovarian origin, DHEA from adrenal origin, and androstenedione from adrenal or ovarian origin

Pelvic Ultrasound

  • indicated if concerned for PCOS

Ovarian Ultrasound and/or Adrenal Ultrasound

  • for concern about androgen-producing tumor

 

Management/Treatment

  • Management guided by the degree to which the patient is bothered by the hair growth

Cosmetic Management

  • Bleaching
  • Shaving
  • Eflornithine hydrochloride cream (Vaniqa) for facial hirsutism
  • Electrolysis
    • Works by destroying individual hair follicles
  • Laser treatment
    • Has less pain and side effects than electrolysis, decreases cosmetic measures for months, can permanently decrease hair density after 3-4 treatments

Hormonal Management

  • Anti-androgens (high dose spirinolactone)
    • high-dose spironolactone is first-line in the United States
    • a recent randomized controlled trial showed that the clinical efficacy of spironolactone and flutamide are similar. However, hepatocellular toxicity is associated with flutamide.
    • Off-label use - there is a risk of pseudohermaphroditism in male fetuses if woman becomes pregnant
  • Estrogen-Progestin (Oral Contraceptives) - need to use nonandrogenic progestins
  • Finasteride, a 5-alpha-reductase inhibitor - less effective than antiandrogens

 

References

  1. Loriaux, D.L. (2012). An approach to the patient with hirsutism. JCEM, 97(9), 2957-2968. 
  2. Moghetti, P., et. al. (2000). Comparison of spironolactone, flutamide, and finasteride efficacy in the treatment of hirsutism: a randomized, double blind, placebo controlled trial. JCEM, 85(1), 89-94.
  3. Plouffe Jr., L. (2000). Disorders of excessive hair growth in the adolescent. Obstetrics and Gynecology Clinics of North America, 27(1), 79-99.
  4. Rosenfield, R.L. (2005). Hirsutism. NEJM.  353(24), 2578-2588.
  5. Stricker, T., et. al. (2001). Visual diagnosis: an adolescent female who has increasing hair growth. Pediatrics in Review, 22(7), 240-244.