General internal medicine & health services research case conference teaching module

GENERAL INTERNAL MEDICINE & HEALTH SERVICES RESEARCH CASE
CONFERENCE TEACHING MODULE
Hirsutism - Answer key
Reviewed by Lisa Skinner, MD
July 2011
Articles:
#1: Endocrine Society Clinical Practice Guideline
#2: A Practical Approach to Hirsutism
#3: Evaluation and treatment of Women with Hirsutism (just look at Figure 1, page 2569)
#4: Evaluation of Women with Hirsutism (Table 2 only)

Susan Silverman is a 22 year old woman without significant past medical history. She
presents with a 6-month history of increased body hair. She reports slight increase in hair
growth since puberty but has noticed significant increased growth of hair on her face, back
and legs for the last 6 months.

She reports that she's been also feeling depressed lately about how she looks and has been
gaining weight over the last year. Another doctor had started her on Prozac recently but
she decided not to take it since she thinks her depression is only related to her self-image.

1) What further elements of the history might help you determine the cause of her hair
growth?
-Evidence of anovulation, typically associated with menstrual irregularities
-Early puberty.
-Signs/symptoms of virilization: deep voice, male pattern balding, decreased breast tissue,
increased muscle mass, skin changes, clitoromegaly
-Evidence of endocrinopathy, such as galactorrhea (prolactinoma), acromegaly, cushingoid
habitus
-Medication list

She reports that her periods have always been irregular. Her family history is negative for
hirsutism. She is not taking any medications and does not smoke or drink. She does have
acne, denies other evidence of endocrinopathy.

2) What is the difference between hirsutism and hypertrichosis? How can you quantify hair
growth on physical exam? What are some limitations to this formalized quantification?
Hypertrichosis: generalized increase in hair, not in androgen dependent areas and usually
hereditary
Hirsutism: excessive terminal hairs (darker and thicker) in androgen dependent areas
Quantify by Ferriman-Gallwey score (see Article #1, Figure 1) each of 9 body areas rated on
amount of hair growth from 1 to 4, a score of over 8 suggests hirsutism. Limited by the subjective
nature, the failure to account for focal high score, lack of consideration of certain areas like the
sideburns and buttocks, lack of allowance for ethnic variations, and problem of patients
employing hair-removal strategies prior to examination.

3) What are important aspects of the physical exam?
Vitals: blood pressure, weight, height
Skin for acne, acanthosis nigrans (PCOS)
Abdominal/pelvic masses
Galactorrhea
Signs of Cushing's: striae, central obesity

4) What is in your differential diagnosis?
See Article #4, Table 2
Increased peripheral androgen
Idiopathic
PCOS Hyperthecosis Nonclassical Congenital Adrenal Hyperplasia Neoplasm Ovarian Functional Adrenal Adenoma Carcinoma Cushing's Drug induced (anabolic steroids, danazol, valproic acid)
On exam her bp is 120/75 and she is slightly obese. She has noticeable increased hair
growth on her face, chest, lower abdomen and back with moderate acne on her face. A
pelvic exam is normal and she has no other evidence of virilizatton.

5) What labs/studies are you going to order as part of your initial evaluation?
Guidelines recommend testing for elevated androgens in women with moderate to severe
hirsutism OR 1.) sudden onset 2.) rapid progression 3.) menstrual irregularity 4.) central obesity
5.)acanthosis nigricans or 6.) clitoromegaly (virilization). If hirsutism is isolated and mild, no
need for laboratory testing and can proceed with treatment.

See Article #3, Figure 1 Algorithm. Since she has menstrual irregularities but no virilization, can
pursue moderate initial testing: TSH, prolactin, free testosterone and 17-OH progesterone. Can
also consider DHEA-S to rule out adrenal cause of androgen production.
Endocrine society Guidelines algorithm (Figure 2) recommends simply starting with AM plasma
free testosterone as initial evaluation and pursuing additional workup if testosterone is elevated.
This may be more cost-effective, but involves more blood draws and appointments for the
patient.

A word about testosterone tests: Assays vary, but plasma free testosterone is significantly more
sensitive than total testosterone. At UCLA lab, the intial test would be "Testosterone free and
total". There is another test, "Testosterone, bioavailable" which can be sent to a referral lab.
This would be useful if the initial evaluation is negative but patient is clinically progressing and
you have a high suspicion of an initial false negative for hyperandrogenemia.

Plasma free testosterone is slightly elevated. What are the most likely causes of the
patient's symtoms? Do you want to do any more testing?
PCOS is the most likely cause of hyperandrogenic hirsuitism. However, if the testosterone is
>200ng per dL, need to rule out ovarian tumor with pelvic ultrasound. If DHEA-S (the adrenal
androgen) elevated, should pursue adrenal imaging.

Androgen excess is confirmed on early morning testosterone testing. DHEA-S, TSH,
prolactin, and 17-0H progesterone levels are normal. You diagnose Susan with PCOS;
however, she remains very concerned about her appearance.

6) What are the pharmacological and non-pharmacological treatments are available?
Weight loss is recommended.
OCPs
Anti-androgens (teratogenic to male fetuses, must use with reliable birth control)
Spironolactone-androgen antagonist Finasteride CPA (not available in the USA) Flutamide (GnRH antagonist- not recommended due to modest benefit with significant side effects) Vaniqa (eflornithine hydrochloride)
Laser/electrolysis
* Metformin has not really been shown to be effective for hirsutism (though likely important for
other effects of PCOS)

7) You decide to start her on a birth control pill as first line. What dose of estrogen and
what formulation of progesterone are you looking for in the pill that you choose?

Theoretically, you want 30-35mcg of estradiol instead of the low dose 20mcg pills, but there is
no evidence to support this. Also, theoretically avoid levonorgestrel (most androgenic progestin)
and favor drospirenone (anti-androgenic) or norgestimate and desogestrel.
Examples:
Yaz (drospirenone/ethinyl estradiol) 3mg/20mcg
Yasmin/Ocella (drospirenone/ethinyl estradiol) 3mg/30mcg
Desogen / Ortho-Cept / Reclipsen (desogestrel/ethinyl estradiol) 0.15mg/30mcg
Sprintec / Ortho-Cyclen (ethinyl estradiol/norgestimate) 35mcg/0.25mg

Susan returns to clinic after two months of taking the medications you prescribed and
reports that her acne is better but the hirsutism is about the same.

How long does hirsutism take to respond to therapy?
It may take 9-12 months to show a response to treatment

References:
Article#1:
Martin KA, Chang RJ, Ehrmann DA, Ibanez L, Lobo RA, Rosenfield RL, Shapiro J, Montori VM, Swiglo BA. J Clin Endocrinol Metab. 2008 Apr;93(4):1105-20. Epub 2008 Feb 5. Review. Gilchrist VJ, Hecht BR. Am Fam Physician. 1995 Nov 1;52(6):1837-46. Review. Hunter MH, Carek PJ. Am Fam Physician. 2003 Jun 15;67(12):2565-72. Review. Am Fam Physician. 1996 Jul;54(1):117-24. Review.

Source: http://www.medres.med.ucla.edu/Education/Lectures_and_Conferences/IMS_pdf/Hirsutism%20answer%20key.pdf