1. Hirsutism
Andrew Rodin
1st March 2016

2. What is hirsutism?
Development of androgen-dependent terminal body hair in a woman in places in which terminal hair is normally not found
Terminal body hairs are thick, dark, pigmented hairs normally seen in men on the face, chest, abdomen and back

3. What is hirsutism?
Differences in female body hair in different geographical populations
A woman’s definition of hirsutism may differ depending on her ethnic origin and her subjective view of normal body hair distribution

4. What causes hirsutism? Increased production rate of androgens
Found in nearly all hirsute women
Usually testosterone, but serum testosterone might not be above the normal range
Increased conversion of testosterone to dihydrotestosterone in peripheral tissue, including hair follicles

5. Androgen biosynthesis in women

6. Causes of hirsutism Functional androgen excess disorders
Polycystic ovary syndrome (80%)
Idiopathic hirsutism (10%)
Specific identifiable disorders
Non-classic congenital adrenal hyperplasia
Thyroid dysfunction
Hyperprolactinaemia
Hyperandrogenism, insulin resistance and acanthosis nigricans (HAIR-AN)
Virilising ovarian tumour
Virilising adrenal tumour
Hyperthecosis
Cushing’s disease
Acromegaly
Drugs (danazol, testosterone, anabolic steroids, androgenic progestogens)

7. Idiopathic hirsutism Diagnosis of exclusion
Applies to women with hirsutism and no other clinical abnormalities
No menstrual irregularity
Serum androgens usually normal or only mildly elevated
May be part of the PCOS spectrum

8. Polycystic ovary syndrome
Most common cause of androgen excess
6-8% women of reproductive age
Evidence of hyperandrogenism and menstrual irregularity
Rotterdam consensus criteria for diagnosis:
2 of the following:
Oligo-/amenorrhoea
Clinical or biochemical hyperandrogenism
Characteristic appearance of ovaries by ultrasound

9. Polycystic ovary syndrome
Androgen excess usually becomes evident about the time of puberty or soon after
Symptoms may develop or worsen in association with weight gain

10. PCOS pathogenesis

11. Congenital adrenal hyperplasia
Excess adrenal androgen production driven by ACTH is key feature of most forms of CAH
Disorders may be recognised at birth or in early infancy
Late onset or non-classical forms occur (21-hydroxlase deficiency most common)
Prevalence of non-classical CAH among hirsute women varies from 1-15%
Affected women present peripubertally with hirsutism and menstrual disturbance

12. Ovarian hyperthecosis
Characterised by severe hyperandrogenism and insulin resistance
Seen primarily in post-menopausal women
Women typically present with slowly progressive acne and hirsutism
Likely to be virilised - clitoral enlargement, male pattern baldness, deepening of the voice, and a male habitus

13. Ovarian hyperthecosis
Severe form of PCOS
Significantly increased stromal tissue with luteinized theca-like cells scattered throughout large sheets of fibroblast-like cells
Hyperinsulinaemia - an important pathophysiological factor
Increased risk of type 2 diabetes
Risk of endometrial carcinoma

14. Androgen-secreting ovarian tumours
5% of all ovarian tumours (Sertoli-Leydig cell tumours, granulosa-theca cell tumours, hilus cell tumours)
Hirsutism likely to start later and progress more rapidly than in PCOS
Testosterone >5nmol/L and often much higher
Affected women become virilised
Tumours identified by transvaginal ultrasound

15. Adrenal tumours Rare cause of androgen excess
Some are adrenal adenomas that secrete mostly testosterone
Most are carcinomas that often secrete cortisol and testosterone

16. Adrenal tumours
Clinical picture is that of a woman who becomes virilised and has Cushing’s syndrome
DHEAS produced almost exclusively by adrenal glands and high levels suggest adrenal pathology

17. Severe insulin resistance
Women with severe insulin resistance and hyperinsulinaemia often have hirsutism
Hyperinsulinaemia causes ovarian hyperandrogenism through:
Stimulation of theca cell receptors for IGF-1
Reduction of SHBG production by liver resulting in increased free testosterone

18. Clinical evaluation
Most important information is the time course of symptoms and whether or not the woman is virilised
Ascertain age at onset, rate of progression, and any change with any treatment or with fluctuations in weight

19. Assessment of hirsutism using the Ferriman and Gallwey score

20. Physical examination Hirsutism Body habitus
Other signs of androgen excess
Acne, seborrhoea, temporal balding
Virilisation
Deep voice
Android body shape
Frontal balding
Clitoromegaly (>10mm)
Body habitus
Shape, weight, BMI
Breasts
Galactorrhoea
Skin
Acanthosis nigricans
Striae, thin skin, bruising BP
Hypertension
Abdomen and pelvis
Mass lesions

21. Clinical pointers to a rare cause for hyperandrogenism
Abrupt onset
Short duration
Sudden, progressive worsening of hirsutism
Onset in 3rd decade of life or later, rather than near puberty
Symptoms or signs of virilisation

22. Initial investigations
The clinical picture will determine the initial strategy for investigations in women with hirsutism
Clinical picture
Initial investigations
Long-standing hirsutism
Serum testosterone
Long-standing hirsutism and irregular menstrual cycles
Serum testosterone, LH, FSH, prolactin
Short history of hirsutism or progressive hirsutism
Serum testosterone, DHEAS

23. Further investigations
Planned according to clinical suspicion and results of preliminary investigations
Indication
Next investigations
Hirsutism + virilisation
Testosterone >5nmol/L
DHEAS normal
Transvaginal ultrasound to look for ovarian tumour
DHEAS elevated
CT/MR adrenals to look for an adrenal tumour
Early-onset hirsutism
Short Synacthen test to measure 17-
hydroxyprogesterone response or urine steroid
profiling to test for congenital adrenal hyperplasia
Clinical features of
Cushing’s syndrome
Low dose dexamethasone suppression test

24. Case history – Mrs SD Aged 66
Referred because of vitamin D deficiency and secondary hyperparathyroidism
COPD diagnosed in 2013
Ex-heavy smoker
Drugs: Symbicort, Tiotropium, omeprazole, co-dydramol, sertraline, simvastatin

25. Mrs SD Overweight – weight increased 2 stones
Impaired fasting glycaemia (6.4mmol/L)
Bruising more easily and thinning of her hair over last 5 years
Fatigue++
Menopause in 50’s
2 children, 3 miscarriages

26. Mrs SD - Examination 80.3kg, BP 145/88 mmHg
Appeared Cushingoid with central adiposity
No deepening of voice
Androgenic hair distribution over scalp
No acanthosis nigricans
Facial hirsutism and acne

27. Summary
Incidental finding of hyperandrogenism with gradually worsening symptoms in a post-menopausal woman

28. Mrs SD - investigations
Testosterone 18nmol/L (<1.2)
LH 19iu/L, FSH 45iu/L, oestradiol 155pmol/L
DHEAS 1.8umol/L ( )
Prolactin 160mU/L (<800)
Free T4 11.9pmol/L, TSH 0.53mU/L

29. Mrs SD - investigations
Ultrasound ovaries: no ovarian tumour
CT abdomen: no adrenal tumour
1mg overnight dexamethasone suppression test: normal suppression of cortisol

30. Mrs SD - investigations
Long-acting GnRH agonist challenge
Leuprorelin 3.75mg s/c
Day 1: serum testosterone 25nmol/l
Day 30: serum testosterone 0.9nmol/l
Clinical diagnosis - ovarian hyperthecosis

31. Mrs SD - management Treated with Zoladex prior to surgery
Laparoscopic bilateral oophorectomy

32. Post-surgery follow-up
2 weeks post-surgery:
No acne
No further hair loss
Weight loss of 3kg
Lots more energy
Feeling very well
Serum testosterone 0.9mmol/L
Fasting blood glucose 4.3mmol/L

33. Learning points Hirsutism is a common symptom
History crucial in assessment – particularly age at onset, progression, virilisation
Testosterone >5nmol/L always requires further investigation
Referral recommended if testosterone >3.5nmol/L
In post-menopausal women, testosterone should be very low and hyperandrogenism should be investigated