PCOS and DD of hyperandrogegism TOG 2013 Flashcards
What can androgen excess cause?
Hirsuitism
Androgenic alopecia
Acne
Ovarian Dysfunction
Virilisation
Masculinsation
Main androgen produced by adrenal gland
DHEA and DHEA-S
What androgens does the ovary produce
20% of DHEA
50% of androstenedione
25% of testosterone
How does testosterone circulate in blood stream
80% bound SHBG
19% bound albumin
1% free testosterone or its active dihydrotestosterone
Bound androgens (DHEA-S, DHEA, androstenedione is converted to testosterone by peripheral tissues)
Clinical assessment for androgen excess
Height, weight and body mass index.
Distribution and extent of adiposity.
Skin thinning or bruising (seen in Cushing’s syndrome).
Acne, especially over the face, neck, back and chest.
Degree, pattern and severity of hirsutism.
Acanthosis nigricans (velvety skin hyperpigmentation), associated with insulin resistance.
Deepened voice.
Male pattern balding.
Breast atrophy.
Clitoromegaly.
Loss of normal feminine body shape.
What scoring system is used to scale hirsutism?
Ferriman-Gallwey
9 Sites 0 = no terminal hair 4= complete and heavy cover
8-15 mild hirsutism
> moderate/severe
How to use testosterone levels in assessment of hyperandrogegism
2-5 mol/L - likely PCOS
>5 - other causes ?andoren secreting tumour
Gold standard for testosterone quantitation
Mass spectrometry
What are the differentials for hyperadrogenism?
PCOS
Ovarian hyperthecosis
Congenital adrenal hyperplasia
Cushing’s syndrome
Androgen-secreting tumour
- Adrenal origin
- Ovarian origin
Exogenous androgen administration
Gestational hyperandrogenism
Presentation of CAH with classical 21 hydroxylase deficiency
Female infants virlised
Adrenal crisis
Low cortisol, low aldosterone, high androgens
Low Na, High K
Biochemical findings in PCOS
Mild to moderate elevation in free and total testosterone
Elevated DHEA-S
Low SHBG
LH/FSH ratio elevated
Explained hyperthecosis.
- In whom does it typically present
- How high are testosterone levels
Describes lutenised theca cells in ovarian storm
Typically postmenopausal
Severe hyperandrogegism, testosterone >7 - virilisation
Most common enzyme deficiency in CAH, which metabolite is raised
21 hydroxylase deficiency
17-OHP raised
When to patients present with non classical 21 hydroxylase deficiency
Cortisol/aldosterone pathway maintained 20-60% normal function.
Present early adults with menstrual disturbance or hirsutism. Precocious puberty.
How does 11B hydroxylase deficiency present. What is its metabolite which is raised?
Metabolite 11 deoxycortisol
Low cortisol
High aldosterone
High androgens
Amibigious genitalia in female
No adrenal crisis
High Na, Low K
What proportion of women with cushings syndrome have hirsutism?
80%
What hormone is raised in cushings? How does it present?
High cortisol
Central weight gain
Facial plethora
Supraclaviclular fat pads
Abdominal striae
High androgen - hirsutism, acne, male pattern baldness
What are the causes of Cushing syndrome?
ACTH secreting pituitary tunmours (Cushings disease)
Autonomous cortisol secretion by adrenal gland - neoplasm or hyperplasia
Exogenous glucocorticoids
Ectopic ACTH from neoplasia - small cell lung cancer
How do androgen secreting tumours typically present? Most common virilising ovarian tumour?
Mimic PCOS but sudden onset and rapid progression
Sertoli leydig tumours
Hormone profile of ovarian androgen securing tumours vs adrenal androgen secreting tumour
High testosterone
Normal DHEA-S and 17 ketosteroids
Adrenal tumours - high DHE-A and urinary 17 ketosteroids levels, not suppressed by dexamethasone
