HYPERANDROGENISM Flashcards
What is androgen excess?
Increased level of androgen
What is hirsutism?
Excessive growth of terminal hair in a male pattern.
What is hypertrichosis?
Generalized overgrowth of fine vellus hair
What is virilization?
Condition associated with markedly elevated levels of circulating testosterone (>2 ng/ml)
What is the Ferriman-Gallwey scoring system used for?
Classifying hirsutism as mild
What are the components of the pilosebaceous unit (PSU)?
Sebaceous component and pilary component from which the hair shaft arises.
What conditions arise from abnormalities of the sebaceous and pilary components of the PSU?
Sebaceous abnormalities lead to acne; pilary abnormalities lead to excessive growth (hirsutism) or excessive shedding (alopecia).
What are the three phases of hair growth?
Anagen (growing phase
What enzyme converts testosterone in peripheral tissue and is linked to hirsutism?
5-alpha reductase.
What are the three sources of androgen production in women?
Ovaries
What is the daily testosterone production from the ovaries?
0.1 mg/day.
What androgen is primarily produced by the adrenal glands?
Dehydroepiandrosterone sulfate (DHEAS)
What is the active form of androgens in peripheral tissue?
3𝞪-diol-G.
What is the role of 5-alpha reductase in androgen metabolism?
Converts testosterone into the more potent androgen dihydrotestosterone (DHT).
What percentage of testosterone is tightly bound to sex hormone-binding globulin (SHBG)?
Approximately 85%.
What percentage of testosterone is loosely bound to albumin?
10-15%.
What percentage of testosterone is free and biologically active?
1-2%.
Where is sex hormone-binding globulin (SHBG) produced?
The liver.
What is the most accurate indicator of peripheral androgen metabolism?
3𝞪-diol-G levels in serum.
What is the main androgen produced by the ovaries?
Testosterone.
What is the main androgen produced by the adrenal glands?
DHEAS.
What is the main androgen marker for peripheral metabolism?
3-alpha-diol-G.
How is idiopathic hirsutism related to 5-alpha reductase?
Idiopathic hirsutism is associated with increased 5-alpha reductase activity despite normal circulating androgen levels.
What are the cutoff scores for the Modified Ferriman-Gallwey scoring system?
<6-8: normal
What condition is associated with hirsutism
acne
What are some ovarian causes of hirsutism?
PCOS
What are some adrenal causes of hirsutism?
Adrenal tumors
What are non-specific causes of hirsutism?
Exogenous androgen intake
What pregnancy-related condition can cause androgen excess?
Luteoma or hyperreactio luteinalis.
What is the source of idiopathic hirsutism?
Peripheral conversion of androgens.
What are the causes of hyperandrogenism?
Idiopathic hirsutism
What are the possible organ sources of hyperandrogenism?
Ovary
What pregnancy-related condition can cause androgen excess?
Luteoma or hyperreactio luteinalis.
What are the key features of idiopathic hirsutism?
Signs of hirsutism with regular menstrual cycles and normal circulating androgen levels.
What is the primary cause of idiopathic hirsutism?
Increased 5-alpha reductase activity leading to enhanced androgen action in the pilosebaceous unit (PSU).
What laboratory finding suggests idiopathic hirsutism?
Increased levels of 3α-diol-G
What type of disorder is idiopathic hirsutism classified as?
A peripheral disorder of androgen metabolism.
What treatment is effective for idiopathic hirsutism?
Antiandrogens that block peripheral testosterone action or interfere with 5-alpha reductase.
What are the three diagnostic criteria for PCOS according to the Rotterdam criteria?
Menstrual irregularity (amenorrhea
What is functional or idiopathic hyperandrogenism?
A condition diagnosed when androgens are elevated (either ovarian or adrenal) with regular
How does functional hyperandrogenism differ from PCOS?
Women with functional hyperandrogenism may be ovulatory and lack polycystic ovary morphology.
What is stromal hyperthecosis?
A benign ovarian disorder with bilateral ovarian enlargement and increased testosterone production.
What are the histopathological features of stromal hyperthecosis?
Nests of luteinized theca cells within the ovarian stroma
How does stromal hyperthecosis present clinically?
Gradual onset of anovulation
What testosterone level suggests stromal hyperthecosis?
Testosterone > 1.5 ng/mL but < 2 ng/mL.
What is a distinguishing feature of androgen-producing tumors?
Rapid progression of hirsutism and virilization.
What types of ovarian tumors can produce androgens?
Sertoli-Leydig cell tumors
What are the common features of Sertoli-Leydig cell tumors?
Occur in reproductive age
What are the common features of hilus cell tumors?
Occur in menopause
What hormone level is markedly elevated in androgen-producing adrenal tumors?
DHEAS (> 8 µg/mL).
What imaging study is used to diagnose adrenal tumors?
CT scan or MRI of the adrenal glands.
How do adrenal adenomas contribute to hyperandrogenism?
They secrete large amounts of DHEAS and testosterone (>1.5 ng/mL).
What is late-onset 21-hydroxylase deficiency (LOHD)?
A mild form of congenital adrenal hyperplasia caused by 21-hydroxylase deficiency
What is the key biochemical abnormality in LOHD?
Increased 17-hydroxyprogesterone due to impaired cortisol biosynthesis.
How does LOHD typically present in women?
Postpubertal onset of hirsutism
What differentiates LOHD from PCOS?
Women with LOHD often have a history of prepubertal accelerated growth
What test confirms LOHD?
An ACTH stimulation test measuring 17-hydroxyprogesterone response.
What 17-hydroxyprogesterone level suggests LOHD?
> 8 ng/mL at baseline or >10 ng/mL after ACTH stimulation.
How is LOHD inherited?
Autosomal recessive transmission at the CYP21B locus
What treatment is used for LOHD in women desiring fertility?
Corticosteroids to restore ovulatory function.
What is Cushing syndrome?
Excessive adrenal glucocorticoid production due to increased ACTH secretion (Cushing disease) or adrenal tumors.
What are the clinical features of Cushing syndrome?
Hirsutism
What cortisol level is diagnostic of Cushing syndrome in a 24-hour urinary free cortisol test?
> 100 µg/24 hours; >240 µg is highly diagnostic.
What late-night salivary cortisol level is suggestive of Cushing syndrome?
> 0.4 µg/dL.
What test can be used to screen for Cushing syndrome?
Overnight dexamethasone suppression test (DST).
What dexamethasone suppression test result suggests Cushing syndrome?
Morning plasma cortisol >5 µg/dL after 1 mg dexamethasone at 11 PM.
What laboratory tests help differentiate causes of hyperandrogenism?
Testosterone
Which tumors should be treated by operative removal?
Adrenal adenomas and carcinomas
What is the prognosis for adrenal carcinomas after metastasis?
Poor, despite chemotherapy
What is the best treatment for stromal hyperthecosis?
Bilateral salpingo-oophorectomy
What happens to acne and oiliness after removal of androgen-producing tumors?
They disappear
What happens to breast size and clitoral size after removal of androgen-producing tumors?
Breast size increases, clitoral size decreases
How does excess central hair change after tumor removal?
Becomes finer and grows less rapidly but does not disappear
What procedures can effectively remove body hair after tumor removal?
Electrolysis or laser treatment
How is late-onset 21-hydroxylase deficiency (LOCAH) treated if the primary complaint is androgen excess and menstrual irregularity?
With oral contraceptives, similar to PCOS treatment
What treatment is used for women with LOCAH who wish to conceive?
Glucocorticoids such as hydrocortisone, prednisone, or dexamethasone
What is the goal of glucocorticoid treatment in LOCAH?
To suppress androstenedione and normalize 17-hydroxyprogesterone and progesterone levels
How are ovarian and adrenal tumors best identified?
By high-grade imaging techniques
What is the typical laterality of Sertoli-Leydig cell tumors?
Almost always unilateral
What is the preferred treatment for unilateral Sertoli-Leydig cell tumors in women who wish to preserve fertility?
Unilateral salpingo-oophorectomy
How are hilus cell tumors in postmenopausal women best treated?
Bilateral salpingo-oophorectomy to prevent recurrence
What is the mainstay of PCOS treatment?
Oral contraceptives (OCPs) with an added antiandrogen
Which progestogens are preferred in OCPs for PCOS treatment?
Less androgenic progestogens (norgestimate, desogestrel, drospirenone)
Why should antiandrogens be used with OCPs in PCOS treatment?
To prevent exposure during pregnancy
How do oral contraceptives help in PCOS?
They suppress ovarian androgens by inhibiting LH stimulation
How do OCPs affect adrenal androgens?
They decrease DHEAS by about 30% and inhibit 5α-reductase activity
How does ethinyl estradiol in contraceptives affect testosterone levels?
Increases SHBG, lowering free/unbound testosterone
Which hyperandrogenic disorder has the highest treatment success rate?
Acne vulgaris (~90% response rate)
What role do androgens play in acne development?
They stimulate sebum production
What percentage of women with acne have androgen excess?
About 52%
What is the most common androgen abnormality in women with acne?
Increased unbound testosterone
What enzyme activity is enhanced in acne?
5α-reductase, mostly type 1
What is the first-line treatment for acne in hyperandrogenic women?
Combination oral contraceptives (OCPs)
Which OCPs are preferred for acne treatment?
OCPs with less androgenic progestogens
What can be added if OCPs alone are not effective for acne?
Antiandrogens
