| What receptors does DHT bind? | DHT is the most potent androgen, binds delta-4 receptors and get stored by becoming 3a androstendione. |
| What receptors does DHT bind? | DHT is the most potent androgen, binds delta-4 receptors and get stored by becoming 3a androstendione. |
| How is the pathophysiology of Hirsuism? | We have overproduction of testosterone and delta-4- androstendione
For testosterone: it can be from ovarian or extra-ovarian origin as the production of 1/3 of testosterone is from ovary and 2/3 is at extraovarian |
| What is Hirsutism? | Excessive hair development in unusual places for females (face and body)
It is the most common type of hyperandrogenism for females |
| What is the difference between Hirsutism and Hypertrichosis? | Hypertrichosis is excess hair development in usual places, while Hirsutism is excess in unusual places |
| How does hyperandrogenism cause hair loss on the scalp? | They stimulate sebaceous glands and thus causing hair loss in the scalp |
| What are the signs of virilization that may accompany hyperandrogenism? | Minor signs (acne/ seborrhea- scalp sebaccous accumulation) these signs are not that serious
Major signs (clitoris hypertrophy, alopecia (صلع), muscular hypertrophy, mammarian atrophy...) these signs are more serious and may lead to malignancy. |
| What are the main androgens present? | Testosterone and delta-4- androstendione.
There is a correlation between their levels and the clinical severity. |
| What are the two types of Hirsutism? | Idiopathic (unknown origin of Hirsutism, hypersensitivity of receptors)
Hyperproduction (of androgens and androgen precursors) |
| What are the etiologies for hyperproduction type of Hirsutism? | PCOS (most common type)
Enzyme deficiency (Most common is 21-hydroxylase deficiency)
Cushing's (syndrome)
Tumors (ovarian or adrenal) |
| How is the pathophysiology of Hirsuism? | We have overproduction of testosterone and delta-4- androstendione
For testosterone: it can be from ovarian or extra-ovarian origin as the production of 1/3 of testosterone is from ovary and 2/3 is at extraovarian (by bioconversion of delta 4 androstendione in skin, adrenals and lipid...)
they diffuse to cells and become DHT by 5a reductase
Delta-4- androstendione produced by ovaries and adrenals in equal proportions (50/50) |
| What receptors does DHT bind? | DHT is the most potent androgen, binds delta-4 receptors and get stored by becoming 3a androstendione. |
| What is the pathophysiology for DHEA? | it is mostly of adrenal origin, become delta 4 in skin, may be sulfated in order to have a longer half life. |
| What are the Etiologies for Hirsutism? | Of Adrenal Origin:
Congenital adrenal hyperplasia (21 hydroxylase deficiency, 11-hydroxylase deficiency, 3-beta-HSD deficiency)
Virilizing tumors (rapid and severe changes)
Cushing's (ACTH dependent (either pituitary issue/ ectopic production) and ACTH independent) |
| What is the difference between Cushing's syndrome and disease? | Syndrome= any excess in coritsol
Disease= pituitary origin of cortisol excess |
| What is 21-hydroxylase deficiency? | It is an autosomal recessive ch6 short arm disorder
It is very polymorphic (could be complete deficiency or incomplete one) if incomplete it may present during puberty not from childhood |
| How is the pathophysiology of 21-hydroxylase deficiency? | Decrease in aldosterone and cortisol production, increase in ACTH, adrenal hyperplasia, and accumulate 17-OH-Progesterone which will eventually give delta 4 androstendione and testosterone
This leads to hypotension, hyperkalemia and loss of water (no aldosterone) and hyponatremia. |
| What is the classic form of 21-hydroxylase deficiency? | Complete deficiency, appears at birth, pseudohermaphrodism feminin (looks like a male)
loss of 2/3 of salt
Rare. |
| What is the non-classic form of 21-hydroxylase deficiency? | It is more common, partial deficiency, appears in peri-puberty, variable from one female to another, mostly can be asymptomatic and only seen with serum testing |
| What are the signs of 21-hydroxylase deficiency? | Android aspect of the body
Abnormal Puberty (irregular and late menses)
Any Family History |
| How do we get a diagnosis of 21-hydroxylase deficiency primarily? | Dosage of 17-OH-P can be measured in day-3/4 of menses.
it can be high (in case of classic type) or moderate (in case of non-classic)
We can also perform Synacthene test (ACTH stimulation) to confirm the diagnosis, measure 17-OH-P after 1 hour of administration of ACTH 0.25mg, if higher than 10ng/ml then confirmed. |
| How do we get a diagnosis of 21-hydroxylase deficiency using androgen levels? | we can see an increase in delta 4 by 3 to 4 times of normal values, and of testosterone by 2-3 times
and they increase with syncathene test
However in partial deficit testosterone appears normal |
| What are the other two congenital adrenal hyperplasia etiologies? | 11-hydroxylase deficiency (rare, presents with HTN and virilization)
3-beta-HSD deficiency |
| What are the virilizing tumors in andrenal glands causing hirsutism? | They are tumors of fasicular or reticular origin of adrenals, tumors have a very rapid and sudden onset of signs, and present with virilizing syndrome (major signs)
Aldosterone here is not affected as much as cortisol and androgens |
| What do adrenal tumors cause? | Very brutal hirsutism, with acne, seborrhea, and progressive alopecia
Comes with oligo-amenorrhea, virilizing signs (major ones like clitoris hypertrophy, muscular hypertrophy, mammary atrophy |
| What biological changes occur with adrenal tumors? | Increase in DHEA and DHEAS (by 100 times!)
Increase in testo and 4-delta (by 2-20 times) |
| What happens if adrenal tumors appear pre puberty? | Rapid bone growth and closing early so they will be taller at first and then block at a low height so they turn out short.
Causes primary amenorrhea |
| How is the diagnosis of adrenal tumors? | By imaging (CT scan, they usually appear as huge tumors so easy to dx)
Or by catheterization (of both adrenals veins to measure hormone levels and see if there is any variability) |
| Talk about ACTH dependent Cushing's causing hirsutism. | increase ACTH, increase cortisol and androgens
comes with hirsutism, facio-trunck obesity, muscular atrophy (at limbs) Vergetures (skin extended red-puprle) ecchymosis, HTN and osteoporosis and moon face. |
| What are the types of Hirsutism of ovarian origin? | Virilizing tumors of ovaries, Polycystic ovary syndrome (PCOS), Ovarian Hypertrophy syndrome. |
| How are virilizing tumors of ovaries? | They are rare, and have an intense presentation
Biologically we have increase in androgens (>2ng/ml testo) with no responsiveness to OCP (oral contraceptives)
We can locate them using CT scan, Endovaginal US (Echo), or catheterization of ovarian veins to get testo and delta 4 doses. |
| What are the types of virilizing tumors of ovaries? | Arrhenoblastoma, Gonadoblastoma, Lipidic cell tumors, Luteoma (more for GYN than endocrino dr) |
| What is the polycystic ovary disease? | It presents as anovulation, hirsutism, and multicysts at the ovaries (these are the criteria of dx, if 2 out of 3 are expressed--> PCOS Rotterdam While NIH needs all 3)
AKA Stein-Leventhal syndrome
presents clinically as disrupted menses (spaniomenorrhea, amenorrhea), acne, hirsutism (not severe), obesity (50% due to insulin resistance), no major virilization, acanthosis nigricans (ببين وسخ الجلد ع الرقبة اسود) |
| How does PCOS present biologically? | Increase in androgens (Testo and delta 4 by 2-3 times normal level)
Can be suppressed by OCP (unlike tumors)
increase LH but normal FSH due to increase ovarian stroma productions only
Has two types I and II, type I is more severe than II |
| What are the tests for PCOS? | GnRH stimulation test (if LH explosive reaction--> PCOS) |
| What is ovarian hypertrophy syndrome? | Very Rare, post menopausal, Hypertrophy of ovarian stroma, presents either like PCOS or as severe as tumors (virilizing pseudotumoral)
Treated surgically by GYN, dx by histo study |
| How are the Hirsutism of idiopathic origin? | Most common, when all possibilities are eliminated, present with childhood.
Variable severity (could be moderate -->severe)
occurs with a family history usually
Clinically no vilirlization, no hypercoleserol, normal radio, Biology may be normal and maybe high DHEA
Pathophysio:
Hypersensitivity of receptors (increase 5a reductase) or/ increase usage by skin |
| What are the Iatrogenic origins of Hirsutism? | Estrogen/Androgen therapies, Danazol (for endometriosis), Adrogens for dermatological disease, Anabolites, Other medications (phenylhydatoine, cyclosporine, diazoxide) |
| How do we get a dx for hirsutism? | Hx (Personal, family, medications...)
Physical Exam (Ferriman and Gallway Score (from 0-4 each place, 4-9 --> Hirsutism) Virilizing signs (major and minor))
Test (testosterone (as TeBG) and delta 4/ DHT (not asked for)/ DHEAS (adrenal origin sus)/ LH-FSH ratio (PCOS sus)/ Dynamic Tests (Syncatehene test in case hyperplasia adrenal sus) / Imaging (After hormonal workup to not get haloma)/ Catheterization (if radio not enough) |
