DSD Flashcards by S'bongiseni Mashinini

What germ cell layer does the reproductive system develop from. Be specific

Mesoderm
- There are 3 layers:
- paraxial ( closest to the spinal cord)
- intermediate
- lateral plate
- the lateral plate mesoderm closest to the gut = splanchnic plate mesoderm
- closest to the ectoderm = somatic mesoderm

Intermediate mesoderm gives rise to reproductive system

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Name the structures relevant to the reproductive system and what they give rise to

Intermediate mesoderm condenses gives rise to urogenital ridge
- UR :
- Ductal system I.e mesonephric and parametric ducts
- Gonads
- primordial cells migrate from the yolk sack and invade the UR giving ride to gamets (sperm and Oocytes)

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Name the structures relevant to the reproductive system and what they give rise to

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Name structures relevant to the reproductive system and what they give rise to

Fore gut
Mid Gut
Hind gut
Yolk sak: - primordial germ cells - will migrate up the duct/stalk to infiltrate the Urogen ridge

In hind gut you get cloaca
Anterior: urogenital sinus eventually forms external genitalia
Post: anal canal
Separated by a septum - urorectal septum

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Name structures relevant to the reproductive system and what they give rise to

Fore gut
Mid Gut
Hind gut
Yolk sak: - primordial germ cells - will migrate up the duct/stalk to infiltrate the Urogen ridge

In hind gut you get cloaca
Anterior: urogenital sinus eventually forms external genitalia
Post: anal canal
Separated by a septum - urorectal septum

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Name the structures

The ducts all empty into the urogen sinus

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Describe the process of gonadal differentiation into male anatomy

Testosterone is acted on by 5 alpha reductase converting it to DHT. DHT leads to development of male external genitalia

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Describe the process of gonadal differentiation into male anatomy

Testosterone is acted on by 5 alpha reductase converting it to DHT. DHT leads to development of male external genitalia

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Describe the process of gonadal differentiation as it relates to female anatomy

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Describe the process of gonadal differentiation as it relates to female anatomy

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What structures does the urogenital sinus give rise to

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Identify each for these structures

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What structures do these develop into in the female and male and how? What hormones are involved?

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Sexual determination vs differentiation

Determination = Gene signalling and development of Gonads into female and male.

Differentiation = Development of internal and external genitalia into female and male

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What do women with CAH not have internally male organs

Persistence of the mesonephric duct requires high levels of local testosterone.

This can only be achieved when the ipsilateral gonad/testes secretes testosterone

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Describe the process and compleation of sexual differentiation in males. Including relevant hormones

BHCG and LH ( from the fetal pituitary gland) stimulate the testes to produce testosterone.

The cytoplasm of the external genitalia has the enzyme 5 alpha reductase which converts testosterone to DHT. DHT is much more potent leads to development and maturation of male external genitalia.

Urogenital folds fuse: forming the urethra, Labioscrotal swelling fuses leading to scrotum, genitalia tubercle elongates forming penis. all complete by 15 weeks.

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Describe the process of sexual differentiation with regards to females.

In the absence of androgens default ovary develops. Ovary secretes oestrogen which helps with differentiation.

urogenital folds form the urethra, labioscrotal the labia minora and genital tubercle the clitoris
urogenital sinus becomes the vaginal vestibule ( meaning ant. hall or looby next the opening/door of a building)

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What 4 groups can you devide DSD into ?

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Where is the adrenal gland located anatomically

Superiormedial aspect of the kidney, between the diaphragm and the kidney

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What are the layers of the adrenals and what do they produce?

Cortex has 3 layers: acronym GFR and ACT
- Zona Glomerularis: Aldosterone
- Zona Fasiculata: Cortisol
- Zona Reticulata: Testosterone

Medulla: Catecholamines

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Explain Hypothalamic, Pituitary, Adrenal patheay

Hypothalamus: Corticotropin releasing Hormone CRH
Pituitary: ACTH
Adrenal: Cortisol

Cortisol = negative feedback on Hypothalamus and Pituitary

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Define CAH

Autosomal recessive disorder ( actually a group of 7 autosomal recessive diseases) that leads to an enzyme deficiency in the cholesterol to Cortisol pathway. Abnormal abundance of precursors leads to abnormalities in the mineralocorticoid and sex steroid production pathway

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Which enzyme deficiency is most responsible for CAH

21 hydroxylase deficiency accounts for more than 95% of cases

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Name the gene most commonly involved in 21 - OH deficiency

Name the gene most commonly involved in 21 - OH deficiency

How would you classify 21 - OH deficiency

Describe the clinical presentation of 21 OH classical type

Simple Virelising form: Consider in Bilateral non palpable gonads Female infant: range form clitiromegally, labioscrotal fusion, urogenital sinus to phallus (Retains normal internal genitalia) Male: subtle signs - hyperpigmented scrotum, enlarged phallus ( Normal male internal genitalia)

Describe presentation of Nonclassic 21- OH Deficiency

Describe presentation of 11B Hydroxlase deficiency

Describe 17 alpha hydroxylase deficiency

Summarise the most common CAH deficiency with regards to Salt wasting, Hypertension, virilisation, and Sex hormone deficiency

How to diagnose CAH

How to diagnose CAH 21 OH deficiency type

How to screen for CAH primarily 21 OH deficiency type

Acute Management of CAH

Pharmacological maintenance therapy for CAH

Glucocorticoids: - work by suppressing ACTH production with negative feedback in HP Axis leading to less androgen circulation. - Need in lowest effective dose to prevent adrenal crisis Monitoring = 17 OH levels, renin activity, electrolytes 10 - 14 days post initiation of therapy Dosing: Higher doses typically needed at the beginning to suppression ACTH then can be lowered - side effect: can impair growth Side note: Mineralocorticoid recommended in all cases classic cases Stress Dosing: Needed in periods of illness with fever, trauma, vomiting and diarrhoea - Mineralocorticoid I.e fluerocortisone don't need to be adjusted - Glucocorticoids I.e. hydrocortisone need increase in dose and frequency for duration of illness Also beware hypoglycemia monitor and treat Increase fluid intake Other therapies: Infertility: Can be rx with glucocorticoid therapy if not responsive consider alternatives like IVF Anti-HPT therapy: for 11Beta OH and 17OH deficiency Anti androgen therapy Sex steroid replacement: sex steroid deficiency cused by CAH oral meds and transdermal patches- this is to induce Puberty, secondary sexual characteristics, ensure Pubertal growth spurt Precocious Puberty: May need GnRh analog

Non Pharmacological (not acute)

- Medi alert bracket - Dietician: Frequncy of feeds and Sodium replacement - Supplement: Bone growth affected by steroids - Vit D and calcium age appropriate may be needed MDT: Counciling and psychology Surgical options: - Cosmetic - Functional: e.g non migrated internal testes

Broadly classify how DSDs happen to a lay person

Broadly - start with the genes: - are you 46 xx, 46 xy or is the problem with the chromosomes. Then If 46 xx - Gonads - did they not develop ie dysgenesis, did they not split Ovitesticular or do you still have SRY gene on X chromosome I.e testicular DSD. Next: Are you gonads fine but you're producing too many androgens - I.e CAH 21 OH and 3 B type Are the androgens not coming from you: I.e maternal excess or tumor, or drugs Are you syndrome For 46 xy: - gonads: dysgenesis ( Sry gene not functioning), ovotesticular or testicular regression - if gonads are fine is there a problem with you synthesising androgens: CAH 17oh and 3 Beta, are the angrogens not being converted into active forms 5 alpha reductase deficiency, is there insensitivity to the adrogens produced - are you syndromic

Causes of 46 Xy DSD

Causes of 46 XX DSD

What is the most common type of DSD in black South africans

Ovotesticular DSD

Classify anatomical qaht type of Ovo lenticular DSDs can occur

Who should be investigated for DSD

Severe hypospadius meaning perinial or penoscrotal esp if paired with something else like undefended testes or micropenis

How would you know labia are viralised?

Hyperpigmentation, rugation, fusion

Normal genital measurements

What on examination and history are you specifically looking for for DSD

Describe two scoring systems which can be used to help gauge degree of under or overvirilisation

Prader virlisation scale or external masculinisation score can be used

How to investigate DSD

1st 24 hours - Bedside: Glucose, Blood pressure, urine dipstix ( looking for proteinnin Congenital nephrotic if oedematous can be associated with Mutation in WAT -1. One of the causes on nephrotic syndrome and DSD) Blood: - electrolytes - Urine: PCR Genetic: - QF PCR (sex chromosomes) - Karyotype- only way to detect mosaism Imaging - Sonar ( renal anatomy, adrenals, testicular/gonadal sites, presence of female internal organs ) Urine steroid profile: not available in SA Testosterone stim test can't do as no B HCG in SA DHT - Not done in SA Often can't get to a final diagnosis in SA

Give a flow or order of investigations for DSD

What types of surgery are available for patients with DSD

Who needs urgent surgery DSD

Basically only if they is malignant potential or potential for loss of function

Who needs urgent surgery DSD

Basically only if they is malignant potential or potential for loss of function