feminizing genitoplasty in cah patients

Feminizing Feminizing genitoplastygenitoplasty

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Normal Sexual Differentiation has 3 Normal Sexual Differentiation has 3 stages:stages:

1.1.Establishment of chromosomal sexEstablishment of chromosomal sex

2.2.Development of the undifferentiated Development of the undifferentiated gonadsgonads

3.3.Differentiation of internal ducts & Differentiation of internal ducts & genitaliagenitalia

IntroductionIntroduction

Normal Sexual Normal Sexual DifferentiationDifferentiation

Genital Ridge

Bipotential Gonad

SF-1

SF-1Ovary

Follicular Cells

Theca Cells

Follicles

Mullerian Duct

Female Genitalia

Leydig Cells

Sertoli Cells

SF-1

SF-1

Testosterone

AMH

Testis

Mullerian Duct Regression

Wolffian Duct

GenitalTubercle

UrogenitalSinus

MaleInternal Genitalia

PenisProstate

DHT

The Big PictureThe Big Picture……

Ovarian cords develop in the absence Ovarian cords develop in the absence of SRYof SRY2 X Chromosomes are necessary for 2 X Chromosomes are necessary for normal development (ovarian normal development (ovarian dysgenesis in 45 XO)dysgenesis in 45 XO)They appear to differentiate granulosa They appear to differentiate granulosa cells into the protective granulosa cell cells into the protective granulosa cell layerlayerGerm cells undergo exhaustive mitosis Germ cells undergo exhaustive mitosis creating 20 million cells by 20 weekscreating 20 million cells by 20 weeks

Ovarian DifferentiationOvarian Differentiation

Oestrogen synthesis is Oestrogen synthesis is detectable at 8 weeksdetectable at 8 weeksOestrogens are NOT necessary Oestrogens are NOT necessary for normal female differentiation for normal female differentiation but in males, they can inhibit the but in males, they can inhibit the effects of MIS on Mullerian tissue effects of MIS on Mullerian tissue

Gonadal Function - OvaryGonadal Function - Ovary

It all starts with the Y chromosomeIt all starts with the Y chromosome……

FemaleFemaleWolffian ducts regress due to lack of testosteroneWolffian ducts regress due to lack of testosteroneMullerian ducts grow in the absence of MISMullerian ducts grow in the absence of MISCephalic end forms Fallopian tubesCephalic end forms Fallopian tubesCaudal end fuses to form the UterusCaudal end fuses to form the UterusMeets the Urogenital sinus to form the Uterovaginal Meets the Urogenital sinus to form the Uterovaginal plate and ultimately the vaginal lumenplate and ultimately the vaginal lumen

Phenotypic DifferentiationPhenotypic Differentiation

FemaleFemale

Genital tubercle develops into the clitorisGenital tubercle develops into the clitorisGenital swellings become the labia majoraGenital swellings become the labia majoraUrethral folds become the labia minoraUrethral folds become the labia minoraThe Introitus develops between the urethral The Introitus develops between the urethral foldsfolds

Phenotypic DifferentiationPhenotypic Differentiation

Abnormal Sexual DevelopmentAbnormal Sexual Development

Virilised FemalesVirilised Females 46 XX, normal ovaries, internal genitalia46 XX, normal ovaries, internal genitalia Varying degrees virilisation Varying degrees virilisation –– depends on time, depends on time,

amount of androgen exposureamount of androgen exposure Early Early –– retention of urogenital sinus, retention of urogenital sinus,

labioscrotal fusionlabioscrotal fusion Later Later –– clitoral hypertrophy clitoral hypertrophy MMüüllerian duct differentiationllerian duct differentiation normalnormal CAUSESCAUSES::

Fetal androgens - Congenital Adrenal Hyperplasia Fetal androgens - Congenital Adrenal Hyperplasia (CAH)(CAH)

Maternal androgens Maternal androgens –– anabolic steroids, Danazol, anabolic steroids, Danazol, ovarian / adrenal tumoursovarian / adrenal tumours

Syndromes Syndromes ––Beckwith-WiedemannBeckwith-Wiedemann IdiopathicIdiopathic

Congenital Adrenal Hyperplasia (CAH)Congenital Adrenal Hyperplasia (CAH)

Constitutes 60% of Constitutes 60% of allall intersex cases in literature (however intersex cases in literature (however in South Africa true hermaphroditism is dominant)in South Africa true hermaphroditism is dominant)

Possible medical emergencyPossible medical emergency Results from block in steroid synthesis pathway Results from block in steroid synthesis pathway –– excess of excess of

precursors, deficiency of end-productprecursors, deficiency of end-product Decreased negative feedback Decreased negative feedback –– increased ACTH increased ACTH –– adrenal adrenal

hyperplasia, pigmentationhyperplasia, pigmentation Manifestations depend on level of blockManifestations depend on level of block 90% of cases 90% of cases –– 21 Hydroxylase deficiency 21 Hydroxylase deficiency

Salt-wasting, hyperkalaemia, hypotension, vascular collapseSalt-wasting, hyperkalaemia, hypotension, vascular collapse Autosomal recessiveAutosomal recessive

An approach to the newborn An approach to the newborn DSDDSD

History & Physical examinationHistory & Physical examination

Biochemical studiesBiochemical studies

ElectrolytesElectrolytes

1717 OH progesteroneOH progesterone

Genetic evaluationGenetic evaluation

KaryotypeKaryotype

FISH for SRY geneFISH for SRY gene

Radiographic studiesRadiographic studies

U/SU/S

GenitogramGenitogram

LaparoscopyLaparoscopy

Gonadal biopsyGonadal biopsy??

Physical examinationPhysical examination

• •Measurement of genitaliaMeasurement of genitalia- Micropenis: <2 cm- Micropenis: <2 cm

Clitoromegaly: >1 cmClitoromegaly: >1 cm - -

- Gonad palpation- Gonad palpation

FedermanFederman’’s rule: a palpable gonad below the inguinal s rule: a palpable gonad below the inguinal ligament is testes until proven otherwisligament is testes until proven otherwis

Physical examinationPhysical examination

Bilateral palpable, descended gonadsBilateral palpable, descended gonadsmost likelymost likely hypospadias hypospadias

Unilateral nonpalpable testesUnilateral nonpalpable testesmost likelymost likely gonadal dysgeneis gonadal dysgeneis

Bilateral nonpalpable gonadsBilateral nonpalpable gonadsmost likelymost likely CAH CAH

DSD Team ParticipantsDSD Team Participants

Medical GeneticsMedical Genetics

Pediatric UrologyPediatric Urology

Pediatric EndocrinologyPediatric Endocrinology

NeonatologistNeonatologist

Pediatric GynecologyPediatric Gynecology

Pediatric PsychologyPediatric Psychology

NurseNurse

Medical EthisicitMedical Ethisicit

Social WorkerSocial Worker

Prader ClassificationPrader Classification

Preoperative preparationPreoperative preparation

Hormonal treatment and endocrine Hormonal treatment and endocrine consultationconsultation

Genitography Genitography Endoscopy either before or at the Endoscopy either before or at the

time of definitive repair:time of definitive repair:Length of the urogenital sinusLength of the urogenital sinusIntroduction of urethral and vaginal Introduction of urethral and vaginal

catheterscatheters

ENDOSCOPYENDOSCOPY

surgerysurgery

AgeAge

What is the proper time for repair?What is the proper time for repair?3-9 months (1st year of life)3-9 months (1st year of life)

Do we wait till puberty?Do we wait till puberty?Controversial issueControversial issue

CLITOROPLASTYCLITOROPLASTY

- Corporeal body excisionCorporeal body excision- Neurovascular bundle conservationNeurovascular bundle conservation- Ligation of both proximal ends of Ligation of both proximal ends of

erectile tissueerectile tissue- Excision of a ventral wedge for Excision of a ventral wedge for

reduction glanuloplastyreduction glanuloplasty

LabioplastyLabioplasty

Surgical correction of low Surgical correction of low confluenceconfluence

Cutback vaginoplasty:Cutback vaginoplasty:- Performed in patients with labial Performed in patients with labial

fusionfusion- Incision of the skin in midline Incision of the skin in midline

posteriorly to the perineum to posteriorly to the perineum to expose the vaginal orificeexpose the vaginal orifice

- The incised lateral edges are The incised lateral edges are oversewnoversewn

Flap vaginoplasty:Flap vaginoplasty:- In low confluence UGS- Inverted U skin incision- Sutured to the vagina after opening

the UGS posteriorly- Alone, not a solution- Should be ass. With mobilization

Surgical correction of the Surgical correction of the high confluencehigh confluence

Pull-through vaginoplasty- Inverted U incision- Dissection till vaginal catheter is

encountered- Division of the vagina at its entrance

to the sinus& mobilized extensively- Closure of UGS & used as a

functional urethra

Monfort transtrigonal approachMonfort transtrigonal approach- Midline incision in the posterior wall Midline incision in the posterior wall

of the urinary bladderof the urinary bladder- In very high lesionsIn very high lesionsPosterior sagittal approachPosterior sagittal approach- In cloacal anomaliesIn cloacal anomalies- High UGS High UGS

COMPLEX FLAPSCOMPLEX FLAPS

Gonzalez:Gonzalez:- Flaps of phallic skin to construct the Flaps of phallic skin to construct the

distal vaginadistal vaginaPassereni:Passereni:- Distal UGS anteriorly opened to Distal UGS anteriorly opened to

construct the distal vaginaconstruct the distal vaginaRink:Rink:

- Lateral incision of UGS with spiral - Lateral incision of UGS with spiral construction of the distal vaginaconstruction of the distal vagina

Total UGS mobilizationTotal UGS mobilization

Vaginal replacement

Skin graft:Skin graft:- From thighFrom thigh- ContractureContracture- Needs lubricantNeeds lubricant- Split thickness or full thicknessSplit thickness or full thickness- Daily dilatationDaily dilatation

Rotational flaps:Rotational flaps:- Gracilis myocutaneous flapsGracilis myocutaneous flaps- Pudendal thigh flapsPudendal thigh flaps- Labia minora flapsLabia minora flaps- Flaps after tissue expantionFlaps after tissue expantion

Bowel vaginaBowel vagina- Better than skinBetter than skin- Sigmoid colon is preferedSigmoid colon is prefered- May use ileumMay use ileum

Medico legal aspectMedico legal aspect