Page 1063 - TNFlipTest

Toronto Notes 2019 Endocrinology Pediatrics P29
Prognosis
• excellentoutcomeiftreatmentstartedwithin1-2moofbirth
• iftreatmentstartedafter3-6moofage,mayresultinpermanentdevelopmentaldelayand/ordisability
(mild to profound), intellectual impairment, poor growth, hearing loss
Sexual Development
AMBIGUOUS GENITALIA
Definition
• newbornorchildwhosegenderisdifficulttoassignbasedontheappearanceofgenitalia
• subtypeofDSD:aconditioninwhichdevelopmentofchromosomal,gonadal,oranatomicsexis
atypical
• subtypes:46,XXDSD,46,XYDSD,ovotesticularDSD(truehermaphrodite)
Epidemiology
• incidenceofgenitalabnormalitiesatbirthisashighas1:300
• prevalenceofcomplexanomalieswithtruesexualambiguitymuchlowerat~1:5,000
Etiology
• 46,XYDSD
■ inborn error of testosterone biosynthesis or Leydig cell hypoplasia
■ 5-α-reductase deficiency, androgen receptor deficiency or insensitivity ■ LH/hCGunresponsiveness
• 46,XXDSD
■ virilizing CAH (most common)
■ maternal source: virilizing ovarian or adrenal tumours, untreated maternal CAH, placental
aromatase deficiency • ovotesticularDSD
■ both ovarian follicles and seminiferous tubules in the same patient with a 46,XX karyotype ■ mixed gonadal dysgenesis
Risk Factors
• parentalconsanguinity,positivefamilyhistoryofambiguousgenitalia,earlychildhoodillness/death,or primary amenorrhea, maternal medications during pregnancy (e.g. androgens, progesterones, danazol, phenytoin, aminoglutethimide, endocrine disruptors)
Clinical Presentation
• history
■ thorough obstetrical history, including prenatal screens and maternal medications
■ family history: autosomal recessive pattern may suggest CAH, X-linked recessive pattern may
suggest androgen insensitivity syndrome • physicalexam
■ male pseudohermaphrodite (XY): small phallus, hypospadias, undescended testicles
■ female pseudohermaphrodite (XX): clitoral hypertrophy, labioscrotal fusion
■ look for concurrent midline defects, dysmorphic features, and congenital abnormalities
• investigations
■ karyotype and genetic workup as indicated
■ blood work: electrolytes and renin (evidence of salt-wasting in CAH); 17-OH-progesterone,
androgens, FSH, and LH
■ imaging: abdominal U/S to look for uterus, testicles, ovaries
Management
• avoidannouncementofprobablesexoruseofpersonalpronounsuntilalltestsarecomplete • continuouspsychosocialsupportforparentsandchildduringdevelopment
• electivesurgicalreconstructionofgenitaliaissometimespossible
CONGENITAL ADRENAL HYPERPLASIA
Definition
• autosomalrecessivedisordercharacterizedbythepartialortotaldefectofvarioussyntheticenzymes required for cortisol and aldosterone production in the adrenal cortex
■ adrenal cortex normally produces balanced levels of aldosterone, cortisal and androgens
Epidemiology
• occursin~1:15,000livebirths
• mostcommoncauseofambiguousgenitaliaingenotypicallynormalfemales(46XX)
Etiology
• forbiosyntheticpathwaysofadrenalcortex,seeEndocrinology,E30
• 21-OHresponsiblefor~95%ofCAHcases
• results in i cortisol and aldosterone production with shunting toward hh androgens • cortisoldeficiencyleadstoelevatedACTH,whichcausesadrenalhyperplasia
• rarercausesincludedeficienciesin11-OH,cholesteroldesmolase,17-OH,and3-HSD