TY  - CHAP
M1  - Book, Section
TI  - Congenital Adrenal Hyperplasia
A1  - Donohoue, Patricia A.
A1  - Parker, Keith L.
A1  - Migeon, Claude J.
A2  - Valle, David L.
A2  - Antonarakis, Stylianos
A2  - Ballabio, Andrea
A2  - Beaudet, Arthur L.
A2  - Mitchell, Grant A.
PY  - 2019
T2  - The Online Metabolic and Molecular Bases of Inherited Disease
AB  - Congenital  adrenal  hyperplasia  (CAH,  MIM  300200)  is  a  group  of  diseases  whose  common  feature  is  an  enzymatic  defect  in  the  steroidogenic  pathway  leading  to  the  biosynthesis  of  cortisol.  This  relative  decrease  in  cortisol  production  causes  an  increase  in  adrenocorticotropic  hormone  (ACTH)  secretion  and  consequent  hyperplasia  of  the  adrenal  cortex.  All  forms  of  CAH  are  inherited  in  an  autosomal  recessive  manner.  The  variable  phenotypes  are  determined  by  the  effects  produced  by  deficient  hormones  and  by  excess  production  of  steroids  unaffected  by  the  enzymatic  block.The  biochemical  pathways  of  adrenal  steroid  production  are  interrelated.  The  three  zones  of  the  adrenal  cortex  produce  three  classes  of  steroid  hormones:  glucocorticoids  and  androgens  (zona  fasciculata/reticularis)  and  mineralocorticoids  (zona  glomerulosa).  All  but  one  of  the  enzymatic  steps  are  mediated  by  members  of  the  cytochrome  P450  (CYP)  family  of  mixed-function  oxidases.  The  first  step  in  the  production  of  all  steroid  hormones,  mediated  by  CYP11A,  is  the  conversion  of  cholesterol  to  pregnenolone.  Pregnenolone  may  then  be  acted  on  by  CYP17  to  form  17-hydroxypregnenolone  and  then  dehydroepiandrosterone  (DHEA),  or  it  may  be  converted  to  progesterone  by  the  non-P450  enzyme  3β-hydroxysteroid  dehydrogenase  (3β-HSD).  3β-HSD  also  converts  17-hydroxypregnenolone  to  17-hydroxyprogesterone  and  DHEA  to  androstenedione,  an  androgen  precursor.  Progesterone  and  17-hydroxyprogesterone  are  then  converted  by  CYP21  to  11-deoxycorticosterone  (a  mineralocorticoid)  and  11-deoxycortisol,  respectively.  These  two  products  are  then  converted  by  CYP11B1  to  corticosterone  and  cortisol  (the  major  glucocorticoid),  respectively.  Aldosterone,  the  major  mineralocorticoid,  is  produced  from  corticosterone  by  the  enzyme  CYP11B2  (aldosterone  synthase).Control  of  adrenal  steroid  production  is  multifaceted.  Glucocorticoid  production  is  stimulated  primarily  by  the  anterior  pituitary  hormone  ACTH,  which  itself  is  controlled  by  the  hypothalamic  corticotropin-releasing  hormone  (CAH).  Aldosterone  secretion  is  modulated  by  the  renin-angiotensin  system.  Adrenal  androgen  secretion  is  stimulated  by  excessive  ACTH,  but  physiologic  control  is  through  an  unidentified  factor.In  keeping  with  their  different  physiologic  regulations,  the  secretion  rates  of  the  various  adrenocortical  hormones  vary  independently.  The  cortisol  secretion  rate  is  approximates  12  mg/m2  of  body  surface  area  per  day.  This  rate  is  somewhat  higher—but  quite  variable—in  newborn  infants  and  significantly  higher  during  periods  of  physiologic  stress,  such  as  fever  and  surgery.  The  aldosterone  secretion  rate  (approximately  100  μg/day)  remains  fairly  constant  throughout  life.  Adrenal  androgen  secretion  is  quite  low  during  infancy  and  childhood  and  increases  gradually  to  maximal  levels  during  puberty  and  early  adulthood,  with  age-related  declines  thereafter.21-Hydroxylase  (CYP21)  deficiency  is  the  most  common  form  of  CAH,  accounting  for  over  90  percent  of  cases.  The  incidence  varies  from  1  in  10,000  to  18,000  live  births.  There  is  a  continuum  of  degrees  of  CYP21  deficiency  that  results  in  a  continuum  of  severity  of  clinical  presentations.  The  most  marked  deficiency  results  in  the  salt-losing  form  of  CAH,  characterized  by  both  mineralocorticoid  and  glucocorticoid  deficiencies.  The  steroid  precursors  prior  to  the  enzymatic  block  (progesterone  and  17-hydroxyprogesterone)  accumulate  due  to  excessive  ACTH  stimulation  of  the  gland  and  are  shunted  into  the  androgen  biosynthetic  pathway,  which  is  unaffected  by  the  block.  The  resulting  androgen  excess  produces  prenatal  masculinization  (ambiguous  genitalia)  in  females  and  postnatal  virilization  in  both  sexes.  In  the  simple  virilizing  form,  milder  CYP21  ...
SN  - 
PB  - McGraw-Hill Education
CY  - New York, NY
Y2  - 2024/04/17
UR  - ommbid.mhmedical.com/content.aspx?aid=1170104139
ER  -