Normal male external genitalia do not rule out CYP11A1 deficiency

BMJ Case Rep. 2019 Jul 8;12(7):e228235. doi: 10.1136/bcr-2018-228235.


Defects in the initial steps of steroidogenesis usually present with female external genitalia in both 46,XX and 46,XY. Hence, they are not often considered in the differential diagnosis of primary adrenal insufficiency children with normal male external genitalia. Here, we report a boy with normal male external genitalia who presented with hyperpigmentation since the age of 2 years but diagnosis was delayed till 11 years of age. Evaluation revealed low-serum cortisol with elevated adrenocorticotropic hormone and direct renin level confirming primary adrenal insufficiency. Clinical exome sequencing analysis revealed a homozygous c.1351C>T (p.R451W) mutation in exon 8 of the CYP11A1 gene which was confirmed on Sanger sequencing. Both parents were heterozygous for the variation. To conclude, we report the first case of CYP11A1 deficiency from India. The report reiterates the existence of non-classic CYP11A1 deficiency characterised by primary adrenal insufficiency and normal male external genitalia in 46,XY.

Keywords: adrenal disorders; thyroid disease.

Publication types

  • Case Reports

MeSH terms

  • Addison Disease / blood
  • Addison Disease / diagnosis*
  • Addison Disease / drug therapy
  • Addison Disease / genetics*
  • Adrenal Cortex Hormones / therapeutic use
  • Child
  • Cholesterol Side-Chain Cleavage Enzyme / deficiency*
  • Cholesterol Side-Chain Cleavage Enzyme / genetics*
  • Exome Sequencing
  • Genitalia, Male
  • Homozygote
  • Humans
  • Hyperpigmentation / diagnosis
  • Hyperpigmentation / etiology
  • India
  • Male
  • Mutation
  • Treatment Outcome


  • Adrenal Cortex Hormones
  • Cholesterol Side-Chain Cleavage Enzyme