Adrenal gland and paraganglia

Author: Severino Rey Nodar, M.D., Ph.D. (see Authors page)

Revised: 8 August 2017, last major update March 2013

Copyright: (c) 2002-2017,, Inc.
Cite this page: Embryology. website. Accessed November 20th, 2018.
Definition / general
  • Adrenal medulla and cortex have different embryonic origins
  • Adrenal medulla (inner core) originates from neural crest; has large eosinophilic cells mixed with small nodules of primitive neuroblastic cells; represents 75% of cortical volume at birth, but then involutes due to apoptosis with only stroma present by one year; mesenchyme surrounding these cells differentiates to form an outer adrenal cortex, which is later replaced by adult cortex
  • The outer adrenal cortex is derived from mesothelium and is further divided into 3 distinct layers (zona reticularis, zona fasiculata, zona glomerulosa), each with distinct hormonal functions
  • Premature, stillborn and some neonates with in utero stress have microscopic cystic changes in adrenal glands

  • By day 25 of gestation, bilateral adrenal primordium develops as cords of large polyhedral cells in coelomic epithelium medial to mesonephros and urogenital ridge
  • By day 45, adrenal glands enlarge to 1 mg, and primitive sympathetic cells with nerve tracts migrate to form medulla
  • By week 7, paraganglionic cells replicate and differentiate into chromaffin cells; primitive sympathicoblasts form neuroblastic nodules that peak at weeks 17-20 and usually regress; persistent nodules may be confused with small neuroblastomas
  • By week 8, each gland weighs 4 mg, with outer (definitive) cortex distinct from inner (fetal) cortex
  • From week 8-9, adrenal cortex synthesizes cortisol and is maximal at 8-9 weeks post conception under the regulation of ACTH (also stimulates androstenedione and testosterone secretion)

  • Fetal adrenal gland is relatively large: at week 18, is 4x kidney, but at birth, weighs 5 grams and is only 1/3 size of kidney due to rapid regression of inner cortex
  • At age 1 year, almost completely disappears, but by age 4-5 years, the permanent adult-type adrenal cortex has fully developed

Anatomic anomalies
  • Agenesis of an adrenal gland is usually associated with ipsilateral agenesis of kidney
  • Fused adrenal glands (2 glands join across midline posterior to aorta) are also associated with a fused kidney
  • Adrenal hypoplasia occurs as hypoplasia / absence of fetal cortex with a poorly formed medulla or as disorganized fetal cortex and medulla with no permanent cortex present
  • Adrenal heterotopia describes a normal adrenal gland in an abnormal location
  • Congenital Adrenal Hyperplasia is a family of inherited disorders of adrenal steroidogenesis enzymes which impairs cortisol production by adrenal cortex

Placenta and adrenal gland
  • Placenta and fetal adrenal work together to meet fetal steroidogenic needs
  • Placenta makes progesterone, which fetal cortex converts to cortisol, which triggers type II cell development and surfactant production in lungs
  • Fetal adrenal supplies substrates for placental estrogen synthesis
  • After birth, placental connection is lost, and childs adrenal becomes more like adult adrenal
Microscopic (histologic) images

Images hosted on PathOut server:

Contributed by Dr. Grigory Demyashkin, I. M. Sechenov First Moscow State Medical University (Russia) - 6-8 week embryo:

Left: metanephros; right: adrenal gland medulla

Left: metanephros; right: adrenal gland medulla

Center: adrenal gland, medulla & final kidney (metanephros)