• 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

• 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 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 child’s adrenal becomes more like adult adrenal

Fetal and adult cortex

• Endocr Rev 2011;32:317, Endocr Dev 2008;13:19, Endocr Res 1998;24:919

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