Adrenal gland & paraganglia


Anatomy & history-adrenal medulla & paraganglia

Last author update: 1 April 2013
Last staff update: 7 March 2023

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PubMed Search: Adrenal medulla histology physiology

Severino Rey Nodar, M.D., Ph.D.
Pallav Gupta, M.D.
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Cite this page: Nodar SR, Gupta P. Anatomy & history-adrenal medulla & paraganglia. website. Accessed March 30th, 2023.
Definition / general
  • Synthesizes and secretes primarily catecholamines (norepinephrine and epinephrine) in response to signals from preganglionic nerve fibers in sympathetic nervous system
Essential features
  • Region with basophilic staining cells with granular cytoplasm and no stored lipid
  • Composed of neural crest cells called chromaffin cells (also called pheochromocytes, medullary cells) with a multilineage differentiation potential
  • Produces catecholamines (norepinephrine and epinephrine)
Anatomy - adrenal medulla
  • 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, it is 4 times kidney but at birth, weighs 5 grams and is only one - third the size of the kidney due to rapid regression of inner cortex
  • At age 1 year, almost completely disappears but by 4 - 5 years, the permanent adult type adrenal cortex has fully developed
  • References: Endocr Rev 2011;32:317, Endocr Dev 2008;13:19, Endocr Res 1998;24:919
  • Chromaffin cells: take up chromium salts strongly, turn brown-black after exposure to Zenker solution (potassium dichromate), produce catecholamines
  • Norepinephrine: local transmitter, chiefly of sympathetic postganglionic neurons
  • Epinephrine: systemic transmitter, interacts with alpha and beta adrenergic receptors
  • Innervated by axons from lower thoracic and lumbar preganglionic neurons via splanchnic nerves
  • Dopamine, which is precursor of norepinephrine, is found in adrenal medulla and peripheral sympathetic nerves and acts as a neurotransmitter in CNS
  • Catecholamines affect cardiovascular and metabolic processes, causing increase in heart rate, blood pressure, myocardial contractility and cardiac conduction velocity (Melmed: Williams Textbook of Endocrinology, 12th Edition, 2011)
  • Neural crest origin
  • Paraganglion system is formed by neuroepithelial chief cells scattered throughout the body in 3 chains (branchiomeric, intravagal, aorticosympathetic), associated with the sympathetic (epinephrine secreting) or parasympathetic (norepinephrine secreting) nervous system
    • Also present in viscera
  • Sympathetic paraganglia are paravertebral and paraaortic
    • Parasympathetic are in head and neck
  • Terminology based on site of origin, not secretory products
  • Chief cells are arranged in well defined nests (zellballen) surrounded by rim of sustentacular cells
  • Chief cells have cytoplasmic neurosecretory granules containing catecholamines
    • Cannot determine function of cells by their appearance
  • Called chromaffin cells because they stain yellow-brown with chromium salts
  • Adrenal medulla is considered part of paraganglion system
Paraganglia terminology
  • Branchiomeric chain:
    • Associated with parasympathetic nervous system, along jugular vein, vagus and larynx
  • Intravagal chain:
    • Associated with parasympathetic nervous system
    • Distributed along vagus nerve
  • Aorticosympathetic chain:
    • Associated with sympathetic nervous system
    • Along abdominal aorta
  • Organ of Zuckerkandl:
    • Between renal artery and aortic bifurcation, part of aorticosympathetic group
    • First described by Emil Zuckerkandl in 1901 (University of Vienna)
    • May maintain blood pressure in early fetal life, involutes after eighth month of gestation
  • Visceral paraganglia:
    • Within bladder, other organs
  • Carotid body paraganglia:
    • Part of branchiomeric system
    • Small ovoid structure on medial side of carotid bifurcation bilaterally
    • Mean total weight is 12 mg
    • Chemoreceptors that respond to changes in arterial O2, CO2 and pH
  • Glomus coccygeum:
    • Also called Luschka's gland
    • Small (2.5 mm), ovoid vascular structure near tip of coccyx
    • Composed of epithelioid cells in layers around vascular channels
    • No known function
Diagrams / tables

Images hosted on other servers:

Synthesis of catecholamines

Microscopic (histologic) description
  • Chromaffin cells:
    • Arranged in small nests and cords separated by prominent vasculature
    • Large polygonal cells with poorly outlined borders
    • Abundant granular and usually basophilic cytoplasm
    • Mild variation in cell size
    • Occasionally has PAS+ hyaline droplets
  • Sustentacular cells:
    • Supporting spindle cells at periphery of nests of chromaffin cells
    • Associated with rich vasculature
    • Difficult to identify with routine staining
  • Ganglion cells:
    • Occasional single cells or small clusters associated with myelinated nerve bundles
  • Vasculature:
    • Central vein has thick wall of smooth muscle
    • Also many venous channels which drain blood from cortical sinusoids, pass through medulla to drain into medullary vein
Microscopic (histologic) images

Contributed by Debra Zynger, M.D. and Grigory Demyashkin, M.D., Ph.D.

Basophilic cells

Nested architecture

Left: metanephros; right: adrenal gland medulla

Left: metanephros; right: adrenal gland medulla

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

Images hosted on other servers:
Missing Image

Carotid bodies

Missing Image

Glomus coccygeum

Positive stains
Electron microscopy description
  • Numerous mitochondria
  • Norepinephrine producing cells have 250 nm electron opaque neurosecretory granules, with prominent halo between granule membrane and dense core
  • Epinephrine producing cells have 190 nm finely granular neurosecretory granules, filling the enclosing membrane and no halo
  • Moderate amount of rough endoplasmic reticulum, interdigitating blunt cytoplasmic processes with poorly developed cell junctions
  • Sustentacular cells have moderate amounts of rough endoplasmic reticulum and occasional lipid droplets but no neurosecretory granules
Board review style question #1
    Which of the following is expressed in the adrenal medulla? 

  1. Chromogranin and GATA3
  2. CK7 and CK20
  3. Inhibin and calretinin
  4. MelanA and SF1
Board review style answer #1
A. Chromogranin and GATA3. Inhibin, calretinin, MelanA and SF1 are expressed in the adrenal cortex but not the adrenal medulla. CK7 and CK20 are not expressed in the adrenal medulla or adrenal cortex.

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