Adrenal gland

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A drawing of the adrenal glands.

Adrenal gland is a little organ that hangs-out above the kidney. Pathologists rarely see it. It uncommonly is affected by tumours.

Anatomy & histology

Adrenal cortical rest redirects here.


  • Cortex.
  • Medulla.


  • Adrenal tissue may be associated with gonads or between gonads and adrenal gland proper.[1]


It is composed of a cortex and a medulla.


It has three layers - mnemonic: GFR (from superficial to deep):

  1. Zona glomerulosa - salt (e.g. aldosterone).
    • Eosinophilic cytoplasm. (???)
    • Layer normally discontinuous.
  2. Zona fasciculata - sugar (e.g. cortisol).
    • Clear cytoplasm - key feature.
    • Largest part of the cortex ~ 70%.
    • Cells in cords/nests. (???)
  3. Zona reticularis - steroid (e.g. dehydroepiandrosterone).
    • Marked eosinophilia of cytoplasm - key feature.
    • Granular/reticular cytoplasm.


  • Normal cortex may not be completely encapsulated, i.e. the adrenal capsule may have defects.[2]
    • In other words: the cortex may "spill" into the surrounding fat.


It consists of two cell types:[3]

  1. Chromaffin cells.
    • Arise of neural crest.
  2. Sustentacular cells (supporting cells).

Produce NED: norepinephrine, epinephrine, dopamine.



Adrenal cortex:[4]

  • Chromogranin A -ve.
  • Synaptophysin +ve.
  • Alpha-inhibin +ve.
  • Vimentin +ve.
  • Melan A +ve.
  • AE1/AE3 -ve.
  • RCC -ve (0 +ve of 63 cases[5]).
  • EMA -ve (0 +ve of 63 cases[5]).

A panel that may be useful for adenoma versus carcinoma:[6][7]

  • Beta-catenin, p53, reticulin, inhibin, melan A, Ki-67.


Patients getting a bilateral adrenalectomy get pre-treatment with steroids.[8]

Adrenal insufficiency is an immediate danger post-op.[9]


The section covers non-neoplastic pathologies of the adrenal gland. These uncommonly come to the pathologist.

  • Adrenal incidentalomas[10]
    • Adrenal tumors
    • Greater than 1 cm
    • Identified on imaging performed for other indications
  • Found in up to 10% of patients undergoing abdominal imaging.
  • Management problematic
    • Guidelines incorporate lesion size, functional status and imaging features.
    • Resection is generally advocated for
      • Functioning lesions.
      • Radiographic features suggestive of malignancy.
      • Growth during observation.

Stress response

Spironolactone bodies

Hemorrhagic adrenalitis

  • AKA Waterhouse-Friderichsen syndrome.


  • Classically thought to be only due to Neisseria meningitidis; however, more recently also associated with Staphylococcus aureus,[12] and Streptococcus pneumoniae.[13]



  • Massive haemorrhage within the substance of the adrenal gland.

DDx (autopsy):

  • Post-mortem changes.



  • Massive haemorrhage within the substance of the adrenal gland.

Image: Haemorrhage in adrenal (

Adrenal cytomegaly

  • AKA adrenocortical cytomegaly.
  • AKA adrenal gland with cytomegaly.


May be associated with:[14]



  • Large cells in the adrenal cortex.[15]

Addison disease


  • Chronic adrenocortical insufficiency.


  • Brown skin - due POMC (a precursor of ACTH and melanocyte stimulating hormone (MSH)).[16]
  • Hypotension.
  • Nausea and vomiting.



  • Secondary adrenocortical insufficiency (due to pituitary pathology):[18]
    • No hyperpigmentation (as no POMC).
    • Aldosterone usu. normal.



  • Atrophy adrenal cortex - specifically zona fasciculata and zona reticularis.


  • There is preservation of zona glomerulosa and medulla.

Benign neoplasms

Adrenal hemangioma

Radiographic incidentalomas but may be large and calcified raising a radiographic ddx of adrenal cortical carcinoma.

  • Rare.
  • 40 and 70 years.
  • 2:1 female-to-male ratio

Adrenal cortical adenoma


Adrenal ganglioneuroma



  • Solid.
  • White.
  • Firm.
  • Well-circumscribed.
  • May be nodular.

DDx (gross):




  • Ganglion cells - key feature.
    • Large cells with large nucleus.
      • Prominent nucleolus.
  • Disordered fibrinous material.


Adrenal myelolipoma

Adenomatoid tumour

See: Adenomatoid tumours (uterine tumours).

Malignant neoplasms

Adrenocortical carcinoma

  • AKA adrenal cortical carcinoma.
  • Abbreviated ACC.


See also


  1. Barwick, TD.; Malhotra, A.; Webb, JA.; Savage, MO.; Reznek, RH. (Sep 2005). "Embryology of the adrenal glands and its relevance to diagnostic imaging.". Clin Radiol 60 (9): 953-9. doi:10.1016/j.crad.2005.04.006. PMID 16124976.
  2. Mills, Stacey E. (2012). Histology for Pathologists (4th ed.). Lippincott Williams & Wilkins. pp. 1236. ISBN 978-1451113037.
  3. Kumar, Vinay; Abbas, Abul K.; Fausto, Nelson; Aster, Jon (2009). Robbins and Cotran pathologic basis of disease (8th ed.). Elsevier Saunders. pp. 1159. ISBN 978-1416031215.
  4. De Padua, M.; Rajagopal, V. (May 2008). "Myxoid adrenal adenoma with focal pseudoglandular pattern.". Indian J Med Sci 62 (5): 199-203. PMID 18579979.
  5. 5.0 5.1 Sangoi, AR.; Fujiwara, M.; West, RB.; Montgomery, KD.; Bonventre, JV.; Higgins, JP.; Rouse, RV.; Gokden, N. et al. (May 2011). "Immunohistochemical distinction of primary adrenal cortical lesions from metastatic clear cell renal cell carcinoma: a study of 248 cases.". Am J Surg Pathol 35 (5): 678-86. doi:10.1097/PAS.0b013e3182152629. PMID 21490444.
  6. Kovach, AE.; Nucera, C.; Lam, QT.; Nguyen, A.; Dias-Santagata, D.; Sadow, PM.. "Genomic and immunohistochemical analysis in human adrenal cortical neoplasia reveal beta-catenin mutations as potential prognostic biomarker.". Discoveries (Craiova) 3 (2). doi:10.15190/d.2015.32. PMID 26317117.
  7. Arola, J.; Salmenkivi, K.; Liu, J.; Kahri, AI.; Heikkilä, P. (Nov 2000). "p53 and Ki67 in adrenocortical tumors.". Endocr Res 26 (4): 861-5. PMID 11196463.
  8. URL: Accessed on: 21 August 2010.
  9. URL: Accessed on: 21 August 2010.
  10. Aljabri, KS.; Bokhari, SA.; Alkeraithi, M.. "Adrenal hemangioma in a 19-year-old female.". Ann Saudi Med 31 (4): 421-3. doi:10.4103/0256-4947.76411. PMID 21293064.
  11. Becker MJ, Becker AE (September 1976). "Fat distribution in the adrenal cortex as an indication of the mode of intrauterine death". Hum. Pathol. 7 (5): 495–504. PMID 964978.
  12. Adem PV, Montgomery CP, Husain AN, et al. (September 2005). "Staphylococcus aureus sepsis and the Waterhouse-Friderichsen syndrome in children". N. Engl. J. Med. 353 (12): 1245–51. doi:10.1056/NEJMoa044194. PMID 16177250.
  13. Hamilton D, Harris MD, Foweraker J, Gresham GA (February 2004). "Waterhouse-Friderichsen syndrome as a result of non-meningococcal infection". J. Clin. Pathol. 57 (2): 208–9. PMC 1770213. PMID 14747454.
  14. URL: Accessed on: 3 January 2012.
  15. 15.0 15.1 Aterman, K.; Kerenyi, N.; Lee, M. (1972). "Adrenal cytomegaly.". Virchows Arch A Pathol Pathol Anat 355 (2): 105-22. PMID 4336262.
  16. 16.0 16.1 Kumar, Vinay; Abbas, Abul K.; Fausto, Nelson; Aster, Jon (2009). Robbins and Cotran pathologic basis of disease (8th ed.). Elsevier Saunders. pp. 1157. ISBN 978-1416031215.
  17. Kumar, Vinay; Abbas, Abul K.; Fausto, Nelson; Aster, Jon (2009). Robbins and Cotran pathologic basis of disease (8th ed.). Elsevier Saunders. pp. 1155. ISBN 978-1416031215.
  18. Mitchell, Richard; Kumar, Vinay; Fausto, Nelson; Abbas, Abul K.; Aster, Jon (2011). Pocket Companion to Robbins & Cotran Pathologic Basis of Disease (8th ed.). Elsevier Saunders. pp. 585. ISBN 978-1416054542.