Difference between revisions of "Adrenal gland"

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*Cortex.
*Cortex.
*Medulla.
*Medulla.
Note:
*Adrenal tissue may be associated with gonads or between gonads and adrenal gland proper.<ref>{{Cite journal  | last1 = Barwick | first1 = TD. | last2 = Malhotra | first2 = A. | last3 = Webb | first3 = JA. | last4 = Savage | first4 = MO. | last5 = Reznek | first5 = RH. | title = Embryology of the adrenal glands and its relevance to diagnostic imaging. | journal = Clin Radiol | volume = 60 | issue = 9 | pages = 953-9 | month = Sep | year = 2005 | doi = 10.1016/j.crad.2005.04.006 | PMID = 16124976 }}</ref>


===Microscopic===
===Microscopic===
Line 39: Line 42:
<gallery>
<gallery>
Image:Adrenal_gland_(medulla).JPG | Adrenal medulla. (WC)
Image:Adrenal_gland_(medulla).JPG | Adrenal medulla. (WC)
Image:Adrenal_cortical_carcinoma_-_low_mag.jpg | Adrenal cortex, medulla and tumour. (WC/Nephron)
Image:Adrenal_cortical_carcinoma_-_low_mag.jpg | Adrenal cortex & medulla (right of image), and tumour (left of image). (WC/Nephron)
</gallery>
</gallery>
www:
<gallery>
Image:Adrenal rest - epididymis -- low mag.jpg | Adrenal rest - low mag. (WC/Nephron)
Image:Adrenal rest - epididymis -- intermed mag.jpg | Adrenal rest - intermed. mag. (WC/Nephron)
Image:Adrenal rest - epididymis -- high mag.jpg | Adrenal rest - high mag. (WC/Nephron)
</gallery>
 
=====www=====
*[http://www.webpathology.com/image.asp?case=78&n=5 Adrenal medulla (webpathology.com)].
*[http://www.webpathology.com/image.asp?case=78&n=5 Adrenal medulla (webpathology.com)].


Line 52: Line 61:
*Melan A +ve.
*Melan A +ve.
*AE1/AE3 -ve.
*AE1/AE3 -ve.
*RCC -ve (0 +ve of 63 cases<ref name=pmid21490444>{{Cite journal  | last1 = Sangoi | first1 = AR. | last2 = Fujiwara | first2 = M. | last3 = West | first3 = RB. | last4 = Montgomery | first4 = KD. | last5 = Bonventre | first5 = JV. | last6 = Higgins | first6 = JP. | last7 = Rouse | first7 = RV. | last8 = Gokden | first8 = N. | last9 = McKenney | first9 = JK. | title = Immunohistochemical distinction of primary adrenal cortical lesions from metastatic clear cell renal cell carcinoma: a study of 248 cases. | journal = Am J Surg Pathol | volume = 35 | issue = 5 | pages = 678-86 | month = May | year = 2011 | doi = 10.1097/PAS.0b013e3182152629 | PMID = 21490444 }}</ref>).
*EMA -ve (0 +ve of 63 cases<ref name=pmid21490444/>).
A panel that may be useful for [[adrenal cortical adenoma|adenoma]] versus [[adrenal cortical carcinoma|carcinoma]]:<ref name=pmid26317117>{{Cite journal  | last1 = Kovach | first1 = AE. | last2 = Nucera | first2 = C. | last3 = Lam | first3 = QT. | last4 = Nguyen | first4 = A. | last5 = Dias-Santagata | first5 = D. | last6 = Sadow | first6 = PM. | title = Genomic and immunohistochemical analysis in human adrenal cortical neoplasia reveal beta-catenin mutations as potential prognostic biomarker. | journal = Discoveries (Craiova) | volume = 3 | issue = 2 | pages =  | month =  | year =  | doi = 10.15190/d.2015.32 | PMID = 26317117 }}
</ref><ref name=pmid11196463>{{Cite journal  | last1 = Arola | first1 = J. | last2 = Salmenkivi | first2 = K. | last3 = Liu | first3 = J. | last4 = Kahri | first4 = AI. | last5 = Heikkilä | first5 = P. | title = p53 and Ki67 in adrenocortical tumors. | journal = Endocr Res | volume = 26 | issue = 4 | pages = 861-5 | month = Nov | year = 2000 | doi =  | PMID = 11196463 }}</ref>
*Beta-catenin, p53, reticulin, inhibin, melan A, Ki-67.


==Clinical==
==Clinical==
Line 146: Line 161:


=Benign neoplasms=
=Benign neoplasms=
==Adrenal cortical adenoma==
===General===
Epidemiology:
*Often an incidental finding.
Pathologic/clinical:
*May be hormonally active.
*Radiologists are good at identifying adenomas, as they are usually lipid rich and have a characteristic low HU signal.<ref>URL: [http://emedicine.medscape.com/article/376240-overview http://emedicine.medscape.com/article/376240-overview].</ref>
Indications for excision:<ref name=pmid10870039>{{Cite journal  | last1 = Luton | first1 = JP. | last2 = Martinez | first2 = M. | last3 = Coste | first3 = J. | last4 = Bertherat | first4 = J. | title = Outcome in patients with adrenal incidentaloma selected for surgery: an analysis of 88 cases investigated in a single clinical center. | journal = Eur J Endocrinol | volume = 143 | issue = 1 | pages = 111-7 | month = Jul | year = 2000 | doi =  | PMID = 10870039 }}
</ref><ref name=pmid19035218>{{Cite journal  | last1 = Liu | first1 = XK. | last2 = Liu | first2 = XJ. | last3 = Dong | first3 = X. | last4 = Kong | first4 = CZ. | title = [Clinical research about treatment for adrenal incidentalomas] | journal = Zhonghua Wai Ke Za Zhi | volume = 46 | issue = 11 | pages = 832-4 | month = Jun | year = 2008 | doi =  | PMID = 19035218 }}</ref>
*Lesions >30 mm.
*Hormonally active.
*Non-incidental finding. (???)
Notes:
*[[Cushing disease]] is due to the ACTH over-production by the [[pituitary]].
*In cortisol producing tumours (''Cushing syndrome''): atrophy of the non-hyperplastic cortex (due to feedback inhibition from the [[pituitary gland]]).
===Microscopic===
Classic features:
*Well-defined cell borders.
*Clear cells (abundant, finely vacuolated cytoplasm)
*Polygonal pink cells.
*Most of the nuclei are bland, central and round.
*May have foci of [[necrosis]]/degeneration and nuclear atypia.


==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
<gallery>
<gallery>
Image: Adrenal CorticalAdenoma DSCN5001 PA.JPG|Adrenal Cortical Adenoma (SKB)
Image:Adrenal Hemangioma LP CTR.jpg|Adrenal hemangioma - low power (SKB)
Image: Adrenal CorticalAdenoma DSCN5002 PA.JPG|Adrenal Cortical Adenoma (SKB)
Image:Adrenal Hemangioma MP CTR.jpg|Adrenal hemangioma - medium power (SKB)
Image: Adrenal CorticalAdenoma DSCN5004 PA.JPG|Adrenal Cortical Adenoma (SKB)
Image: Adrenal CorticalAdenoma DSCN5005 PA.JPG|Adrenal Cortical Adenoma (SKB)
Image: Adrenal CorticalAdenoma MP CTR.jpg|Adrenal Cortical Adenoma - Medium power (SKB)
Image: Adrenal CorticalAdenoma HP CTR.jpg|Adrenal Cortical Adenoma - High power.  Abundant clear cytoplasm.  Round, regular nuclei. (SKB)
Image: Adrenal CorticalAdenoma MP PA.JPG|Adrenal Cortical Adenoma - Some pleomorphism - Medium power (SKB)
Image: Adrenal LipoAdenoma MP PA.JPG|Adrenal cortical adenoma with fat - "lipoadenoma" (SKB)
</gallery>
</gallery>


Note:
==Adrenal cortical adenoma==
*In aldosterone producing tumours:
{{Main|Adrenal cortical adenoma}}
**May extend outside of the capsule (should ''not'' be diagnosed as ''[[adrenal cortical carcinoma]]'').
**No atrophy of non-hyperplastic cortex.
**May show spironolactone bodies if hypertension treated with spironolactone prior to surgery.
 
DDx:
*Adrenal cortical nodule.<ref name=Ref_EP200>{{Ref EP|200}}</ref>
*[[Adrenal cortical hyperplasia]].
**Hyperplasia is multifocal.<ref>IAV. 18 February 2009.</ref>
*[[Adrenal cortical carcinoma]].


==Pheochromocytoma==
==Pheochromocytoma==
Line 244: Line 222:


==Neuroblastoma==
==Neuroblastoma==
:See also: ''[[olfactory neuroblastoma]]''.
{{Main|Neuroblastoma}}
===General===
Epidemiology:
*Usually paediatric population.
 
Laboratory findings:
*Increased urine homovanillic acid.
 
Predictors of a poor prognosis:<ref name=Ref_PCPBoD8_254>{{Ref PCPBoD8|254}}</ref>
*High mitotic-karyorrhectic index.
*Lack of schwannian stroma.
*>18 months.
*Near ploidy.
*N-MYC amplification.
*Lymph node spread.
*Distant spread.
 
Classification:
*In a grouping known as ''neuroblastic tumours'' which includes:<ref name=pmid10421272>{{cite journal |author=Shimada H, Ambros IM, Dehner LP, Hata J, Joshi VV, Roald B |title=Terminology and morphologic criteria of neuroblastic tumors: recommendations by the International Neuroblastoma Pathology Committee |journal=Cancer |volume=86 |issue=2 |pages=349–63 |year=1999 |month=July |pmid=10421272 |doi= |url=}}</ref>
**[[Ganglioneuroma]] (benign).
**[[Ganglioneuroblastoma]] (intermediate).
**Neuroblastoma (aggressive).
 
===Gross===
*Typically an abdominal mass.
**~40% arise in the [[adrenal gland]].<ref name=Ref_PCPBoD8_253>{{Ref PCPBoD8|253}}</ref>
 
===Microscopic===
Features:<ref name=pmid18635637>{{cite journal |author=Chung EM, Murphey MD, Specht CS, Cube R, Smirniotopoulos JG |title=From the Archives of the AFIP. Pediatric orbit tumors and tumorlike lesions: osseous lesions of the orbit |journal=Radiographics |volume=28 |issue=4 |pages=1193–214 |year=2008 |pmid=18635637 |doi=10.1148/rg.284085013 |url=}}</ref>
*[[small round cell tumour|Small round blue cell]]s separated by thin (pink) fibrous septa.
*Homer-Wright rosettes.
**Rosette with a small (~100 micrometers - diameter) meshwork of fibers (neuropil) at the centre.<ref name=pmid16551982>{{cite journal |author=Wippold FJ, Perry A |title=Neuropathology for the neuroradiologist: rosettes and pseudorosettes |journal=AJNR Am J Neuroradiol |volume=27 |issue=3 |pages=488–92 |year=2006 |month=March |pmid=16551982 |doi= |url=}}</ref>
*Neuropil-like stroma = paucicellular stroma with a cotton candy-like appearance; see comparison below.
**>50% neuropil-like stroma -- otherwise it's a [[ganglioneurona]] or ganglioblastoma.
 
Notes:
*The fibrous septa are especially useful for differentiation from lymphoma.
 
DDx:
*[[Small round cell tumours]].
**[[Wilms tumour]].
**Lymphoma.
**[[Hepatoblastoma]].
 
Images:
<gallery>
Image:Adrenal Neuroblastoma MP CTR.jpg|Neuroblastoma - medium power]]
Image:Adrenal Neuroblastoma 2 MP CTR.jpg|Neuroblastoma - medium power (SKB)
Image:Adrenal Neuroblastoma M2P PA.JPG|Neuroblastoma  - medium power]]
Image:Adrenal Neuroblastoma VascularInvasion MP CTR.jpg|thumb|Neuroblastoma  - vascular invasion - medium power]]
Image:Adrenal Neuroblastoma MP3 PA.JPG|Neuroblastoma  - medium power]]
Image:Adrenal Neuroblastoma MP PA.JPG|Neuroblastoma  - medium power]]
Image:Adrenal Neuroblastoma 2 HP CTR.jpg|Neuroblastoma - high power (SKB)
Image:Adrenal Neuroblastoma 3 HP CTR.jpg|Neuroblastoma  - high power - blue cells arrayed around a core of fluffy pink neuropil (SKB)
Image:Adrenal Neuroblastoma HP2 CTR.jpg|Neuroblastoma -  high power]]
Image:Adrenal Neuroblastoma HP CTR.jpg|Neuroblastoma  -  high power]]
</gallery>
*[http://radiographics.rsna.org/content/28/4/1193/F42.expansion Neuroblastoma (radiographics.rsna.org)].<ref>URL: [http://radiographics.rsna.org/content/28/4/1193.full http://radiographics.rsna.org/content/28/4/1193.full]. Accessed on: 12 January 2011.</ref>
*[http://commons.wikimedia.org/wiki/File:Neuroblastoma_rosettes.jpg Neuroblastoma (WC)].
*[http://farm3.static.flickr.com/2259/2274260465_afbea05f9b.jpg Neuroblastoma (flickr.com)].
 
====Schwannian vs. neuropil====
{| class="wikitable sortable" style="margin-left:auto;margin-right:auto"
| Feature
| Schwannian
| Neuropil
|-
| Cellularity
| high ~ spacing of cells < 30 µm
| low ~ spacing of cells > 100 µm
|-
| Fibrillary
| yes, long fine strands
| no
|-
| Associations
| ganglion cells
| neuroblasts
|-
| Cytoplasmic vacuolation
| yes
| ?
|-
|}
 
====Classification/grading====
Commonly grouped by the ''Shimada classification'', which depends on the presence a number of things including:
*Mitoses/karyorrhectic cells.
*Molecular abnormalities.
 
===IHC===
*PGP 9.5 +ve.<ref>{{Cite journal  | last1 = Ootsuka | first1 = S. | last2 = Asami | first2 = S. | last3 = Sasaki | first3 = T. | last4 = Yoshida | first4 = Y. | last5 = Nemoto | first5 = N. | last6 = Shichino | first6 = H. | last7 = Chin | first7 = M. | last8 = Mugishima | first8 = H. | last9 = Suzuki | first9 = T. | title = Useful markers for detecting minimal residual disease in cases of neuroblastoma. | journal = Biol Pharm Bull | volume = 31 | issue = 6 | pages = 1071-4 | month = Jun | year = 2008 | doi =  | PMID = 18520032 }}</ref>
**PGP = protein gene product.
*NB-84 +ve.<ref name=pmid9500774>{{Cite journal  | last1 = Miettinen | first1 = M. | last2 = Chatten | first2 = J. | last3 = Paetau | first3 = A. | last4 = Stevenson | first4 = A. | title = Monoclonal antibody NB84 in the differential diagnosis of neuroblastoma and other small round cell tumors. | journal = Am J Surg Pathol | volume = 22 | issue = 3 | pages = 327-32 | month = Mar | year = 1998 | doi =  | PMID = 9500774 }}</ref>
**More sensitive that synaptophysin.
*Synaptophysin +ve.
*CD99 -ve.
 
===EM===
Distinctive EM appearance:<ref name=pmid1196755>{{Cite journal  | last1 = Mackay | first1 = B. | last2 = Masse | first2 = SR. | last3 = King | first3 = OY. | last4 = Butler | first4 = J. | title = Diagnosis of neuroblastoma by electron microscopy of bone marrow aspirates. | journal = Pediatrics | volume = 56 | issue = 6 | pages = 1045-9 | month = Dec | year = 1975 | doi =  | PMID = 1196755 }}</ref>
*Dendritic processes with longitudinally oriented microtubules.
*Membrane bound electron-dense granules (contain catecholamines).
*Desmosomes
**Not seen in [[EWS]], [[RMS]], lymphomas.
*Membrane densities.
 
Pertinent negative:<ref name=pmid1196755/>
*No glycogen.
**Seen in [[EWS]].


=See also=
=See also=

Latest revision as of 18:21, 6 March 2018

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.

Anatomy

  • Cortex.
  • Medulla.

Note:

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

Microscopic

It is composed of a cortex and a medulla.

Cortex

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.

Note:

  • 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.

Medulla

It consists of two cell types:[3]

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

Produce NED: norepinephrine, epinephrine, dopamine.

Images

  • Adrenal medulla. (WC)

  • Adrenal cortex & medulla (right of image), and tumour (left of image). (WC/Nephron)

  • Adrenal rest - low mag. (WC/Nephron)

  • Adrenal rest - intermed. mag. (WC/Nephron)

  • Adrenal rest - high mag. (WC/Nephron)

www

IHC

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.

Clinical

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

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

Benign

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

Main article: Spironolactone bodies

Hemorrhagic adrenalitis

  • AKA Waterhouse-Friderichsen syndrome.

General

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

Gross

Features:

  • Massive haemorrhage within the substance of the adrenal gland.

DDx (autopsy):

  • Post-mortem changes.

Microscopic

Features:

  • Massive haemorrhage within the substance of the adrenal gland.

Image: Haemorrhage in adrenal (nih.gov).

  • Adrenal hemorrhage -low power - E. coli sepsis (SKB)

  • Adrenal hemorrhage - medium power - E. coli sepsis (SKB)

Adrenal cytomegaly

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

General

May be associated with:[14]

Microscopic

Features:

  • Large cells in the adrenal cortex.[15]

Addison disease

General

  • Chronic adrenocortical insufficiency.

Clinical:

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

DDx:[17]

Notes:

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

Microscopic

Features:[16]

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

Notes:

  • 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 hemangioma - low power (SKB)

  • Adrenal hemangioma - medium power (SKB)

Adrenal cortical adenoma

Main article: Adrenal cortical adenoma

Pheochromocytoma

Main article: Pheochromocytoma

Adrenal ganglioneuroma

Main article: Ganglioneuroma

General

Gross

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

DDx (gross):

Images:

Microscopic

Features:

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

Images:

Adrenal myelolipoma

Main article: Adrenal myelolipoma

Adenomatoid tumour

See: Adenomatoid tumours (uterine tumours).

Malignant neoplasms

Adrenocortical carcinoma

  • AKA adrenal cortical carcinoma.
  • Abbreviated ACC.
Main article: Adrenocortical carcinoma

Neuroblastoma

Main article: Neuroblastoma

See also

References

  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: http://www3.interscience.wiley.com/cgi-bin/fulltext/119909358/PDFSTART. Accessed on: 21 August 2010.
  9. ↑ URL: http://ats.ctsnetjournals.org/cgi/content/full/62/5/1516. 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. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1770213/.
  14. ↑ URL: http://www.humpath.com/?adrenal-cytomegaly. 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.
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