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{{SI}}
'''For patient information, click [[Insert page name here (patient information)|Insert page name here]]'''
{{CMG}}
{{CMG}}
{{SK}}
== Overview ==
== Overview ==


==Historical Perspective==
* In 1903 Erdheim described the case of an acromegalic patient with a [[pituitary adenoma]] and three enlarged [[parathyroid gland]]s.
* In 1953 Underdahl ''et al.'' reported a case series of 8 patients with a [[syndrome]] of [[pituitary]], [[parathyroid]], and pancreatic islet [[adenoma]]s.
* In 1954 Wermer noted that this [[syndrome]] was transmitted as a dominant trait.
* In 1959 Hazard ''et al.'' described medullary (solid) [[thyroid carcinoma]].
* In 1961 Sipple described a combination of a [[pheochromocytoma]], [[medullary thyroid carcinoma]] and [[parathyroid adenoma]].
* In 1966 Williams ''et al.'' described the combination of mucosal neuromas, [[pheochromocytoma]] and [[medullary thyroid carcinoma]].
* In 1968 Steiner ''et al.'' introduced the term "multiple endocrine neoplasia" (MEN) to describe disorders featuring combinations of [[endocrine]] [[tumor]]s and proposed the terms '[[Wermer syndrome]]' for MEN 1 and '[[Sipple syndrome]]' for MEN 2.
* In 1974 Sizemore ''et al.'' showed that the MEN 2 category included two groups of patients with MTC and [[pheochromocytoma]]: one with [[parathyroid]] [[disease]] and a normal appearance (MEN 2A) and the other without [[parathyroid]] [[disease]] but with mucosal neuromas and mesodermal abnormalities ([[MEN 2B]]).
* In 1988 the [[MEN1]] [[locus]] was assigned to [[Chromosome]] 11 (11q13).
* In 1993  [[mutation]]s in the RET [[oncogene]] were shown to be the cause of MEN 2A by Lois Mulligan, working in the laboratory of Dr Bruce Ponder in Cambridge.<ref>Germ-line [[mutation]]s of the [[RET]] proto-[[oncogene]] in [[multiple endocrine neoplasia type 2]]A.
Mulligan LM, Kwok JB, Healey CS, Elsdon MJ, Eng C, Gardner E, Love DR, Mole SE, Moore JK, Papi L, et al. ''Nature'' 1993 Jun 3;363(6428) 458-60 PMID 8099202</ref>
* In 1998 the MEN1 gene was cloned<ref name="Guru1998">Guru SC, Manickam P, Crabtree JS, Olufemi SE, Agarwal SK, Debelenko LV. Identification and characterization of the [[multiple endocrine neoplasia type 1]] (MEN1) gene. ''J Intern Med'' 243(6) 433-9</ref>
==Classification==
==Classification==
{{Familytree/start}}
{{Familytree|boxstyle=background: #E0FFFF;| | | | | | | | | | | | | | A01 | | | | | | | | | | | | | | | | | | |A01= Multiple endocrine neoplasia}}
{{Familytree|boxstyle=background: #E0FFFF;| | | | | | | | | |,|-|-|-|-|^|-|-|-|-|v|-|-|-|-|-|-|-|-|-|-|-|.| | | | | | |}}
{{Familytree|boxstyle=background: #E0FFFF;| | | | | | | | | B01 | | | | | | | | B02 | | | | | | | | | | B03 | | | | |B01= Multiple endocrine neoplasia type 1|B02= Multiple endocrine neoplasia type 2|B03= Multiple endocrine neoplasia type 4}}
{{Familytree|boxstyle=background: #E0FFFF;| | | | | | | | | | | | | | | | | |,|-|^|-|-|-|-|-|-|-|-|-|.| | | | |}}
{{Familytree|boxstyle=background: #E0FFFF;| | | | | | | | | | | | | | | | | C01 | | | | | | | | | | C02 | | | |C01= Multiple endocrine neoplasia type 2A|C02= Multiple endocrine neoplasia type 2B}}
{{Familytree|boxstyle=background: #E0FFFF;| | | | | | | | | | | |,|-|-|-|v|-|^|-|-|v|-|-|-|.| | | | |!| | | | | | | | | | | | | |}}
{{Familytree|boxstyle=background: #E0FFFF;| | | | | | | | | | | D01 | | D02 | | | D03 | | D04 | | | D05 | | | | | | | | | | |D01= Multiple endocrine neoplasia type 2A classical|D02= Multiple endocrine neoplasia type 2A with cutaneous lichen amyloidosis|D03= Multiple endocrine neoplasia type 2A with [[hirschsprung disease]]|D04= Familial medullary cancer without [[pheochromocytoma]] or [[parathyroid]] hyperplasia|D05= [[Medullary thyroid cancer]], [[pheochromocytoma]] and [[mucosal neuroma]]s or intestinal [[ganglioneuroma]]s and [[marfanoid habitus]]}}
{{Familytree/end}}


== Pathophysiology==
== Pathophysiology==
* The term multiple endocrine neoplasia (MEN) encompasses several distinct [[syndrome]]s featuring [[Endocrine gland neoplasm|tumors of endocrine gland]]s, each with its own characteristic pattern.  In some cases, the [[tumor]]s are [[malignant]], in others, [[benign]]. [[Benign]] or [[malignant]] [[tumor]]s of nonendocrine [[tissue]]s occur as components of some of these [[tumor]] [[syndrome]]s.
* The term multiple endocrine neoplasia (MEN) encompasses several distinct [[syndrome]]s featuring [[Endocrine gland neoplasm|tumors of endocrine gland]]s, each with its own characteristic pattern.  In some cases, the [[tumor]]s are [[malignant]], in others, [[benign]]. [[Benign]] or [[malignant]] [[tumor]]s of nonendocrine [[tissue]]s occur as components of some of these [[tumor]] [[syndrome]]s.
* MEN syndromes are inherited as [[autosomal dominant]] disorders.<ref>{{DorlandsDict|six/000070637|multiple endocrine neoplasia}}</ref>
* MEN syndromes are inherited as [[autosomal dominant]] disorders.<ref>{{DorlandsDict|six/000070637|multiple endocrine neoplasia}}</ref>
=== Genetics ===
=== Associated Conditions===
* [[Von Hippel-Lindau disease]]
* [[Carney complex]]
*
===Gross Pathology===
===Microscopic Pathology===
==Causes==
===Life Threatening Causes===
Life-threatening causes include conditions which may result in death or permanent disability within 24 hours if left untreated.


===Common Causes===
===Comparison===
 
[[File:Multiple endocrine neoplasia.png|thumb|center|500px|Presentations of Multiple endocrine neoplasia.]]
===Causes by Organ System===
Percentages in table below refer to how large fraction of people with the MEN type develop the [[neoplasia]] type.
 
{| class="wikitable"
{|style="width:80%; height:100px" border="1"
|style="height:100px"; style="width:25%" border="1" bgcolor="LightSteelBlue" | '''Cardiovascular'''
|style="height:100px"; style="width:75%" border="1" bgcolor="Beige" | No underlying causes
|-
|-bgcolor="LightSteelBlue"
| '''Chemical / poisoning'''
|bgcolor="Beige"| No underlying causes
|-
|-bgcolor="LightSteelBlue"
| '''Dermatologic'''
|bgcolor="Beige"| No underlying causes
|-
|-bgcolor="LightSteelBlue"
| '''Drug Side Effect'''
|bgcolor="Beige"| No underlying causes
|-
|-bgcolor="LightSteelBlue"
| '''Ear Nose Throat'''
|bgcolor="Beige"| No underlying causes
|-
|-bgcolor="LightSteelBlue"
| '''Endocrine'''
|bgcolor="Beige"| No underlying causes
|-
|-bgcolor="LightSteelBlue"
| '''Environmental'''
|bgcolor="Beige"| No underlying causes
|-
|-bgcolor="LightSteelBlue"
| '''Gastroenterologic'''
|bgcolor="Beige"| No underlying causes
|-
|-bgcolor="LightSteelBlue"
| '''Genetic'''
|bgcolor="Beige"| No underlying causes
|-
|-bgcolor="LightSteelBlue"
| '''Hematologic'''
|bgcolor="Beige"| No underlying causes
|-
|-bgcolor="LightSteelBlue"
| '''Iatrogenic'''
|bgcolor="Beige"| No underlying causes
|-
|-
|-bgcolor="LightSteelBlue"
! rowspan="2" | Feature
| '''Infectious Disease'''
! rowspan="2" | [[Multiple endocrine neoplasia type 1|MEN 1]]
|bgcolor="Beige"| No underlying causes
! colspan="3" | [[Multiple endocrine neoplasia type 2|MEN 2]]
|-
|-
|-bgcolor="LightSteelBlue"
! [[Multiple endocrine neoplasia type 2|MEN 2A]]
| '''Musculoskeletal / Ortho'''
! Multiple endocrine neoplasia type 2b|MEN 2B
|bgcolor="Beige"| No underlying causes
! [[Medullary thyroid cancer|FMTC]]
|-
|-
|-bgcolor="LightSteelBlue"
| Eponym
| '''Neurologic'''
| Wermer syndrome
|bgcolor="Beige"| No underlying causes
| Sipple syndrome
| (multiple)
| (none)
|-
|-
|-bgcolor="LightSteelBlue"
| [[OMIM]]
| '''Nutritional / Metabolic'''
| {{OMIM4|131100}}
|bgcolor="Beige"| No underlying causes
| {{OMIM4|171400}}
| {{OMIM4|162300}}
| {{OMIM4|155240}}
|-
|-
|-bgcolor="LightSteelBlue"
| [[Pancreatic]] tumors
| '''Obstetric/Gynecologic'''
| [[gastrinoma]] (50%<ref name=agabegi2nd4-7/>), <br>[[insulinoma]] (20%<ref name=agabegi2nd4-7/>), <br>[[vipoma]], <br>[[glucagonoma]], <br>[[PPoma]]
|bgcolor="Beige"| No underlying causes
| -
| -
| -
|-
|-
|-bgcolor="LightSteelBlue"
| [[Pituitary adenoma]]
| '''Oncologic'''
| 66%<ref name=agabegi2nd4-7>Table 4-7 in:{{cite book |author=Elizabeth D Agabegi; Agabegi, Steven S. |title=Step-Up to Medicine (Step-Up Series) |publisher=Lippincott Williams & Wilkins |location=Hagerstwon, MD |year=2008 |pages= |isbn=0-7817-7153-6 |oclc= |doi= |accessdate=}}</ref>
|bgcolor="Beige"| No underlying causes
| -
| -
| -
|-
|-
|-bgcolor="LightSteelBlue"
| [[Angiofibroma]]
| '''Opthalmologic'''
| 64%*<ref name=Asgharian>{{cite journal|last=Asgharian|first=B |author2=Turner, ML |author3=Gibril, F |author4=Entsuah, LK |author5=Serrano, J |author6=Jensen, RT|title=Cutaneous tumors in patients with multiple endocrine neoplasm type 1 (MEN1) and gastrinomas: prospective study of frequency and development of criteria with high sensitivity and specificity for MEN1.|journal=The Journal of Clinical Endocrinology and Metabolism|date=November 2004|volume=89|issue=11|pages=5328–36|pmid=15531478|doi=10.1210/jc.2004-0218}}</ref>
|bgcolor="Beige"| No underlying causes
| -
| -
| -
|-
|-
|-bgcolor="LightSteelBlue"
| [[Lipoma]]
| '''Overdose / Toxicity'''
| 17%*<ref name=Asgharian />
|bgcolor="Beige"| No underlying causes
| -
| -
| -
|-
|-
|-bgcolor="LightSteelBlue"
| [[Parathyroid]] hyperplasia
| '''Psychiatric'''
| 90%<ref name=agabegi2nd4-7/>
|bgcolor="Beige"| No underlying causes
| 50%<ref name=agabegi2nd4-7/>
| -
| -
|-
|-
|-bgcolor="LightSteelBlue"
| [[Medullary thyroid carcinoma]]
| '''Pulmonary'''
| -
|bgcolor="Beige"| No underlying causes
| 100%<ref name=agabegi2nd4-7/>
| 85%<ref name=agabegi2nd4-7/>
| 100%
|-
|-
|-bgcolor="LightSteelBlue"
| [[Pheochromocytoma]]
| '''Renal / Electrolyte'''
| -
|bgcolor="Beige"| No underlying causes
| >33%<ref name=agabegi2nd4-7/>
| 50%
| -
|-
|-
|-bgcolor="LightSteelBlue"
| [[Marfan syndrome|Marfanoid]] body habitus
| '''Rheum / Immune / Allergy'''
| -
|bgcolor="Beige"| No underlying causes
| -
| 80%
| -
|-
|-
|-bgcolor="LightSteelBlue"
| Mucosal [[neuroma]]
| '''Sexual'''
| -
|bgcolor="Beige"| No underlying causes
| -
| 100%<ref name=agabegi2nd4-7/>
| -
|-
|-
|-bgcolor="LightSteelBlue"
| [[Gene]](s)
| '''Trauma'''
| [[MEN1]] ({{OMIM4|131100}})
|bgcolor="Beige"| No underlying causes
| [[RET proto-oncogene|RET]] ({{OMIM4|164761}})
| [[RET proto-oncogene|RET]] ({{OMIM4|164761}})
| [[RET proto-oncogene|RET]] ({{OMIM4|164761}}),<br/>[[NTRK1]] ({{OMIM4|191315}})
|-
|-
|-bgcolor="LightSteelBlue"
| Approx. [[prevalence]]
| '''Urologic'''
| 1 in 35,000 <br> (1 in 20,000 to<br> 1 in 40,000)<ref>[http://www.dovepress.com/getfile.php?fileID=5129] 123I labeled metaiodobenzylguanidine for diagnosis of neuroendocrine tumors. Jiang L, Schipper ML, Li P, Cheng Z, Reports in Medical Imaging. 2009: 2 79-89</ref>
|bgcolor="Beige"| No underlying causes
| 1 in 40,000<ref>{{cite journal |author=Dora JM, Siqueira DR, Meyer EL, Puñales MK, Maia AL |title=Pancreatitis as the first manifestation of multiple endocrine neoplasia type 2A |journal=Arq Bras Endocrinol Metabol |volume=52 |issue=8 |pages=1332–6 |date=November 2008 |pmid=19169490 |doi= 10.1590/S0004-27302008000800021|url=}}</ref>
|-
| 1 in 1,000,000<br/>(1 in 600,000<ref>{{cite book |last=Marx |first=Stephen J |editor-last=Melmed |editor-first=Shlomo |title=Williams Textbook of Endocrinology, 12th ed. |year=2011 |pages=1728–1767 |chapter=Chapter 41: Multiple endocrine neoplasia }}</ref> to<br/>1 in 4,000,000<ref>{{cite journal |author=Moline J, Eng C. |title= Multiple endocrine neoplasia type 2: An overview|journal=Genetics in Medicine |volume=13 |issue=9 |pages=755–764 |year=2011 |pmid= 21552134 |url=http://www.nature.com/gim/journal/v13/n9/full/gim2011127a.html |doi=10.1097/GIM.0b013e318216cc6d}}</ref>)<ref>{{cite book |author=Martino Ruggieri |title=Neurocutaneous Disorders : The Phakomatoses |publisher=Springer |location=Berlin |year=2005 |pages= |isbn=3-211-21396-1 |oclc= |doi= |accessdate=}} - Chapter: ''Multiple Endocrine Neoplasia Type 2B '' by Electron Kebebew, Jessica E. Gosnell and Emily Reiff. Pages 695-701. [http://www.springerlink.com/content/qu78313220701167/]  This reference quotes a prevalence of 1 in 40,000, but this figure is inconsistent with the same reference's calculated incidence of 4 per 100 million per year for MEN2B.</ref>
|-bgcolor="LightSteelBlue"
|
| '''Dental'''
|bgcolor="Beige"| No underlying causes
|-
|-bgcolor="LightSteelBlue"
| '''Miscellaneous'''
|bgcolor="Beige"| No underlying causes
|-
|-
| Initial description (year)
| 1954<ref>{{cite journal |author=Wermer P |title=Genetic aspects of adenomatosis of endocrine glands |journal=Am. J. Med. |volume=16 |issue=3 |pages=363–71 |year=1954 |pmid=13138607 |doi= 10.1016/0002-9343(54)90353-8|url=http://linkinghub.elsevier.com/retrieve/pii/0002-9343(54)90353-8}}</ref>
| 1961<ref>{{cite journal |author=Sipple JH |title=The association of pheochromocytoma with carcinoma of the thyroid gland |journal=Am. J. Med. |volume=31 |issue= |pages=163–6 |year=1961 |pmid= |doi= 10.1016/0002-9343(61)90234-0|url=}}</ref>
| 1965
|
|}
|}
<nowiki>*</nowiki>- of patients with MEN1 and gastrinoma


===Causes in Alphabetical Order===
=== Associated Conditions===
 
* [[Von Hippel-Lindau disease]]
*A...
* [[Carney complex]]
*Z...
==Treatment==
 
=== Surgery===  
Make sure that each diagnosis is linked to a page.
* Surgery is the mainstay of treatment for tumors of multiple endocrine neoplasia.
 
==Differentiating type page name here from other Diseases==
 
== Epidemiology and Demographics ==
===Age===
===Gender===
===Race===
===Developed Countries===
===Developing Countries===
 
== Risk Factors ==
 
== Screening ==
 
== Natural History, Complications and Prognosis==
 
== Diagnosis ==
===Diagnostic Criteria===
If available, the diagnostic criteria are provided here.
 
===History===
A directed history should be obtained to ascertain
 
=== Symptoms ===
"Type symptom here" is pathognomonic of the "type disease name here".
 
"Type non specific symptoms" may be present.
 
===Past Medical History===
 
===Family History===
 
===Social History===
====Occupational====
====Alcohol====
The frequency and amount of alcohol consumption should be characterized.
====Drug Use====
====Smoking====
 
===Allergies===
 
=== Physical Examination ===
 
==== Appearance of the Patient ====
 
====Vital Signs====
 
====Skin====
 
====Head====
 
==== Eyes ====
 
==== Ear ====
 
====Nose====
 
====Mouth====
 
====Throat ====
 
==== Heart ====
 
==== Lungs ====
 
==== Abdomen ====
 
==== Extremities ====
 
==== Neurologic ====
 
====Genitals====
 
==== Other ====
 
=== Laboratory Findings ===
 
==== Electrolyte and Biomarker Studies ====
 
==== Electrocardiogram ====
 
==== Chest X Ray ====
 
====CT ====
 
==== MRI ====
 
==== Echocardiography or Ultrasound ====
 
==== Other Imaging Findings ====
 
=== Other Diagnostic Studies ===
 
== Treatment ==
=== Pharmacotherapy ===
 
==== Acute Pharmacotherapies ====
 
==== Chronic Pharmacotherapies ====
 
=== Surgery and Device Based Therapy ===
 
==== Indications for Surgery ====
 
==== Pre-Operative Assessment ====
 
==== Post-Operative Management ====
 
==== Transplantation ====
 
=== Primary Prevention ===
 
=== Secondary Prevention ===
 
=== Cost-Effectiveness of Therapy ===
 
=== Future or Investigational Therapies ===


==References==
==References==
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[[Category:Disease]]
[[Category:Disease]]
[[Category:Help]]
[[Category:Oncology]]

Latest revision as of 03:36, 1 October 2015

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [3]

Overview

Classification

 
 
 
 
 
 
 
 
 
 
 
 
 
Multiple endocrine neoplasia
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Multiple endocrine neoplasia type 1
 
 
 
 
 
 
 
Multiple endocrine neoplasia type 2
 
 
 
 
 
 
 
 
 
Multiple endocrine neoplasia type 4
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Multiple endocrine neoplasia type 2A
 
 
 
 
 
 
 
 
 
Multiple endocrine neoplasia type 2B
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Multiple endocrine neoplasia type 2A classical
 
Multiple endocrine neoplasia type 2A with cutaneous lichen amyloidosis
 
 
Multiple endocrine neoplasia type 2A with hirschsprung disease
 
Familial medullary cancer without pheochromocytoma or parathyroid hyperplasia
 
 
Medullary thyroid cancer, pheochromocytoma and mucosal neuromas or intestinal ganglioneuromas and marfanoid habitus
 
 
 
 
 
 
 
 
 
 

Pathophysiology

Comparison

Presentations of Multiple endocrine neoplasia.

Percentages in table below refer to how large fraction of people with the MEN type develop the neoplasia type.

Feature MEN 1 MEN 2
MEN 2A MEN 2B FMTC
Eponym Wermer syndrome Sipple syndrome (multiple) (none)
OMIM Template:OMIM4 Template:OMIM4 Template:OMIM4 Template:OMIM4
Pancreatic tumors gastrinoma (50%[2]),
insulinoma (20%[2]),
vipoma,
glucagonoma,
PPoma 		- - -
Pituitary adenoma 66%[2] - - -
Angiofibroma 64%*[3] - - -
Lipoma 17%*[3] - - -
Parathyroid hyperplasia 90%[2] 50%[2] - -
Medullary thyroid carcinoma - 100%[2] 85%[2] 100%
Pheochromocytoma - >33%[2] 50% -
Marfanoid body habitus - - 80% -
Mucosal neuroma - - 100%[2] -
Gene(s) MEN1 (Template:OMIM4) RET (Template:OMIM4) RET (Template:OMIM4) RET (Template:OMIM4),
NTRK1 (Template:OMIM4)
Approx. prevalence 1 in 35,000
(1 in 20,000 to
1 in 40,000)[4] 		1 in 40,000[5] 1 in 1,000,000
(1 in 600,000[6] to
1 in 4,000,000[7])[8]
Initial description (year) 1954[9] 1961[10] 1965

*- of patients with MEN1 and gastrinoma

Associated Conditions

Treatment

Surgery

  • Surgery is the mainstay of treatment for tumors of multiple endocrine neoplasia.

References

  1. ↑ Template:DorlandsDict
  2. ↑ 2.0 2.1 2.2 2.3 2.4 2.5 2.6 2.7 2.8 Table 4-7 in:Elizabeth D Agabegi; Agabegi, Steven S. (2008). Step-Up to Medicine (Step-Up Series). Hagerstwon, MD: Lippincott Williams & Wilkins. ISBN 0-7817-7153-6.
  3. ↑ 3.0 3.1 Asgharian, B; Turner, ML; Gibril, F; Entsuah, LK; Serrano, J; Jensen, RT (November 2004). "Cutaneous tumors in patients with multiple endocrine neoplasm type 1 (MEN1) and gastrinomas: prospective study of frequency and development of criteria with high sensitivity and specificity for MEN1". The Journal of Clinical Endocrinology and Metabolism. 89 (11): 5328–36. doi:10.1210/jc.2004-0218. PMID 15531478.
  4. ↑ [1] 123I labeled metaiodobenzylguanidine for diagnosis of neuroendocrine tumors. Jiang L, Schipper ML, Li P, Cheng Z, Reports in Medical Imaging. 2009: 2 79-89
  5. ↑ Dora JM, Siqueira DR, Meyer EL, Puñales MK, Maia AL (November 2008). "Pancreatitis as the first manifestation of multiple endocrine neoplasia type 2A". Arq Bras Endocrinol Metabol. 52 (8): 1332–6. doi:10.1590/S0004-27302008000800021. PMID 19169490.
  6. ↑ Marx, Stephen J (2011). "Chapter 41: Multiple endocrine neoplasia". In Melmed, Shlomo. Williams Textbook of Endocrinology, 12th ed. pp. 1728–1767.
  7. ↑ Moline J, Eng C. (2011). "Multiple endocrine neoplasia type 2: An overview". Genetics in Medicine. 13 (9): 755–764. doi:10.1097/GIM.0b013e318216cc6d. PMID 21552134.
  8. ↑ Martino Ruggieri (2005). Neurocutaneous Disorders : The Phakomatoses. Berlin: Springer. ISBN 3-211-21396-1. - Chapter: Multiple Endocrine Neoplasia Type 2B by Electron Kebebew, Jessica E. Gosnell and Emily Reiff. Pages 695-701. [2] This reference quotes a prevalence of 1 in 40,000, but this figure is inconsistent with the same reference's calculated incidence of 4 per 100 million per year for MEN2B.
  9. ↑ Wermer P (1954). "Genetic aspects of adenomatosis of endocrine glands". Am. J. Med. 16 (3): 363–71. doi:10.1016/0002-9343(54)90353-8. PMID 13138607.
  10. ↑ Sipple JH (1961). "The association of pheochromocytoma with carcinoma of the thyroid gland". Am. J. Med. 31: 163–6. doi:10.1016/0002-9343(61)90234-0.


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