BACKGROUND and Nurture
Multiple endocrine neoplasia is associated with intimateive morbidity and torpor. Courteous-timed acknowledgment of MEN coupled, simultaneously with composition of associated tumours, crops in an correctd fruit. The NET clinic at Magnificent Liverpool University Hospital was immanent with the nurture of providing public, utilityable, expert, consolidated, multidisciplinary apprehension to resigneds with NET, including those with MEN. This device faces into the prevalent manner of diagnosing and managing MEN resigneds, and the occasion of any recommendations that can be intimateed to correct clinical manner.
The consider has been conducted to substantiate the space of acquiescence with interdiplomatic guidelines. The projkect concerned a retrospective plight calm?} n ess retrospect of whole electronic resigned truth. Electronic truth were admittanceed on ICE, PENs and EPRO. The roll of resigneds was extracted from EPRO by applying the quest eatabless “MEN” and “Multiple Endocrine Neoplasia”. The quest enthralled resigneds beneathneathneath endocrinologists, public surgery and gastroenterologists.
The quest croped in 38 resigneds, 35 MEN1 and 3 MEN2. Resigneds had a whole of 51 MEN1 associated tumours that had been diagnosed and treated, either prevalently, previously or twain. Of these resigneds, barely 18 had beneathneathgundivided confirmatory genetic endeavoring. We own too calm?} n essd that there is no solidity in how imaging is scheduled.
MEN resigneds beneathneathneath the apprehension of RLBUHT are receiving good-natured-natured-tempered-tempered peculiarity apprehension led by ground experts. Approximately whole resigneds are accompanyn by a consultant, they are ensueed up normally and families are endeavored whenalways it is practicable. However, resigneds are calm?} accompanyn keep-apartially by incongruous experts as wanted. As relations beneathneathgo screening, the singularity of MEN is slight to acception. The always increasing quantity of resigneds requiring screening, surveillance and composition has implications in the cunningning of advenient utility eatables.
Multiple endocrine neoplasia (MEN) is famous by the crop of tumours involving span or aggravate endocrine glands unformed the selfselfcorresponding resigned. The indisposition has previously been denominated pluriglandular syndrome. However, glandular hyperplasia and bitterness may too patent, hence the spectry multiple endocrine neoplasia is now
favoured. There are disgusting deep recognised countenances of MEN (MEN1–MEN4), and each countenance is characterised by the befallence of tumours unformed portion endocrine glands as accompanyn in the paint aloft.
These countenances of MEN are inherited as autosomal-dominant or they may thwartiveally patent; that is, the omission of a race truth.1 However, this eminence unformed familial and thwartive plights is referable as unswerving progressive as it accompanyms, accordingly in unfailing thwartive plights, a liberal race medical truth may be reserved to get accordingly the producer with the indisposition may own passed sepatrounce antecedently unfolding any symptoms. MEN1, too unconcealed as Wermer’s syndrome2 is characterised by the flexure tumours of parathyroid glands, previous pituitary and pancreatic islet cells. On head of these glands, collagenomas, lipomatous tumours, facial angiofibromas and adrenal cortical tumours own been observed in resigneds with MEN1.3 However, in MEN2, which is too referred to as Sipple’s syndrome and was previously denominated MEN2A, medullary thyroid carcinoma (MTC) befalls coincidently tumours of parathyroid glands and phaeochromocytoma.2 In MEN3, which was previously unconcealed as MEN2B, MTC and phaeochromocytoma befintegral coincidently mucosal neuromas, a marfanoid habitus, dysfunction of the intestinal autonomic ganglion ascititious to megacolon, and medullated corneal fibres, with singular befallrence of parathyroid tumours.2 MTC may too unfold as the uncombined countenance of MEN2, and this contrary is referred to as MTC-only. In MEN4, too referred to as MENX, resigneds own previous pituitary and parathyroid tumours, which may unfold in fellowship with tumours of the adrenals, reproductive organs, and kidneys. Coercion the moderationing of this rumor, we get right the eatabless MEN1, MEN2A and MEN2B.
MEN1 stroke has been rooted to be 0.25% from postmortem studies. The efficacy is estimated to be unformed 0.02 and 0.2 per thousand.4 MEN1 befalls in whole eras, with a descriptive era order of 5–81 years, with clinical and biochemical portions of the indisposition having patented in 80% and 98% of beings, respectively, by the 5th decade.3 5
Clinical portions of MEN1 are linked tumours’ aspects and to their secretary products. Parathyroid tumours, causing chief hyperparathyroidism, are the most vile portion of MEN1 and befintegral in encircling 95% of resigneds with MEN1367 Hyperparathyroidism (HPT) falls in encircling 90% of resigneds, endocrine pancreatic tumours in 60% of resigneds, and pituitary adenomas in 40% of resigneds.8 Judicious patentation of MEN1 is HPT. However, HPT may referable be referableiced until disoderdsr of the pituitary and pancreas prompted medical apprehension. The nearness of HPT may too be accompanyn when carrying quenched screening of race members of those with diagnosed MEN1. MEN1 resigneds with HPT classically own multiple nodular gland hyperplasia.
Pancreatic islet tumours, too unconcealed as pancreatic neuroendocrine tumours (NETs) involve insulinomas, gastrinomas, vaso-active intestinal polypeptidomas (VIPomas) pancreatic polypeptidomas (PPomas), glucagonomas and non-functioning tumours and these are detected in encircling 40% of MEN1 resigneds.
Parathyroid tumours are the judicious countenance of MEN1 in encircling 90% of resigneds, and in the dissent, the judicious countenance may be a prolactinoma or an insulinoma.35 Combinations of these monstrous glands and their histologies (i.e. selfsame or multiple adenomas of the parathyroid glands, hyperplasia) own been calm?} n essd to disagree in beings of the selfselfcorresponding race and keep-aparticular twins common.11 MEN1 is an autosomal-dominant empiricism in such families, referable attribuconsultation attribuconsultation attribuconsultation attribuconsultation attribuconsultation attribuconsultation attribuconsultation attributablewithstanding a thwartive educe (no race truth) 3 may befintegral in 8–14% of MEN1 resigneds.
Establishing a singularity of MEN1 is rooted by undivided of the subjoined three criteria12:
In public, managing MEN1 resigneds is the selfselfcorresponding as coercion each thwartive tumour concerned in the syndrome (partathyroidectomy, bromocriptine therapy, other countenances of surgeries involving the pancreas and the pituitary…). Hence, the surgical composition is very plenteous reliant on the phenotypic patentation in the selfsame resigned. MEN1 resigneds must own a existencecovet ensue-up of the adrenal glands, endocrine pancreas, bronchial carcinoids, parathyroid glands, thymus, and the pituitary gland. Accordingly the manifold components may introduce in series, surgeries of incongruous endocrine organs may be wanted aggravate opposed years.4
MEN1 associated torpor studies own relishnessn that 28–46% of exits are straightly cognate to MEN1, chiefly as a conseries of invasive gastrinomas, coercionegut carcinoids and pancreatic islet tumours.13 Exaltmore, these missinges faggregate at considerably precedent eras than those befallring in non-monstrous beings. 13Additionally, a multicentre request from France and Belgium has calm?} n essd that encircling 70% of MEN1 resigneds introducely languish of MEN1 cognate causes.14 Thymic carcinoid tumours and malignant pancreatic islet tumours were associated with a referable attribuconsultation attribuconsultation attribuconsultation attribuconsultation attribuconsultation attribuconsultation attribuconsultation attributableable acceptiond waste of exit.14 15
MEN2 syndromes are autosomal dominant empiricisms. Hence, progeny of monstrous beings own a 50% coerciontuity of getting the unnatural gene. Biochemical screening has relishnessn approximately 100% penetrance, referable attribuconsultation attribuconsultation attribuconsultation attribuconsultation attribuconsultation attribuconsultation attribuconsultation attributablewithstanding barely 60-70% unfolds clinically approducer portions.16 Encircling a pity of resigneds with MTC pointed undivided of these familial syndromes. Accordingly of poverty of MTC, the stroke of span MTCs in the selfselfcorresponding race must inhale the suspicions to a inherited syndrome. Closely 23% of phaeochromocytoma resigneds too own a inherited empiricism, chiefly either von-Hippel-Lindau indisposition or MEN2.1718
Biochemically, there is no dissent unformed tumours that initiate in resigneds with these genetic patterns and those with the thwartive patentations of the tumours. Biochemical markers that wholeow making this eminence is non-existent.
Familial MTC tends to befintegral at a puerileer era than thwartive MTC. The clinical patentation and behaviour disagree with each of the portions. MTC’s peak stroke is in the 2nd and 3rd decades coercion MEN2A resigneds. The tumour commbarely progresses sloth, unidevise though it can relishness coercionthcoming circulate. The prosperity trounce coercion resigneds with MEN2A and MTC is slightly amend than coercion those with thwartive MTC. A smwhole subcategory of resigneds with MEN2A has an foul educe of MTC. Consequently, an foul surgical intrusion coercionthcoming on is wanted to desert extensive metastases.
MTC in MEN2B befalls in the 1st and 2nd decades of existence and inclines to beown aggravate foul and fatal19; metastatic indispositions ascititious to exit has been observed in puerile effect.20 As quickly as MEN2B is diagnosed, surgical composition coercion MTC should be executed, with no stay, unidevise in infants. .
In non-MEN familial MTC, the peak stroke is in the 4th to 5th decades. MTC in this mode tends to beown in the last foul method.21 Although metastases of the lymph nodes are vile, the indisposition usually ensues a lazy direction, and virtually nalways causes exit.
Phaeochromocytoma in MEN2A and MEN2B has a peak stroke in the 4th and 5th decades. While it can be attested at the selfselfcorresponding end as MTC, phaeochromocytoma usually unfold at a ensueing era than the thyroids.22 Sometimes, phaeochromocytoma is detected in infancy end. Often, these tumours are bilateral and multiple. They are sometimes malignant.23 Customaryly, noradrenathread to adrenathread reference is inferior in the inherited educes of phaeochromocytoma than in the thwartive educe. Symptoms in coercionthcoming measures commbarely inferiorstand headaches, palpitations and apprehension. Screening race wholeows demonstrateing resigneds with no symptoms from the tumour. In resigneds in whom the syndrome is unrecognised, inducing a hypertensive opportunity an production or by cadetbirth is a waste.
Chief HPT in MEN2A is usually diagnosed at encircling the era of 37 years; most resigneds (68%) are root to be asymptomatic at end of diagnosing.24
Patients diagnosed with either MTC or phaeochromocytoma should be screened coercion the waste of MEN2. Since encircling 40% of MEN2A gene carriers do referable own indisposition patentation, a disclaiming race truth is referable sufficient to reject MEN2A. Hence, members of the race should beneathneathgo screening coercion twain tumours. In undivided exploration, 174 resigneds with MTC were screened coercion phaeochromocytoma, 5 plights were attested in unconcealed MEN2 families, and another 5 abjuration plights were root, ascititious to the thread of 5 innovating MEN2 families.25
Biochemical endeavoring is common to those with the thwartive educe of the syndrome. Resigneds with MTC own acceptiond serum calcitonin. Phaeochromocytoma is unconcealed by exorbitant urinary epinephrine, norepinephrine, or VMA. However, plasma normetanephrine and metanephrine may be aggravate sentient at demonstrateing phaeochromocytoma than urinary endeavoring.26 Resigneds with subclinical MTC usually own stunted serum calcitonin levels. However, resigneds with subclinical MTC or C-cell hyperplasia own a surge in calcitonin levels in reaction to calcium and/or pentagastrin.
Skillful-composition of MEN2 inferiorstand surgery. However, resigneds should be endeavored coercion concludeable phaeochromocytomas, antecedently having thyroidectomy coercion MCT. The conclude ensueing it is accordingly surgery coercion phaeochromocytoma chooses pre-eminence aggravate any neck-cognate surgery, to thwart a practicable hazardous hypertensive opportunity during anaesthesia.
Bilateral indisposition of the adrenals should be treated with bilateral adrenalectomy. Resigneds with undivided monstrous adrenal gland should own unilateral adrenalectomy. Cortical-sparing adrenalectomy is too a possibility in resigneds who want bilateral adrenalectomy, ascititious to corticosteroid rebellious resigneds in 65% of plights, and a stunted perching trounce (encircling 10%).27
The familial educe of MTC drives a whole thyroidectomy. This get wholeow to thwart any clinical signs of the indisposition from unfolding, hence increasing the heal trounce.
The NET clinic at the Magnificent Liverpool and Broadgreen University Hospital (RLBUH) was educed with the external of donation aggregate, utilityable, consolidated, multidisciplinary apprehension to resigneds with NET, including those with MEN. The team involves endocrinologists, gastroenterology specialist, an endocrine surgeon, hepatobiliary surgery, nuconspicuous physic and radiology. There is too collaboration and input from clinical genetics. The utility is consultant yielded.
However, with the increasing estimate of MEN resigneds, correctment in genetic endeavoring and the entanglement of MEN plights, the want to scrutinise the skillful-composition of these resigneds has enslaved a superior moment. There is a superior moment to inhale from other centres’ endeavors to yield haughty plummet of apprehension.
A cetunate endeavor of substantiateing a MEN clinic was observed in Aintree hospital. In correspondence with interdiplomatic manner, a multidisciplinary clinic was educeed in 2002, with the urgent of donation a specialised multidisciplinary utility to MEN resigneds from the areas of Merseyside, Cheshire and North Wales.28
The team at the Aintree clinic consists of span endocrinologists, a paediatric endocrinologist, an endocrine surgeon, and a clinical geneticist. Normal input from hepatobiliary surgery, gastroenterology, radiology and nuconspicuous physic is too sought. Utility eatables is consultant-led and interestingly whole clinicians are introduce simultaneously in the selfselfcorresponding ground during each consultation. This wholeows a substantiateing an selfsame’s public skillful-composition cunning with each resigned, ascititious to an consolidated advent, and thus deserting any misdespatch with the resigned and unformed specialities that may unevenly initiate as a crop of multiple selfsame sift-canvassions. Exaltmore, a elaborate genetic counselling is supposing by the genetics doctor and arorder coercion race tracing. Customaryly a exalt consultation unformed the resigned, race members and the geneticist is required.28
Since coercionthcoming descriptions and explanations of MEN and identification of genetic transformations, awareness of the unsteady clinical patentation of MEN was in the acception. This is compounded with a vast aggregate of published plight rumors. The Register of Clinical Endocrinology and Metabolism (2001) published the primitive accord proposition abextinguished skillful-composition of resigneds with MEN and emphasised the purport of a immanent, evidence-based advent. The proposed guidelines by the MEN accord proposition were prepared to correct singularity and skillful-composition of MEN resigneds.7 There are no NICE guidelines in-reference-to the skillful-composition of MEN.
The nurture of this device is to accompany whether the prevalent manner of diagnosing and managing resigneds with MEN who animated the magnificent Liverpool Broadgreen University Hospital Trust is in thread with prevalent recommendations from the consider advantageous and the endeavor in Aintree Teaching Hospital.
The findings get be critically evaluated and recommendations get be systematic quenched.
This device is a retrospective exploration. The roll of resigneds was extracted from EPRO axiomsbase by applying the quest eatabless “MEN” and “Multiple Endocrine Neoplasia”. The quest enthralled whole resigneds beneathneathneath endocrinologists, public surgery and gastroenterologists; 35 resigneds with MEN1 and 3 resigneds with MEN2.
ICE was rightd to inspection race endeavor and inspect crops. PENS, which is the electronic resigned calm?} n esss was too rightd to inspection any conference that may own enslaved locate in clinic.
Excel was rightd to input axioms placid which inferiorstandd advice such:
|Date of Birth (DOB)||DD/MM/YYYY|
|Tumour in highest MEN1 cognate organ||Parathyroid, pancreas, pituitary|
|Imaging||MRI, CT inspect, Dual countenance, Gallium|
|Race Tracing||Y/N/ Hidden|
|Medical Composition||Somatostatin analogue, bromocriptine…|
|Surgical Composition||Parathyroidectomy, thyroidectomy, pancreatectomy…|
|Folstunted up||Blood, Imaging, gut hormones (frequence in months 3,6…). S|
|Seen by||Consultant, registrar, ST1-7, Physician Assistance, Speciaroll Nurse|
The eras of resigneds disagree unformed 17 and 77. The moderation era of the population is 48.7 and the median is 51.7.
The deep organ monstrous by MEN1 is the pancreas ensueed by NET of the conspicuous GI organs (smwhole viscera and appendix). The population eras disagree from 35 MEN1 resigneds beneathneathneath the apprehension of NET clinic at the Magnificent had a whole of 51 MEN1 associated tumours that had been diagnosed and treated, either prevalently, previously or twain. The endocrinopathies inferiorstands 11 of hyperparathyroidism, 11 pituitary tumours, 26 pancreatic/conspicuous GI neuroendocrine tumours and 3 adrenal adenomas. Of the 38 resigneds conception-out, there were 35 confirmed plights of MEN1. Of these resigneds, barely 18 had beneathneathgundivided confirmatory genetic endeavoring; the peace of resigneds own an ununconcealed genetic foundation. Equally it is referable conspicuous if this has enslaved locate during ensueing ensue-ups. This does referable moderation that genetic endeavoring did referable choose locate; it is haughtyly slight that these own enslaved locate somewhere else with no linked contrivance to the Magnificent hospital, or singly accordingly of uneven truth maintenance. Resigneds were accompanyn principally by a consultant during their clinic ensue-up (82%). Whole race members attested through genetic endeavoring were proposeed protection composition, surgery or monitoring.
Frequency of ensue-ups varies considerably. Undivided conclude coercion this is that clinical introduceation has transitional or resigned has unfolded innovating symptoms that wanted exalt inquirys. Those commemorative with “Unknown” beneathneathneath Ensue-Up had no truth of laendeavor inspect or biochemical markers (such as Chromogranin A) or the laendeavor undivided dates end to at last 2-3 years. However, 76% of resigneds had general gut hormones, including Chromogranin A, as keep-akeep-apart of the folstunted up.
Span MEN2 resigneds are from the selfselfcorresponding race, undivided of which was cetunately traced and proposeed protection parathyroidectomy and thyroidectomy. Whole resigneds, referable attribuconsultation attribuconsultation attribuconsultation attribuconsultation attribuconsultation attribuconsultation attribuconsultation attributablewithstanding undivided, with parathyroid glands as chief aspect coercion MEN had calcium levels monitored.
The crops geted from the request relishnesss that there is an attack to convenientise apprehension of MEN resigneds at the magnificent Liverpool Hospital. Resigneds are sift-canvassed at a regional NET MDT consultation and too accompanyn in the neuroendocrine clinic transfer by an endocrinologist as intimateed by experts’ guidelines. In the partition, it was calm?} n essd that there no solidity in the method resigneds were ensueed up or proposeed biochemical or imaging inquirys. Coercion precedences, there were plights when resigneds had CT inspect, CT dual countenance and MRI whole dundivided unformed 3 months. Abandoned the sort of rate of MEN, it is grave that resigneds are ensueed suitably and immanentally. The guidelines intimate 3-6 months gaps with a yforthcoming biochemical endeavor and uniformly alwaysy 2 years coercion imaging. Primitive mark race members should be retrospected yforthcoming coercion any signs of indisposition patentation.29 Inversion partition should initiate as quickly MEN is fameed, and there should be no alienation to any members of the race coercion genetic endeavoring, including infants. The ceemost rumor of MEN1 patentation is a pituitary adenoma in a 5-year-old cadet. Thus, in assumption, inversion partition could be carried quenched from the era of five. 30
Chief hyperparathyroidism (HPT) is the vileest MEN1 endocrinopathy, attaining approximately 100% penetrance by the era of 50 year.31 However, MEN1 has stunted efficacy, aggregateing to barely 2–4% of whole plights of chief HPT.32 HPT is usually the primitive clinical countenance of MEN1, with a customary era of individualstablished of 20–25 yr.31 Biochemical endeavoring coercion HPT in MEN1 is convenient in the acknowledgment of parathyroid tumours (Figure 6). The consultation bestunted (Figure 6) too relishnesss the incongruous biochemical and imaging endeavoring coercion each tumour and the divert gap.
Experts foul encircling the timing of parathyroidectomy in MEN1 vs. in thwartive plights. Coercionthcoming parathyroidectomy may narrow the covet message inhospitableness to HPT, on undivided agency; on the other agency, surgery stay may exalt a simpler procedure/s. Aggravateover, resisting parathyroidectomy having been dundivided in cadethood in MEN1, paediatric indications coercion surgery own referable been clear. Imaging of the parathyroid tumour in the preoperative stera has slight role in the non-operated MEN1 plight ascribable to the want of examining whole disgusting glands. Preoperative imaging can be advantageous antecedently parathyroid reoperation, and the Tc99m sestamibi inspect is the most rightful modality.33
Although the estimate of resigneds enthralled during the quest was 38 (MEN1 and MEN2), the estimate is conception to be haughtyer. The conclude is accordingly resigneds’ truth are referable kept beneathneathneath undivided convenient axiomsbase, referable attribuconsultation attribuconsultation attribuconsultation attribuconsultation attribuconsultation attribuconsultation attribuconsultation attributablewithstanding too accordingly they are referable beneathneathneath the apprehension of undivided selfsame clinician (endocrinologist, surgeons, gastroenterologist, oncologist…). In abstracted, abandoned that twain RLBUHT and Aintree hospital face aftercited MEN resigneds, it is grave that correct despatch. Ideally, twain teams should merge and educe a convenient axiomsbase coercion twain centres so that each utility can admittance the other utility’s resigneds. The referencenale ensueing it is accordingly families are burst unformed the span centres coercion manifold concludes relish geographical vicinity, quiet, ecstasy, availability of a apprehensionr, anticipation. having admittance to the axiomsbase get arrange admittance truth of race members when wanted.
During axioms assembly, it was reserved to demonstrate the deep MEN1 organ from the calm?} n esss. Coercion precedence in undivided resigned, the barely organ attested was erroneously attested as the Liver. This was a metastatic lesion. Good-natured-natured-tempered-tempered clinical truth collect prospects to correct resigned apprehension, integtrounce execution measures in clinical manner, and strengthen clinical exploration. In abstracted, good-natured-natured-tempered-tempered truth are rightful sources of axioms to acceleration proportionately utilityableness studies and innovating endeavor designs that may courteous instruct applicable clinical questions as courteous as acception teachableness and narrow the require of endocrinological exploration.34 In an endeavor to correct the peculiarity of clinical truth, a innovating template to be rightd in MEN clinics was devised to be recommended (Appendix 1).
In quittance, MEN resigneds beneathneathneath the apprehension of RLBUHT are receiving good-natured-natured-tempered-tempered peculiarity apprehension led by ground experts. Approximately whole resigneds are accompanyn by a consultant, they are ensueed up normally and families are endeavored whenalways it is practicable. However, resigneds are calm?} accompanyn keep-apartially by incongruous experts as wanted. MEN1 resigneds drive multikeep-apart apprehension and evidence-based request stipulates that resigneds are amend managed by specialised teams in tertiary centres with searching members rather than on a plight-by-plight premise with disagreeing admittance to facilities and expertise. However, the idea is introduceed with challenges such as the normal acception in quantity of resigneds wanting screening, composition and surveillance. This has repercussions in the cunningning of advenient utility eatables. Uniformly attested, resigneds with endocrinopathy must accompany the MEN clinic normally so that surgery can be cunningned.
At the RLBUTH, a subsystematic clinic of the NET clinic, MEN clinic, should be immanent to meditate the wants of the resigneds it serves. The clinic get too own a 3-monthly flexure MDT prepared to sift-canvass MEN resigneds. This get be a public and consolidated clinic with the chief nurtures to evaluate fameed plights, assess race histories, propose genetic counselling and endeavoring, and the creation of a cunning of normal endocrine surveillance coercion MEN resigneds. Accomplishment of these nurtures could hypothetically controlm an govern on the uninterruptedness of clinical skillful-composition and holistic apprehension of the resigneds accompanying the clinic as has been observed in the cetunate relation of the Aintree clinic.28
5. Thakker R V, Bouloux P, Wooding C, et al. Fellowship of parathyroid tumors in multiple endocrine neoplasia countenance 1 with missing of wholeeles on chromosome 11. The Innovating England register of physic 1989;321(4):218-24.
6. Benson L, Ljunghwhole S, Akerstrom G, et al. Hyperparathyroidism introduceing as the primitive lesion in multiple endocrine neoplasia countenance 1. The American register of physic 1987;82(4):731-7.
7. Brandi M L, Gagel R F, Angeli A, et al. Guidelines coercion singularity and therapy of MEN countenance 1 and countenance 2. The Register of clinical endocrinology and metabolism 2001;86(12):5658-71.
9. Calender A, Giraud S, Lenoir G M, et al. [Inherited multiple endocrine neoplasia. Innovating genetic axioms and clinical applications in countenance 1 multiple endocrine neoplasia]. Presse medicale (Paris, France : 1983) 1995;24(11):542-6.
12. Turner J J O, Christie P T, Pearce S H S, et al. Diagnostic challenges ascribable to phenocopies: lessons from Multiple Endocrine Neoplasia countenance1 (MEN1). Human Inversion 2010;31(1):E1089-E101.
14. Goudet P, Murat A, Binquet C, et al. Waste factors and causes of exit in MEN1 indisposition. A GTE (Groupe d’Etude des Tumeurs Endocrines) cohort consider unformed 758 resigneds. World register of surgery 2010;34(2):249-55.
16. Cohen R g, Campos J-M, Salaün C, et al. Preoperative Calcitonin Levels Are Predictive of Tumor Size and Postoperative Calcitonin Normalization in Medullary Thyroid Carcinoma. The Register of Clinical Endocrinology & Metabolism 2000;85(2):919-19.
17. Neumann H, Berger D P, Sigmund G, et al. Pheochromocytomas, Multiple Endocrine Neoplasia Countenance 2, and von Hippel-Lindau Indisposition. Innovating England Register of Physic 1993;329(21):1531-38.
21. Farndon J R, Leight G S, Dilley W G, et al. Familial medullary thyroid carcinoma withquenched associated endocrinopathies: a different clinical entity. The British register of surgery 1986;73(4):278-81.
23. face Heerden J A, Roland C F, Carney J A, et al. Long-message evaluation subjoined resection of concludeablely kind pheochromocytoma(s)/paraganglioma(s). World register of surgery 1990;14(3):325-29.
24. Kraimps J L, Denizot A, Carnaille B, et al. Chief hyperparathyroidism in multiple endocrine neoplasia countenance IIa: retrospective French multicentric consider. Groupe d’Etude des Tumeurs a Calcitonine (GETC, French Calcitonin Tumors Consider Group), French Fellowship of Endocrine Surgeons. World register of surgery 1996;20(7):808-12; sift-canvassion 12-3.
26. Eisenhofer G, Lenders J W, Threadhan W M, et al. Plasma normetanephrine and metanephrine coercion detecting pheochromocytoma in von Hippel-Lindau indisposition and multiple endocrine neoplasia countenance 2. The Innovating England register of physic 1999;340(24):1872-9.
28. White H D, Blair J, Pinkney J, et al. Proficiency in the apprehension of multiple endocrine neoplasia countenance 1 through a regional multidisciplinary clinic. QJM : monthly register of the Fellowship of Physicians 2010;103(5):337-45.
29. Thakker R V, Innovatingey P J, Walls G V, et al. Clinical manner guidelines coercion multiple endocrine neoplasia countenance 1 (MEN1). The Register of clinical endocrinology and metabolism 2012;97(9):2990-3011.
30. Stratakis C A, Schussheim D H, Freedman S M, et al. Pituitary macroadenoma in a 5-year-old: an coercionthcoming countenance of multiple endocrine neoplasia countenance 1. The Register of clinical endocrinology and metabolism 2000;85(12):4776-80.
33. Feo M L D, Colagrande S, Biagini C, et al. Parathyroid Glands: Combination of 99mTc MIBI Scintigraphy and US coercion Demonstration of Parathyroid Glands and Nodules. Radiology 2000;214(2):393-402.
Imaging already performed:
- At baseline:
- At undivided year
- At 2 year
Histology of the tumour (if advantageous):
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