Materiały źródłowe

• #1 Multiple Endocrine Neoplasia Type 2 – GeneReviews® – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK1257/

  Multiple endocrine neoplasia type 2 (MEN2) includes the following phenotypes: MEN2A, familial medullary thyroid carcinoma (FMTC, which may be a variant of MEN2A), and MEN2B. […] The diagnosis of MEN2 is established in a proband who fulfills existing clinical diagnostic criteria or by identification of a heterozygous germline gain-of-function variant in RET on molecular genetic testing. […] Molecular genetic testing is recommended in all individuals with a clinical diagnosis due to genotype-specific surveillance and treatment recommendations and to allow family studies. […] Clinical diagnostic criteria for multiple endocrine neoplasia type 2 (MEN2) have been published. […] MEN2A should be suspected in individuals with one or more specific endocrine tumor(s): medullary thyroid carcinoma (MTC), pheochromocytoma, or parathyroid adenoma/hyperplasia.

• #2 Multiple endocrine neoplasia type 2: An overview | Genetics in Medicine

  https://www.nature.com/articles/gim2011127

  Multiple endocrine neoplasia type 2 is historically composed of three clinical subtypes, all of which are associated with germline mutations in the RET proto-oncogene. […] Clinical recognition and accurate diagnosis of individuals and families who are at risk of harboring a germline RET mutation is critical for the prevention and management of potentially life-threatening neoplasms. […] MEN 2 includes the phenotypes MEN 2A, FMTC, and MEN 2B. Each can be diagnosed based on clinical features; but with the advances of RET testing, genotype-specific risks, and management, molecular genetic testing is virtually mandatory and is most often used to distinguish sporadic from hereditary MTC. […] MEN 2A is diagnosed clinically by the occurrence of two or more specific endocrine tumors (MTC, pheochromocytoma, or parathyroid adenoma/hyperplasia) in a single individual or in close relatives.

• #3 Multiple Endocrine Neoplasia Type 2 – GeneReviews® – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK1257/

  Multiple endocrine neoplasia type 2 (MEN2) includes the following phenotypes: MEN2A, familial medullary thyroid carcinoma (FMTC, which may be a variant of MEN2A), and MEN2B. […] The diagnosis of MEN2 is established in a proband who fulfills existing clinical diagnostic criteria or by identification of a heterozygous germline gain-of-function variant in RET on molecular genetic testing. […] Molecular genetic testing is recommended in all individuals with a clinical diagnosis due to genotype-specific surveillance and treatment recommendations and to allow family studies. […] Clinical diagnostic criteria for multiple endocrine neoplasia type 2 (MEN2) have been published. […] MEN2A should be suspected in individuals with one or more specific endocrine tumor(s): medullary thyroid carcinoma (MTC), pheochromocytoma, or parathyroid adenoma/hyperplasia.

• #4 Multiple endocrine neoplasia type 2: An overview | Genetics in Medicine

  https://www.nature.com/articles/gim2011127

  FMTC is historically operationally diagnosed in families with four or more cases of MTC in the absence of pheochromocytoma or parathyroid adenoma/hyperplasia. […] MEN 2B is diagnosed clinically by the presence of mucosal neuromas of the lips and tongue, as well as medullated corneal nerve fibers, distinctive facies with enlarged lips, an asthenic Marfanoid body habitus, and MTC. […] RET is the only gene known to be associated with MEN 2. RET molecular genetic testing is indicated in all individuals with a diagnosis of MTC, a clinical diagnosis of MEN 2, or primary CCH. […] All individuals with MTC, irregardless of other features or family history, and those with clinical features suspicious for MEN 2 and/or with family history suspicious of MEN 2 should be offered germline RET testing for exons 10, 11, and 1316; ideally, testing should be completed preoperatively and with genetic counseling. […] Molecular genetic testing should be performed as soon as possible after birth in all children known to be at risk for MEN 2B. […] In families with MEN 2A or FMTC, molecular genetic testing should be offered to at-risk children by age 5 years, as MTC has been documented in childhood.

• #5 Multiple Endocrine Neoplasia Type 2 (MEN2) (PDQ®): Genetics – Health Professional Information [NCI] | Kaiser Permanente

  https://healthy.kaiserpermanente.org/health-wellness/health-encyclopedia/he.multiple-endocrine-neoplasia-type-2-men2-pdq%C2%AE-genetics-health-professional-information-nci.ncicdr0000813377

  MEN2 is a well-defined hereditary cancer syndrome. Genetic testing is an important management tool that defines who has an MEN2 diagnosis. It can also provide family members with predictive genetic testing options. There are also rare cases of suspected MEN2 in which a genetic variant has not been identified. […] Germline DNA testing for RET pathogenic variants is recommended for all individuals with medullary thyroid cancer (MTC) by the American Thyroid Association and the National Comprehensive Cancer Network. Testing is recommended regardless of whether there is a personal or family history suggestive of MEN2. […] The identification of these features can prompt early diagnosis of MEN2B and provide the opportunity to prevent or cure MTC. […] While most MTC cases are sporadic, approximately 20% to 25% are hereditary. These hereditary cases are caused by pathogenic variants in the RET proto-oncogene. Between 1% and 10% of individuals with apparently sporadic MTC carry a germline RET pathogenic variant, underscoring the importance of genetic testing for all individuals diagnosed with MTC.

• #6 Multiple Endocrine Neoplasia Type 2 – GeneReviews® – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK1257/

  FMTC should be suspected in families with more than one individual diagnosed with MTC in the absence of pheochromocytoma or parathyroid adenoma/hyperplasia. […] MEN2B should be suspected in individuals with distinctive facies including lip mucosal neuromas resulting in thick vermilion of the upper and lower lip, mucosal neuromas of the lips and tongue, medullated corneal nerve fibers, marfanoid habitus, and MTC. […] The clinical diagnosis of MEN2 can be established in a proband based on clinical diagnostic criteria, or the molecular diagnosis can be established in a proband with suggestive findings and a heterozygous germline gain-of-function pathogenic (or likely pathogenic) variant in RET identified by molecular genetic testing. […] Molecular genetic testing approaches can include single-gene testing or use of a multigene panel.

• #7 Multiple Endocrine Neoplasia Type 2 – GeneReviews® – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK1257/

  Single-gene testing. Sequence analysis of RET detects missense, nonsense, and splice site variants and small intragenic deletions/insertions. […] Targeted analysis for RET pathogenic variants p.Met918Thr and p.Ala883Phe can be considered first in those with suspected MEN2B. […] Molecular genetic testing should be offered to at-risk children by age five years. […] Molecular genetic testing should be performed as soon as possible after birth in all children known to be at risk.

• #8 Multiple Endocrine Neoplasia (MEN): Types & Symptoms

  https://my.clevelandclinic.org/health/diseases/23088-multiple-endocrine-neoplasia-men

  A person is diagnosed with MEN type 2 if they have medullary thyroid cancer (MTC) and pheochromocytoma and/or parathyroid enlargement (hyperplasia) or tumor (adenoma). […] Before a healthcare provider can diagnose MEN type 2, they need to diagnose medullary thyroid cancer (MTC) and other types of tumors in the individual. […] A variety of blood tests can detect elevated levels of certain hormones, which can be a sign of MTC and other tumors. For example: Higher-than-normal levels of calcitonin can indicate MTC. […] Healthcare providers then use imaging tests, such as CT (computed tomography) scans or MRI (magnetic resonance imaging) scans, to help find and diagnose tumors associated with MEN type 2. […] Providers can also confirm a MEN type 2 diagnosis through genetic testing of the RET gene.

• #9 Multiple Endocrine Neoplasia (MEN Syndrome) – Dermatology Advisor

  https://www.dermatologyadvisor.com/home/decision-support-in-medicine/dermatology/multiple-endocrine-neoplasia-men-syndrome/

  Multiple endocrine neoplasias (MENs) are autosomal dominant inherited disorders that can result in significant morbidity and mortality. MEN2A and MEN2B, also known as Sipples syndrome, are characterized by the presence of medullary thyroid carcinoma (MTC) presenting clinically as a thyroid mass or nodule, and pheochromocytomas. Diagnosis of MEN syndrome is based on genetic testing, biochemical evaluation, and imaging. Guidelines for MEN2 genetic testing for the RET germline mutation include index case patients with a clinically confirmed diagnosis. Given the clinical importance of identifying the RET mutation, all individuals with seemingly sporadic MTC or pheochromocytoma should be tested for the mutation. Genetic testing identifies RET mutations in 95% of people with clinical symptoms of MEN2A and MEN2B, and in approximately 88% of families with FMTC. The diagnosis of MEN1 should be considered in patients presenting with early-onset hyperparathyroidism, multiple gland parathyroid disease, or rare neuroendocrine tumors.

• #10 Multiple Endocrine Neoplasia Type 2 – GeneReviews® – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK1257/

  Multiple endocrine neoplasia type 2 (MEN2) includes the following phenotypes: MEN2A, familial medullary thyroid carcinoma (FMTC, which may be a variant of MEN2A), and MEN2B. […] The diagnosis of MEN2 is established in a proband who fulfills existing clinical diagnostic criteria or by identification of a heterozygous germline gain-of-function variant in RET on molecular genetic testing. […] Molecular genetic testing is recommended in all individuals with a clinical diagnosis due to genotype-specific surveillance and treatment recommendations and to allow family studies. […] Clinical diagnostic criteria for multiple endocrine neoplasia type 2 (MEN2) have been published. […] MEN2A should be suspected in individuals with one or more specific endocrine tumor(s): medullary thyroid carcinoma (MTC), pheochromocytoma, or parathyroid adenoma/hyperplasia.

• #11 Multiple endocrine neoplasia type 2: An overview | Genetics in Medicine

  https://www.nature.com/articles/gim2011127

  Multiple endocrine neoplasia type 2 is historically composed of three clinical subtypes, all of which are associated with germline mutations in the RET proto-oncogene. […] Clinical recognition and accurate diagnosis of individuals and families who are at risk of harboring a germline RET mutation is critical for the prevention and management of potentially life-threatening neoplasms. […] MEN 2 includes the phenotypes MEN 2A, FMTC, and MEN 2B. Each can be diagnosed based on clinical features; but with the advances of RET testing, genotype-specific risks, and management, molecular genetic testing is virtually mandatory and is most often used to distinguish sporadic from hereditary MTC. […] MEN 2A is diagnosed clinically by the occurrence of two or more specific endocrine tumors (MTC, pheochromocytoma, or parathyroid adenoma/hyperplasia) in a single individual or in close relatives.

• #12 Multiple Endocrine Neoplasia Type 2 – GeneReviews® – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK1257/

  Multiple endocrine neoplasia type 2 (MEN2) includes the following phenotypes: MEN2A, familial medullary thyroid carcinoma (FMTC, which may be a variant of MEN2A), and MEN2B. […] The diagnosis of MEN2 is established in a proband who fulfills existing clinical diagnostic criteria or by identification of a heterozygous germline gain-of-function variant in RET on molecular genetic testing. […] Molecular genetic testing is recommended in all individuals with a clinical diagnosis due to genotype-specific surveillance and treatment recommendations and to allow family studies. […] Clinical diagnostic criteria for multiple endocrine neoplasia type 2 (MEN2) have been published. […] MEN2A should be suspected in individuals with one or more specific endocrine tumor(s): medullary thyroid carcinoma (MTC), pheochromocytoma, or parathyroid adenoma/hyperplasia.

• #13 Multiple Endocrine Neoplasia Type 2: Diagnosis and Treatment

  https://www.massgeneral.org/children/multiple-endocrine-neoplasia-type-2/diagnosis-treatment

  How do doctors diagnose multiple endocrine neoplasia type 2 (MEN2)? […] How doctors diagnose MEN2 depends on whether your child has MEN2A or MEN2B. […] Children are usually diagnosed because a parent or relative has MEN2A. Doctors can diagnose MEN2A in the following ways: Medical and family history, Physical exam, Genetic testing, If your child or close relatives have at least 2 of the 3 following conditions: MTC, pheochromocytomas, parathyroid adenoma or hyperplasia (when an organ or tissue becomes enlarged). […] If your child has a combination of MTC and mucosal neuromas. […] Physical exam for the following features: protruding lips, thin facial features, a thin body type and medullated corneal nerve fibers in the eye. […] Early and consistent screening is extremely important because many symptoms of MEN2 are not noticeable until adulthood.

• #14 Multiple Endocrine Neoplasia Type 2 – GeneReviews® – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK1257/

  FMTC should be suspected in families with more than one individual diagnosed with MTC in the absence of pheochromocytoma or parathyroid adenoma/hyperplasia. […] MEN2B should be suspected in individuals with distinctive facies including lip mucosal neuromas resulting in thick vermilion of the upper and lower lip, mucosal neuromas of the lips and tongue, medullated corneal nerve fibers, marfanoid habitus, and MTC. […] The clinical diagnosis of MEN2 can be established in a proband based on clinical diagnostic criteria, or the molecular diagnosis can be established in a proband with suggestive findings and a heterozygous germline gain-of-function pathogenic (or likely pathogenic) variant in RET identified by molecular genetic testing. […] Molecular genetic testing approaches can include single-gene testing or use of a multigene panel.

• #15 Hormones.gr

  http://www.hormones.gr/preview.php?c_id=504

  Multiple endocrine neoplasia type 2 (MEN2) is an autosomal dominant tumour syndrome caused by germline activating mutations of the RET proto-oncogene. […] Recommendations on the timing of prophylactic thyroidectomy and extent of surgery are based on a classification of RET mutations into three risk levels using the genotype-phenotype correlations. […] The diagnosis of FMTC can only be considered when four or more family members across a wide range of ages have isolated MTC. […] The association between disease phenotype and RET mutation genotype may have important implications for the clinical management of MEN2 patients and their families. […] Recommendations for the timing of prophylactic thyroidectomy and the extent of surgery are based upon a model that utilizes these genotype-phenotype correlations to stratify mutations into three risk levels. […] This genotype-phenotype correlation of age at onset and aggressiveness of MTC is the basis for decision making in clinical management, especially in pre-symptomatic RET mutation carriers, as prophylactic thyroidectomy has to be performed prior to the development of cancer.

• #16 Multiple Endocrine Neoplasia Type 2 – GeneReviews® – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK1257/

  FMTC should be suspected in families with more than one individual diagnosed with MTC in the absence of pheochromocytoma or parathyroid adenoma/hyperplasia. […] MEN2B should be suspected in individuals with distinctive facies including lip mucosal neuromas resulting in thick vermilion of the upper and lower lip, mucosal neuromas of the lips and tongue, medullated corneal nerve fibers, marfanoid habitus, and MTC. […] The clinical diagnosis of MEN2 can be established in a proband based on clinical diagnostic criteria, or the molecular diagnosis can be established in a proband with suggestive findings and a heterozygous germline gain-of-function pathogenic (or likely pathogenic) variant in RET identified by molecular genetic testing. […] Molecular genetic testing approaches can include single-gene testing or use of a multigene panel.

• #17 Multiple Endocrine Neoplasia Type 2: Diagnosis and Treatment

  https://www.massgeneral.org/children/multiple-endocrine-neoplasia-type-2/diagnosis-treatment

  How do doctors diagnose multiple endocrine neoplasia type 2 (MEN2)? […] How doctors diagnose MEN2 depends on whether your child has MEN2A or MEN2B. […] Children are usually diagnosed because a parent or relative has MEN2A. Doctors can diagnose MEN2A in the following ways: Medical and family history, Physical exam, Genetic testing, If your child or close relatives have at least 2 of the 3 following conditions: MTC, pheochromocytomas, parathyroid adenoma or hyperplasia (when an organ or tissue becomes enlarged). […] If your child has a combination of MTC and mucosal neuromas. […] Physical exam for the following features: protruding lips, thin facial features, a thin body type and medullated corneal nerve fibers in the eye. […] Early and consistent screening is extremely important because many symptoms of MEN2 are not noticeable until adulthood.

• #18 Multiple Endocrine Neoplasia (MEN): Types & Symptoms

  https://my.clevelandclinic.org/health/diseases/23088-multiple-endocrine-neoplasia-men

  A person is diagnosed with MEN type 2 if they have medullary thyroid cancer (MTC) and pheochromocytoma and/or parathyroid enlargement (hyperplasia) or tumor (adenoma). […] Before a healthcare provider can diagnose MEN type 2, they need to diagnose medullary thyroid cancer (MTC) and other types of tumors in the individual. […] A variety of blood tests can detect elevated levels of certain hormones, which can be a sign of MTC and other tumors. For example: Higher-than-normal levels of calcitonin can indicate MTC. […] Healthcare providers then use imaging tests, such as CT (computed tomography) scans or MRI (magnetic resonance imaging) scans, to help find and diagnose tumors associated with MEN type 2. […] Providers can also confirm a MEN type 2 diagnosis through genetic testing of the RET gene.

• #19 Multiple Endocrine Neoplasia Type 2 (MEN2) Workup: Approach Considerations, Genetic Testing, Screening for Cancer and Hyperparathyroidism

  https://emedicine.medscape.com/article/123447-workup

  Genetic testing is the mainstay in the diagnosis of multiple endocrine neoplasia type 2 (MEN2) syndromes. Perform genetic screening for RET mutations in all index patients. If a mutation is identified, also screen family members who are at risk. […] For individuals identified with a mutation or for persons who are at risk, biochemical screening consists of baseline calcitonin levels, serum calcium and parathyroid hormone (PTH) levels, along with urine collection for catecholamines and metanephrine concentrations. (However, a plasma metanephrine level can be used for screening.) […] Patients who have been diagnosed with medullary thyroid carcinoma require serial calcitonin (with or without provocative testing) and carcinoembryonic antigen (CEA) testing after neck surgery to assess for persistent or recurrent disease.

• #20 Multiple Endocrine Neoplasia Type 2 (MEN2) Workup: Approach Considerations, Genetic Testing, Screening for Cancer and Hyperparathyroidism

  https://emedicine.medscape.com/article/123447-workup

  Calcitonin is the principal biochemical marker in medullary thyroid carcinoma (MTC); measurement of calcitonin is used for detection, staging, postoperative management, and determining prognosis. The higher the calcitonin levels are above normal, the greater the likelihood of MTC; basal levels of 100 pg/mL have been found to have 100% positive predictive value for MTC. […] Traditionally, a pentagastrin-induced rise in calcitonin secretion has been used to diagnose MTC; however, pentagastrin is not available in the United States, and DNA testing for RET has replaced this diagnostic method in familial cases. […] Urinary catecholamine and metanephrine levels screen for pheochromocytomas. If these are elevated, imaging studies of the adrenals are recommended. […] Serum calcium and PTH levels screen for hyperparathyroidism. An inappropriately normal or elevated PTH level in relation to the elevated serum calcium is consistent with primary hyperparathyroidism. If the 24-hour urine calcium level is low, the presence of familial hypocalciuric hypercalcemic syndrome should be considered. […] Diagnostic studies for medullary thyroid cancer, primary hyperparathyroidism, pheochromocytoma, etc. as mentioned above.

• #21 Multiple Endocrine Neoplasia (MEN) Type 2 | American Thyroid Association

  https://www.thyroid.org/multiple-endocrine-neoplasia-men-type-2/

  MEN 2 (Multiple Endocrine Neoplasia Syndrome type 2) is a group of diseases including a type of thyroid cancer called Medullary Thyroid Cancer (MTC). […] This gene mutation can be found with a blood test for genetic testing. […] It is important for your doctor to know the exact change you have in the RET gene to know your risk for getting the diseases in MEN2. […] If you are diagnosed with either form of MEN2, you will need life-long monitoring by an endocrinologist. […] MTC is diagnosed when a lump is found in your thyroid gland on exam, neck ultrasound or other type of X-ray. […] You might have high levels of calcitonin and/or CEA on a blood test. […] A biopsy of the lump in your thyroid gland can show MTC cells. […] In MEN 2, PHEO is usually a benign tumor and not cancer. […] Testing for HD can include: X-ray of the abdomen, Biopsy (sample of tissue) from your large intestine.

• #22 Multiple Endocrine Neoplasia Type 2 (MEN2) Workup: Approach Considerations, Genetic Testing, Screening for Cancer and Hyperparathyroidism

  https://emedicine.medscape.com/article/123447-workup

  Genetic testing is the mainstay in the diagnosis of multiple endocrine neoplasia type 2 (MEN2) syndromes. Perform genetic screening for RET mutations in all index patients. If a mutation is identified, also screen family members who are at risk. […] For individuals identified with a mutation or for persons who are at risk, biochemical screening consists of baseline calcitonin levels, serum calcium and parathyroid hormone (PTH) levels, along with urine collection for catecholamines and metanephrine concentrations. (However, a plasma metanephrine level can be used for screening.) […] Patients who have been diagnosed with medullary thyroid carcinoma require serial calcitonin (with or without provocative testing) and carcinoembryonic antigen (CEA) testing after neck surgery to assess for persistent or recurrent disease.

• #23 Multiple Endocrine Neoplasia Type 2 (MEN2) Workup: Approach Considerations, Genetic Testing, Screening for Cancer and Hyperparathyroidism

  https://emedicine.medscape.com/article/123447-workup

  Calcitonin is the principal biochemical marker in medullary thyroid carcinoma (MTC); measurement of calcitonin is used for detection, staging, postoperative management, and determining prognosis. The higher the calcitonin levels are above normal, the greater the likelihood of MTC; basal levels of 100 pg/mL have been found to have 100% positive predictive value for MTC. […] Traditionally, a pentagastrin-induced rise in calcitonin secretion has been used to diagnose MTC; however, pentagastrin is not available in the United States, and DNA testing for RET has replaced this diagnostic method in familial cases. […] Urinary catecholamine and metanephrine levels screen for pheochromocytomas. If these are elevated, imaging studies of the adrenals are recommended. […] Serum calcium and PTH levels screen for hyperparathyroidism. An inappropriately normal or elevated PTH level in relation to the elevated serum calcium is consistent with primary hyperparathyroidism. If the 24-hour urine calcium level is low, the presence of familial hypocalciuric hypercalcemic syndrome should be considered. […] Diagnostic studies for medullary thyroid cancer, primary hyperparathyroidism, pheochromocytoma, etc. as mentioned above.

• #24 Diagnosis and surgical treatment of multiple endocrine neoplasia type 2A | World Journal of Surgical Oncology | Full Text

  https://wjso.biomedcentral.com/articles/10.1186/1477-7819-12-8

  Pheochromocytoma is an adrenal gland tumor that produces excess adrenaline; VMA is a terminal metabolite of adrenaline. Some researchers have demonstrated that urinary VMA is specific and sensitive to the diagnosis of pheochromocytoma. […] Imaging examinations such as B-mode ultrasonography, MRI, and CT, play a vital role in initial tumor localization and the management of MEN 2A. […] Surgical excision is the main mode of management of MEN 2A patients. […] In conclusion, MEN 2A can be diagnosed by biochemical tests and imaging examination when genetic testing is not available. Surgical excision is the predominant way to treat MEN 2A and pheochromocytoma should be excised at first when pheochromocytoma and MTC occur simultaneously.

• #25 Multiple Endocrine Neoplasia Type 2 (MEN2) Workup: Approach Considerations, Genetic Testing, Screening for Cancer and Hyperparathyroidism

  https://emedicine.medscape.com/article/123447-workup

  Calcitonin is the principal biochemical marker in medullary thyroid carcinoma (MTC); measurement of calcitonin is used for detection, staging, postoperative management, and determining prognosis. The higher the calcitonin levels are above normal, the greater the likelihood of MTC; basal levels of 100 pg/mL have been found to have 100% positive predictive value for MTC. […] Traditionally, a pentagastrin-induced rise in calcitonin secretion has been used to diagnose MTC; however, pentagastrin is not available in the United States, and DNA testing for RET has replaced this diagnostic method in familial cases. […] Urinary catecholamine and metanephrine levels screen for pheochromocytomas. If these are elevated, imaging studies of the adrenals are recommended. […] Serum calcium and PTH levels screen for hyperparathyroidism. An inappropriately normal or elevated PTH level in relation to the elevated serum calcium is consistent with primary hyperparathyroidism. If the 24-hour urine calcium level is low, the presence of familial hypocalciuric hypercalcemic syndrome should be considered. […] Diagnostic studies for medullary thyroid cancer, primary hyperparathyroidism, pheochromocytoma, etc. as mentioned above.

• #26 Multiple Endocrine Neoplasia Type 2 (MEN2) Workup: Approach Considerations, Genetic Testing, Screening for Cancer and Hyperparathyroidism

  https://emedicine.medscape.com/article/123447-workup

  Calcitonin is the principal biochemical marker in medullary thyroid carcinoma (MTC); measurement of calcitonin is used for detection, staging, postoperative management, and determining prognosis. The higher the calcitonin levels are above normal, the greater the likelihood of MTC; basal levels of 100 pg/mL have been found to have 100% positive predictive value for MTC. […] Traditionally, a pentagastrin-induced rise in calcitonin secretion has been used to diagnose MTC; however, pentagastrin is not available in the United States, and DNA testing for RET has replaced this diagnostic method in familial cases. […] Urinary catecholamine and metanephrine levels screen for pheochromocytomas. If these are elevated, imaging studies of the adrenals are recommended. […] Serum calcium and PTH levels screen for hyperparathyroidism. An inappropriately normal or elevated PTH level in relation to the elevated serum calcium is consistent with primary hyperparathyroidism. If the 24-hour urine calcium level is low, the presence of familial hypocalciuric hypercalcemic syndrome should be considered. […] Diagnostic studies for medullary thyroid cancer, primary hyperparathyroidism, pheochromocytoma, etc. as mentioned above.

• #27 Multiple Endocrine Neoplasia (MEN): Types & Symptoms

  https://my.clevelandclinic.org/health/diseases/23088-multiple-endocrine-neoplasia-men

  A person is diagnosed with MEN type 2 if they have medullary thyroid cancer (MTC) and pheochromocytoma and/or parathyroid enlargement (hyperplasia) or tumor (adenoma). […] Before a healthcare provider can diagnose MEN type 2, they need to diagnose medullary thyroid cancer (MTC) and other types of tumors in the individual. […] A variety of blood tests can detect elevated levels of certain hormones, which can be a sign of MTC and other tumors. For example: Higher-than-normal levels of calcitonin can indicate MTC. […] Healthcare providers then use imaging tests, such as CT (computed tomography) scans or MRI (magnetic resonance imaging) scans, to help find and diagnose tumors associated with MEN type 2. […] Providers can also confirm a MEN type 2 diagnosis through genetic testing of the RET gene.

• #28 Diagnosis and surgical treatment of multiple endocrine neoplasia type 2A | World Journal of Surgical Oncology | Full Text

  https://wjso.biomedcentral.com/articles/10.1186/1477-7819-12-8

  Pheochromocytoma is an adrenal gland tumor that produces excess adrenaline; VMA is a terminal metabolite of adrenaline. Some researchers have demonstrated that urinary VMA is specific and sensitive to the diagnosis of pheochromocytoma. […] Imaging examinations such as B-mode ultrasonography, MRI, and CT, play a vital role in initial tumor localization and the management of MEN 2A. […] Surgical excision is the main mode of management of MEN 2A patients. […] In conclusion, MEN 2A can be diagnosed by biochemical tests and imaging examination when genetic testing is not available. Surgical excision is the predominant way to treat MEN 2A and pheochromocytoma should be excised at first when pheochromocytoma and MTC occur simultaneously.

• #29 Orphanet: Multiple endocrine neoplasia type 2

  https://www.orpha.net/en/disease/detail/653

  A rare multiple endocrine neoplasia (MEN) syndrome that is principally characterized by the association of medullary thyroid carcinoma (MTC) with other endocrine tumors. The variant MEN 2A is defined by MTC associated with pheochromocytoma and/or primary hyperparathyroidism (MEN2A); the variant MEN 2B is defined as an aggressive form of MTC in association with pheochromocytoma but without primary hyperparathyroidism. […] Clinical diagnosis involves identification of MTC, PCC, and eventually PHPT. MTC is diagnosed by ultrasound (US) of the neck and serum levels of calcitonic (Ctn) and carcinoembryonic antigen (CEA). Screening of PCC consists of measuring metanephrines and normetanephrines from either free plasma or a 24-hour urine test. Adrenal imaging with CT or MRI is indicated in patients with positive biochemical results. A positive genetic test of RET confirms the clinical diagnosis in affected patients.

• #30 Multiple Endocrine Neoplasia (MEN) Type 2 | American Thyroid Association

  https://www.thyroid.org/multiple-endocrine-neoplasia-men-type-2/

  MEN 2 (Multiple Endocrine Neoplasia Syndrome type 2) is a group of diseases including a type of thyroid cancer called Medullary Thyroid Cancer (MTC). […] This gene mutation can be found with a blood test for genetic testing. […] It is important for your doctor to know the exact change you have in the RET gene to know your risk for getting the diseases in MEN2. […] If you are diagnosed with either form of MEN2, you will need life-long monitoring by an endocrinologist. […] MTC is diagnosed when a lump is found in your thyroid gland on exam, neck ultrasound or other type of X-ray. […] You might have high levels of calcitonin and/or CEA on a blood test. […] A biopsy of the lump in your thyroid gland can show MTC cells. […] In MEN 2, PHEO is usually a benign tumor and not cancer. […] Testing for HD can include: X-ray of the abdomen, Biopsy (sample of tissue) from your large intestine.

• #31 Orphanet: Multiple endocrine neoplasia type 2

  https://www.orpha.net/en/disease/detail/653

  A rare multiple endocrine neoplasia (MEN) syndrome that is principally characterized by the association of medullary thyroid carcinoma (MTC) with other endocrine tumors. The variant MEN 2A is defined by MTC associated with pheochromocytoma and/or primary hyperparathyroidism (MEN2A); the variant MEN 2B is defined as an aggressive form of MTC in association with pheochromocytoma but without primary hyperparathyroidism. […] Clinical diagnosis involves identification of MTC, PCC, and eventually PHPT. MTC is diagnosed by ultrasound (US) of the neck and serum levels of calcitonic (Ctn) and carcinoembryonic antigen (CEA). Screening of PCC consists of measuring metanephrines and normetanephrines from either free plasma or a 24-hour urine test. Adrenal imaging with CT or MRI is indicated in patients with positive biochemical results. A positive genetic test of RET confirms the clinical diagnosis in affected patients.

• #32 Multiple Endocrine Neoplasia Type 2 (MEN2) | Doctor

  https://patient.info/doctor/multiple-endocrine-neoplasia-type-2-men2

  The diagnosis of MEN2 is established when a RET pathological variant is detected by molecular genetic testing. […] Screening test for phaeochromocytoma is 24 hours urine for elevated catecholamines and catecholamine metabolites, especially vanillyl-mandelic acid (VMA). […] Clinical suspicion or elevated urinary catecholamine values demand an abdominal MRI scan. A metaiodobenzylguanidine (MIBG) scan is useful for localising phaeochromocytomas. […] MTC is suspected with an elevated plasma calcitonin concentration. This is a specific and sensitive marker. In provocative testing, plasma calcitonin concentration is measured before and two and five minutes after intravenous administration of calcium. […] Thyroid tumours can be investigated initially by ultrasound and fine-needle aspiration. […] Parathyroid abnormalities are diagnosed when there are simultaneously elevated serum calcium and parathyroid hormone levels with an elevated urinary calcium to creatinine ratio.

• #33 Multiple Endocrine Neoplasia Type 2 (MEN2) (PDQ®): Genetics – Health Professional Information [NCI] | Kaiser Permanente

  https://healthy.kaiserpermanente.org/health-wellness/health-encyclopedia/he.multiple-endocrine-neoplasia-type-2-men2-pdq%C2%AE-genetics-health-professional-information-nci.ncicdr0000813377

  Diagnosis of the two MEN2 clinical subtypes relies on a combination of clinical findings, family history, and molecular genetic testing of the RET gene. […] The risk of developing a PHEO is elevated in individuals with multiple endocrine neoplasia type 2A (MEN2A) and multiple endocrine neoplasia type 2B (MEN2B). However, the degree of risk depends on which specific RET pathogenic variant is involved. […] Confirmation of the diagnosis can be made using iodine I 131-metaiodobenzylguanidine scintigraphy or positron emission tomography imaging. […] Genetic testing can identify people with asymptomatic MEN2. These individuals can consider biochemical screening and early thyroidectomy as preventive measures. All MEN2 subtypes are inherited in an autosomal dominant manner. The risk of inheriting the RET pathogenic variant is 50% in children of individuals with MEN2. […] In rare circumstances, genetic testing is negative in a patient with a personal or family history suggestive of MEN2. Negative pathogenic variant analysis in at-risk relatives is informative only after a disease-causing pathogenic variant has been identified in an affected relative.

• #34 Multiple endocrine neoplasia, type 2 (MEN 2) – Symptoms and causes – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/men-2/symptoms-causes/syc-20540486

  Multiple endocrine neoplasia, type 2, also called MEN 2, is a rare condition. Genetic testing can find the changed gene that causes MEN 2. Health care providers can treat the health issues that gene may cause. […] People diagnosed with medullary thyroid cancer are screened regularly for MEN 2. […] Genetic testing is used to find out if someone has a changed gene that causes MEN 2. Children of someone who has this changed gene could inherit it and develop MEN 2. Parents and siblings also could have the changed gene even if they don’t have symptoms. […] If someone in your family is diagnosed with MEN 2, your health care provider will likely recommend you and your family members have genetic testing. This is because MEN 2 can be treated or managed by removing the thyroid gland early in life. Being screened for parathyroid or adrenal tumors also can help.

• #35 Multiple Endocrine Neoplasias Type 2 – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK519054/

  The type of mutations not only determine the expressivity and penetrance of the disease but also spares the effort to test for all the possible mutations in all the family members and determine when to start the screening process for associated tumors and when to do the prophylactic surgery. […] For an index patient with suspected MEN2A, evaluation begins with testing for the most common mutated codons in exons 10 and 11, and if negative, we move on to look for other common mutations in descending order. […] The same is done for the index patient with MEN2B phenotype. […] Once the RET genotyping is positive in index patients or an asymptomatic patient with positive family history, biochemical and radiological screening for other tumors is started as described below. […] The goal for screening in patients with known RET mutations but without clinically apparent disease is to perform a prophylactic thyroidectomy before MTC develops or when it is still confined to the thyroid gland.

• #36 Orphanet: Multiple endocrine neoplasia type 2

  https://www.orpha.net/en/disease/detail/653

  Prenatal diagnosis is possible where the mutation has previously been identified in a family member. […] RET mutation predicts the clinical phenotype and guides treatment. As recommended by the American thyroid association, management and treatment is stratified according to risk of aggressive MTC: highest risk (HST); high risk (H); moderate risk (MOD). All patients require evaluation of serum Ctn every 6 months for the first year, then annually if serum Ctn remains normal or undetectable. Annual US of the neck is indicated for both H and HST categories. Total thyroidectomy (TTX) should be performed when the serum Ctn level becomes elevated in MOD, and at or before 5 years of age (based on serum Ctn levels) for H and HST risk groups. Life-long thyroid hormone supplementation is needed after thyroid removal. The tyrosine kinase inhibitors, vandetanib and cabozantinib, are approved (in the USA and Europe) for the treatment of patients with advanced progressive MTC. MEN2A patients in the H and MOD risk groups should be simultaneously screened for PHPT and PCC. Only visibly enlarged parathyroids should be resected.

• #37 Multiple Endocrine Neoplasia Type 2 – GeneReviews® – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK1257/

  Single-gene testing. Sequence analysis of RET detects missense, nonsense, and splice site variants and small intragenic deletions/insertions. […] Targeted analysis for RET pathogenic variants p.Met918Thr and p.Ala883Phe can be considered first in those with suspected MEN2B. […] Molecular genetic testing should be offered to at-risk children by age five years. […] Molecular genetic testing should be performed as soon as possible after birth in all children known to be at risk.

• #38 Multiple endocrine neoplasia type 2: An overview | Genetics in Medicine

  https://www.nature.com/articles/gim2011127

  FMTC is historically operationally diagnosed in families with four or more cases of MTC in the absence of pheochromocytoma or parathyroid adenoma/hyperplasia. […] MEN 2B is diagnosed clinically by the presence of mucosal neuromas of the lips and tongue, as well as medullated corneal nerve fibers, distinctive facies with enlarged lips, an asthenic Marfanoid body habitus, and MTC. […] RET is the only gene known to be associated with MEN 2. RET molecular genetic testing is indicated in all individuals with a diagnosis of MTC, a clinical diagnosis of MEN 2, or primary CCH. […] All individuals with MTC, irregardless of other features or family history, and those with clinical features suspicious for MEN 2 and/or with family history suspicious of MEN 2 should be offered germline RET testing for exons 10, 11, and 1316; ideally, testing should be completed preoperatively and with genetic counseling. […] Molecular genetic testing should be performed as soon as possible after birth in all children known to be at risk for MEN 2B. […] In families with MEN 2A or FMTC, molecular genetic testing should be offered to at-risk children by age 5 years, as MTC has been documented in childhood.

• #39 Multiple Endocrine Neoplasias Type 2 – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK519054/

  For children tested positive for high-risk mutations, monitoring starts at three years of age, and for children with moderate risk mutations, monitoring starts at five years of age. […] The presence of primary hyperthyroidism alone does not indicate for further testing as their is less than 20% association with MEN2A and no association with MEN2B. […] Prior to unilateral or bilateral adrenalectomy, patients should be treated with alpha-blockade preoperatively; the patient should receive glucocorticoid stress coverage while awaiting transfer to the surgery.

• #40 Multiple Endocrine Neoplasia in Childhood: An Update on Diagnosis, Screening, Management and Treatment

  https://www.mdpi.com/2673-396X/3/1/7

  Children born to parents with MEN2B should obtain genetic testing for RET mutations. […] Annual serum calcitonin screening should begin at age 6 months in children with MEN2B and age 3 to 5 years in those with MEN2A or history of FMTC. […] The decision for bilateral or unilateral adrenalectomy depends upon the presence of bilateral or unilateral PHEOs, respectively, but also the risk for adrenal insufficiency.

• #41 Multiple Endocrine Neoplasia Type 2: Diagnosis and Treatment

  https://www.massgeneral.org/children/multiple-endocrine-neoplasia-type-2/diagnosis-treatment

  Children with MEN2 need follow-up care and screening for the remainder of their lives. They should also be screened every year for pheochromocytoma and hyperparathyroidism, even after removal of the thyroid gland. […] If your child has a thyroidectomy for MCT, they will need physical exams and tests every 3-6 months. Follow-up exams can be done yearly if your child’s symptoms get better over an extended period.

• #42 Multiple Endocrine Neoplasia Type 2 | Children’s Hospital of Philadelphia

  https://www.chop.edu/conditions-diseases/multiple-endocrine-neoplasia-type-2

  Children diagnosed with MEN2 will need lifelong follow-up care and cancer screening. In the first few years after thyroidectomy, your child will require physical exams and laboratory tests every three to six months. […] All patients diagnosed with MEN2 even if they have no symptoms should be screened annually for the presence of pheochromocytoma and hyperparathyroidism. The American Thyroid Association recommends yearly screening for these tumors beginning at age 11 for patients with MEN2B, and by age 16 for patients with MEN2A.

• #43 Multiple Endocrine Neoplasia Type 2 | Children’s Hospital of Philadelphia

  https://www.chop.edu/conditions-diseases/multiple-endocrine-neoplasia-type-2

  Children diagnosed with MEN2 will need lifelong follow-up care and cancer screening. In the first few years after thyroidectomy, your child will require physical exams and laboratory tests every three to six months. […] All patients diagnosed with MEN2 even if they have no symptoms should be screened annually for the presence of pheochromocytoma and hyperparathyroidism. The American Thyroid Association recommends yearly screening for these tumors beginning at age 11 for patients with MEN2B, and by age 16 for patients with MEN2A.

• #44 Multiple endocrine neoplasia, type 2 (MEN 2) – Symptoms and causes – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/men-2/symptoms-causes/syc-20540486

  If no gene changes are found in family members, usually no other screening tests are needed. However, genetic testing doesn’t find all MEN 2 gene changes. If MEN 2 isn’t found in people who may have it, they and their family members will have regular blood and imaging tests over time to check for signs of the disease.

• #45 Multiple Endocrine Neoplasia (MEN) Type 2 | American Thyroid Association

  https://www.thyroid.org/multiple-endocrine-neoplasia-men-type-2/

  MEN 2 (Multiple Endocrine Neoplasia Syndrome type 2) is a group of diseases including a type of thyroid cancer called Medullary Thyroid Cancer (MTC). […] This gene mutation can be found with a blood test for genetic testing. […] It is important for your doctor to know the exact change you have in the RET gene to know your risk for getting the diseases in MEN2. […] If you are diagnosed with either form of MEN2, you will need life-long monitoring by an endocrinologist. […] MTC is diagnosed when a lump is found in your thyroid gland on exam, neck ultrasound or other type of X-ray. […] You might have high levels of calcitonin and/or CEA on a blood test. […] A biopsy of the lump in your thyroid gland can show MTC cells. […] In MEN 2, PHEO is usually a benign tumor and not cancer. […] Testing for HD can include: X-ray of the abdomen, Biopsy (sample of tissue) from your large intestine.

• #46 Multiple Endocrine Neoplasia Type 2: Diagnosis and Treatment

  https://www.massgeneral.org/children/multiple-endocrine-neoplasia-type-2/diagnosis-treatment

  Children with MEN2 need follow-up care and screening for the remainder of their lives. They should also be screened every year for pheochromocytoma and hyperparathyroidism, even after removal of the thyroid gland. […] If your child has a thyroidectomy for MCT, they will need physical exams and tests every 3-6 months. Follow-up exams can be done yearly if your child’s symptoms get better over an extended period.

• #47 Orphanet: Multiple endocrine neoplasia type 2

  https://www.orpha.net/en/disease/detail/653

  Prenatal diagnosis is possible where the mutation has previously been identified in a family member. […] RET mutation predicts the clinical phenotype and guides treatment. As recommended by the American thyroid association, management and treatment is stratified according to risk of aggressive MTC: highest risk (HST); high risk (H); moderate risk (MOD). All patients require evaluation of serum Ctn every 6 months for the first year, then annually if serum Ctn remains normal or undetectable. Annual US of the neck is indicated for both H and HST categories. Total thyroidectomy (TTX) should be performed when the serum Ctn level becomes elevated in MOD, and at or before 5 years of age (based on serum Ctn levels) for H and HST risk groups. Life-long thyroid hormone supplementation is needed after thyroid removal. The tyrosine kinase inhibitors, vandetanib and cabozantinib, are approved (in the USA and Europe) for the treatment of patients with advanced progressive MTC. MEN2A patients in the H and MOD risk groups should be simultaneously screened for PHPT and PCC. Only visibly enlarged parathyroids should be resected.

• #48 Orphanet: Multiple endocrine neoplasia type 2

  https://www.orpha.net/en/disease/detail/653

  Prenatal diagnosis is possible where the mutation has previously been identified in a family member. […] RET mutation predicts the clinical phenotype and guides treatment. As recommended by the American thyroid association, management and treatment is stratified according to risk of aggressive MTC: highest risk (HST); high risk (H); moderate risk (MOD). All patients require evaluation of serum Ctn every 6 months for the first year, then annually if serum Ctn remains normal or undetectable. Annual US of the neck is indicated for both H and HST categories. Total thyroidectomy (TTX) should be performed when the serum Ctn level becomes elevated in MOD, and at or before 5 years of age (based on serum Ctn levels) for H and HST risk groups. Life-long thyroid hormone supplementation is needed after thyroid removal. The tyrosine kinase inhibitors, vandetanib and cabozantinib, are approved (in the USA and Europe) for the treatment of patients with advanced progressive MTC. MEN2A patients in the H and MOD risk groups should be simultaneously screened for PHPT and PCC. Only visibly enlarged parathyroids should be resected.

• #49 Multiple endocrine neoplasia 2 (MEN2) | Macmillan Cancer Support

  https://www.macmillan.org.uk/cancer-information-and-support/worried-about-cancer/pre-cancerous-and-genetic-conditions/multiple-endocrine-neoplasia-2-men2

  The tests can also be used to check for MEN2 tumours before you have any symptoms. This is called screening or monitoring. Screening helps your doctor find and treat tumours at an early stage, usually before symptoms begin to cause problems. […] You will have a blood test every year to check your calcium and PTH levels. It is important to tell your doctor if you have any symptoms that may be caused by high levels of calcium in between screening tests.

• #50 Multiple endocrine neoplasia 2 (MEN2) | Macmillan Cancer Support

  https://www.macmillan.org.uk/cancer-information-and-support/worried-about-cancer/pre-cancerous-and-genetic-conditions/multiple-endocrine-neoplasia-2-men2

  The tests can also be used to check for MEN2 tumours before you have any symptoms. This is called screening or monitoring. Screening helps your doctor find and treat tumours at an early stage, usually before symptoms begin to cause problems. […] You will have a blood test every year to check your calcium and PTH levels. It is important to tell your doctor if you have any symptoms that may be caused by high levels of calcium in between screening tests.

• #51 Clinical manifestations and diagnosis of multiple endocrine neoplasia type 2 – UpToDate

  https://www.uptodate.com/contents/clinical-manifestations-and-diagnosis-of-multiple-endocrine-neoplasia-type-2/print

  Clinical manifestations and diagnosis of multiple endocrine neoplasia type 2 […] Multiple endocrine neoplasia type 2 (MEN2) is an autosomal dominant disorder with an estimated prevalence of 1 per 30,000 in the general population. MEN2 is subclassified into two distinct syndromes: types 2A (MEN2A) and 2B (MEN2B). Within MEN2A, there are four variants: classical MEN2A, MEN2A with cutaneous lichen amyloidosis (CLA), MEN2A with Hirschsprung disease (HD), and familial medullary thyroid cancer (FMTC) (table 1). […] The genetic defect in these disorders involves the RET proto-oncogene on chromosome 10. MEN2A and 2B are inherited in an autosomal dominant pattern with very high penetrance. In both syndromes, there is an occurrence of multicentric tumor formation in all organs where the RET proto-oncogene is expressed. The thyroid, parathyroid, and adrenal glands are at risk for developing tumors that may reduce life expectancy and quality of life. The excellent prognosis for medullary thyroid cancer (MTC) diagnosed at its earliest stage underscores the importance of early diagnosis for sporadic and hereditary MTC. […] This topic will review the clinical manifestations, diagnosis, and evaluation of MEN2. The genetics and treatment of this disorder are discussed separately. Sporadic MTC is also discussed separately.

• #52 Multiple Endocrine Neoplasia Type 2 (MEN2) (PDQ®): Genetics – Health Professional Information [NCI] | Kaiser Permanente

  https://healthy.kaiserpermanente.org/health-wellness/health-encyclopedia/he.multiple-endocrine-neoplasia-type-2-men2-pdq%C2%AE-genetics-health-professional-information-nci.ncicdr0000813377

  Diagnosis of the two MEN2 clinical subtypes relies on a combination of clinical findings, family history, and molecular genetic testing of the RET gene. […] The risk of developing a PHEO is elevated in individuals with multiple endocrine neoplasia type 2A (MEN2A) and multiple endocrine neoplasia type 2B (MEN2B). However, the degree of risk depends on which specific RET pathogenic variant is involved. […] Confirmation of the diagnosis can be made using iodine I 131-metaiodobenzylguanidine scintigraphy or positron emission tomography imaging. […] Genetic testing can identify people with asymptomatic MEN2. These individuals can consider biochemical screening and early thyroidectomy as preventive measures. All MEN2 subtypes are inherited in an autosomal dominant manner. The risk of inheriting the RET pathogenic variant is 50% in children of individuals with MEN2. […] In rare circumstances, genetic testing is negative in a patient with a personal or family history suggestive of MEN2. Negative pathogenic variant analysis in at-risk relatives is informative only after a disease-causing pathogenic variant has been identified in an affected relative.

• #53 Multiple Endocrine Neoplasia, Type 2A (MEN 2A) – Endocrine and Metabolic Disorders – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/endocrine-and-metabolic-disorders/multiple-endocrine-neoplasia-men-syndromes/multiple-endocrine-neoplasia-type-2a-men-2a

  Multiple endocrine neoplasia, type 2A (MEN 2A) is an autosomal dominant syndrome characterized by medullary carcinoma of the thyroid, pheochromocytoma, parathyroid hyperplasia or adenomas (causing hyperparathyroidism), and occasionally cutaneous lichen amyloidosis. […] Diagnosis is confirmed by genetic testing. Hormonal and imaging tests help locate the tumors, which are removed surgically when possible. […] Serum calcitonin for medullary thyroid carcinoma […] Plasma free metanephrines or urinary catecholamine and metanephrine levels for pheochromocytoma […] Genetic testing should be done in all patients with medullary thyroid carcinoma. […] The diagnosis can be confirmed with genetic testing. […] Genetic screening of family members of MEN 2A patients is the diagnostic test of choice; the availability of such testing has made biochemical screening for early medullary thyroid carcinoma largely obsolete. […] Prophylactic thyroidectomy is recommended; timing of the surgery may be influenced by the specific mutation.

• #54 Multiple Endocrine Neoplasia Type 2 | St. Jude Care & Treatment

  https://www.stjude.org/care-treatment/treatment/genetic-syndromes/multiple-endocrine-neoplasia-type-2.html

  Multiple endocrine neoplasia type 2 diagnosis […] A health care provider may suspect that your child has MEN2 after studying their medical and family cancer history. […] Your provider or genetics counselor may recommend genetic testing if they suspect MEN2. […] A blood sample is sent to a genetic testing lab. The lab runs genetic tests that look for changes in the RET gene. […] If your child has a RET mutation, a genetic counselor will work with your family to: Work with your family to see if other family members should be tested, Help your family understand their increased cancer risk, Give you information to help you with decisions about prenatal genetic testing. […] Patients have a clinical diagnosis of MEN2A when they or their close relatives have 2 or more of these conditions: Medullary thyroid cancer, Pheochromocytomas, Parathyroid adenoma/ hyperplasia. […] A person may be diagnosed with type MEN2B if they have medullary thyroid cancer and some of these conditions: Mucosal neuromas of the lips and tongue, Unusual features, such as a long face and lips that stick outward, A tall and slender body type, Abnormal nerves in the clear covering of the eyeball (medullated corneal nerve fibers). […] The diagnosis of familial medullary thyroid cancer is given if: A family has 4 or more family members with medullary thyroid cancer, None of the family members have pheochromocytomas, parathyroid adenoma, or parathyroid hyperplasia.

• #55 Clinical manifestations and diagnosis of multiple endocrine neoplasia type 2 – UpToDate

  https://www.uptodate.com/contents/clinical-manifestations-and-diagnosis-of-multiple-endocrine-neoplasia-type-2/print

  Clinical manifestations and diagnosis of multiple endocrine neoplasia type 2 […] Multiple endocrine neoplasia type 2 (MEN2) is an autosomal dominant disorder with an estimated prevalence of 1 per 30,000 in the general population. MEN2 is subclassified into two distinct syndromes: types 2A (MEN2A) and 2B (MEN2B). Within MEN2A, there are four variants: classical MEN2A, MEN2A with cutaneous lichen amyloidosis (CLA), MEN2A with Hirschsprung disease (HD), and familial medullary thyroid cancer (FMTC) (table 1). […] The genetic defect in these disorders involves the RET proto-oncogene on chromosome 10. MEN2A and 2B are inherited in an autosomal dominant pattern with very high penetrance. In both syndromes, there is an occurrence of multicentric tumor formation in all organs where the RET proto-oncogene is expressed. The thyroid, parathyroid, and adrenal glands are at risk for developing tumors that may reduce life expectancy and quality of life. The excellent prognosis for medullary thyroid cancer (MTC) diagnosed at its earliest stage underscores the importance of early diagnosis for sporadic and hereditary MTC. […] This topic will review the clinical manifestations, diagnosis, and evaluation of MEN2. The genetics and treatment of this disorder are discussed separately. Sporadic MTC is also discussed separately.

• #56 Multiple Endocrine Neoplasia, Type 2B (MEN 2B) – Endocrine and Metabolic Disorders – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/endocrine-and-metabolic-disorders/multiple-endocrine-neoplasia-men-syndromes/multiple-endocrine-neoplasia-type-2b-men-2b

  Multiple endocrine neoplasia, type 2B (MEN 2B) is an autosomal dominant syndrome characterized by medullary thyroid carcinoma, pheochromocytoma, multiple mucosal neuromas and intestinal ganglioneuromas, and often a marfanoid habitus and other skeletal abnormalities. […] Diagnosis is confirmed by genetic testing. Hormonal and imaging tests help locate the tumors, which are removed surgically when possible. […] MEN 2B is suspected in patients with a family history of MEN 2B, pheochromocytoma, multiple mucosal neuromas, or medullary thyroid carcinoma. Genetic testing is highly accurate and is done to confirm the disorder. Genetic testing also is done to screen 1st-degree relatives and any symptomatic family members of patients with MEN 2B, as in MEN 2A. […] Laboratory testing for medullary thyroid carcinoma with serum calcitonin measurements should be done. […] Patients should have genetic testing for RET proto-oncogene mutations, serum calcitonin measurement, blood or urine tests for pheochromocytoma, and imaging studies of the neck and adrenal glands.

• #57 Multiple endocrine neoplasia type 2B

  https://dermnetnz.org/topics/multiple-endocrine-neoplasia-type-2b

  Diagnosis of MEN type 2B is made clinically by the presence of: mucosal neuromas of the lips and tongue, medullated corneal nerve fibres in the eye, distinctive facies with enlarged lips, asthenic Marfanoid body habitus, medullary carcinoma of the thyroid. […] Molecular genetic testing can be used to confirm the diagnosis, for predictive testing and for prenatal diagnosis.

• #58

  https://link.springer.com/article/10.1007/s12020-021-02607-2

  Medullary thyroid carcinoma (MTC) in childhood is rare and has an unfavorable prognosis. To improve outcome, early diagnosis is essential. W pacjentach z zespołem mnogiej gruczołowej nowotworowej typu 2B (MEN2B) MTC może wystąpić już przed ukończeniem 1 roku życia. […] Neonatalne objawy ze strony przewodu pokarmowego oferują najważniejsze okno możliwości wczesnego wykrywania MEN2B. […] MEN2B gene analysis should follow detection of IGN and when confirmed should prompt possibly still curative thyroid surgery. […] Timely detection of the MEN2B syndrome is only possible if the complex of symptoms is recognized. […] Prevention or curation of MTC can be reached if IGN is timely recognized as the first non-endocrine manifestation of MEN2B. […] Oral neuromas/neurofibromas were the trigger to perform genetic analysis in two cases, while among the presenting symptoms in one more (out of eight cases), making it a second key element in diagnosing MEN2B. […] It is important to detect IGN in rectal biopsies even when the primary focus usually lies on the possible absence of ganglion cells, as by identification of IGN a harmful delay of diagnosis of MEN2B can be avoided.

• #59 Multiple endocrine neoplasia type 2: An overview | Genetics in Medicine

  https://www.nature.com/articles/gim2011127

  FMTC is historically operationally diagnosed in families with four or more cases of MTC in the absence of pheochromocytoma or parathyroid adenoma/hyperplasia. […] MEN 2B is diagnosed clinically by the presence of mucosal neuromas of the lips and tongue, as well as medullated corneal nerve fibers, distinctive facies with enlarged lips, an asthenic Marfanoid body habitus, and MTC. […] RET is the only gene known to be associated with MEN 2. RET molecular genetic testing is indicated in all individuals with a diagnosis of MTC, a clinical diagnosis of MEN 2, or primary CCH. […] All individuals with MTC, irregardless of other features or family history, and those with clinical features suspicious for MEN 2 and/or with family history suspicious of MEN 2 should be offered germline RET testing for exons 10, 11, and 1316; ideally, testing should be completed preoperatively and with genetic counseling. […] Molecular genetic testing should be performed as soon as possible after birth in all children known to be at risk for MEN 2B. […] In families with MEN 2A or FMTC, molecular genetic testing should be offered to at-risk children by age 5 years, as MTC has been documented in childhood.

• #60 Multiple Endocrine Neoplasia Type 2 | St. Jude Care & Treatment

  https://www.stjude.org/care-treatment/treatment/genetic-syndromes/multiple-endocrine-neoplasia-type-2.html

  Multiple endocrine neoplasia type 2 diagnosis […] A health care provider may suspect that your child has MEN2 after studying their medical and family cancer history. […] Your provider or genetics counselor may recommend genetic testing if they suspect MEN2. […] A blood sample is sent to a genetic testing lab. The lab runs genetic tests that look for changes in the RET gene. […] If your child has a RET mutation, a genetic counselor will work with your family to: Work with your family to see if other family members should be tested, Help your family understand their increased cancer risk, Give you information to help you with decisions about prenatal genetic testing. […] Patients have a clinical diagnosis of MEN2A when they or their close relatives have 2 or more of these conditions: Medullary thyroid cancer, Pheochromocytomas, Parathyroid adenoma/ hyperplasia. […] A person may be diagnosed with type MEN2B if they have medullary thyroid cancer and some of these conditions: Mucosal neuromas of the lips and tongue, Unusual features, such as a long face and lips that stick outward, A tall and slender body type, Abnormal nerves in the clear covering of the eyeball (medullated corneal nerve fibers). […] The diagnosis of familial medullary thyroid cancer is given if: A family has 4 or more family members with medullary thyroid cancer, None of the family members have pheochromocytomas, parathyroid adenoma, or parathyroid hyperplasia.

• #61 Clinical manifestations and diagnosis of multiple endocrine neoplasia type 2 – UpToDate

  https://www.uptodate.com/contents/clinical-manifestations-and-diagnosis-of-multiple-endocrine-neoplasia-type-2/print

  Clinical manifestations and diagnosis of multiple endocrine neoplasia type 2 […] Multiple endocrine neoplasia type 2 (MEN2) is an autosomal dominant disorder with an estimated prevalence of 1 per 30,000 in the general population. MEN2 is subclassified into two distinct syndromes: types 2A (MEN2A) and 2B (MEN2B). Within MEN2A, there are four variants: classical MEN2A, MEN2A with cutaneous lichen amyloidosis (CLA), MEN2A with Hirschsprung disease (HD), and familial medullary thyroid cancer (FMTC) (table 1). […] The genetic defect in these disorders involves the RET proto-oncogene on chromosome 10. MEN2A and 2B are inherited in an autosomal dominant pattern with very high penetrance. In both syndromes, there is an occurrence of multicentric tumor formation in all organs where the RET proto-oncogene is expressed. The thyroid, parathyroid, and adrenal glands are at risk for developing tumors that may reduce life expectancy and quality of life. The excellent prognosis for medullary thyroid cancer (MTC) diagnosed at its earliest stage underscores the importance of early diagnosis for sporadic and hereditary MTC. […] This topic will review the clinical manifestations, diagnosis, and evaluation of MEN2. The genetics and treatment of this disorder are discussed separately. Sporadic MTC is also discussed separately.

• #62 Multiple Endocrine Neoplasia Type 2 (MEN2): Practice Essentials, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/123447-overview

  Multiple endocrine neoplasias type 2 (MEN2) is an inherited disorder characterized by the development of medullary thyroid cancer (MTC), parathyroid tumors, and pheochromocytoma. MEN2 results from germline mutations in the RET proto-oncogene and is transmitted in an autosomal dominant fashion. There are two MEN2 syndromes: MEN2A and MEN2B. […] Early total thyroidectomy remains effective in preventing the development of MTC in the long term. […] Point mutations associated with MEN2A and the FMTC-only subtype have been identified in exons 10 and 11. […] The overall frequency of MEN2 in the United States is 1 case per 30,000-50,000 population. […] Early treatment of medullary thyroid carcinoma (MTC) can prevent death, and careful monitoring for pheochromocytomas can decrease the chance of hypertensive episodes.

• #63 Molecular diagnosis and comprehensive treatment of multiple endocrine neoplasia type 2 in Southeastern Chinese | Hereditary Cancer in Clinical Practice | Full Text

  https://hccpjournal.biomedcentral.com/articles/10.1186/s13053-015-0026-1

  Multiple endocrine neoplasia type 2 (MEN2) is an autosomal dominant inherited endocrine malignancy syndrome. […] MEN2 patients can be diagnosed early through systematic pedigree investigation and RET proto-oncogene screening. […] In recent years, combined detection of RET mutations and pre-operative calcitonin (pre-Ct) levels have been considered for comprehensive decision-making regarding the timing or surgical extent of prophylactic TT. […] Based on our results, integrated RET screening and the pre-operative calcitonin level is an excellent strategy to ensure earlier diagnosis and standard thyroidectomy. […] The asymptomatic RET carriers who underwent surgery benefited greatly from genetic screening and were a significantly younger age at the time of surgery and had a smaller tumor diameter compared with symptomatic patients. […] The disease-free survival (DFS) increased in the asymptomatic RET carriers who underwent surgery compared to the symptomatic patients. […] For advanced MTC, vandetanib provides novel treatment options. […] In patients with PHEOs, CSA can be utilized to preserve adrenocortical function.

• #64 Multiple Endocrine Neoplasias Type 2 – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK519054/

  The type of mutations not only determine the expressivity and penetrance of the disease but also spares the effort to test for all the possible mutations in all the family members and determine when to start the screening process for associated tumors and when to do the prophylactic surgery. […] For an index patient with suspected MEN2A, evaluation begins with testing for the most common mutated codons in exons 10 and 11, and if negative, we move on to look for other common mutations in descending order. […] The same is done for the index patient with MEN2B phenotype. […] Once the RET genotyping is positive in index patients or an asymptomatic patient with positive family history, biochemical and radiological screening for other tumors is started as described below. […] The goal for screening in patients with known RET mutations but without clinically apparent disease is to perform a prophylactic thyroidectomy before MTC develops or when it is still confined to the thyroid gland.

• #65 Multiple Endocrine Neoplasia | MD Anderson Cancer Center

  https://www.mdanderson.org/cancer-types/multiple-endocrine-neoplasia.html

  Multiple endocrine neoplasia type 2 (MEN2) is divided into three types: […] Genetic testing of blood samples can confirm a diagnosis of MEN2 and identify family members at risk of developing the disease. […] General recommendations are to remove the thyroid gland: […] However, these recommendations depend on the patient’s personal and family history. […] Pheochromocytoma is a tumor that occurs in the adrenal medulla that makes excess hormones called catecholamines (such as adrenaline). A pheochromocytoma is diagnosed in about 50% of people with MEN2A and MEN2B, although they do not occur in true FMTC. […] If detected early, pheochromocytomas are easily treated. However, if not treated, they may be potentially fatal due to dangerously high blood pressures that can occur during accidents, surgery, childbirth or other physically stressful situations.

• #66 Multiple endocrine neoplasia syndromes – Symptoms, diagnosis and treatment | BMJ Best Practice

  https://bestpractice.bmj.com/topics/en-gb/866

  Multiple endocrine neoplasia syndromes are hereditary tumour syndromes with distinct patterns of organ involvement. […] Mutations in the RET proto-oncogene typically cause type 2 multiple endocrine neoplasia (MEN2). […] Prophylactic thyroidectomy in childhood is indicated in MEN2. […] Medical management of hormonal hypersecretion is important for symptom control. […] Most tumours require surgical evaluation, although surgical cure is not always possible. […] Genetic carriers require lifelong monitoring, even after successful operations. […] Morbidity and mortality result from both hormonal hypersecretion and metastases. […] Key diagnostic factors include young age, positive family history, episodic triad of sweating, palpitations, and headache, and palpable thyroid nodule. […] 1st investigations to order include serum calcitonin, serum carcinoembryonic antigen, plasma metanephrines, and thyroid biopsy.

• #67 Molecular diagnosis and comprehensive treatment of multiple endocrine neoplasia type 2 in Southeastern Chinese | Hereditary Cancer in Clinical Practice | Full Text

  https://hccpjournal.biomedcentral.com/articles/10.1186/s13053-015-0026-1

  Multiple endocrine neoplasia type 2 (MEN2) is an autosomal dominant inherited endocrine malignancy syndrome. […] MEN2 patients can be diagnosed early through systematic pedigree investigation and RET proto-oncogene screening. […] In recent years, combined detection of RET mutations and pre-operative calcitonin (pre-Ct) levels have been considered for comprehensive decision-making regarding the timing or surgical extent of prophylactic TT. […] Based on our results, integrated RET screening and the pre-operative calcitonin level is an excellent strategy to ensure earlier diagnosis and standard thyroidectomy. […] The asymptomatic RET carriers who underwent surgery benefited greatly from genetic screening and were a significantly younger age at the time of surgery and had a smaller tumor diameter compared with symptomatic patients. […] The disease-free survival (DFS) increased in the asymptomatic RET carriers who underwent surgery compared to the symptomatic patients. […] For advanced MTC, vandetanib provides novel treatment options. […] In patients with PHEOs, CSA can be utilized to preserve adrenocortical function.

• #68 Molecular diagnosis and comprehensive treatment of multiple endocrine neoplasia type 2 in Southeastern Chinese | Hereditary Cancer in Clinical Practice | Full Text

  https://hccpjournal.biomedcentral.com/articles/10.1186/s13053-015-0026-1

  Multiple endocrine neoplasia type 2 (MEN2) is an autosomal dominant inherited endocrine malignancy syndrome. […] MEN2 patients can be diagnosed early through systematic pedigree investigation and RET proto-oncogene screening. […] In recent years, combined detection of RET mutations and pre-operative calcitonin (pre-Ct) levels have been considered for comprehensive decision-making regarding the timing or surgical extent of prophylactic TT. […] Based on our results, integrated RET screening and the pre-operative calcitonin level is an excellent strategy to ensure earlier diagnosis and standard thyroidectomy. […] The asymptomatic RET carriers who underwent surgery benefited greatly from genetic screening and were a significantly younger age at the time of surgery and had a smaller tumor diameter compared with symptomatic patients. […] The disease-free survival (DFS) increased in the asymptomatic RET carriers who underwent surgery compared to the symptomatic patients. […] For advanced MTC, vandetanib provides novel treatment options. […] In patients with PHEOs, CSA can be utilized to preserve adrenocortical function.

• #69 Multiple Endocrine Neoplasia Type 2 | Children’s Hospital of Philadelphia

  https://www.chop.edu/conditions-diseases/multiple-endocrine-neoplasia-type-2

  Most individuals are diagnosed with MEN2 because they or a close family member develops MTC. […] The true prevalence of MEN2 is likely underestimated because the disease may go unrecognized in certain individuals. It is important to identify this hereditary cancer syndrome early, as it often confers a high risk of tumors, which may occur at a younger-than-expected age. […] At Childrens Hospital of Philadelphia, a diagnosis of MEN2 begins with a complete medical and family history, as well as a comprehensive physical exam. […] In order to determine on a molecular level if your child has MEN2, a genetic test must be performed. A sample of your childs blood will be collected, then their DNA will be isolated and analyzed to determine if there are any alternations to the RET gene. […] It is important to note that not all patients with MEN2 carry a detectable alteration in the RET gene. Therefore, the failure to identify an alteration in the RET gene does not exclude the diagnosis of MEN2.

• #70 Multiple Endocrine Neoplasia Type 2 | Children’s Hospital of Philadelphia

  https://www.chop.edu/conditions-diseases/multiple-endocrine-neoplasia-type-2

  Most individuals are diagnosed with MEN2 because they or a close family member develops MTC. […] The true prevalence of MEN2 is likely underestimated because the disease may go unrecognized in certain individuals. It is important to identify this hereditary cancer syndrome early, as it often confers a high risk of tumors, which may occur at a younger-than-expected age. […] At Childrens Hospital of Philadelphia, a diagnosis of MEN2 begins with a complete medical and family history, as well as a comprehensive physical exam. […] In order to determine on a molecular level if your child has MEN2, a genetic test must be performed. A sample of your childs blood will be collected, then their DNA will be isolated and analyzed to determine if there are any alternations to the RET gene. […] It is important to note that not all patients with MEN2 carry a detectable alteration in the RET gene. Therefore, the failure to identify an alteration in the RET gene does not exclude the diagnosis of MEN2.

• #71 Multiple Endocrine Neoplasia Type 2 (MEN2) (PDQ®): Genetics – Health Professional Information [NCI] Health Library

  https://paleymd.com/patient-education/healthwise?DOCHWID=ncicdr0000813377

  While most MTC cases are sporadic, approximately 20% to 25% are hereditary. These hereditary cases are caused by pathogenic variants in the RET proto-oncogene. Between 1% and 10% of individuals with apparently sporadic MTC carry a germline RET pathogenic variant, underscoring the importance of genetic testing for all individuals diagnosed with MTC. […] The risk of inheriting the RET pathogenic variant is 50% in children of individuals with MEN2. Because early detection of at-risk individuals affects medical management, testing children without MEN2 symptoms can be beneficial. […] In rare circumstances, genetic testing is negative in a patient with a personal or family history suggestive of MEN2. Negative pathogenic variant analysis in at-risk relatives is informative only after a disease-causing pathogenic variant has been identified in an affected relative.

• #72 Multiple Endocrine Neoplasia Type 2 | Children’s Hospital of Philadelphia

  https://www.chop.edu/conditions-diseases/multiple-endocrine-neoplasia-type-2

  Most individuals are diagnosed with MEN2 because they or a close family member develops MTC. […] The true prevalence of MEN2 is likely underestimated because the disease may go unrecognized in certain individuals. It is important to identify this hereditary cancer syndrome early, as it often confers a high risk of tumors, which may occur at a younger-than-expected age. […] At Childrens Hospital of Philadelphia, a diagnosis of MEN2 begins with a complete medical and family history, as well as a comprehensive physical exam. […] In order to determine on a molecular level if your child has MEN2, a genetic test must be performed. A sample of your childs blood will be collected, then their DNA will be isolated and analyzed to determine if there are any alternations to the RET gene. […] It is important to note that not all patients with MEN2 carry a detectable alteration in the RET gene. Therefore, the failure to identify an alteration in the RET gene does not exclude the diagnosis of MEN2.

• #73 A Unique Presentation of Multiple Endocrine Neoplasia Type 2A | ACS

  https://www.facs.org/for-medical-professionals/news-publications/journals/case-reviews/issues/v4n8/20-romero-arenas-men2/

  This unique case of multiple endocrine neoplasia exemplifies the overlap between the two closely related syndromes, MEN2A and MEN2B. The patients presentation displayed features of both subtypes, highlighting the phenotypic variability within MEN2. Additionally, this case expands the known spectrum of mutations potentially associated with the MEN2A-megacolon phenotype by identifying a mutation on exon 11 beyond the previously reported mutations on exon 10. This finding suggests a broader mutational landscape for this rare complication.

• #74 Diagnosis and surgical treatment of multiple endocrine neoplasia type 2A | World Journal of Surgical Oncology | Full Text

  https://wjso.biomedcentral.com/articles/10.1186/1477-7819-12-8

  This study aims to introduce the diagnosis and surgical treatment of the rare disease multiple endocrine neoplasia type 2A (MEN 2A). […] Thirteen cases of MEN 2A were diagnosed as medullary thyroid carcinoma (MTC) and pheochromocytoma by biochemical tests and imaging examination. […] We confirmed that MEN 2A can be diagnosed by biochemical tests and imaging examination when genetic testing is not available. […] Genetic testing is currently the main method of MEN 2A diagnosis in developed countries. However, it has not yet been extensively spread in developing countries because of economic and technical limitations. Therefore, MEN 2A is normally diagnosed by biochemical tests and imaging examinations. […] Calcitonin is a specific tumor marker which is critical in the diagnosis of MTC as well as in determining whether the tumor has been completely excised and in monitoring of tumor recurrence.

• #75 Diagnosis and surgical treatment of multiple endocrine neoplasia type 2A | World Journal of Surgical Oncology | Full Text

  https://wjso.biomedcentral.com/articles/10.1186/1477-7819-12-8

  This study aims to introduce the diagnosis and surgical treatment of the rare disease multiple endocrine neoplasia type 2A (MEN 2A). […] Thirteen cases of MEN 2A were diagnosed as medullary thyroid carcinoma (MTC) and pheochromocytoma by biochemical tests and imaging examination. […] We confirmed that MEN 2A can be diagnosed by biochemical tests and imaging examination when genetic testing is not available. […] Genetic testing is currently the main method of MEN 2A diagnosis in developed countries. However, it has not yet been extensively spread in developing countries because of economic and technical limitations. Therefore, MEN 2A is normally diagnosed by biochemical tests and imaging examinations. […] Calcitonin is a specific tumor marker which is critical in the diagnosis of MTC as well as in determining whether the tumor has been completely excised and in monitoring of tumor recurrence.

• #76 Understanding Multiple Endocrine Neoplasia Type 2: From Risk Factors to Home Remedies – The Kingsley Clinic

  https://thekingsleyclinic.com/thyroid-and-parathyroid/understanding-multiple-endocrine-neoplasia-type-2-from-risk-factors-to-home-remedies/

  Diagnosing MEN2 involves a combination of clinical evaluation, family history, laboratory tests, imaging studies, and genetic testing. Because MEN2 is a genetic condition, a diagnosis can be confirmed or ruled out with near certainty through genetic testing for mutations in the RET gene. […] Genetic testing is the gold standard for diagnosing MEN2. This involves a blood test where DNA is extracted and examined for mutations in the RET gene, the gene known to cause MEN2. This test is crucial for individuals with a family history of MEN2 and for those who have tumors suggestive of the condition. […] Results indicating a mutation in the RET gene confirm a diagnosis of MEN2. However, a negative result does not entirely exclude the disease, especially in patients showing clinical signs of MEN2. In such cases, the result may indicate the presence of a different genetic mutation not yet associated with the disease.

• #77 Multiple Endocrine Neoplasia in Childhood: An Update on Diagnosis, Screening, Management and Treatment

  https://www.mdpi.com/2673-396X/3/1/7

  Multiple endocrine neoplasia (MEN) is a group of heterogenous syndromes characterized by the occurrence of two or more endocrine gland tumors in a patient or related individuals in the same family. […] MEN2 is further divided into MEN2A, MEN2B (formerly known MEN3), and familial medullary thyroid carcinoma (FMTC). […] Although MEN syndromes are rare, it is crucial to identify individuals at risk for potentially life-threatening neoplasias. This review article provides an update on each MEN syndrome, its genetics, diagnosis, and management in children. […] In this review, we provided an update on MEN syndromes and their genetics as well as guidelines for screening and management considerations in children. Identifying at-risk individuals is crucial in preventing and treating potentially life-threatening endocrine and non-endocrine neoplasias, thereby improving and prolonging life.

• #78 Molecular diagnosis and comprehensive treatment of multiple endocrine neoplasia type 2 in Southeastern Chinese | Hereditary Cancer in Clinical Practice | Full Text

  https://hccpjournal.biomedcentral.com/articles/10.1186/s13053-015-0026-1

  Multiple endocrine neoplasia type 2 (MEN2) is an autosomal dominant inherited endocrine malignancy syndrome. […] MEN2 patients can be diagnosed early through systematic pedigree investigation and RET proto-oncogene screening. […] In recent years, combined detection of RET mutations and pre-operative calcitonin (pre-Ct) levels have been considered for comprehensive decision-making regarding the timing or surgical extent of prophylactic TT. […] Based on our results, integrated RET screening and the pre-operative calcitonin level is an excellent strategy to ensure earlier diagnosis and standard thyroidectomy. […] The asymptomatic RET carriers who underwent surgery benefited greatly from genetic screening and were a significantly younger age at the time of surgery and had a smaller tumor diameter compared with symptomatic patients. […] The disease-free survival (DFS) increased in the asymptomatic RET carriers who underwent surgery compared to the symptomatic patients. […] For advanced MTC, vandetanib provides novel treatment options. […] In patients with PHEOs, CSA can be utilized to preserve adrenocortical function.

• #79 Orphanet: Multiple endocrine neoplasia type 2

  https://www.orpha.net/en/disease/detail/653

  Prenatal diagnosis is possible where the mutation has previously been identified in a family member. […] RET mutation predicts the clinical phenotype and guides treatment. As recommended by the American thyroid association, management and treatment is stratified according to risk of aggressive MTC: highest risk (HST); high risk (H); moderate risk (MOD). All patients require evaluation of serum Ctn every 6 months for the first year, then annually if serum Ctn remains normal or undetectable. Annual US of the neck is indicated for both H and HST categories. Total thyroidectomy (TTX) should be performed when the serum Ctn level becomes elevated in MOD, and at or before 5 years of age (based on serum Ctn levels) for H and HST risk groups. Life-long thyroid hormone supplementation is needed after thyroid removal. The tyrosine kinase inhibitors, vandetanib and cabozantinib, are approved (in the USA and Europe) for the treatment of patients with advanced progressive MTC. MEN2A patients in the H and MOD risk groups should be simultaneously screened for PHPT and PCC. Only visibly enlarged parathyroids should be resected.

• #80 Multiple Endocrine Neoplasia Clinic | MD Anderson Cancer Center

  https://www.mdanderson.org/patients-family/diagnosis-treatment/care-centers-clinics/endocrine-center/multiple-endocrine-neoplasia-clinic.html

  MD Andersons Multiple Endocrine Neoplasia (MEN) Clinic offers screening, surveillance, diagnosis and disease management for individuals affected by multiple endocrine neoplasia syndromes types 1 and 2, hereditary paraganglioma/pheochromocytoma syndromes and related conditions. […] If a hereditary endocrine neoplasia syndrome runs in your family, we offer comprehensive genetic testing and counseling to help you understand and manage your risk. […] We are enrolling people from families with a confirmed or suspected condition that causes an increased risk for endocrine tumors and cancers, including: Multiple endocrine neoplasia type 2 (MEN2) including MEN2A, MEN2B, or familial medullary thyroid cancer (FMTC). […] The registry examines both types of MTC: hereditary disease, which is inherited from a parent; and sporadic disease, which is not passed down within families. […] People from families with a confirmed or suspected diagnosis of Multiple Endocrine Neoplasia 2A or 2B (MEN2A or MEN2B) or familial medullary thyroid cancer are invited to participate in the registry.

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