Materiały źródłowe

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

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

  How is MEN2 treated? There is no cure for MEN2, but there are ways to ease symptoms and lower the risk for the associated tumors. Early and consistent screening is extremely important because many symptoms of MEN2 are not noticeable until adulthood. […] Treatment for MEN2: Tumor removal […] Medications to manage hormonal imbalances resulting from partial or complete removal of an endocrine gland […] For children with MEN2 who have a higher risk of developing MTC, a thyroidectomy (removal of the thyroid gland). Whether this is necessary and the timing of surgery depends on the specific mutation in the RET gene, blood tests for calcitonin and carcinoembryonic antigen (the two proteins associated with MTC) and thyroid ultrasound results. If you choose, your child can have a thyroidectomy before tumors start to develop. You can also choose to wait (with close monitoring by your child’s care team) for blood tests and a thyroid ultrasound to determine whether a tumor has developed. If the thyroid is removed, your child needs to take a thyroid hormone replacement pill for the rest of their lives. Once MTC spreads, it is difficult to cure.

• #2 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

  Treating MEN2 tumours involves a team of specialists who discuss the best treatment options for the patient. They are called a multidisciplinary team (MDT). The MDT looks at national treatment guidelines or the latest evidence for the type of cancer the patient has. If the patient has any treatment preferences, the doctor will inform the team about this. […] Your treatment will depend on the type of tumour, where it is located, and how early it was diagnosed. You may need surgery to remove tumours and drugs to control symptoms. […] Your doctors will talk to you about the best way to manage any tumours. They will discuss your treatment options and explain any tests you might need to monitor your health during and after treatment. […] Your doctors may ask you to take part in a clinical trial to find out more about MEN2 and to look at new treatments. They will talk to you about the trial so you fully understand what it involves. You can choose not to take part or leave the trial at any stage. You will still get the standard treatment available.

• #3 Multiple endocrine neoplasia, type 2 (MEN 2) // Middlesex Health

  https://middlesexhealth.org/36C7EC93-08D7-E826-3D819A712A9D667A

  In MEN 2, tumors can grow on the thyroid, parathyroid and adrenal glands. These tumors can lead to various conditions, all of which can be treated. These conditions and treatments may include: […] Medullary thyroid cancer. Thyroid cancer, including cancer that has spread to other parts of the body, is treated by removing the thyroid gland and the lymph nodes around it with surgery. Medicines also can be used if the disease has spread and can’t be removed with surgery. […] Parathyroid enlargement. The parathyroid glands can become enlarged and make too much parathyroid hormone. The usual treatment is surgery to remove all or part of the parathyroid glands that are enlarged, while leaving any glands that are not affected. […] Adrenal tumors. For these types of tumors, your health care provider will likely recommend removing one or both of the adrenal glands, depending on what is shown on the CT or MRI.

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

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

  All people with MEN type 2 will develop medullary thyroid cancer (carcinoma), known as MTC. Medullary thyroid cancer represents approximately 1% to 2% of thyroid cancers in the United States. MTC is different from other types of thyroid cancers because it originates from a certain type of cell called C cells of the thyroid gland. These cells do not make thyroid hormone, like other cells in your thyroid do. C cells make a hormone called calcitonin, which lowers blood calcium levels. […] The primary treatment for MTC is surgery in which a surgeon removes your thyroid (thyroidectomy). […] Treatment may include: medications to treat symptoms and to counteract the effects of excess hormones; surgery to remove tumors or entire affected glands, such as the thyroid; replacement hormones if an endocrine gland is surgically removed; cancer treatment, such as chemotherapy and radiation therapy, if cancer has metastasized (spread to other areas of your body). […] There is currently no cure for multiple endocrine neoplasia, but it is manageable. Healthcare providers treat the changes in each gland as they happen with surgery or with medications.

• #5 Multiple Endocrine Neoplasia Type 2 (MEN2) Guidelines: Guidelines Summary, Pheochromocytoma, Parathyroid Disease

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

  Both ATA and NCCN guidelines recommend prophylactic thyroidectomy for individuals who have a documented RET mutation and are at risk for aggressive medullary thyroid carcinoma. […] Total thyroidectomy has been recommended for patients as young as 3 years for MEN2A if they contain the genetic mutation. In patients with the RET genetic mutation for MEN 2B, total thyroidectomy is recommended in infancy because medullary thyroid carcinoma behaves more aggressively in these patients. […] Surgical strategies […] Total thyroidectomy with central neck dissection is recommended for all patients with proven or probable medullary thyroid carcinoma. […] Patients who have late-stage medullary thyroid cancer with symptomatic or progressive disease who are not surgical candidates may benefit from treatment with vandetanib, a tyrosine-kinase inhibitor that inhibits vascular endothelial growth factor and epidermal growth factor. […] The treatment of persistent or recurrent elevations of calcitonin with random testing or following pentagastrin stimulation has been a clinical dilemma.

• #5 Multiple Endocrine Neoplasia Type 2 (MEN2) Guidelines: Guidelines Summary, Pheochromocytoma, Parathyroid Disease

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

  The ATA and NCCN guidelines recommend removal of pheochromocytoma prior to surgery for MTC or hyperparathyroidism to prevent a possible hypertensive crisis. […] Pheochromocytoma should be resected by laparoscopic or retroperitoneoscopic adrenalectomy. Subtotal adrenalectomy to preserve adrenal cortical function should be considered as an alternative procedure. Patients with no adrenal glands require glucocorticoid and mineralocorticoid replacement therapy and should be carefully monitored to ensure that their steroid levels are adequate. Patients should be educated regarding the risk of adrenal crisis and wear a bracelet or a necklace indicating that they have no adrenal glands and are on corticosteroid replacement therapy. Glucocorticoid supplementation will be required if they become severely ill or are injured.

• #6 Multiple Endocrine Neoplasia Type 2: Causes and Treatment

  https://www.healthline.com/health/multiple-endocrine-neoplasia-type-2

  Prophylactic thyroidectomy, also called a risk-reducing thyroidectomy, is the treatment of choice for people with MEN2 since almost everybody develops MTC. This procedure involves removing the thyroid gland before cancer develops. Its often performed in the first month of life in children with MEN2B or around 5 years for children with high risk MEN2A. […] Thyroidectomy may not be required for people with low risk mutations until late childhood or adulthood. […] You’ll need lifelong thyroid hormone replacement therapy after having your thyroid removed. […] The drugs vandetanib and cabozantinib are Food and Drug Administration (FDA)-approved for people with progressive metastatic MTC ineligible for surgery. […] Pheochromocytoma is often treated with laparoscopic adrenalectomy to remove one or both adrenal glands. […] High calcium levels may not require treatment until symptoms are unmanageable. You may receive a total or partial removal of the parathyroid glands or medications. […] Part of your gland may be transplanted to a different part of your body, often your non-dominant forearm.

• #7

  https://link.springer.com/article/10.1007/s11864-004-0022-6

  Multiple endocrine neoplasia type 2 (MEN-2) is a hereditary syndrome that is transmitted in an autosomal dominant pattern. […] Patients who are RET germline mutation carriers but without clinical or biochemical evidence of MTC should have a prophylactic total thyroidectomy. The optimal age of thyroidectomy should be based on the RET genotype (eg, high-risk mutations [codons 634, 883, 918, and 922] within the first year of life, intermediate-risk mutations [codons 611, 618, and 620] by 5 years of age, and low-risk mutations [codons 609, 630, 768, 790, 791, 804, and 891] by 10 years of age). […] Patients who are diagnosed with clinical or biochemical evidence of MTC should have a total or a near total thyroidectomy and at least a central neck lymph node dissection. […] Patients who have pheochromocytoma and a unilateral adrenal tumor on a localizing study should have a unilateral laparoscopic adrenalectomy after preoperative -blockade. However, patients with bilateral adrenal tumors on localizing studies should have bilateral laparoscopic adrenalectomy. A cortical-sparing (subtotal) adrenalectomy may be considered, if technically feasible, to avoid long-term steroid dependence and to reduce the risk of Addisonian crisis.

• #8 Multiple Endocrine Neoplasia Type 2 (MEN2) (PDQ®) – NCI

  https://www.cancer.gov/publications/pdq/information-summaries/genetics/men2-hp-pdq

  Risk-reducing thyroidectomy (also referred to as early thyroidectomy and previously referred to as prophylactic thyroidectomy) is the oncological treatment of choice for patients with MEN2. Children with the M918T RET pathogenic variant may benefit from a thyroidectomy in the first year of life, perhaps in the first months of life. […] The standard treatment for adults with MTC is surgical removal of the entire thyroid gland, including the posterior capsule and central lymph node dissection. […] The MEN2B RET variant M918T is associated with approximately 100% incidence of MTC in the first years of life and is considered the most aggressive MEN2 phenotype. […] A therapeutic central neck dissection is typically performed if there is radiographic evidence of metastatic lymph node involvement or if the serum calcitonin level is higher than 40 pg/mL.

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

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

  As DNA analysis has improved in recent decades, strong genotype-phenotype correlations have been established and have helped to facilitate guidelines for pediatric MEN2 treatment. Previously, calcitonin levels alone were used to determine candidacy for thyroidectomy. However, this led to some children being subjected to thyroidectomy when no RET mutation was identified by DNA analysis. With DNA analysis, certain mutations have been determined to be more aggressive, especially in regards to MTC, and, therefore, specific treatment strategies have been recommended accordingly. […] MTC is treated surgically. The goal is for the patient to undergo thyroidectomy before metastasis occurs, as MTC, at that point, is considered incurable and the most common cause of tumor death in individuals with MEN2A. Prophylactic thyroidectomy is defined as thyroid gland removal in children who have an inherited RET mutation. Those who do not undergo prophylactic thyroidectomy at an early age are more likely to develop metastatic MTC. The average survival expectancy in MEN2B carriers was approximately 21 years prior to the current, more standardized, recommendations for prophylactic thyroidectomy.

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

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

  In children with MEN2A with a RET codon 634 mutation (ATA-H category), MTC develops in the first few years of life. Children are recommended to have annual physical examinations, thyroid ultrasounds, and serum calcitonin measurements starting at age 3. Children with mutations in the ATA-MOD category have similar screening recommendations but begin later at age 5; thyroidectomy in these patients is expected to occur in childhood or young adulthood depending on the serum calcitonin level. Despite prophylactic thyroidectomy, it is important to note that certain RET mutations appear to be associated with persistent or recurrent disease (i.e., codons 620 and 634). […] With regards to MEN2B, MTC is usually highly aggressive and thus prophylactic thyroidectomy occurs much earlier in life. Those with known hereditary MEN2B are recommended to have a thyroidectomy in the first year of life, especially if they have a RET codon M918T mutation. Thyroidectomy should be performed by an experienced surgeon in children, especially since the risk of hypoparathyroidism and subsequent hypocalcemia is higher. If an experienced surgeon is not available, some suggest that thyroidectomy should be delayed to 2 years of age. As surgical management can be challenging, parents known to be carriers for MEN2B mutations are encouraged to consider in vitro fertilization and preimplantation genetic diagnosis technologies.

• #11 Multiple Endocrine Neoplasia Type 2 (MEN2) Treatment & Management: Approach Considerations, Medullary Thyroid Carcinoma Surgery, Parathyroid Disease Surgery

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

  Total thyroidectomy has been recommended for patients as young as 3 years for MEN2A if they contain the genetic mutation. In patients with the RET genetic mutation for MEN 2B, total thyroidectomy is recommended in infancy because medullary thyroid carcinoma behaves more aggressively in these patients. […] The extent of surgery is controversial. Total thyroidectomy with central neck dissection is recommended for all patients with proven or probable medullary thyroid carcinoma. […] Patients who have late-stage MTC with symptomatic or progressive disease who are not surgical candidates may benefit from treatment with vandetanib, a tyrosine-kinase inhibitor that inhibits vascular endothelial growth factor and epidermal growth factor. […] The treatment of persistent or recurrent elevations of calcitonin with random testing or following pentagastrin stimulation has been a clinical dilemma.

• #11 Multiple Endocrine Neoplasia Type 2 (MEN2) Treatment & Management: Approach Considerations, Medullary Thyroid Carcinoma Surgery, Parathyroid Disease Surgery

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

  Multiple endocrine neoplasia type 2 (MEN2) is treated with surgery. The surgical procedures for individual components of MEN2 are as follows: Parathyroidectomy, Thyroidectomy, Adrenalectomy, Cryoablation for inoperable thyroid masses. […] Radiation therapy either as primary or adjuvant therapy for various tumors. Preoperative medical treatment may consist of prostaglandin inhibitors to alleviate diarrhea that may be associated with medullary thyroid cancer. […] Patients presenting with severe hypercalcemia should first be hydrated, after which they may be treated with furosemide. If they remain severely hypercalcemic, consider treatment with calcitonin, denosumab, or bisphosphonates (eg, pamidronate, zoledronic acid). […] Thyroid hormone supplementation is necessary following total thyroidectomy in carriers of RET mutations or following a diagnosis of medullary thyroid carcinoma.

• #12 Diagnosis and surgical treatment of multiple endocrine neoplasia type 2A

  https://pmc.ncbi.nlm.nih.gov/articles/PMC3895851/

  This study aims to introduce the diagnosis and surgical treatment of the rare disease multiple endocrine neoplasia type 2A (MEN 2A). […] Surgical excision is the predominant treatment of MEN 2A. […] Surgical excision is the predominant way to treat MEN 2A; pheochromocytoma should be excised at first when pheochromocytoma and MTC occur simultaneously. […] All patients were treated with surgical operation; 9 patients received adrenal open operation and the remaining 4 received peritoneoscope minimally invasive treatment. […] Pheochromocytoma should be excised initially in those patients with simultaneous MTC and pheochromocytoma. […] In MEN 2A patients, most pheochromocytomas are bilateral in nature, and should be preferably removed by bilateral tumor excision. […] Total thyroidectomy with bilateral lymph node dissection should be carried out and the parathyroid glands should be explored at the same time even in unilateral MTC.

• #13 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

  Surgical excision of identified tumors. […] Prophylactic thyroidectomy. […] In patients presenting with pheochromocytoma and either medullary thyroid carcinoma or hyperparathyroidism, the pheochromocytoma should be removed first, even if asymptomatic because it greatly increases risk during other surgeries. Patients undergoing resection of a pheochromocytoma should receive adequate alpha blockade (typically using phenoxybenzamine, doxazosin, or prazosin) prior to surgery. Laparoscopic adrenalectomy, which has lower morbidity, is preferred to open laparotomy. Because bilateral pheochromocytomas are common, adrenal-sparing surgery may be appropriate in some patients. […] Surgery for medullary thyroid carcinoma should include total thyroidectomy and central compartment lymph node dissection, with additional lymph node dissection if indicated based on preoperative imaging. Postsurgical assessment for residual or recurrent disease should include measurement of serum calcitonin and imaging with neck ultrasonography and, when indicated, CT or MRI of neck and chest, bone scan, or positron emission tomography (PET) scan.

• #14 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

  Once medullary thyroid carcinoma has metastasized, tyrosine kinase inhibitors, including selpercatinib, cabozantinib, and vandetanib, can lengthen progression-free survival. […] Cytotoxic chemotherapy and radiation therapy are largely ineffective in lengthening survival but may slow disease progression. […] Postoperative adjuvant external beam radiation should be considered in patients at high risk of local recurrence and those at risk for airway obstruction. […] Some studies have shown lengthened survival with immunotherapy (eg, tumor-derived vaccines, tumor cell transfectants) and radioimmunotherapy (eg, radioisotope-coupled monoclonal antibodies). […] Once genetic testing identifies a child as having a RET mutation, prophylactic thyroidectomy is recommended. Depending on the particular mutation, prophylactic thyroidectomy as early as the first months of life may be indicated. Medullary thyroid cancer can be cured or prevented by early thyroidectomy.

• #15 Multiple Endocrine Neoplasia Type 2 (MEN2) (PDQ®) – NCI

  https://www.cancer.gov/publications/pdq/information-summaries/genetics/men2-hp-pdq

  The decision to perform a risk-reducing central neck dissection is generally made based on multiple factors such as patient age, pathogenic variant, presence of concomitant primary hyperparathyroidism (PHPT), and the viability of in situ parathyroid glands. […] The use of vandetanib and cabozantinib are FDA-approved for adult patients with progressive metastatic MTC who are ineligible for surgery. […] Targeted molecular therapies are being explored to manage MTC. RET inhibitors and multikinase inhibitors are being used to block RET activity. […] Two U.S. Food and Drug Administration (FDA)-approved RET inhibitors (pralsetinib and selpercatinib) are available for patients with MTC who have a RET single nucleotide variant. […] A phase III study found that PFS was longer in adults who received vandetanib than in those who received placebo.

• #16 MEN2: Overview, symptoms, and more

  https://www.medicalnewstoday.com/articles/multiple-endocrine-neoplasia-type-2

  Chemotherapy and radiation therapy: If MTC has metastasized, doctors may suggest treatment with chemotherapy or radiation therapy. […] Treatment for the condition involves surgery such as thyroidectomy, medication, and sometimes chemotherapy and radiation therapy. The outlook is usually positive, especially for individuals with early stage MTC.

• #17 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/

  The following procedures may be employed in the treatment of MEN2: Thyroidectomy, the surgical removal of the thyroid gland, is the first-line treatment for MTC. It’s often performed early to prevent cancer spread. […] Parathyroidectomy, the removal of one or more parathyroid glands, is performed if hyperparathyroidism occurs. […] Adrenalectomy, the surgical removal of one or both adrenal glands, is performed in cases of pheochromocytoma. […] Lymph node dissection may be done during thyroidectomy if the MTC has spread to nearby lymph nodes. […] Radiofrequency ablation and Cryoablation are minimally invasive procedures used to treat smaller MTCs or in patients who can’t undergo surgery. […] Chemotherapy and Radiation therapy are options for controlling advanced or recurrent MTC that can’t be treated with surgery or targeted therapy.

• #18 Multiple endocrine neoplasia type 2A | Endocrine Conditions

  https://www.yourhormones.info/endocrine-conditions/multiple-endocrine-neoplasia-type-2a/

  How is MEN2A treated? The exact treatment depends upon the type of tumours present: […] MTC essentially all patients who are found to have a RET gene mutation are advised to undergo total thyroid removal. For MEN2A this is typically recommended before the age of 5 years. This is to prevent the development of MTC. If a patient is found to already have MTC, then the operation may be more extensive, removing the thyroid gland as well as lymph nodes in the neck. If the cancer has spread to other parts of the body outside the neck, surgery or radiotherapy is sometimes given to the affected area. There are also some other options including drugs called tyrosine kinase inhibitors or radiolabelled peptide therapy, which may be offered to patients with widespread disease, and patients can also be referred to specialist cancer centres if they would like to consider being involved in clinical trials. Treatment can also be given to relieve the classical symptoms of MTC, such as diarrhoea, flushing and pain. Examples of these treatments include loperamide to relieve the diarrhoea, or somatostatin analogue injections, which may relieve the diarrhoea, flushing and pain in some patients.

• #19 Multiple Endocrine Neoplasia Type 2 (MEN2) Treatment & Management: Approach Considerations, Medullary Thyroid Carcinoma Surgery, Parathyroid Disease Surgery

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

  Hyperparathyroidism is the least common manifestation of MEN2A. […] To reduce the risk of postoperative hypocalcemia, remove only grossly abnormal parathyroid glands. […] While all MEN2A patients may have bilateral adrenal medullary hyperplasia, the tumors may or may not be present bilaterally at the time of initial operation. […] Cortical sparing is a surgical technique in which the surgeon leaves a small amount of vascularized unilateral or bilateral adrenal tissue that will be sufficient to maintain the normal function of the adrenal cortex for a prolonged period of time. […] Patients should be monitored lifelong for evidence of recurrent disease. […] The management of patients with calcitonin/CEA elevations has been controversial. Resect any palpable cervical disease. […] Both ATA and NCCN guidelines recommend prophylactic thyroidectomy for individuals who have a documented RET mutation and are at risk for aggressive medullary thyroid carcinoma.

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

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

  Treatment for hyperparathyroidism: Removal of the affected parathyroid gland (gland located behind the thyroid in the neck). Hyperparathyroidism is associated with increased calcium in the blood and urine and an elevated (higher than usual) or normal parathyroid hormone level. To determine which parathyroid gland is enlarged, a neck ultrasound or scan may be done. […] Treatment for pheochromocytomas: Annual blood and urine tests to monitor symptoms and elevated epinephrine and related hormone levels. Epinephrine (also called adrenaline) is a stress hormone made by the adrenal glands. Pheochromocytomas are adrenal tumors created from the cells that produce epinephrine. Doctors can detect these tumors based on symptoms and elevated epinephrine-related hormone levels in blood or urine. Annual blood and urine screening allows tumors to be diagnosed earlier and when they are smaller. This may allow only one part of the adrenal gland to be removed instead of all of it. […] Medication to control blood pressure before surgery and adrenal hormone replacement therapy after surgery.

• #21 Multiple endocrine neoplasia type 2A | Endocrine Conditions

  https://www.yourhormones.info/endocrine-conditions/multiple-endocrine-neoplasia-type-2a/

  Phaeochromocytomas are surgically removed in all patients where possible. The preparation for surgery and surgery itself takes place in specialist hospitals. A period of preparation is required before surgery to ensure that the effects of the stress hormones produced from the tumours are blocked, and that blood pressure is well controlled. In the UK, this involves a minimum of three weeks of taking drugs called alpha-blockers such as phenoxybenzamine, and beta-blockers such as propranolol or bisoprolol before a patient is ready for surgery. Extra intravenous fluids may also be given as part of the pre-operative preparation. It is crucial to prepare patients properly for surgery to safely remove a phaeochromocytoma and care of these patients should be undertaken in specialist centres that manage these patients regularly.

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

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

  If both MTC and PHEO are identified in a patient, the PHEO should be resected first given the significant morbidity and risk of stress-induced cardiovascular mortality. To note, since PHEOs primarily occur later in adolescence, obtaining plasma or urine metanephrines and normetanephrines before prophylactic thyroidectomy is not indicated. […] The decision for bilateral or unilateral adrenalectomy depends upon the presence of bilateral or unilateral PHEOs, respectively, but also the risk for adrenal insufficiency. Individuals with solitary PHEO are recommended to have a unilateral adrenalectomy even though many will ultimately develop a contralateral PHEO. The reason for this decision is based on the high risk for adrenal insufficiency after bilateral adrenalectomy. Laparoscopic adrenalectomy or retroperitoneoscopic adrenalectomy are the procedures of choice with no apparent difference in outcomes. Adrenal-sparing surgery in bilateral PHEOs has also been shown to be successful and preferred if feasible and safe.

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

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

  Standard treatment for MTC is surgical removal of the thyroid with regional lymph node dissection. Standard chemotherapy and radiation are not effective in the treatment of MTC. Resection and autotransplantation of parathyroid tissue are not typically performed at the time of thyroidectomy unless there is evidence of HPT. It is always important to ensure that pheochromocytomas are not coexistent before thyroid surgery (see later). […] Pheochromocytomas detected by biochemical testing and radionuclide imaging are removed by adrenalectomy, which may be performed using video-assisted laparoscopy. Antihypertensive treatment before adrenalectomy involves the use of – and -adrenergic receptor blockade. Historically, some specialists recommended bilateral adrenalectomy at the time of demonstration of tumor even within a single adrenal gland because of the strong probability that the other adrenal gland would develop a tumor within 10 years. However, because of the risk of adrenal insufficiency and Addisonian crisis after bilateral adrenalectomy, most experts now recommend unilateral adrenalectomy in unilateral tumors and cortical-sparing adrenal surgery with close monitoring of the remnant tissue in persons with one remaining adrenal gland or bilateral pheochromocytoma.

• #24 Diagnosis and surgical treatment of multiple endocrine neoplasia type 2A

  https://pmc.ncbi.nlm.nih.gov/articles/PMC3895851/

  Prognosis of MEN 2A is primarily dependent upon the staging of MTC. […] Therefore, it is very important to monitor serum calcitonin regularly. […] 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 Neoplasias Type 2 | Treatment & Management | Point of Care

  https://www.statpearls.com/point-of-care/25357

  Primary hyperparathyroidism has only 10% to 25% association with MEN2A, and it does not occur at all in MEN2B families. Prophylactic parathyroidectomy is not recommended in asymptomatic patients as the disease is usually mild, appears late, and is often clinically obscure. […] Surgery is reserved for the patients who develop worsening hypercalcemia, bone loss, and renal impairment.

• #26

  https://link.springer.com/article/10.1007/s11864-004-0022-6

  Patients with biochemical evidence of primary hyperparathyroidism should have a bilateral neck exploration and total parathyroidectomy and autotransplantation (30-60 mg of the most normal parathyroid tissue) to the nondominant forearm if asymmetric parathyroid hyperplasia is present. […] All unresected parathyroid glands should be marked with a clip because patients with MEN-2A have a high risk of persistent and recurrent primary hyperparathyroidism.

• #27 Multiple endocrine neoplasia type 2A | Endocrine Conditions

  https://www.yourhormones.info/endocrine-conditions/multiple-endocrine-neoplasia-type-2a/

  Primary hyperparathyroidism is usually treated by surgical removal of the affected parathyroid glands. Usually an operation will involve removal of some or all parathyroid glands and patients will then require life-long supplements of activated vitamin D and possibly calcium also to maintain a normal healthy blood calcium level.

• #28 Multiple Endocrine Neoplasia Type 2 (MEN2) (PDQ®) – NCI

  https://www.cancer.gov/publications/pdq/information-summaries/genetics/men2-hp-pdq

  A phase I/phase II study of children with MEN2B found an objective partial response rate of 47% with vandetanib. […] The risks, benefits, and potential of life-threatening adrenal insufficiency should be considered at the time of the initial operative planning. […] Treatment of hyperparathyroidism typically employs some surgical removal of the involved glands. […] Cure of hyperparathyroidism was achieved surgically in 89% of one large series of MEN2A patients. […] Medical therapy of hyperparathyroidism has gained popularity with the advent of calcimimetics, agents that sensitize the calcium-sensing receptors on the parathyroid glands to circulating calcium levels and thereby reduce circulating parathyroid hormone (PTH) levels.

• #29 Advances in the management of MEN2: from improved surgical and medical treatment to novel kinase inhibitors in: Endocrine-Related Cancer Volume 25 Issue 2 (2018)

  https://erc.bioscientifica.com/view/journals/erc/25/2/ERC-17-0325.xml

  Lifelong follow-up is indicated, beginning every three months postoperatively, and at longer intervals if there is no evidence of persistent or recurrent disease in the first year after thyroidectomy. […] In patients whose advanced MTC is not amenable to surgery, the treatment options are chemotherapy, a molecular targeted therapeutic (MTT) or continued observation. […] The first MTT to show efficacy in patients with a malignant disease (chronic myelogenous leukemia (CML)) was the tyrosine kinase inhibitor (TKI), gleevec (imatinib). […] The first TKI approved by the FDA for any thyroid cancer was ZD6474, or vandetanib, an orally available anilinoquinazoline that in preclinical studies blocked the enzymatic activity of RET-derived oncoproteins. […] Based on results of the phase III trial, the FDA approved vandetanib for the treatment of patients with progressive, advanced metastatic MTC. […] In a phase I/II trial of cabozantinib in patients with advanced MTC, 29% had a partial remission and 68% had stable disease. […] Based on the results of the phase III clinical trial, the FDA approved cabozantinib for the treatment of patients with advanced MTC.

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

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

  Recommended screenings for people with MEN2 include: Yearly physical exams by a health care provider who is familiar with MEN2, Yearly neck ultrasound and serum calcitonin (blood test) starting in the first few months of life to ages 35 years, depending on the RET mutation, Yearly free plasma metanephrines and normetanephrines blood work starting at 8 years old, with follow-up imaging through CT or MRI if results are abnormal, Yearly calcium and vitamin D blood work starting at 11 or 16 years old, depending on the type of RET mutation. […] People with MEN2 should avoid certain kinds of medicines. These include: Dopamine D2 receptor antagonists (such as metoclopramide and veralipride), Beta blockers, Monoamine oxidase inhibitors, Sympathomimetics (e.g., ephedrine), Certain peptide and corticosteroid hormones. […] Check with a health care provider who is experienced in managing patients with MEN2 about the safety of any medicines.

• #31 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. […] All patients diagnosed with MEN2 even if they have no symptoms should be screened annually for the presence of pheochromocytoma and hyperparathyroidism. […] As your child with MEN2 grows into adulthood, they may consider starting a family of their own. […] For families that are interested, reproductive options exist for individuals with an alteration in the RET gene who do not wish to pass this alteration onto future children.

• #32 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

  There is a genotype-phenotype correlation for patients with RET mutations that may provide information about age of onset and clinical course of medullary thyroid cancer and this impact the timing of surgery for an affected child. […] Psychological distress appears to be common and chronic in patients with MEN 2. Contributing factors include low amount of information on the disease, having children with the mutation, number of surgeries, and presence of comorbidities; psychological assessment to identify and treat affected individuals is recommended.

• #33 Azthena logo with the word Azthena

  https://www.news-medical.net/health/Multiple-Endocrine-Neoplasia-Type-2A-(MEN2A).aspx

  The primary aim of treatment for patients with MEN2A is to reduce morbidity and mortality of patients. This can be through prophylactic removal of the thyroid gland or regular screening for MTC to enable early intervention when necessary. […] Other treatments may include: […] Bilateral adrenalectomy for patients with adrenal medullary hyperplasia or phaeochromocytoma […] Total thyroidectomy for patients with a known genetic mutation […] Subtotal parathyroidectomy for patients with hyperparathyroidism […] Cervical thymectomy for patients with hyperparathyroidism. […] The prognosis for patients with MEN2A is typically better than that for patients with MEN2B. […] If a mutation in the RET proto-oncogene is confirmed, genetic counseling is required to inform the patient about the familial nature of the condition and the best options for family planning.

• #34 Advances in the management of MEN2: from improved surgical and medical treatment to novel kinase inhibitors in: Endocrine-Related Cancer Volume 25 Issue 2 (2018)

  https://erc.bioscientifica.com/view/journals/erc/25/2/ERC-17-0325.xml

  Medullary thyroid carcinoma (MTC), a tumor derived from the neural crest, occurs either sporadically or as the dominant component of the type 2 multiple endocrine neoplasia (MEN) syndromes, MEN2A and MEN2B. […] The discovery also led to the development of molecular targeted therapeutics (MTTs), mainly tyrosine kinase inhibitors, which were effective in the treatment of patients with locally advanced or metastatic MTC. […] Clinical investigators and the pharmaceutical industry are focusing on the development of the next generation of MTTs, which have minimal toxicity and greater specificity for mutated RET. […] In families with MEN2A, it is critical to establish a genetic screening program to identify members who have inherited a mutated RET allele and offer them genetic counseling. […] The preferred operation for most patients is total thyroidectomy with dissection of lymph nodes in the central neck.

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

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

  Clinical trials of tyrosine kinase inhibitors, such as vandetanib (ZD6474), are currently underway. In a Phase II trial, 73% (22/30) of individuals with hereditary metastatic MTC who were treated with vandetanib experienced a partial response or stable disease. Tyrosine kinase inhibitors are promising potential treatments for patients with unresectable, locally advanced, or metastatic MTC.

• #36 Multiple Endocrine Neoplasia | MD Anderson Cancer Center

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

  Multiple endocrine neoplasia (MEN) syndromes are treated in MD Anderson’s Endocrine Center, one of the nation’s most active programs for diagnosis and treatment of these complex and rare diseases. […] Your care is personalized by a team of renowned experts from many specialties. Working closely with each other and with you, they customize your treatment plan and deliver the most advanced therapies with the least impact on your body. […] If surgery is needed, our surgeons have vast experience in proven procedures to treat multiple endocrine neoplasia. […] As one of the leaders in endocrine disorders, we are constantly researching new ways to treat MEN-related diseases. This means we are able to offer clinical trials, which may be difficult to find in other programs. […] MD Anderson patients have access to clinical trials offering promising new treatments that cannot be found anywhere else.

• #37 Multiple endocrine neoplasia type 2 — Knowledge Hub

  https://www.genomicseducation.hee.nhs.uk/genotes/knowledge-hub/multiple-endocrine-neoplasia-type-2/

  Management of MTC, phaeochromocytoma or primary hyperparathyroidism in patients with MEN2 should be led by a specialist multidisciplinary team. […] Prophylactic thyroidectomy should be offered in childhood or if calcitonin becomes elevated based on the RET gene risk (table 1). […] For patients diagnosed with MEN2 in adulthood, the thyroid should be assessed using a combination of thyroid ultrasound, serum calcitonin and fine needle aspiration before planning thyroid surgery, and a phaeochromocytoma should be excluded before surgery is undertaken. […] Patients with MEN2 should be offered surveillance for phaeochromocytoma and primary hyperparathyroidism as per their RET gene risk (table 1). […] Patients with phaeochromocytoma should be managed by an experienced team, and can be considered for a cortical sparing surgery as they are at risk of developing a metachronous phaeochromocytoma.

• #38 Multiple Endocrine Neoplasia-Type 2 | SpringerLink

  https://link.springer.com/10.1007/978-3-319-89497-3_9

  Multiple endocrine neoplasia type 2 (MEN2) is diagnosed in 25% of all cases of medullary thyroid cancer (MTC). […] Despite being a rare syndrome, MEN2 is important to recognize with its two subtypes MEN2A and MEN2B, so as to allow instauration of proper treatment and of the adequate surveillance of patients, as well as to offer early detection of the disease in their children and family. […] The type of mutation of the RET gene, the levels of pre- and postoperative calcitonin, and the TNM stage of the MTC allow to define the proper timing and extent of the surgical intervention, the prognosis of the disease, and the frequency and type of surveillance necessary. […] The timing of total thyroidectomy in RET gene mutation carriers could be personalized and safely planned on the basis of serum calcitonin: 18 years experience at one single center.

• #39 Multiple endocrine neoplasia | City of Hope

  https://www.cancercenter.com/risk-factors/multiple-endocrine-neoplasia

  Treatment requires a team of specialists working together to care for the patients needs. Members of this care team are likely to include: […] Treatment depends on a number of factors, including: […] The thyroid may be removed during a procedure known as a thyroidectomy. This is often a preventive step. Once its removed, the patient may need to take thyroid replacement supplements. […] MEN2 PHPT (parathyroid tumors) may be treated with medication. Some people undergo surgery to remove the parathyroid gland. Some healthy tissue from the parathyroid gland may be replanted in the forearm, so the patient doesnt develop post-op hypoparathyroidism, which requires treatment with calcium and vitamin D for the duration of life. […] PHEO is also treated with removal of one or both of the adrenal glands. The patient may need chemotherapy and radiation as follow-up for any tumors that have spread or are malignant.

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

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

  If a family member is diagnosed with MEN2, or your child is diagnosed with a cancer associated with MEN2 (MTC, hyperparathyroidism or pheochromocytoma), you should be referred to a dedicated program, like the Pediatric Thyroid Center at Childrens Hospital of Philadelphia (CHOP), which has the experience, expertise and resources to fully evaluate your child. Your family should also be scheduled in the CHOP Cancer Predisposition Program for genetic counseling. […] Because many of the symptoms of MEN2 are not apparent until adulthood, screening for the related tumors is critical to optimize a patients health. Evaluation by a specialist is necessary for accurate diagnosis and treatment, including knowing when to screen and when to consider surgical treatment. […] Although there is no cure for MEN2, there are options to minimize symptoms and decrease your childs risk of certain cancers. Early and regular screening is the most important path to allow MEN2 patients to lead happy, productive and healthy lives.

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