{"id":4422646,"date":"2025-01-12T08:59:25","date_gmt":"2025-01-12T14:59:25","guid":{"rendered":"https:\/\/myendoconsult.com\/learn\/topics\/men-2\/"},"modified":"2025-01-12T09:06:05","modified_gmt":"2025-01-12T15:06:05","slug":"men-2","status":"publish","type":"oen_topic","link":"https:\/\/myendoconsult.com\/learn\/topics\/men-2\/","title":{"rendered":"MEN 2"},"content":{"rendered":"\n<h2 class=\"wp-block-heading\">Overview Of MEN2<\/h2>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Definition &amp; Subtypes<\/strong>\n<ul class=\"wp-block-list\">\n<li>Autosomal dominant disorder involving medullary <a href=\"https:\/\/myendoconsult.com\/learn\/topics\/thyroid-carcinomas\/\"  data-wpil-monitor-id=\"306\">thyroid carcinoma<\/a> (MTC) in all subtypes<\/li>\n\n\n\n<li>Three clinical variants:\n<ol class=\"wp-block-list\">\n<li><strong>MEN 2A<\/strong>: MTC, pheochromocytoma (\u224850%), <a href=\"https:\/\/myendoconsult.com\/learn\/topics\/primary-hyperparathyroidism\/\"  data-wpil-monitor-id=\"307\">primary hyperparathyroidism<\/a> (\u224820%), cutaneous lichen amyloidosis (\u22485%)<\/li>\n\n\n\n<li><strong>MEN 2B<\/strong>: MTC, pheochromocytoma (\u224850%), mucocutaneous neuromas, intestinal ganglioneuromas (including Hirschsprung disease), skeletal abnormalities<\/li>\n\n\n\n<li><strong>Familial Medullary Thyroid Cancer (FMTC)<\/strong>: MTC only (or very minimal additional features)<\/li>\n<\/ol>\n<\/li>\n<\/ul>\n<\/li>\n\n\n\n<li><strong>Estimated Prevalence<\/strong>\n<ul class=\"wp-block-list\">\n<li>~2.5 per 100,000 in the general population<\/li>\n<\/ul>\n<\/li>\n\n\n\n<li><strong>Genetics<\/strong>\n<ul class=\"wp-block-list\">\n<li>Caused by germline gain-of-function mutations in the <strong>RET<\/strong> proto-oncogene on chromosome 10<\/li>\n\n\n\n<li>High penetrance for MTC<\/li>\n\n\n\n<li>Genotype\u2013phenotype correlations guide prophylactic thyroidectomy timing<\/li>\n\n\n\n<li>Example: Codon 918 (MEN 2B) -> earliest\/aggressive MTC<\/li>\n<\/ul>\n<\/li>\n<\/ul>\n\n\n\n<hr class=\"wp-block-separator has-alpha-channel-opacity\"\/>\n\n\n\n<h2 class=\"wp-block-heading\">Medullary Thyroid Carcinoma (MTC)<\/h2>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Pathophysiology &amp; Features<\/strong>\n<ul class=\"wp-block-list\">\n<li><a href=\"https:\/\/myendoconsult.com\/learn\/neuroendocrine-tumor-imaging-with-in-111-octreoscan\/\"  data-wpil-monitor-id=\"308\">Neuroendocrine tumor<\/a> arising from parafollicular C cells of the thyroid<\/li>\n\n\n\n<li>C cells secrete <strong><a href=\"https:\/\/myendoconsult.com\/learn\/calcitonin\/\"  data-wpil-monitor-id=\"311\">calcitonin<\/a><\/strong> (tumor marker); serum calcitonin correlates with tumor burden<\/li>\n\n\n\n<li>MTC is <strong>multicentric<\/strong>, often located in upper thyroid lobes (where C cells concentrate)<\/li>\n\n\n\n<li>~25% of all MTC cases are heritable (MEN 2 or FMTC)<\/li>\n<\/ul>\n<\/li>\n\n\n\n<li><strong>Clinical Presentation<\/strong>\n<ul class=\"wp-block-list\">\n<li>Thyroid mass, cervical lymphadenopathy, or incidental imaging finding<\/li>\n\n\n\n<li><strong>MEN 2B subtype<\/strong>: more aggressive MTC, earlier onset, metastases often found in children<\/li>\n\n\n\n<li><strong>MEN 2A\/FMTC<\/strong>: typically present in adolescence\/early adulthood<\/li>\n<\/ul>\n<\/li>\n\n\n\n<li><strong>Management<\/strong>\n<ul class=\"wp-block-list\">\n<li><strong>Prophylactic thyroidectomy<\/strong> in childhood or early adulthood, guided by RET mutation codon<\/li>\n\n\n\n<li>Goal: complete removal of thyroid before invasive MTC develops<\/li>\n\n\n\n<li><strong>Calcitonin<\/strong> and <strong>carcinoembryonic antigen (CEA)<\/strong> are tumor markers used in postoperative follow-up<\/li>\n<\/ul>\n<\/li>\n<\/ul>\n\n\n\n<hr class=\"wp-block-separator has-alpha-channel-opacity\"\/>\n\n\n\n<h2 class=\"wp-block-heading\">Pheochromocytoma<\/h2>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Prevalence in MEN 2<\/strong>\n<ul class=\"wp-block-list\">\n<li>~50% of patients with MEN 2A or 2B<\/li>\n\n\n\n<li>Often bilateral and multicentric<\/li>\n<\/ul>\n<\/li>\n\n\n\n<li><strong>Clinical Presentation<\/strong>\n<ul class=\"wp-block-list\">\n<li>May be asymptomatic initially, detected by routine screening (plasma <a href=\"https:\/\/myendoconsult.com\/learn\/metanephrines\/\"  data-wpil-monitor-id=\"309\">metanephrines<\/a>, urinary fractionated metanephrines)<\/li>\n\n\n\n<li>Symptomatic patients: episodic headache, hypertension, palpitations, diaphoresis, pallor (\u201cthe 5 P\u2019s\u201d)<\/li>\n<\/ul>\n<\/li>\n\n\n\n<li><strong>Management<\/strong>\n<ul class=\"wp-block-list\">\n<li><strong>Preoperative \u03b1-adrenergic blockade<\/strong> followed by possible \u03b2-blockade if needed<\/li>\n\n\n\n<li>Surgical resection of involved adrenal(s); often bilateral adrenalectomy needed<\/li>\n<\/ul>\n<\/li>\n<\/ul>\n\n\n\n<hr class=\"wp-block-separator has-alpha-channel-opacity\"\/>\n\n\n\n<h2 class=\"wp-block-heading\">Primary Hyperparathyroidism (MEN 2A only)<\/h2>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Incidence<\/strong>\n<ul class=\"wp-block-list\">\n<li>~20% of MEN 2A patients<\/li>\n\n\n\n<li>Typically <strong>multigland<\/strong> involvement<\/li>\n<\/ul>\n<\/li>\n\n\n\n<li><strong>Diagnosis &amp; Treatment<\/strong>\n<ul class=\"wp-block-list\">\n<li>Biochemical <a href=\"https:\/\/myendoconsult.com\/learn\/topics\/hypercalcemia\/\"  data-wpil-monitor-id=\"310\">hypercalcemia with inappropriately high parathyroid<\/a> hormone (PTH)<\/li>\n\n\n\n<li>Surgical resection of enlarged glands (often 3.5 gland resection)<\/li>\n\n\n\n<li>Less common in MEN 2A than in MEN 1<\/li>\n<\/ul>\n<\/li>\n<\/ul>\n\n\n\n<hr class=\"wp-block-separator has-alpha-channel-opacity\"\/>\n\n\n\n<h2 class=\"wp-block-heading\">MEN 2B\u2013Specific Features<\/h2>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Mucocutaneous Neuromas<\/strong>\n<ul class=\"wp-block-list\">\n<li>Appear on the lips, tongue, eyelids \u2192 thickened \u201cblubbery\u201d lips, everted eyelids<\/li>\n<\/ul>\n<\/li>\n\n\n\n<li><strong>Skeletal Deformities<\/strong>\n<ul class=\"wp-block-list\">\n<li>Kyphoscoliosis, lordosis, joint laxity<\/li>\n<\/ul>\n<\/li>\n\n\n\n<li><strong>Intestinal Ganglioneuromas<\/strong>\n<ul class=\"wp-block-list\">\n<li>Can lead to <strong>Hirschsprung disease<\/strong> (aganglionic megacolon)<\/li>\n<\/ul>\n<\/li>\n\n\n\n<li><strong>Aggressive MTC<\/strong>\n<ul class=\"wp-block-list\">\n<li>Earlier onset, often metastatic in childhood<\/li>\n<\/ul>\n<\/li>\n<\/ul>\n\n\n\n<hr class=\"wp-block-separator has-alpha-channel-opacity\"\/>\n\n\n\n<h2 class=\"wp-block-heading\">Cutaneous Lichen Amyloidosis (MEN 2A)<\/h2>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Description<\/strong>\n<ul class=\"wp-block-list\">\n<li>Rare, pruritic, scaly, pigmented lesion (often in the interscapular region)<\/li>\n\n\n\n<li>5% of individuals with MEN 2A may have this<\/li>\n<\/ul>\n<\/li>\n<\/ul>\n\n\n\n<hr class=\"wp-block-separator has-alpha-channel-opacity\"\/>\n\n\n\n<h2 class=\"wp-block-heading\">RET Mutations &amp; Genotype\u2013Phenotype Correlations<\/h2>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>MEN 2A \/ FMTC<\/strong>\n<ul class=\"wp-block-list\">\n<li>Commonly in <strong>cysteine codons<\/strong> in RET (exons 10\u201311, particularly codon 634)<\/li>\n\n\n\n<li>Risk of pheochromocytoma and MTC is high; parathyroid involvement in MEN 2A<\/li>\n<\/ul>\n<\/li>\n\n\n\n<li><strong>MEN 2B<\/strong>\n<ul class=\"wp-block-list\">\n<li>Usually <strong>codon 918<\/strong> (p.Met918Thr) in exon 16 \u2192 most aggressive MTC<\/li>\n\n\n\n<li>Alternative: codon 883 in exon 15 (less common)<\/li>\n<\/ul>\n<\/li>\n\n\n\n<li><strong>Guided Prophylaxis<\/strong>\n<ul class=\"wp-block-list\">\n<li>Codons 918, 883, 922 \u2192 earliest prophylactic thyroidectomy (often infancy)<\/li>\n\n\n\n<li>Codons 611, 618, 620, 634 \u2192 removal of thyroid by age 5 years<\/li>\n\n\n\n<li>Codons 609, 768, 790, 791, 804, 891 \u2192 generally less aggressive MTC, thyroidectomy may be delayed (e.g., up to age 10)<\/li>\n<\/ul>\n<\/li>\n<\/ul>\n\n\n\n<hr class=\"wp-block-separator has-alpha-channel-opacity\"\/>\n\n\n\n<h2 class=\"wp-block-heading\">Clinical Screening &amp; Management<\/h2>\n\n\n\n<ol class=\"wp-block-list\">\n<li><strong>Genetic Testing<\/strong>\n<ul class=\"wp-block-list\">\n<li>Offered to all first-degree relatives once a RET mutation is discovered in an index case<\/li>\n\n\n\n<li>Children with MEN 2B\u2013associated mutations \u2192 prophylactic thyroidectomy within first 6 months of life<\/li>\n<\/ul>\n<\/li>\n\n\n\n<li><strong>Biochemical Screening<\/strong>\n<ul class=\"wp-block-list\">\n<li>Annual screening for <strong>pheochromocytoma<\/strong> (plasma or urinary metanephrines) if patient has a known \u201cpheo-associated\u201d RET codon<\/li>\n\n\n\n<li>Serum <strong>calcitonin<\/strong> and <strong>CEA<\/strong> levels for MTC<\/li>\n\n\n\n<li>Calcium and PTH measurements if MEN 2A to detect hyperparathyroidism<\/li>\n<\/ul>\n<\/li>\n\n\n\n<li><strong>Therapeutic Interventions<\/strong>\n<ul class=\"wp-block-list\">\n<li><strong>Total thyroidectomy<\/strong> + central node dissection at timing based on mutation risk<\/li>\n\n\n\n<li><strong>Pheochromocytoma resection<\/strong> after appropriate medical management<\/li>\n\n\n\n<li><strong>Parathyroidectomy<\/strong> if needed for hyperparathyroidism<\/li>\n<\/ul>\n<\/li>\n<\/ol>\n","protected":false},"excerpt":{"rendered":"<p>Overview Of MEN2 Medullary Thyroid Carcinoma (MTC) Pheochromocytoma Primary Hyperparathyroidism (MEN 2A only) MEN 2B\u2013Specific Features Cutaneous Lichen Amyloidosis (MEN 2A) RET Mutations &amp; Genotype\u2013Phenotype Correlations Clinical Screening &amp; Management<\/p>\n","protected":false},"featured_media":0,"template":"","oen_topic_chapter":[690],"class_list":["post-4422646","oen_topic","type-oen_topic","status-publish","hentry","oen_topic_chapter-rare-genetic-conditions","post-wrapper","thrv_wrapper"],"_links":{"self":[{"href":"https:\/\/myendoconsult.com\/learn\/wp-json\/wp\/v2\/oen_topic\/4422646","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/myendoconsult.com\/learn\/wp-json\/wp\/v2\/oen_topic"}],"about":[{"href":"https:\/\/myendoconsult.com\/learn\/wp-json\/wp\/v2\/types\/oen_topic"}],"version-history":[{"count":3,"href":"https:\/\/myendoconsult.com\/learn\/wp-json\/wp\/v2\/oen_topic\/4422646\/revisions"}],"predecessor-version":[{"id":4422649,"href":"https:\/\/myendoconsult.com\/learn\/wp-json\/wp\/v2\/oen_topic\/4422646\/revisions\/4422649"}],"wp:attachment":[{"href":"https:\/\/myendoconsult.com\/learn\/wp-json\/wp\/v2\/media?parent=4422646"}],"wp:term":[{"taxonomy":"oen_topic_chapter","embeddable":true,"href":"https:\/\/myendoconsult.com\/learn\/wp-json\/wp\/v2\/oen_topic_chapter?post=4422646"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}