Two multiple endocrine neoplasia (MEN) syndromes are described in the literature - MEN 1 and MEN 2, and multiple endocrine neoplasia type 2B, is one of the subtypes of MEN 2, presenting with several distinguishing features [1] [2] [3] [4] [5]:

• Medullary thyroid cancer (MTC) - Virtually all patients who suffer from MEN type 2B develop an aggressive MTC that appears during the first several months of life, which is why total thyroidectomy is often indicated, both as a prophylactic and as a therapeutic measure [5] [6] [7]. Main complaints related to MTC are localized pain in the neck, often accompanied by a palpable mass [3] [8].
• Pheochromocytoma - In approximately 50% of cases, tumors of the adrenal gland (either unilateral or bilateral) are recorded and cause blood pressure changes due to the ongoing production of catecholamines (norepinephrine and epinephrine) [3] [4] [6] [9].
• Mucosal neuromas - Defined as one of the crucial clinical features of MEN type 2B, these lesions appear in the oral cavity (the anterior dorsal surface of the tongue, the pharynx, the buccal surfaces, and the palate) in infancy and childhood [3] [6] [8] [10]. Neuromas might appear on the eyelids (causing eversion of the upper eyelid and thickening) and the lips, giving them a "blueberry" color [3].

In addition, other prominent findings are gastrointestinal complaints (feeding difficulties, vomiting, dysphagia, abdominal pain, and either constipation or diarrhea, presumably arising from excessive calcitonin secretion due to MTC), musculoskeletal changes (kyphosis, hip dislocation, a Marfanoid appearance, as well as flat foot and pes cavus), and a flat facies with hypertelorism [3] [6] [10]

• Marfanoid Habitus

  From Wikidata Jump to navigation Jump to search autosomal dominant disease characterized by medullary thyroid carcinoma, pheochromocytoma, multiple mucosal neuromas and intestinal ganglioneuromas, and often a marfanoid habitus and other skeletal abnormalities [wikidata.org]

  A sporadic case of multiple endocrine neoplasia type 2B in a twenty-six year old man who manifested medullary thyroid carcinoma, multiple mucosal neuromas of the tongue and a marfanoid habitus is reported. [ncbi.nlm.nih.gov]

• Fatigue

  However, most people with endocrine disease complain of fatigue and weakness. Blood and urine tests to check your hormone levels can help your doctors determine if you have an endocrine disorder. [webmd.com]

  Hypercalcaemia may lead to constipation, polyuria, polydipsia, memory problems, depression, nephrolithiasis, glucose intolerance, gastro-oesophageal reflux and fatigue. [patient.info]

  Nuclear medicine treatments may cause fatigue and may affect the bone marrow causing anaemia and low platelet count, which can result in bleeding problems, and a low white cell count, which can result in increase risk of infections. [yourhormones.info]

  […] skipped heartbeats) Feelings of anxiety or feelings of extreme fright Pain in the lower chest or upper abdomen Nausea with or without vomiting Weight loss Pale skin Feeling hot or unable to tolerate being in the heat Hyperparathyroidism signs and symptoms Fatigue [stjude.org]

• Hypoxemia

  Intubation and mechanical ventilation were performed because of severe hypoxemia. [ncbi.nlm.nih.gov]

• Turkish

  We report the case of a 19-year-old Turkish girl who presented with skin-colored flat papules scattered all over the trunk and extremities. [ncbi.nlm.nih.gov]

• Localized Pain

  Main complaints related to MTC are localized pain in the neck, often accompanied by a palpable mass. [symptoma.com]

• Mediastinal Disease

  disease by magnetic resonance imaging, proved that the metastases were from his previous adrenal and not thyroid tumor. [ncbi.nlm.nih.gov]

• Abdominal Pain

  The alimentary tract manifestations were diverse: symptoms included constipation, diarrhea, difficulty with feeding, projectile vomiting, crampy abdominal pain, and loud borborygmi; findings included thickened lips, nodules on the anterior third of the [ncbi.nlm.nih.gov]

  In addition, other prominent findings are gastrointestinal complaints (feeding difficulties, vomiting, dysphagia, abdominal pain, and either constipation or diarrhea, presumably arising from excessive calcitonin secretion due to MTC), musculoskeletal [symptoma.com]

  Gastrointestinal symptoms such as FTT, abdominal pain, dysphagia, projectile vomiting, diarrhea, constipation, flatulence, intussusceptions, megacolon, and pseudo obstruction are considered as possible manifestations of MEN2B [ 9 ]. [jmedicalcasereports.biomedcentral.com]

• Nausea

  […] and symptoms Fatigue or weakness Feeling depressed Forgetfulness Bone and joint pain Complaining often of illness with no known cause Fragile bones that easily break (osteoporosis) Kidney stones Increased thirst and urinating too often Pain in abdomen Nausea [stjude.org]

  Adverse events included diarrhea, rash, nausea, hypertension, and headache ( 22 ). [clincancerres.aacrjournals.org]

  Hyperparathyroidism disrupts the normal balance of calcium in the blood, which can lead to kidney stones, thinning of bones, nausea and vomiting, high blood pressure (hypertension), weakness, and fatigue. [endocrine.surgery.ucsf.edu]

  Hyperparathyroidism can cause additional symptoms in some cases including fatigue, weakness, constipation, nausea, ulcers, indigestion, high blood pressure (hypertension), and muscle or bone pain. [rarediseases.org]

• Projectile Vomiting

  The alimentary tract manifestations were diverse: symptoms included constipation, diarrhea, difficulty with feeding, projectile vomiting, crampy abdominal pain, and loud borborygmi; findings included thickened lips, nodules on the anterior third of the [ncbi.nlm.nih.gov]

  Keywords Medullary Thyroid Carcinoma Neuroma Medullary Thyroid Cancer Prophylactic Thyroidectomy Projectile Vomiting Introduction Multiple endocrine neoplasia 2B (MEN2B) is a rare autosomal dominant syndrome [ 1 – 4 ]. [jmedicalcasereports.biomedcentral.com]

• Progressive Dysphagia

  Her late clinical course was dominated by progressive dysphagia, intestinal dysmotility and megacolon associated with unrelenting malnutrition. [ncbi.nlm.nih.gov]

• Borborygmi

  The alimentary tract manifestations were diverse: symptoms included constipation, diarrhea, difficulty with feeding, projectile vomiting, crampy abdominal pain, and loud borborygmi; findings included thickened lips, nodules on the anterior third of the [ncbi.nlm.nih.gov]

• Macroglossia

  Between ages 2 and 4, they develop full lips, large rounded cheeks, a broad nose, and an enlarged tongue ( macroglossia ). The vocal cords also enlarge, which results in a deep, hoarse voice. [ghr.nlm.nih.gov]

• Dry Eyes

  eyes or lack of tears, which is an especially helpful sign in children; delayed puberty. [en.wikipedia.org]

• Conjunctival Hyperemia

  Clinical examination revealed a marfanoid habitus, myelinated corneal nerve fibers, neuromas in the perilimbal area, conjunctival hyperemia with peripheral corneal neovascularization, and posterior blepharitis. [ncbi.nlm.nih.gov]

  A 16-year-old girl was admitted with severe bilateral conjunctival hyperemia and stinging lasting for more than 1 year. [healio.com]

• Blepharitis

  Clinical examination revealed a marfanoid habitus, myelinated corneal nerve fibers, neuromas in the perilimbal area, conjunctival hyperemia with peripheral corneal neovascularization, and posterior blepharitis. [ncbi.nlm.nih.gov]

• Long Arm

  Multipoint analysis of RFLPs at FNRB, D10Z1, RBP3, and D10S15 gave a peak lod score of 7.12 at the midpoint between D10Z1 and RBP3 on the long arm (band q11). [ncbi.nlm.nih.gov]

  People with MEN2B typically have a body type with long arms, legs, and fingers. [rarediseases.info.nih.gov]

• Self-Mutilation

  Oro-dental features include a lack of tongue fungiform papillae, impairment of taste, oro-dental self-mutilation, dental crowding, excessive plaque and calculus accumulation, salivary over production and low caries experience. [ncbi.nlm.nih.gov]

• Self-Mutilation

  Oro-dental features include a lack of tongue fungiform papillae, impairment of taste, oro-dental self-mutilation, dental crowding, excessive plaque and calculus accumulation, salivary over production and low caries experience. [ncbi.nlm.nih.gov]

• Hypertelorism

  […] abdominal pain, and either constipation or diarrhea, presumably arising from excessive calcitonin secretion due to MTC), musculoskeletal changes (kyphosis, hip dislocation, a Marfanoid appearance, as well as flat foot and pes cavus), and a flat facies with hypertelorism [symptoma.com]

• Absent Deep Tendon Reflex

  The typical clinical features consist of somatic abnormalities: failure to thrive, characteristic facies, excessive sweating, labile blood pressure, recurrent aspiration pneumonias, lack of tears, and diminished and later absent deep tendon reflexes with [ncbi.nlm.nih.gov]

The diagnosis of MEN type 2B rests on the ability of the physician to recognize the main signs and symptom that will raise clinical suspicion. Firstly, a detailed patient history and a thorough physical examination should be performed, during which mucosal neuromas must be identified. Although MEN syndromes exhibit an autosomal dominant pattern of inheritance (meaning that a family history can be crucial for making the diagnosis), many patients develop de novo mutations of the RET proto-oncogene, the main event in the pathogenesis of multiple endocrine neoplasia type 2B [5] [9]. As soon as clinical evidence is obtained, laboratory and imaging studies need to be performed. Serum levels of calcitonin and metanephrines (although urine can be a viable sample for the latter) are useful initial methods to suspect toward MTC and pheochromocytoma, respectively [4] [5] [10]. Computed tomography (CT) and magnetic resonance imaging (MRI) are recommended for internal organ evaluation and confirmation of the two tumors in the patients, whereas barium enema and other radiographic studies of the gastrointestinal tract commonly may reveal a megacolon and dilation of the small bowel [3] [4] [10]. MTC should be further solidified by performing a biopsy with subsequent histopathological examination and immunohistochemistry [3].

• Liver Biopsy

  In 1975, angiography revealed extensive hepatic lesions metastatic from the medullary thyroid carcinoma; this finding was confirmed by open liver biopsy in 1988. [ncbi.nlm.nih.gov]

  Liver biopsy showed that hepatic lesions were immunohisto-chemically positive for calcitonin and CEA. [academic.oup.com]

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2. Kouvaraki MA, Shapiro SE, Perrier ND, Cote GJ, Gagel RF, Hoff AO, et al. RET proto-oncogene: a review and update of genotype-phenotype correlations in hereditary medullary thyroid cancer and associated endocrine tumors. Thyroid. 2005;15:531–544.
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