Differentiating crohn's disease from other diseases

https://www.wikidoc.org/index.php/Crohn%27s_disease

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] ; Associate Editor(s)-in-Chief: Aditya Ganti M.B.B.S. [2]

Overview

The most common disease that mimics the symptoms of Crohn's disease is ulcerative colitis, as both are inflammatory bowel diseases that can affect the colon with similar symptoms. It is important to differentiate these diseases, since the course of the diseases and treatments may be different. In some cases, however, it may not be possible to tell the difference, in which case the disease is classified as indeterminate colitis.

Differentiating Crohn's Disease from other Diseases

The most common disease that mimics the symptoms of Crohn's disease is ulcerative colitis, as both are inflammatory bowel diseases that can affect the colon with similar symptoms. It is important to differentiate these diseases, since the course of the diseases and treatments may be different. In some cases, however, it may not be possible to tell the difference, in which case the disease is classified as indeterminate colitis.

Comparisons of various factors in Crohn's disease and ulcerative colitis

	Crohn's disease	Ulcerative colitis
Terminal ileum involvement	Commonly	Seldom
Colon involvement	Usually	Always
Rectum involvement	Seldom	Usually
Involvement around the anus	Common	Seldom
Bile duct involvement	No increase in rate of primary sclerosing cholangitis	Higher rate
Distribution of Disease	Patchy areas of inflammation (Skip lesions)	Continuous area of inflammation
Endoscopy	Deep geographic and serpiginous (snake-like) ulcers	Continuous ulcer
Depth of inflammation	May be transmural, deep into tissues	Shallow, mucosal
Fistulae	Common	Seldom
Stenosis	Common	Seldom
Autoimmune disease	Widely regarded as an autoimmune disease	No consensus
Cytokine response	Associated with Th1	Vaguely associated with Th2
Granulomas on biopsy	Can have granulomas	Granulomas uncommon
Surgical cure	Often returns following removal of affected part	Usually cured by removal of colon
Smoking	Higher risk for smokers	Lower risk for smokers

Oral lesioins of Crohn's disease must be differentiated from other mouth lesions such as oral candidiasis and aphthous ulcer

Disease	Presentation	Risk Factors	Diagnosis	Affected Organ Systems	Important features	Picture
Diseases predominantly affecting the oral cavity
Oral Candidiasis	Dysphagia or odynophagia White patches on the mouth and tongue	Newborn babies Denture users Poorly controlled diabetes As a side effect of medication, most commonly having taken antibiotics. Inhaled corticosteroids for the treatment of lung conditions (e.g, asthma or COPD) may also result in oral candidiasis which may be reduced by regularly rinsing the mouth with water after taking the medication. People with poor nutrition, specifically vitamin A, iron and folate deficiencies. People with an immune deficiency (e.g. as a result of AIDS/HIV or chemotherapy treatment). Women undergoing hormonal changes, like pregnancy or those on birth control pills. Organ transplantation patients	Clinical diagnosis Confirmatory tests rarely needed	Localized candidiasis Oral and esophageal candidasis Candida vulvovaginitis Chronic mucocutaneous candidiasis Invasive candidasis Candidaemia Candida endocarditis Candida osteoarticular disease	Oral candidiaisis is a benign self limiting disease unless accompanied by immunosuppression.	Tongue infected with oral candidiasis - By James Heilman, MD - Own work, CC BY-SA 3.0, httpscommons.wikimedia.orgwindex.phpcurid=11717223.jpg
Herpes simplex oral lesions	Fever Sore throat Painful ulcers	Stress Recent URTI Female sex	Physical examination Viral culture Tzanck smear	Orofacial Infection Anogenital Infection Ocular Infection Herpes Encephalitis Neonatal Herpes Herpetic Whitlow Herpes Gladiatorum	The symptoms of primary HSV infection generally resolve within two weeks	Oral herpes simplex infection - By James Heilman, MD - Own work, CC BY-SA 3.0, httpscommons.wikimedia.orgwindex.phpcurid=19051042.jpg
Aphthous ulcers	Painful, red spot or bump that develops into an open ulcer	Being a female Between the ages of 10-40 Family history of aphthous ulcers	Physical examination Diagnosis of exclusion	Oral cavity	Self-limiting , Pain decreases in 7 to 10 days, with complete healing in 1 to 3 weeks	By Ebarruda - Own work, CC BY-SA 3.0, httpscommons.wikimedia.orgwindex.phpcurid=7903358
Squamous cell carcinoma	Non healing ulcer, nodule, indurated plaque or mass May involve skin, lips, inside the mouth, throat or esophagus	Chronic sun or UV exposure Fair skin Elderly age (>45 yrs) Male sex Smoking	Physical exam Biopsy	Oral Cavity Floor of mouth Lateral tongue Throat Esophagus	Malignant Can spread to TMJ Some times associated with leukoplakia	Squamous cell carcinoma - By Luca Pastore, Maria Luisa Fiorella, Raffaele Fiorella, Lorenzo Lo Muzio - http://www.plosmedicine.org/article/showImageLarge.action?uri=info%3Adoi%2F10.1371%2Fjournal.pmed.0050212.g001, CC BY 2.5, https://commons.wikimedia.org/w/index.php?curid=15252632
Leukoplakia	White leathery spots on the mucous membranes of the tongue and inside of the mouth Lateral borders of tongue	Atypical Tobacco use Chronic irritation Immunodeficiency Bloodroot (sanguinaria)	Physical exam Diagnosis of exclusion Biopsy	Vulvar lesions occur independent of oral lesions	Associated with HIV Persistant white spots Benign but can progress to carcinoma after almost 10 years Oral proliferative verrucous leukoplakia is an aggressive sub type with multiple lesions and higher conversion to warts or carcinoma	Leukoplakia - By Aitor III - Own work, Public Domain, https://commons.wikimedia.org/w/index.php?curid=9873087
Melanoma	A lesion with ABCD Asymmetry Border irregularity Color variation Diameter changes Bleeding from the lesion	UV radiations Genetic predisposition Old age Male gender Family or personal history of melanoma Multiple benign or atypical nevi	ABCD characteristics Bleeding or ulceration may show malignancy Serum LDH may be elevated in case of malignancy Biopsy	Can metastasize All UV radiation or sun exposed areas can be effected independently 1-2 to hundreds of granules	Neural crest cell derivative Development begins with disruption of nevus growth control Progression involves MAPK/ERK pathway N-RAS or BRAF oncogene also involved	Oral melanoma - By Emmanouil K Symvoulakis, Dionysios E Kyrmizakis, Emmanouil I Drivas, Anastassios V Koutsopoulos, Stylianos G Malandrakis, Charalambos E Skoulakis and John G Bizakis - Symvoulakis et al. Head & Face Medicine 2006 2:7 doi:10.1186/1746-160X-2-7 (Open Access), [1], CC BY-SA 2.0, https://commons.wikimedia.org/w/index.php?curid=9839811
Fordyce spots	Rice-like granules or spots Small, painless, raised, pale, red or white 1 to 3 mm in diameter	Greasy skin types Some rheumatic disorders Hereditary nonpolyposis colorectal cancer Lower gingiva (gums) Vestibular mucosa	Physical exam Small keratin-filled pseudocysts May be seen on incidental mucosal biopsy Biopsy not done for them primarily	Oral cavity Vermilion border of the lips Oral mucosa of the upper lip Buccal mucosa in the commissural region often bilaterally Genitals	Benign neoplasms with sebaceous features Visible sebaceous glands No surrounding mucosal change Several adjacent glands may coalesce into a larger cauliflower-like cluster	Fordyce spots - Por Perene - Obra do próprio, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=19772899
Burning mouth syndrome	Burning or tingling on the lips, tongue, or entire mouth	Nutritional deficiencies Chronic anxiety or depression Diabetes type 2 Menopause Oral thrush or dry mouth, or damaged nerves transmitting taste Female gender Menopause	Presentation Physical exam	Oral cavity	Pain typically is low in the morning and builds up over the day Low dosages of benzodiazepines, tricyclic antidepressants or anticonvulsants may be effective
Torus palatinus	Bony growth on midline of the hard palate Nodular mass covered with normal mucosa	Genetic predisposition Autosomal dominant	Physical exam Types Flat tori Spindle tori Nodular tori Lobular tori	Hard palate	More common in Asian and Inuit populations Twice more common in females Repeated trauma can cause bleeding Surgery may be required in symptomatic	Torus palatinus - By Photo taken by dozenist, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=846591
Diseases involving oral cavity and other organ systems
Behcet's disease	Painful mouth sores Acne like skin lesions Headache, fever, poor balance, disorientation Abdominal pain, diarrhea or bleeding Uveitis Joint swelling and joint pain Genital sores wit pain and scaring Aneurysms	Over active immune system	Physical examination	Mouth Genitals GIT Eye Joints Skin Vascular system Brain	Outbreaks of exaggerated inflammation Affects smaller blood vessels	Behcet's disease - By Ahmet Altiner MD, Rajni Mandal MD - http://dermatology.cdlib.org/1611/articles/18_2009-10-20/2.jpg, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=17863021
Crohn's disease	Chronic, episodic diarrhea or constipation Abdominal pain Vomiting Weight loss or weight gain	Smoking Whites and European Jews Hormonal contraception Diets high in microparticles, sweet, fatty or refined foods Industrialized country	Typical history and symptoms Skip lesions on biopsy Anti-Saccharomyces cerevisiae antibodies (ASCA) Anti-neutrophil cytoplasmic antibodies (ANCA)	Eyes Joints Skin	May lead to Obstructions Abscesses Free perforation Hemorrhage
Agranulocytosis	Fever or chills Frequent infections Unusual redness, pain, or swelling around a wound Mouth ulcers Abdominal pain Burning sensation when urinating Sore throat	Medications Cytotoxic chemotherapy Hematologic malignancies Autoimmune disorders	Neutropenia <100 cells per micro litre Eosinopenia Basopenia	Oral cavity Skin GIT Urinary system Conjunctiva	Immunocompromization Types Drug-induced Malignant Autoimmune
Syphilis	Chancre Regional lymphadenopathy	Multiple sexual partners Illicit drug use Unprotected sex Men who have sex with men Residence in highly prevalent areas HIV infection Presence of other STIs Previous history of STIs Intravenous drug use	Darkfield microscopy Non treponemal tests like VDRL and RPR test) Treponemal testsFTA-ABS tests, (TP-PA) assay, enzyme immunoassays, and chemiluminescence immunoassays)	Oral cavity Penis Cervix Labia Anal canal Rectum CNS CVS	Primary syphilis Chancre Secondary syphilis Condylomata lata Latent syphilis Asymptomatic Tertiary syphilis Gummas Neurosyphilis	oral syphilis - By CDC/Susan Lindsley - http://phil.cdc.gov/phil_images/20021114/34/PHIL_2385_lores.jpg, Public Domain, https://commons.wikimedia.org/w/index.php?curid=2134349
Coxsackie virus	Fever Sores in the mouth Rash with blisters Aches	Pregnancy immunodeficiency	History and Physical exam Throat swabs Swabs from the lesion Tzanck test	Oral cavity Skin	Symptomatic treatment
Chicken pox	Conjunctival symptoms Catarrhal symptoms Characteristic spots on the trunk appearing in two or three waves Itching	Pregnancy Premature infants born to susceptible mothers All infants born at less than 28 weeks gestation or who weigh =1000 grams Immunocompromised	History and physical exam PCR to detect VZV in skin lesions (vesicles, scabs, maculopapular lesions)	Oral cavity Skin	Sodium bicarbonate in baths or antihistamines for itching Paracetamol (acetaminophen) for fever Prednisolone is contraindicated	Chickenpox - By James Heilman, MD - Own work, CC BY-SA 4.0, https://commons.wikimedia.org/w/index.php?curid=52872565
Measles	Fever Rash Cough Coryza (runny nose) Conjunctivitis (pink eye) Malaise Koplick spots in mouth	Unvaccinated individuals Crowded and/or unsanitary conditions Traveling to less developed and developing countries Immunocompromized Winter and spring seasons Born after 1956 and never fully vaccinated Health care workers	History and examination PCR for Measles-specific IgM antibody PCR for Measles RNA	Oral cavity Skin Respiratory tract Eyes Throat	Caused by Morbillivirus Primary site of infection is the respiratory epithelium of the nasopharynx Transmitted in respiratory secretions, via aerosol droplets containing virus particles	Koplick spots (Measles) - By CDC - http://phil.cdc.gov/PHIL_Images/20040908/4f54ee8f0e5f49f58aaa30c1bc6413ba/6111_lores.jpg, Public Domain, https://commons.wikimedia.org/w/index.php?curid=824483

The following table differentiates all the diseases presenting with abdominal pain, fever and lower gastrointestinal bleeding.

Disease Clinical manifestations Diagnosis Comments Symptoms Signs Abdominal Pain Fever Rigors and chills Nausea or vomiting Jaundice Constipation Diarrhea Weight loss GI bleeding Hypo- tension Guarding Rebound Tenderness Bowel sounds Lab Findings Imaging Acute diverticulitis LLQ + ± + − + ± − + Positive in perforated diverticulitis + + Hypoactive Leukocytosis CT scan Ultrasound History of constipation Inflammatory bowel disease Diffuse ± − − ± − + + + − − − Normal or hyperactive Anti-neutrophil cytoplasmic antibody (P-ANCA) in Ulcerative colitis Anti saccharomyces cerevisiae antibodies (ASCA) in Crohn's disease String sign on abdominal x-ray in Crohn's disease Extra intestinal findings: Uveitis Arthritis Infective colitis Diffuse + − ± − − + − + Positive in fulminant colitis ± ± Hyperactive Stool culture and studies Shiga toxin in bloody diarrhea PCR CT scan Bowel wall thickening Edema Colon carcinoma Diffuse/localized − − − − ± ± + + ± − − Normal or hyperactive if obstruction present CBC Carcinoembryonic antigen (CEA) Colonoscopy Flexible sigmoidoscopy Barium enema CT colonography  PILLCAM 2: A colon capsule for CRC screening may be used in patients with an incomplete colonoscopy who lacks obstruction Hemochromatosis RUQ − − − − − − − Positive in cirrhotic patients − − − N >60% TS >240 μg/L SF Raised LFT Hyperglycemia Ultrasound shows evidence of cirrhosis Extra intestinal findings: Hyperpigmentation Diabetes mellitus Arthralgia Impotence in males Cardiomyopathy Atherosclerosis Hypopituitarism Hypothyroidism Extrahepatic cancer Prone to specific infections Mesenteric ischemia Periumbilical Positive if bowel becomes gangrenous − + − − + + + Positive if bowel becomes gangrenous Positive if bowel becomes gangrenous − Hyperactive to absent Leukocytosis and lactic acidosis Amylase levels D-dimer CT angiography SMA or SMV thrombosis Also known as abdominal angina that worsens with eating Acute ischemic colitis Diffuse + ± + − − + + + + + + Hyperactive then absent Leukocytosis Abdominal x-ray Distension and pneumatosis CT scan Double halo appearance, thumbprinting Thickening of bowel May lead to shock Ruptured abdominal aortic aneurysm Diffuse ± − + − − − + + + − − N Fibrinogen D-dimer Focused Assessment with Sonography in Trauma (FAST)  Unstable hemodynamics Intra-abdominal or retroperitoneal hemorrhage Diffuse ± − ± − − − − + + − − N ↓ Hb ↓ Hct CT scan History of trauma

Abbreviations: RUQ= Right upper quadrant of the abdomen, LUQ= Left upper quadrant, LLQ= Left lower quadrant, RLQ= Right lower quadrant, LFT= Liver function test, SIRS= Systemic inflammatory response syndrome, ERCP= Endoscopic retrograde cholangiopancreatography, IV= Intravenous, N= Normal, AMA= Anti mitochondrial antibodies, LDH= Lactate dehydrogenase, GI= Gastrointestinal, CXR= Chest X ray, IgA= Immunoglobulin A, IgG= Immunoglobulin G, IgM= Immunoglobulin M, CT= Computed tomography, PMN= Polymorphonuclear cells, ESR= Erythrocyte sedimentation rate, CRP= C-reactive protein, TS= Transferrin saturation, SF= Serum Ferritin, SMA= Superior mesenteric artery, SMV= Superior mesenteric vein, ECG= Electrocardiogram

Differentiating Crohn's disease from other causes of abdominal pain and diarrhea

Crohn's disease must be differentiated from other causes of abdominal pain and diarrhea.

Diseases		Clinical manifestations												Para-clinical findings										Gold standard	Additional findings
		Symptoms						Physical examination
														Lab Findings			Imaging						Histopathology
		Abdominal pain	Diarrhea	Flushing	Dyspnea	Palpitations	Other symptoms	Wheezing	Telangiectasia	Hypotension	Tachycardia	Systolic murmur of tricuspid regurgitation	Other physical findings	Urinary 5-hydroxyindoleacetic acid (5-HIAA)	Serum Chromogranin A (CgA)	Other markers	Abdominal computed tomography (CT)	Abdominal MRI	Somatostatin receptor scintigraphy [SRS], or Octreoscan	Metaiodobenzylguanidine (MIBG) scintigraphy	Other diagnostic studies	Transthoracic echocardiography
Carcinoid Syndrome	Neuroendocrine tumor of midgut	+ Mild	+ Intermittent Secretory diarrhea	+	+	+	Pellagra Dermatitis Diarrhea Dementia Metastatic tumors in the liver: Right upper quadrant pain, hepatomegaly, and early satiety	+	+/-	+/-	+	+	-	+	+	NT-proBNP Screening of carcinoid heart disease Blood Serotonin levels	Neuroendocrine tumor of midgut are difficult to identify on CT because of their small size. Findings: mass-like process with soft tissue "spokes" radiating into the mesenteric fat toward the small bowel causing retraction. Liver metastases	Sensitive for detection of liver metastases	+ Localization of carcinoid tumor	+	68-Ga DOTATATE PET scan Positron emission tomography-computed tomography (PET-CT) using 18-fluoro-dihydroxyphenylalanine Ki-67 labeling index Endoscopy for metastatic Neuroendocrine tumour with an unknown primary site.	Valve thickening with retraction and reduction in the mobility of the tricuspid valve	Enterochromaffin cells stain with potassium chromate (chromaffin). On electron microscopy ,the cells in tumors are found to contain membrane-bound secretory granules with dense-core granules in the cytoplasm.	Somatostatin receptor scintigraphy [SRS], or Octreoscan Biopsy and histopathology	Mesenteric fibrosis Pathognomonic radiological sign of midgut NET.
	Neuroendocrine tumor of lung	+	+	+	+	+	Cough Hemoptysis Chest pain Fever due to post -obstructuve pneuomnia	+	+/-	+/-	+	+	-	+	+	Immunohistochemical stains: Synaptophysin Neuron-specific enolase NT-proBNP Low serotonin content as compared to midgut tumors.	Atypical neuroendocrine tumors have a greater tendency to metastasize to liver,hypervascular, and becomies isodense relative to the liver parenchyma after contrast administration.		Sensitive for detection of liver metastases if present	+	+	Chest X ray: round or oval opacities from 2-5cm with sharp and notched margins Chest CT : Hilar or Perihilar Masses, Endobronchial Nodules,Related to bronchial Obstruction:peripheral atelectasis and postobstructive pneumonia Pulmonary funcation test Bronchoscopy 68-Ga DOTATATE PET scan Fluorodeoxyglucose PET scans for atypical lung NETs .	-	Typical low-grade:bland cells containing regular round nuclei with finely dispersed chromatin and inconspicuous small nucleoli.Mitotic figures are scarce and necrosis is absent. Intermediate-grade atypical: presence of Neuroendocrine morphology and either necrosis or 2 to 10 mitoses per 10 HPF	Biopsy and histopathology
Irritable Bowel Syndrome		+ Perioidic	Intermittent Chronic history of diarhea alternating with constipation	-	-	-	Fibromyalgia Chronic fatigue syndrome Gastroesophageal reflux disease, Functional dyspepsia Non-cardiac chest pain, Major depression ,Anxiety	-	-	-	-	-		-	-		-	-	-	-	Bristol stool form scale should to record stool consistency Abdominal radiograph to assess for stool accumulation and determine the severity. Age-appropriate colorectal cancer screening in all patients	-	-	Rome IV criteria Recurrent abdominal pain, at least 1day/week in the last 3 months, a/s with 2 or more of the following criteria: •Related to defecation •Associated with a change in stool frequency •Associated with a change in stool form (appearance)
Malignant neoplasms of small intestine		+/-	+/-	-	-	+/-	Constipation Fatigue Early satiety	-	-	+/-	-	* Abdominal mass Ascites	-	+	Abdominal CT scan may be diagnostic of small intestine cancer. Findings on CT scan suggestive of small intestine cancer include intrinsic mass with a short segment of bowel wall thickening	MRI and MRI enteroscopy are other advance modalities to diagnose and stage small intestinal cancers	-	-	Enteroscopy, capsule endoscopy and double balloon enteroscopy		Adenocarcinomas may be polypoid, infiltrating, or as annular constricting lesions is small intestine. Polyps and adenomas of small intestine are considered precursor lesions of adenocarcinoma. Lymphomas of small intestine present with suspicious growths in submucosa with normal appearing muscosa. Endoscopic evaluation may show multifocal involvement and large biopsies are required for diagnoses	Biopsy and histopathology
Crohn disease		Right lower quadrant pain	+/-	-	-	-	Gross bloody diarrhea +/- Weight loss Fatigue	-	-	-	-	-	Weight loss Pallor Oral lesions Odynophagia Dysphagia Perianal skin tags Sinus tracts Gallstones Extraintestinal manifestations Arthritis Uveitis, Iritis, and Episcleritis Erythema nodosum and Pyoderma gangrenosum Primary sclerosing cholangitis Secondary amyloidosis Thromboembolism Renal stones Osteoporosis Vitamin B12 deficiency	-	-	CRP may be high p-ANCA and ASCA	CT enterography Small bowel inflammation by displaying mural hyperenhancement and thickening; engorged vasa recta; and perienteric inflammatory changes.		-	-	CBC Blood chemistry including electrolytes Renal function tests liver enzymes Blood glucose ESR CRP Serum iron Vitamin D & vitamin B12 levels Stool D/R and culture for ova and parasites, C. difficile toxin	-	Focal ulcerations and acute and chronic inflammation Granulomas	Colonoscopy:focal ulcerations adjacent to areas of normal appearing mucosa along with polypoid mucosal,skip lesions,pseudopolyps,
Benign cutaneous flushing		-	-	+	-	-		-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-
Systemic mastocytosis		+	+	+	+	-	Maculopapular rash Pruritus	+/-	+/-	+	-	-	Diffuse musculoskeletal pain Neuropsychiatric symptoms	-	-	Activating mutations of KIT Serum Tryptase levels			-	-
Asthma exacerbation		-	-	-	+	+		+	-	-	+	-	Tachypnea Prolonged expiratory phase of respiration (decreased I:E ratio) Seated position with use of extended arms to support the upper chest (tripod position) +/- Pulsus paradoxus	-	-	-	--	-	-	-	Chest X ray	-	Loss of the normal pseudostratified structure of airway epithelium Increase in the proportion of goblet cells Fibrotic thickening of the sub-epithelial reticular basement membrane Increased numbers of myofibroblasts Increased vascularity Increased airway smooth muscle mass Increased extracellular matrix
Anaphylaxis		+	-/+	+	+	+	Vomiting Generalized hives, Pruritus Itching	+/-	-	+	+	-	Swollen lips-tongue-uvula Periorbital edema, Conjunctival swelling	-	-	-	-	-	-	-	plasma tryptase Plasma histamine levels Take proper clinical history and medication history specially beta blockers,ACE-inhibitors,opioids Skin testing with allergen extracts enzyme-linked immunosorbent assays (ELISAs) for quantification of allergen-specific IgE levels	-	-		History of exposure to insect stings,food alllergy,rubber latex,food additives,,allergy to medications,physical factors such s excercise and cold
Histaminergic Angioedema		+/-	+/-	+	+	+	Generalized pruritus Throat tightness Hoarse voice Difficulty swallowing	+	-	+	+	-	Urticaria Localized swelling of skin	-	-	-	Bowel wall edema Circumferential thickening of the small bowel wall with ascites or incomplete obstruction	-	-	-	CBC with differential, Electrolytes Liver function tests C-reactive protein Erythrocyte sedimentation rate Levels of the complement protein C4 Serum total tryptase Allergen-specific IgE immunoassays	-	-	-	Take proper clinical history of previous similar episodes Medication history Any allergy to insects stings , foods or any ingestion within previous 24 hours
Medullary Thyroid Carcinoma		-	+/-	+/-	+/-	-	Neck pain Hoarseness Cough Difficulty swallowing Difficulty breathing Lethargy Bone pain from metastasis	-	-	-	-	-	Solitary thyroid nodule Cervical lymph node involvement Weight loss	-	-	Basal serum calcitonin concentrations Carcinoembryonic antigen (CEA) concentration Thyroid function tests: normal Germline RET testing Serum calcium Plasma fractionated metanephrines	-	-	-	-	Ultrasonography of the neck For metastasis Chest computed tomography Neck CT Three-phase contrast-enhanced liver CT Axial MRI Bone scintigraphy.	-	Immunohistochemical staining for calcitonin Spindle-shaped and frequently pleomorphic cells without follicle development	Fine-needle aspiration (FNA) biopsy TNM staging American Thyroid Association (ATA) Guidelines for Management and evaluation of Medullary Thyroid Cancer