Differentiating carcinoid syndrome from other diseases

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Associate Editor(s)-in-Chief: Parminder Dhingra, M.D. [2]

Overview

Carcinoid syndrome must be differentiated from systemic mastocytosis, medullary thyroid carcinoma, irritable bowel syndrome, malignant neoplasms of the small intestine, benign cutaneous flushing, and recurrent idiopathic anaphylaxis.

Differentiating Carcinoid Syndrome from other Diseases

Carcinoid syndrome must be differentiated from:[1]

On the basis [symptom 1], [symptom 2], and [symptom 3], [disease name] must be differentiated from [disease 1], [disease 2], [disease 3], [disease 4], [disease 5], and [disease 6].

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) MRI Somatostatin receptor scintigraphy [SRS], or Octreoscan Metaiodobenzylguanidine (MIBG) scintigraphy Other diagnostic studies
  • Transthoracic echocardiography
Carcinoid Syndrome[2][3][4][5] Midgut tumours +

Mild

+
  • Intermittent
  • Secretory type
+ + +
  • Pellagra

Dermatitis

Diarrhea

Dementia

+ + + + + + +
  • NT-proBNP
    • Screening of carcinoid heart disease
    • Blood Serotonin levels
+
  • Localization of carcinoid tumor
+
  • Positron emission tomography-computed tomography (PET-CT) using 18-fluoro-dihydroxyphenylalanine
  • Ki-67 labeling index
  • Valve thickening with retraction and reduction in the mobility of the tricuspid valve
  • Somatostatin receptor scintigraphy [SRS], or Octreoscan
  • Mesenteric fibrosis

Pathognomonic radiological sign of midgut NET.

Bronchial carcinoid
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 mas
  • Ascities
- + 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 Biopsy and histopathology
Crohn disease[6]
  • Right lower quadrant pain
+/- - - -
  • Gross bleedy 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
  • Venous and arterial thromboembolism
  • Renal stones
  • Osteoporisis
  • Vitmain B12 deficiancy
  • Pulmonary involvement
- -
  • CRP may be high
  • pANCA 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 leevs
- -
Recurrent idiopathic anaphylaxis
Asthma exacerbation - - - + + + - - + - - - Chest X ray
Acute Urticaria
Anaphylaxis + -/+ + + +
  • Vomintng
  • generalized hives,
  • pruritus
  • itching
+/- - + + -
  • swollen lips-tongue-uvula
  • periorbital edema,
  • conjunctival swelling
- - - - -
  • plasma tryptase
  • Plasma histamine levels
  • Take proper clinical history and medication history specicially beta blockrs,ACE-inhibots,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
Drugs causing flushing
  • Nicotinic acid
  • Levodopa
  • Bromocriptine
  • Diltiazem
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

References

  1. Metcalfe DD (2000). "Differential diagnosis of the patient with unexplained flushing/anaphylaxis". Allergy Asthma Proc. 21 (1): 21–4. PMID 10748948.
  2. Rubin de Celis Ferrari AC, Glasberg J, Riechelmann RP (August 2018). "Carcinoid syndrome: update on the pathophysiology and treatment". Clinics (Sao Paulo). 73 (suppl 1): e490s. doi:10.6061/clinics/2018/e490s. PMC 6096975. PMID 30133565.
  3. Hegyi J, Schwartz RA, Hegyi V (January 2004). "Pellagra: dermatitis, dementia, and diarrhea". Int. J. Dermatol. 43 (1): 1–5. PMID 14693013.
  4. Savelli G, Lucignani G, Seregni E, Marchianò A, Serafini G, Aliberti G, Villano C, Maccauro M, Bombardieri E (May 2004). "Feasibility of somatostatin receptor scintigraphy in the detection of occult primary gastro-entero-pancreatic (GEP) neuroendocrine tumours". Nucl Med Commun. 25 (5): 445–9. PMID 15100502.
  5. Savelli G, Lucignani G, Seregni E, Marchianò A, Serafini G, Aliberti G, Villano C, Maccauro M, Bombardieri E (May 2004). "Feasibility of somatostatin receptor scintigraphy in the detection of occult primary gastro-entero-pancreatic (GEP) neuroendocrine tumours". Nucl Med Commun. 25 (5): 445–9. PMID 15100502.
  6. Hara AK, Swartz PG (2009). "CT enterography of Crohn's disease". Abdom Imaging. 34 (3): 289–95. doi:10.1007/s00261-008-9443-1. PMID 18649092.

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