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==Differentiating Glucagonoma from other Diseases==
==Differentiating Glucagonoma from other Diseases==
Glucagonoma must be differentiated from certain skin lesions in which necrolytic migratory erythema can be found such as:<ref>Glucagonoma. Wikipedia. https://en.wikipedia.org/wiki/Glucagonoma. accessed on October 10, 2015</ref><ref name="pmid25152626">{{cite journal| author=Fang S, Li S, Cai T| title=Glucagonoma syndrome: a case report with focus on skin disorders. | journal=Onco Targets Ther | year= 2014 | volume= 7 | issue=  | pages= 1449-53 | pmid=25152626 | doi=10.2147/OTT.S66285 | pmc=PMC4140234 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25152626  }} </ref>
Glucagonoma must be differentiated from certain skin lesions in which necrolytic migratory erythema can be found and other causes of hyperglucagonemia:<ref>Glucagonoma. Wikipedia. https://en.wikipedia.org/wiki/Glucagonoma. accessed on October 10, 2015</ref><ref name="pmid25152626">{{cite journal| author=Fang S, Li S, Cai T| title=Glucagonoma syndrome: a case report with focus on skin disorders. | journal=Onco Targets Ther | year= 2014 | volume= 7 | issue=  | pages= 1449-53 | pmid=25152626 | doi=10.2147/OTT.S66285 | pmc=PMC4140234 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25152626  }} </ref>
<small><small>
{| class="wikitable"
! rowspan="2" |Disease
! colspan="3" |Clinical Picture
! rowspan="2" |Investigations
! rowspan="2" |Pictures
|-
!History
!Symptoms
!Signs
|-
|Glucagonoma
|A family history of [[multiple endocrine neoplasia type 1]]
|
* [[Necrolytic migratory erythema]] characterized by the spread of erythematous blisters and swelling across areas subject to greater friction and pressure, including the lower [[abdomen]], [[Buttock|buttocks]], [[perineum]], and [[groin]].<sup>[[Glucagonoma history and symptoms#cite note-pmid4793623-2|[2]]]</sup>
* [[Weight loss]]<sup>[[Glucagonoma history and symptoms#cite note-pmid86066272-3|[3]]]</sup>
* [[Glucose intolerance]]<sup>[[Glucagonoma history and symptoms#cite note-pmid6268399-4|[4]]]</sup>
|
* [[Rash|Rash:]] Erythematous, ring shaped [[rash]] that blisters, erodes, and crusts over suggesting [[necrolytic migratory erythema]].
* Muscle [[atrophy]].
* Unilateral [[calf]] or [[thigh]][[erythema]], and [[swelling]].
* Hyporeflexia
* Unilateral/bilateral [[sensory loss]] in the upper/lower extremity
|
* '''Serum glucagon'''<sup>[[Glucagonoma laboratory tests#cite note-pmid15313692-1|[1]]]</sup>
** Increased plasma glucagon levels (>500 pg/mL).<sup>[[Glucagonoma laboratory tests#cite note-pmid8606627-3|[3]]]</sup>
** Concentrations above 1000 pg/mL are diagnostic of glucagonoma.<sup>[[Glucagonoma laboratory tests#cite note-pmid17873310-4|[4]]]</sup>


A[[acrodermatitis enteropathica|crodermatitis enteropathica]]
* CT scans are used to determine the location of the tumor, show the organs nearby. Liver metastases may appear isodense with the liver on a non-contrasted study.<sup>[[Glucagonoma CT#cite note-pmid9574609-4|[4]]]</sup>
|[[File:NEM1.jpg|center|250px]]
|-
|[[Pemphigus foliaceus]] 
|Autoimmune blistering disease of the skin with characteristic lesions that are scaly, crusted erosions, often on an erythematous base.<sup>[[Pemphigus foliaceus#cite note-Fitz2-1|[1]]]</sup>


[[psoriasis|pustular psoriasis]]
Mucosal involvement is absent even with widespread disease.<sup>[[Pemphigus foliaceus#cite note-Bolognia-2|[2]]]</sup>


[[pellagra]]
|
* The main symptom is a cutaneous lesion that usually develops in a seborrheic distribution:<ref name="pmid15993235">{{cite journal| author=Bystryn JC, Rudolph JL| title=Pemphigus. | journal=Lancet | year= 2005 | volume= 366 | issue= 9479 | pages= 61-73 | pmid=15993235 | doi=10.1016/S0140-6736(05)66829-8 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15993235  }}</ref>the scalp, face, and trunk are common sites of involvement. 


[[eczema]]
* The skin lesions may remain localized or may coalesce to cover large areas of skin.
* Pain or burning sensations frequently accompany the cutaneous lesions. Systemic symptoms are usually absent.
|
* The skin lesions usually consist of small, scattered superficial blisters that rapidly evolve into scaly, crusted erosions


<small><small>
* Occasionally, pemphigus foliaceus progresses to involve the entire skin surface as an exfoliative erythroderma.<ref name="pmid159414332">{{cite journal| author=Chams-Davatchi C, Valikhani M, Daneshpazhooh M, Esmaili N, Balighi K, Hallaji Z et al.| title=Pemphigus: analysis of 1209 cases. | journal=Int J Dermatol | year= 2005 | volume= 44 | issue= 6 | pages= 470-6 | pmid=15941433 | doi=10.1111/j.1365-4632.2004.02501.x | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15941433  }}</ref>
* Positive Nikolsky sign<ref name="pmid21353333">{{cite journal| author=Martin LK, Werth VP, Villaneuva EV, Murrell DF| title=A systematic review of randomized controlled trials for pemphigus vulgaris and pemphigus foliaceus. | journal=J Am Acad Dermatol | year= 2011 | volume= 64 | issue= 5 | pages= 903-8 | pmid=21353333 | doi=10.1016/j.jaad.2010.04.039 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21353333  }}</ref>
|Autoimmune [[IgG]] build up in the [[Epidermis (skin)|epidermis]], then nearly almost all of the antibodies are aimed against [[desmoglein 1]]
|[[File:Pemphigus foliaceus08.jpg|center|250px]]
|-
|[[Psoriasis|Pustular psoriasis]]
|
* Positive family history of psoriasis, frequent association with [[histocompatibility]] [[antigen]] (HLA)- Cw6.<sup>[[Psoriasis history and symptoms#cite note-pmid1390163-2|[2]]]</sup>
* A history of a long-term [[erythematous]] scaly area with [[ocular]] and [[joint]] involvement.
* Past medical history of the patient may include [[viral]] or [[bacterial]] infection, [[Diabetes mellitus|diabetes]], [[hypertension]], [[chronic kidney disease]] and/or [[obesity]].<sup>[[Psoriasis history and symptoms#cite note-pmid24790463-3|[3]]]</sup>
|
* [[Pain]], which has been described by patients as unpleasant, superficial, sensitive, itchy, hot or burning. 
* [[Pruritus]]
* High [[fever]]
* Dystrophic nails
* Recent presentation of [[arthralgia]]
|
* [[Papulosquamous disorder|Papulosquamous]] [[disease]] with variable morphology, distribution, severity, and course
* Scaling [[Papule|papules]] and [[Plaque|plaques]]
* [[Koebner phenomenon]]: appearance of new psoriatic lesions at the site of skin injury
* [[Woronoff|Woronoff’s ring]]: ring of peripheral blanching skin around a psoriatic [[plaque]]
* Auspitz’s sign: small [[bleeding]] points are seen upon disruption of a psoriatic scale.
|
* '''Skin biopsy'''
* Perivascular and [[dermal]] [[Inflammatory cells|inflammatory cell]] infiltration
* [[Vascular]] dilation
* Absent [[granular layer]]
* Elongation of [[dermal]] [[Papilla|papillae]]
* Parakeratosis
* Spongiform [[pustules]] of Kogoj (pathognomic of psoriasis)
* Munro's micro abscesses (pathognomic of psoriasis)
* [[Edema]] of [[dermal]] [[papillae]]
* [[Basal cell layer]] is expanded
* Leukocytosis
|[[File:Pus.png|center|250px]]
|-
|[[Acrodermatitis enteropathica]]
|
* An [[autosomal]] [[recessive]] disorder characterized by periorificial and acral [[dermatitis]], [[alopecia]], and [[diarrhea]].
* The genetic base is a [[mutation]] of [[SLC39A4]] which encodes a [[transmembrane protein]] that serves as a zinc uptake protein. 
|
* Symptoms appear in infants after breast milk weaning.
* The appearance of erythematous patches and plaques of dry, scaly skin.
* Diarrhea may occur.
|
* Erythematous patches and plaques of dry, scaly skin.
 
* The lesions may appear eczematous or may evolve further into crusted vesicles, bullae or pustules.
* The lesions are frequent around natural orifices like the mouth perioral and anus peri-anal, and also in hands, feet, and [[scalp]].
* [[paronychia]] 
* Alopecia of the scalp, eyebrows, and eyelashes 
|
* Measurement of zinc in plasma, erythrocytes, neutrophils, lymphocytes, and hair.


* A low plasma zinc usually is defined as a value less than 60 mcg/dL.
* Zinc levels in neutrophils or lymphocytes may be more sensitive than plasma zinc.<ref name="pmid6696358">{{cite journal| author=Prasad AS, Cossack ZT| title=Zinc supplementation and growth in sickle cell disease. | journal=Ann Intern Med | year= 1984 | volume= 100 | issue= 3 | pages= 367-71 | pmid=6696358 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=6696358  }}</ref>
* The criteria for zinc deficiency are decreased zinc level in either lymphocyte.<ref name="pmid1940572">{{cite journal| author=Meftah S, Prasad AS, Lee DY, Brewer GJ| title=Ecto 5' nucleotidase (5'NT) as a sensitive indicator of human zinc deficiency. | journal=J Lab Clin Med | year= 1991 | volume= 118 | issue= 4 | pages= 309-16 | pmid=1940572 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=1940572  }}</ref>
* Depressed serum alkaline phosphatase levels for age provide supportive evidence for zinc deficiency.<ref name="pmid9481631">{{cite journal| author=Kiliç I, Ozalp I, Coŝkun T, Tokatli A, Emre S, Saldamli I et al.| title=The effect of zinc-supplemented bread consumption on school children with asymptomatic zinc deficiency. | journal=J Pediatr Gastroenterol Nutr | year= 1998 | volume= 26 | issue= 2 | pages= 167-71 | pmid=9481631 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9481631  }}</ref>
|[[File:Acrodermatitis enteropathica 05.png|center|250px]]
|-
|[[Pellagra]]
|
* It is a niacin deficiency disease characterized by a photosensitive pigmented dermatitis, diarrhea, and dementia.
* Hisotry of alcoholics, bariatric surgery, anorexia nervosa, or malabsorptive disease.<ref name="pmid12777163">{{cite journal| author=Prousky JE| title=Pellagra may be a rare secondary complication of anorexia nervosa: a systematic review of the literature. | journal=Altern Med Rev | year= 2003 | volume= 8 | issue= 2 | pages= 180-5 | pmid=12777163 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12777163  }}</ref>
* Dietary deficiency especially in infants
* Past history of Carcinoid syndrome
* Prolonged use of isoniazid<ref name="pmid21128910">{{cite journal| author=Wan P, Moat S, Anstey A| title=Pellagra: a review with emphasis on photosensitivity. | journal=Br J Dermatol | year= 2011 | volume= 164 | issue= 6 | pages= 1188-200 | pmid=21128910 | doi=10.1111/j.1365-2133.2010.10163.x | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21128910  }}</ref>
* A family history of Hartnup disease
|
* Photosensitivity
* Pigmented dermatitis in sun-exposed areas
* Diarrhea
* Dementia
|Symmetric hyper pigmented rash, similar in color and distribution to a sunburn, which is present in the exposed areas of skin
|Niacin status can be assessed by measuring urinary N-methylnicotinamide or by measuring the erythrocyte NAD/NADP (ratio). 
|[[File:Pellagra24.jpg|center|250px]]
|-
|[[eczema|Chronic eczema]] (atopic dermatitis)
|
* It is a chronic pruritic inflammatory skin disease that occurs most frequently in children but also affects adults.
* A family history of atopy (eczema, asthma, or allergic rhinitis)
* History of dermatitis involving the skin creases
* Personal or family history of asthma or hay fever
|
* Symptoms beginning in a child before the age of 2 years or, in children <4 years, dermatitis affecting the cheeks or dorsal aspect of extremities.
* Dry skin and severe pruritus that is associated with cutaneous hyperreactivity to various environmental stimuli
* including exposure to food and inhalant allergens, irritants, and infection.
|
* Visible dermatitis involving flexural surfaces.
* Presence of generally dry skin within the past year
* Erythema, papulation, oozing and crusting, excoriation.
|
* Raised [[IgE]] or an [[eosinophilia]]
* [[RAST test|Radioallergosorbent Test]]: blood is mixed separately with many different allergens and the antibody levels measured.
* High levels of antibodies in the blood signify an allergy to that substance
* Skin biopsy: a procedure that removes a small piece of the affected skin and sent for microscopic examination in a pathology laboratory.
|[[File:Atopic Dermatitis27.jpg|center|250px]]
|}
</small></small>
</small></small>


Revision as of 14:24, 4 August 2017

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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] Mohammed Abdelwahed M.D[3]

Overview

Glucagonoma must be differentiated from certain skin lesions (acrodermatitis enteropathica, psoriasis, pellagra, eczema) and other causes of hyperglucagonemia (infection, diabetes mellitus, Cushing syndrome, renal failure, acute pancreatitis, severe stress, and prolonged fasting).

Differentiating Glucagonoma from other Diseases

Glucagonoma must be differentiated from certain skin lesions in which necrolytic migratory erythema can be found and other causes of hyperglucagonemia:[1][2]

Disease Clinical Picture Investigations Pictures
History Symptoms Signs
Glucagonoma A family history of multiple endocrine neoplasia type 1
  • Serum glucagon[1]
    • Increased plasma glucagon levels (>500 pg/mL).[3]
    • Concentrations above 1000 pg/mL are diagnostic of glucagonoma.[4]
  • CT scans are used to determine the location of the tumor, show the organs nearby. Liver metastases may appear isodense with the liver on a non-contrasted study.[4]
Pemphigus foliaceus  Autoimmune blistering disease of the skin with characteristic lesions that are scaly, crusted erosions, often on an erythematous base.[1]

Mucosal involvement is absent even with widespread disease.[2]

  • The main symptom is a cutaneous lesion that usually develops in a seborrheic distribution:[3]the scalp, face, and trunk are common sites of involvement.
  • The skin lesions may remain localized or may coalesce to cover large areas of skin.
  • Pain or burning sensations frequently accompany the cutaneous lesions. Systemic symptoms are usually absent.
  • The skin lesions usually consist of small, scattered superficial blisters that rapidly evolve into scaly, crusted erosions
  • Occasionally, pemphigus foliaceus progresses to involve the entire skin surface as an exfoliative erythroderma.[4]
  • Positive Nikolsky sign[5]
 Autoimmune IgG build up in the epidermis, then nearly almost all of the antibodies are aimed against desmoglein 1
Pustular psoriasis
  • Pain, which has been described by patients as unpleasant, superficial, sensitive, itchy, hot or burning. 
  • Pruritus
  • High fever
  • Dystrophic nails
  • Recent presentation of arthralgia
Acrodermatitis enteropathica
  • Symptoms appear in infants after breast milk weaning.
  • The appearance of erythematous patches and plaques of dry, scaly skin.
  • Diarrhea may occur.
  • Erythematous patches and plaques of dry, scaly skin.
  • The lesions may appear eczematous or may evolve further into crusted vesicles, bullae or pustules.
  • The lesions are frequent around natural orifices like the mouth perioral and anus peri-anal, and also in hands, feet, and scalp.
  • paronychia 
  • Alopecia of the scalp, eyebrows, and eyelashes 
  • Measurement of zinc in plasma, erythrocytes, neutrophils, lymphocytes, and hair.
  • A low plasma zinc usually is defined as a value less than 60 mcg/dL.
  • Zinc levels in neutrophils or lymphocytes may be more sensitive than plasma zinc.[6]
  • The criteria for zinc deficiency are decreased zinc level in either lymphocyte.[7]
  • Depressed serum alkaline phosphatase levels for age provide supportive evidence for zinc deficiency.[8]
Pellagra
  • It is a niacin deficiency disease characterized by a photosensitive pigmented dermatitis, diarrhea, and dementia.
  • Hisotry of alcoholics, bariatric surgery, anorexia nervosa, or malabsorptive disease.[9]
  • Dietary deficiency especially in infants
  • Past history of Carcinoid syndrome
  • Prolonged use of isoniazid[10]
  • A family history of Hartnup disease
  • Photosensitivity
  • Pigmented dermatitis in sun-exposed areas
  • Diarrhea
  • Dementia
 Symmetric hyper pigmented rash, similar in color and distribution to a sunburn, which is present in the exposed areas of skin Niacin status can be assessed by measuring urinary N-methylnicotinamide or by measuring the erythrocyte NAD/NADP (ratio). 
Chronic eczema (atopic dermatitis)
  • It is a chronic pruritic inflammatory skin disease that occurs most frequently in children but also affects adults.
  • A family history of atopy (eczema, asthma, or allergic rhinitis)
  • History of dermatitis involving the skin creases
  • Personal or family history of asthma or hay fever
  • Symptoms beginning in a child before the age of 2 years or, in children <4 years, dermatitis affecting the cheeks or dorsal aspect of extremities.
  • Dry skin and severe pruritus that is associated with cutaneous hyperreactivity to various environmental stimuli
  • including exposure to food and inhalant allergens, irritants, and infection.
  • Visible dermatitis involving flexural surfaces.
  • Presence of generally dry skin within the past year
  • Erythema, papulation, oozing and crusting, excoriation.
  • Raised IgE or an eosinophilia
  • Radioallergosorbent Test: blood is mixed separately with many different allergens and the antibody levels measured.
  • High levels of antibodies in the blood signify an allergy to that substance
  • Skin biopsy: a procedure that removes a small piece of the affected skin and sent for microscopic examination in a pathology laboratory.

Differentiating glucagonoma from other causes of hyperglycemia:

Glucagonoma can be differentiated from other causes of hyperglycemia which include: [11][12][13]

Disease History and symptoms Laboratory findings Additional findings
Polyuria Polydipsia Polyphagia Weight loss Weight gain Serum glucose Urinary Glucose Urine PH Serum Sodium Urinary Glucose 24 hrs cortisol level C-peptide level Serum glucagon
Type 1 Diabetes mellitus ✔ ✔ ✔ ✔ - ↑ ↑ Normal Normal N/↑ Normal ↓ Normal Auto antibodies present (Anti GAD-65 and anti insulin anti bodies)
Type 2 Diabetes mellitus ✔ ✔ ✔ ✔ - ↑ ↑ Normal Normal ↑ Normal Normal ↑ Acanthosis nigricans
MODY ✔ ✔ ✔ - ✔ ↑ ↑ Normal Normal ↑ Normal Normal N -
Psychogenic polydipsia ✔ ✔ - - - Normal Normal Normal ↓ Normal Normal Normal Normal -
Diabetes insipidus ✔ ✔ - - - Normal Normal Normal ↑ Normal Normal Normal Normal -
Transient hyperglycemia - - - - - ↑ ↑ Normal Normal ↑ Normal Normal N/↑ In hospitalized patients especially in ICU and CCU
Steroid therapy ✔ - - - ✔ ↑ ↑ Normal Normal ↑ ↑ N/↑ N/↑ Acanthosis nigricans,
RTA 1 - - - ✔ - Normal Normal ↑ Normal ↑ Normal Normal Normal Hypokalemia, nephrolithiasis
Glucagonoma - - - - - ↑ Normal Normal Normal - Normal Normal ↑ Necrolytic migratory erythema
Cushing syndrome - - - - ✔ ↑ - Normal ↓ N/↑ ↑ Normal Normal Moon face, obesity, buffalo hump, easy bruisibility

References

  1. ↑ Glucagonoma. Wikipedia. https://en.wikipedia.org/wiki/Glucagonoma. accessed on October 10, 2015
  2. ↑ Fang S, Li S, Cai T (2014). "Glucagonoma syndrome: a case report with focus on skin disorders". Onco Targets Ther. 7: 1449–53. doi:10.2147/OTT.S66285. PMC 4140234. PMID 25152626.
  3. ↑ Bystryn JC, Rudolph JL (2005). "Pemphigus". Lancet. 366 (9479): 61–73. doi:10.1016/S0140-6736(05)66829-8. PMID 15993235.
  4. ↑ Chams-Davatchi C, Valikhani M, Daneshpazhooh M, Esmaili N, Balighi K, Hallaji Z; et al. (2005). "Pemphigus: analysis of 1209 cases". Int J Dermatol. 44 (6): 470–6. doi:10.1111/j.1365-4632.2004.02501.x. PMID 15941433.
  5. ↑ Martin LK, Werth VP, Villaneuva EV, Murrell DF (2011). "A systematic review of randomized controlled trials for pemphigus vulgaris and pemphigus foliaceus". J Am Acad Dermatol. 64 (5): 903–8. doi:10.1016/j.jaad.2010.04.039. PMID 21353333.
  6. ↑ Prasad AS, Cossack ZT (1984). "Zinc supplementation and growth in sickle cell disease". Ann Intern Med. 100 (3): 367–71. PMID 6696358.
  7. ↑ Meftah S, Prasad AS, Lee DY, Brewer GJ (1991). "Ecto 5' nucleotidase (5'NT) as a sensitive indicator of human zinc deficiency". J Lab Clin Med. 118 (4): 309–16. PMID 1940572.
  8. ↑ Kiliç I, Ozalp I, Coŝkun T, Tokatli A, Emre S, Saldamli I; et al. (1998). "The effect of zinc-supplemented bread consumption on school children with asymptomatic zinc deficiency". J Pediatr Gastroenterol Nutr. 26 (2): 167–71. PMID 9481631.
  9. ↑ Prousky JE (2003). "Pellagra may be a rare secondary complication of anorexia nervosa: a systematic review of the literature". Altern Med Rev. 8 (2): 180–5. PMID 12777163.
  10. ↑ Wan P, Moat S, Anstey A (2011). "Pellagra: a review with emphasis on photosensitivity". Br J Dermatol. 164 (6): 1188–200. doi:10.1111/j.1365-2133.2010.10163.x. PMID 21128910.
  11. ↑ Barrett TG (2007). "Differential diagnosis of type 1 diabetes: which genetic syndromes need to be considered?". Pediatr Diabetes. 8 Suppl 6: 15–23. doi:10.1111/j.1399-5448.2007.00278.x. PMID 17727381.
  12. ↑ Type 1 Diabetes mellitus "Dennis Kasper, Anthony Fauci, Stephen Hauser, Dan Longo, J. Larry Jameson, Joseph Loscalzo"Harrison's Principles of Internal Medicine, 19e Accessed on December 27th,2016
  13. ↑ "namrata".
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