Addison's disease differential diagnosis: Difference between revisions

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*Serum ACTH level can help distinguish primary from secondary/tertiary adrenal insufficiency
*Serum ACTH level can help distinguish primary from secondary/tertiary adrenal insufficiency
{|  
{|  
|-style="background: #4479BA; color: #FFFFFF; text-align: center;"
|- style="background: #4479BA; color: #FFFFFF; text-align: center;"
!Type of
!Type of
Adrenal insufficiency
Adrenal insufficiency
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!ACTH 
!ACTH 
!Normal ACTH
!Normal ACTH
|-style="background: #DCDCDC; padding: 5px; text-align: center;"
|- style="background: #DCDCDC; padding: 5px; text-align: center;"
|Addison disease
|Addison disease
| +
| +
|>60 ng/mL
|>60 ng/mL
| rowspan="2" |5-30 ng/mL
| rowspan="2" |5-30 ng/mL
|-style="background: #DCDCDC; padding: 5px; text-align: center;"
|- style="background: #DCDCDC; padding: 5px; text-align: center;"
|Secondary /
|Secondary /
tertiary adrenal insufficiency
tertiary adrenal insufficiency
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|}
|}
Addison's disease must be differentiated from other diseases that cause  hypotension, skin pigmentation, and abdominal pain such as myopathies, celiac disease, [[Peutz-Jeghers syndrome]] ,[[anorexia nervosa]], syndrome of inappropriate anti-diuretic hormone (SIADH), neurofibromatosis, porphyria cutanea tarda, salt-depletion nephritis and bronchogenic carcinoma.<ref name="pmid16483775">{{cite journal |vauthors=Selva-O'Callaghan A, Labrador-Horrillo M, Gallardo E, Herruzo A, Grau-Junyent JM, Vilardell-Tarres M |title=Muscle inflammation, autoimmune Addison's disease and sarcoidosis in a patient with dysferlin deficiency |journal=Neuromuscul. Disord. |volume=16 |issue=3 |pages=208–9 |year=2006 |pmid=16483775 |doi=10.1016/j.nmd.2006.01.005 |url=}}</ref><ref name="pmid11427410">{{cite journal |vauthors=Kumar V, Rajadhyaksha M, Wortsman J |title=Celiac disease-associated autoimmune endocrinopathies |journal=Clin. Diagn. Lab. Immunol. |volume=8 |issue=4 |pages=678–85 |year=2001 |pmid=11427410 |pmc=96126 |doi=10.1128/CDLI.8.4.678-685.2001 |url=}}</ref><ref name="pmid9496878">{{cite journal |vauthors=Adams R, Hinkebein MK, McQuillen M, Sutherland S, El Asyouty S, Lippmann S |title=Prompt differentiation of Addison's disease from anorexia nervosa during weight loss and vomiting |journal=South. Med. J. |volume=91 |issue=2 |pages=208–11 |year=1998 |pmid=9496878 |doi= |url=}}</ref><ref name="pmid6414566">{{cite journal |vauthors=Lever EG, Stansfeld SA |title=Addison's disease, psychosis, and the syndrome of inappropriate secretion of antidiuretic hormone |journal=Br J Psychiatry |volume=143 |issue= |pages=406–10 |year=1983 |pmid=6414566 |doi= |url=}}</ref><ref name="pmid13356214">{{cite journal |vauthors=BELL R, PATTEE CJ |title=Addison's disease associated with neurofibromatosis |journal=Can Med Assoc J |volume=75 |issue=5 |pages=415–7 |year=1956 |pmid=13356214 |pmc=1823303 |doi= |url=}}</ref>
Addison's disease must be differentiated from other diseases that cause  hypotension, skin pigmentation, and abdominal pain such as myopathies, celiac disease, [[Peutz-Jeghers syndrome]] ,[[anorexia nervosa]], syndrome of inappropriate anti-diuretic hormone (SIADH), neurofibromatosis, porphyria cutanea tarda, salt-depletion nephritis and bronchogenic carcinoma.<ref name="pmid16483775">{{cite journal |vauthors=Selva-O'Callaghan A, Labrador-Horrillo M, Gallardo E, Herruzo A, Grau-Junyent JM, Vilardell-Tarres M |title=Muscle inflammation, autoimmune Addison's disease and sarcoidosis in a patient with dysferlin deficiency |journal=Neuromuscul. Disord. |volume=16 |issue=3 |pages=208–9 |year=2006 |pmid=16483775 |doi=10.1016/j.nmd.2006.01.005 |url=}}</ref><ref name="pmid11427410">{{cite journal |vauthors=Kumar V, Rajadhyaksha M, Wortsman J |title=Celiac disease-associated autoimmune endocrinopathies |journal=Clin. Diagn. Lab. Immunol. |volume=8 |issue=4 |pages=678–85 |year=2001 |pmid=11427410 |pmc=96126 |doi=10.1128/CDLI.8.4.678-685.2001 |url=}}</ref><ref name="pmid9496878">{{cite journal |vauthors=Adams R, Hinkebein MK, McQuillen M, Sutherland S, El Asyouty S, Lippmann S |title=Prompt differentiation of Addison's disease from anorexia nervosa during weight loss and vomiting |journal=South. Med. J. |volume=91 |issue=2 |pages=208–11 |year=1998 |pmid=9496878 |doi= |url=}}</ref><ref name="pmid6414566">{{cite journal |vauthors=Lever EG, Stansfeld SA |title=Addison's disease, psychosis, and the syndrome of inappropriate secretion of antidiuretic hormone |journal=Br J Psychiatry |volume=143 |issue= |pages=406–10 |year=1983 |pmid=6414566 |doi= |url=}}</ref><ref name="pmid13356214">{{cite journal |vauthors=BELL R, PATTEE CJ |title=Addison's disease associated with neurofibromatosis |journal=Can Med Assoc J |volume=75 |issue=5 |pages=415–7 |year=1956 |pmid=13356214 |pmc=1823303 |doi= |url=}}</ref>


{|  
{|  
|-style="background: #4479BA; color: #FFFFFF; text-align: center;"
|- style="background: #4479BA; color: #FFFFFF; text-align: center;"
! rowspan="2" |Disease
! rowspan="2" |Disease
! colspan="7" |Differentiating symptoms
! colspan="7" |Differentiating symptoms
! colspan="3" |Differentiating laboratory findings
! colspan="3" |Differentiating laboratory findings
! rowspan="2" |Gold standard test
! rowspan="2" |Gold standard test
|-style="background: #4479BA; color: #FFFFFF; text-align: center;"
|- style="background: #4479BA; color: #FFFFFF; text-align: center;"
|'''Hypotension'''
|'''Hypotension'''
|'''Abdominal pain'''
|'''Abdominal pain'''
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|'''Other symptoms'''
|'''Other symptoms'''
|'''Hyponatremia'''
|'''Hyponatremia'''
|'''Cortisol level|Cortisol levels'''
| ' Cortisol level |Cortisol levels
|'''Other labs'''
|'''Other labs'''
|-style="background: #DCDCDC; padding: 5px; text-align: center;"
|- style="background: #DCDCDC; padding: 5px; text-align: center;"
|Addison's disease
|Addison's disease
| +
| +
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| +
| +
|
|
| -
| +
|Low
|Low
|
|
|[[ACTH stimulation test]]
|[[ACTH stimulation test]]
|-style="background: #DCDCDC; padding: 5px; text-align: center;"
|- style="background: #DCDCDC; padding: 5px; text-align: center;"
|[[Myopathies]]
|[[Myopathies]]
([[polymyositis]],  
([[polymyositis]],  
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| -
| -
|[[Muscle biopsy]]
|[[Muscle biopsy]]
|-style="background: #DCDCDC; padding: 5px; text-align: center;"
|- style="background: #DCDCDC; padding: 5px; text-align: center;"
|[[Celiac disease]]
|[[Celiac disease]]
| -
| -
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| -
| -
|Abnormal [[small bowel]] [[biopsy]]
|Abnormal [[small bowel]] [[biopsy]]
|-style="background: #DCDCDC; padding: 5px; text-align: center;"
|- style="background: #DCDCDC; padding: 5px; text-align: center;"
|[[Syndrome of inappropriate antidiuretic hormone|Syndrome of inappropriate anti-diuretic hormone]]
|[[Syndrome of inappropriate antidiuretic hormone|Syndrome of inappropriate anti-diuretic hormone]]
[[Syndrome of inappropriate antidiuretic hormone|(SIADH)]]
[[Syndrome of inappropriate antidiuretic hormone|(SIADH)]]
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* [[Sodium]] in [[urine]] typically >20 mEq/L
* [[Sodium]] in [[urine]] typically >20 mEq/L
|Water deprivation test
|Water deprivation test
|-style="background: #DCDCDC; padding: 5px; text-align: center;"
|- style="background: #DCDCDC; padding: 5px; text-align: center;"
|[[Neurofibromatosis]]
|[[Neurofibromatosis]]
| -
| -
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| -
| -
|[[Skin biopsy|Biopsy of skin tissue]]
|[[Skin biopsy|Biopsy of skin tissue]]
|-style="background: #DCDCDC; padding: 5px; text-align: center;"
|- style="background: #DCDCDC; padding: 5px; text-align: center;"
|[[Peutz-Jeghers syndrome]]
|[[Peutz-Jeghers syndrome]]
|
|
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|
|
|Colonic [[imaging]] showing the [[Small intestine|small intestinal]] [[polyps]]
|Colonic [[imaging]] showing the [[Small intestine|small intestinal]] [[polyps]]
|-style="background: #DCDCDC; padding: 5px; text-align: center;"
|- style="background: #DCDCDC; padding: 5px; text-align: center;"
|[[Porphyria cutanea tarda]]
|[[Porphyria cutanea tarda]]
| -
| -
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|High level of [[porphyrins]] in the [[urine]]
|High level of [[porphyrins]] in the [[urine]]
|
|
|-style="background: #DCDCDC; padding: 5px; text-align: center;"
|- style="background: #DCDCDC; padding: 5px; text-align: center;"
|Salt-depletion [[nephritis]]
|Salt-depletion [[nephritis]]
| +
| +
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|<15:1 [[BUN-to-creatinine ratio|BUN:CR]]
|<15:1 [[BUN-to-creatinine ratio|BUN:CR]]
|
|
|-style="background: #DCDCDC; padding: 5px; text-align: center;"
|- style="background: #DCDCDC; padding: 5px; text-align: center;"
|[[Bronchogenic carcinoma]]
|[[Bronchogenic carcinoma]]
| -
| -
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[[Hypokalemia]]
[[Hypokalemia]]
|[[Cytological]] or [[histological]] [[evidence]] of [[lung cancer]] in [[sputum]], [[pleural fluid]], or tissue
|[[Cytological]] or [[histological]] [[evidence]] of [[lung cancer]] in [[sputum]], [[pleural fluid]], or tissue
|-style="background: #DCDCDC; padding: 5px; text-align: center;"
|- style="background: #DCDCDC; padding: 5px; text-align: center;"
|[[Anorexia nervosa]]
|[[Anorexia nervosa]]
| +
| +

Revision as of 20:58, 7 September 2017

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

Overview

Addison's disease must be differentiated from other diseases that cause hypotension, skin pigmentation, and abdominal pain such as myopathies, celiac disease, Peutz-Jeghers syndrome ,anorexia nervosa, syndrome of inappropriate anti-diuretic hormone (SIADH), neurofibromatosis, porphyria cutanea tarda, salt-depletion nephritis and bronchogenic carcinoma.

Differentiating Addison's disease from other Diseases

Addison's disease (primary adrenal insufficiency) must be first differentiated from secondary and tertiary adrenal insufficiency as all the three of them present with similar symptoms due to cortisol and mineralocorticoid hormone deficiencies.

  • Serum ACTH level can help distinguish primary from secondary/tertiary adrenal insufficiency
Type of

Adrenal insufficiency

Skin Pigmentation ACTH  Normal ACTH
Addison disease + >60 ng/mL 5-30 ng/mL
Secondary /

tertiary adrenal insufficiency

- <5 ng/mL

Addison's disease must be differentiated from other diseases that cause hypotension, skin pigmentation, and abdominal pain such as myopathies, celiac disease, Peutz-Jeghers syndrome ,anorexia nervosa, syndrome of inappropriate anti-diuretic hormone (SIADH), neurofibromatosis, porphyria cutanea tarda, salt-depletion nephritis and bronchogenic carcinoma.[1][2][3][4][5]

Disease Differentiating symptoms Differentiating laboratory findings Gold standard test
Hypotension Abdominal pain Anorexia/

weight loss

Muscle weakness Hypoglycemia Skin pigmentation Other symptoms Hyponatremia Cortisol levels Other labs
Addison's disease + + + + + + + Low ACTH stimulation test
Myopathies

(polymyositis,

hereditary myopathies)

- - - + - Heliotrope rash and

Gottron's sign

- Normal - Muscle biopsy
Celiac disease - + + - - Dermatitis herpetiformis  - Normal - Abnormal small bowel biopsy
Syndrome of inappropriate anti-diuretic hormone

(SIADH)

- - - - - - - + Normal Water deprivation test
Neurofibromatosis - - + + - Axillary- and inguinal-area freckling - - - Biopsy of skin tissue
Peutz-Jeghers syndrome + + - Normal Colonic imaging showing the small intestinal polyps
Porphyria cutanea tarda - + - - - Blisters on sun-exposed sites - Normal or elevated High level of porphyrins in the urine
Salt-depletion nephritis + Flank pain - - - - + Elevated <15:1 BUN:CR
Bronchogenic carcinoma - - + - - + - Elevated Increased ACTH and

Hypokalemia

Cytological or histological evidence of lung cancer in sputum, pleural fluid, or tissue
Anorexia nervosa + - + + + - - Elevated - Psychiatric condition

References

  1. ↑ Selva-O'Callaghan A, Labrador-Horrillo M, Gallardo E, Herruzo A, Grau-Junyent JM, Vilardell-Tarres M (2006). "Muscle inflammation, autoimmune Addison's disease and sarcoidosis in a patient with dysferlin deficiency". Neuromuscul. Disord. 16 (3): 208–9. doi:10.1016/j.nmd.2006.01.005. PMID 16483775.
  2. ↑ Kumar V, Rajadhyaksha M, Wortsman J (2001). "Celiac disease-associated autoimmune endocrinopathies". Clin. Diagn. Lab. Immunol. 8 (4): 678–85. doi:10.1128/CDLI.8.4.678-685.2001. PMC 96126. PMID 11427410.
  3. ↑ Adams R, Hinkebein MK, McQuillen M, Sutherland S, El Asyouty S, Lippmann S (1998). "Prompt differentiation of Addison's disease from anorexia nervosa during weight loss and vomiting". South. Med. J. 91 (2): 208–11. PMID 9496878.
  4. ↑ Lever EG, Stansfeld SA (1983). "Addison's disease, psychosis, and the syndrome of inappropriate secretion of antidiuretic hormone". Br J Psychiatry. 143: 406–10. PMID 6414566.
  5. ↑ BELL R, PATTEE CJ (1956). "Addison's disease associated with neurofibromatosis". Can Med Assoc J. 75 (5): 415–7. PMC 1823303. PMID 13356214.

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