Addison's disease differential diagnosis: Difference between revisions

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__NOTOC__
__NOTOC__
{{Addison's disease}}
[[Image:Home_logo1.png|right|250px|link=https://www.wikidoc.org/index.php/Addison%27s_disease]]


{{CMG}} ; {{AE}} {{ADG}}
{{CMG}} ; {{AE}} {{ADG}}
==Overview==
==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.
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 antidiuretic hormone]] ([[SIADH]]), [[neurofibromatosis]], [[porphyria cutanea tarda]], salt-depletion [[nephritis]] and [[bronchogenic carcinoma]].


==Differentiating Addison's disease from other Diseases==
==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.  
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
*Serum ACTH level can help distinguish primary from secondary/tertiary adrenal insufficiency
{| class="wikitable"
{|  
|- style="background: #4479BA; color: #FFFFFF; text-align: center;"
!Type of
!Type of
Adrenal insufficiency
Adrenal insufficiency
Line 15: Line 16:
!ACTH 
!ACTH 
!Normal ACTH
!Normal ACTH
|-
|- 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;"
|Secondary /
|Secondary /
tertiary adrenal insufficiency
tertiary adrenal insufficiency
Line 26: Line 27:
|<5 ng/mL
|<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.
Addison's disease must be differentiated from other diseases that cause [[hypotension]], [[skin pigmentation]], [[muscle weakness]] and [[abdominal pain]] which include [[myopathies]], [[celiac disease]], [[Peutz-Jeghers syndrome]], [[anorexia nervosa]], [[syndrome of inappropriate antidiuretic 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>
{| class="wikitable"
 
{|  
|- 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;"
|'''[[Hypotension]]'''
|'''Hypotension'''
|'''[[Abdominal pain]]'''
|'''Abdominal pain'''
|'''[[Anorexia]]/'''
|'''Anorexia/'''
'''[[weight loss]]'''
'''weight loss'''
|'''[[Muscle weakness]]'''
|'''Muscle weakness'''
|'''[[Hypoglycemia]]'''
|'''Hypoglycemia'''
|'''[[Skin pigmentation]]'''
|'''Skin pigmentation'''
|'''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;"
|Addison's disease
|Addison's disease
| +
| +
Line 53: Line 56:
| +
| +
|
|
| -
| +
|Low
|Low
|
|
|[[ACTH stimulation test]]
|[[ACTH stimulation test]]
|-
|- style="background: #DCDCDC; padding: 5px; text-align: center;"
|[[Myopathies]]
|[[Myopathies]]
([[polymyositis]],  
([[polymyositis]],  
Line 75: Line 78:
| -
| -
|[[Muscle biopsy]]
|[[Muscle biopsy]]
|-
|- style="background: #DCDCDC; padding: 5px; text-align: center;"
|[[Celiac disease]]
|[[Celiac disease]]
| -
| -
Line 90: Line 93:
| -
| -
|Abnormal [[small bowel]] [[biopsy]]
|Abnormal [[small bowel]] [[biopsy]]
|-
|- 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)]]
| -
| -
|_
| -
| -
| -
| -
| -
Line 107: Line 110:
* [[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;"
|[[Neurofibromatosis]]
|[[Neurofibromatosis]]
| -
| -
Line 122: Line 125:
| -
| -
|[[Skin biopsy|Biopsy of skin tissue]]
|[[Skin biopsy|Biopsy of skin tissue]]
|-
|- style="background: #DCDCDC; padding: 5px; text-align: center;"
|[[Peutz-Jeghers syndrome]]
|[[Peutz-Jeghers syndrome]]
|
|
Line 136: Line 139:
|
|
|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;"
|[[Porphyria cutanea tarda]]
|[[Porphyria cutanea tarda]]
| -
| -
Line 151: Line 154:
|High level of [[porphyrins]] in the [[urine]]
|High level of [[porphyrins]] in the [[urine]]
|
|
|-
|- style="background: #DCDCDC; padding: 5px; text-align: center;"
|Salt-depletion [[nephritis]]
|Salt-depletion [[nephritis]]
| +
| +
Line 168: Line 171:
|<15:1 [[BUN-to-creatinine ratio|BUN:CR]]
|<15:1 [[BUN-to-creatinine ratio|BUN:CR]]
|
|
|-
|- style="background: #DCDCDC; padding: 5px; text-align: center;"
|[[Bronchogenic carcinoma]]
|[[Bronchogenic carcinoma]]
| -
| -
Line 185: Line 188:
[[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;"
|[[Anorexia nervosa]]
|[[Anorexia nervosa]]
| +
| +
Line 201: Line 204:
|[[Psychiatric]] condition
|[[Psychiatric]] condition
|}
|}
[[Addison's disease]] should be differentiated from other diseases causing secondary [[Adrenal insufficiency (patient information)|adrenal insufficiency]] due to [[hypopituitarism]].<ref name="pmid9541295">{{cite journal |vauthors=Sato N, Sze G, Endo K |title=Hypophysitis: endocrinologic and dynamic MR findings |journal=AJNR Am J Neuroradiol |volume=19 |issue=3 |pages=439–44 |year=1998 |pmid=9541295 |doi= |url=}}</ref><ref name="pmid7758238">{{cite journal |vauthors=Powrie JK, Powell M, Ayers AB, Lowy C, Sönksen PH |title=Lymphocytic adenohypophysitis: magnetic resonance imaging features of two new cases and a review of the literature |journal=Clin. Endocrinol. (Oxf) |volume=42 |issue=3 |pages=315–22 |year=1995 |pmid=7758238 |doi= |url=}}</ref><ref name="pmid26262437">{{cite journal |vauthors=Honegger J, Schlaffer S, Menzel C, Droste M, Werner S, Elbelt U, Strasburger C, Störmann S, Küppers A, Streetz-van der Werf C, Deutschbein T, Stieg M, Rotermund R, Milian M, Petersenn S |title=Diagnosis of Primary Hypophysitis in Germany |journal=J. Clin. Endocrinol. Metab. |volume=100 |issue=10 |pages=3841–9 |year=2015 |pmid=26262437 |doi=10.1210/jc.2015-2152 |url=}}</ref><ref name="pmid7629223">{{cite journal |vauthors=Thodou E, Asa SL, Kontogeorgos G, Kovacs K, Horvath E, Ezzat S |title=Clinical case seminar: lymphocytic hypophysitis: clinicopathological findings |journal=J. Clin. Endocrinol. Metab. |volume=80 |issue=8 |pages=2302–11 |year=1995 |pmid=7629223 |doi=10.1210/jcem.80.8.7629223 |url=}}</ref><ref name="pmid8345854">{{cite journal |vauthors=Imura H, Nakao K, Shimatsu A, Ogawa Y, Sando T, Fujisawa I, Yamabe H |title=Lymphocytic infundibuloneurohypophysitis as a cause of central diabetes insipidus |journal=N. Engl. J. Med. |volume=329 |issue=10 |pages=683–9 |year=1993 |pmid=8345854 |doi=10.1056/NEJM199309023291002 |url=}}</ref><ref name="pmid21668725">{{cite journal |vauthors=Hsieh CY, Liu BY, Yang YN, Yin WH, Young MS |title=Massive pericardial effusion with diastolic right ventricular compression secondary to hypothyroidism in a 73-year-old woman |journal=Emerg Med Australas |volume=23 |issue=3 |pages=372–5 |year=2011 |pmid=21668725 |doi=10.1111/j.1742-6723.2011.01425.x |url=}}</ref><ref name="pmid9747750">{{cite journal |vauthors=Dejager S, Gerber S, Foubert L, Turpin G |title=Sheehan's syndrome: differential diagnosis in the acute phase |journal=J. Intern. Med. |volume=244 |issue=3 |pages=261–6 |year=1998 |pmid=9747750 |doi= |url=}}</ref>
<small>
{| class="wikitable"
! style="background: #4479BA; width: 200px;" rowspan="3" | {{fontcolor|#FFF|Diseases}}
! style="background: #4479BA; width: 200px;" rowspan="3" | {{fontcolor|#FFF|Onset}}
! style="background: #4479BA; width: 200px;" colspan="5" | {{fontcolor|#FFF|Manifestations}}
! style="background: #4479BA; width: 200px;" colspan="4" | {{fontcolor|#FFF|Diagnosis}}
|-
! style="background: #4479BA; width: 200px;" colspan="4" | {{fontcolor|#FFF|History and Symptoms}}
! style="background: #4479BA; width: 200px;" rowspan="2" | {{fontcolor|#FFF|Physical examination}}
! style="background: #4479BA; width: 200px;" rowspan="2" | {{fontcolor|#FFF|Laboratory findings}}
! style="background: #4479BA; width: 200px;" rowspan="2" | {{fontcolor|#FFF|Gold standard}}
! style="background: #4479BA; width: 200px;" rowspan="2" | {{fontcolor|#FFF| Imaging}}
! style="background: #4479BA; width: 200px;" rowspan="2" | {{fontcolor|#FFF|Other investigation findings}}
|-
! style="background: #4479BA; width: 200px;" | {{fontcolor|#FFF| Trumatic delivery}}
! style="background: #4479BA; width: 200px;" | {{fontcolor|#FFF| Lactation failure}}
! style="background: #4479BA; width: 200px;" | {{fontcolor|#FFF| Menstrual irregularities}}
! style="background: #4479BA; width: 200px;" | {{fontcolor|#FFF| Other features}}
|-
![[Sheehan's syndrome]]
|Acute
|<nowiki>++</nowiki>
| ++
|[[Oligomenorrhea|Oligo]]/[[amenorrhea]]
|Symptoms of:
* [[Adrenal insufficiency]]
* [[Hypothyroidism]]
|
* [[Breast tissue]] [[atrophy]]
* Decreased [[axillary]] and [[pubic]] hair growth
|
* [[Pancytopenia]]
* [[Eosinophilia]]
* [[Hyponatremia]]
* Low [[fasting plasma glucose]]
* Decreased levels of [[anterior pituitary]] [[hormones]] in blood
|
* Clinical diagnosis 
* Most senitive test: Low baseline [[prolactin]] levels w/o response to [[Thyrotropin-releasing hormone|TRH]]
|CT/MRI:
* Sequential changes of pituitary enlargement followed by:
* Shrinkage and [[necrosis]] leading to decreased sellar volume or [[empty sella]]
|
* Pituitary hormone stimulation tests ([[Metoclopramide]] and [[clomiphene citrate]] stimulation tests)
|-
![[Lymphocytic hypophysitis]]
|Acute
|<nowiki>+/-</nowiki>
|<nowiki>+</nowiki>
|[[Oligomenorrhea|Oligo]]/[[amenorrhea]]
|
* Associated with [[autoimmune]] conditions
* Generalized [[headache]]
* Retro-orbital or Bitemporal [[pain]]
* Mass lesion effect such as [[Visual field defect|visual field defects]]
|
* [[Diabetes insipidus|DI]]
* [[Autoimmune]] [[thyroiditis]]
|
* Decreased pituitary hormones([[Gonadotropins]] most common)
* [[Hyperprolactinemia]](40%)
* [[Growth hormone|GH]] excess
|
* [[Pituitary gland|Pituitary]] [[biopsy]]: [[lymphocytic]] [[Infiltration (medical)|infiltration]]
|
* [[CT]] & [[MRI]]: Features of a [[Pituitary gland|pituitary]] [[mass]]
* Diffuse and homogeneous contrast enhancement
|[[Assay|Assays]] for:
* Anti-TPO 
* Anti-Tg Ab
|-
![[Pituitary apoplexy]]
|Acute
|<nowiki>+/-</nowiki>
|<nowiki>++</nowiki>
|[[Oligomenorrhea|Oligo]]/[[amenorrhea]]
|Severe [[headache]]
* [[Nausea and vomiting]]
* Paralysis of eye muscles ([[diplopia]])
* Changes in vision
|
* [[Visual acuity]] defects
* [[Cranial nerve palsies|CN palsies]] (nerves III, IV, V , and VI)
|
* Decreased levels of [[anterior]] pituitary hormones in blood.
|
* [[Magnetic resonance imaging|MRI]]
|
* [[CT]] scan without [[Contrast medium|contrast]]: Hemorrhag<nowiki/>e on [[CT]] presents as a hyperdense lesion
* [[MRI]]: If inconclusive [[CT]]
|
[[Blood tests]] may be done to check:
* [[PT]]/[[INR]] and [[aPTT]]
* [[Pituitary gland|Pituitary]] [[hormonal]] assay
|-
![[Empty sella syndrome]]
|Chronic
|<nowiki>-</nowiki>
|<nowiki>+</nowiki>
|[[Oligomenorrhea|Oligo]]/[[amenorrhea]]
|
* [[Erectile dysfunction]]
* [[Headache]]
* Low [[libido]]
|
* Signs of raised [[intracranial pressure]] may be present
* [[Nipple discharge|Nipple]] discharge
|
* Decreased levels of  pituitary hormones in blood.
|
* [[MRI]]
|
* [[Empty sella]] containing [[Cerebrospinal fluid|CSF]]
|
* Pituitary hormone stimulation tests ([[Metoclopramide]] and [[clomiphene citrate]] stimulation tests)
|-
![[Simmond's Disease|Simmonds' disease]]/[[Pituitary]] [[cachexia]]
|Chronic
|<nowiki>+/-</nowiki>
| +
|[[Oligomenorrhea|Oligo]]/[[amenorrhea]]
|
* [[Cachexia]]
* [[Premature aging|Premature]] aging
|
* Progressive [[emaciation]]
* Loss of body hair
|
* Decreased levels of anterior pituitary hormones in blood.
|
* [[Magnetic resonance imaging|MRI]]
|
* Done to rule out any pituitary cause
|
* Pituitary hormone stimulation tests ([[Metoclopramide]] and [[clomiphene citrate]] stimulation tests)
|-
! [[Primary hypothyroidism|Hypothyroidism]]
|Chronic
|<nowiki>+/-</nowiki>
|<nowiki>-</nowiki>
|[[Oligomenorrhea]]/[[menorrhagia]]
|
* Cold intolerance
* [[Constipation]]
|
* Dry skin
* [[Bradycardia]]
* Hair loss
* [[Myxedema]]
* Delayed relaxation phase of deep [[Tendon reflex|tendon reflexes]]
|
* Low [[T3]],[[T4]]
* Normal/ low [[Thyroid-stimulating hormone|TSH]]
* Rest of pituitary hormone levels WNL
|
* [[TSH]] levels
|
* Done to rule out any pituitary cause
|
*Assays for anti-TPO and anti-Tg Ab
*FNA biopsy
|-
![[Hypogonadotropic hypogonadism]]
|Chronic
|<nowiki>-</nowiki>
|<nowiki>-</nowiki>
|[[Oligomenorrhea|Oligo]]/[[amenorrhea]]
|
* [[Hot flushes]]
* Energy and mood changes
* Decreased [[libido]]
|
* [[Breast tissue]] [[atrophy]]
* Decreased [[maturation]] of [[vaginal]] [[mucosa]]
|
* Low [[estrogen]], [[testosterone]]
* High [[FSH]]/[[Luteinizing hormone|LH]]
|
* [[FSH]]
* [[Luteinizing hormone|LH]]
|
* Done to rule out any pituitary cause
|
* Genetic tests  ([[karyotype]])
* Measurement of total and free [[testosterone]] and [[17-Hydroxyprogesterone|17-hydroxyprogesterone]] concentrations
|-
!Hypoprolactinemia
|Chronic
|<nowiki>-</nowiki>
|<nowiki>+</nowiki>
|<nowiki>-</nowiki>
|
* [[Infertility]]
* Subfertiliy
|
* Puerperal agalactogenesis
|
* No workup is necessary
|
* Decreased prolactin levels
|
* Done to rule out any pituitary cause
|
* [[Prolactin]] assay in [[3rd trimester]]
* [[Luteinizing hormone|LH]], [[Follicle-stimulating hormone|FSH]]
* [[Thyrotropin]] and free [[thyroxine]]
|-
![[Panhypopituitarism]]
|Chronic
|<nowiki>-</nowiki>
|<nowiki>+</nowiki>
|[[Oligomenorrhea|Oligo]]/[[amenorrhea]]
|
* [[Polyuria]]
* [[Polydipsia]]
* Features of [[hypothyroidism]] and [[hypoadrenalism]]
|
* [[Growth failure]]
* B/L [[hemianopsia]]
* [[Papilledema]]
|
* All pituitary hormones decreased
|
* [[Magnetic resonance imaging|MRI]]
|
* Done to rule out any pituitary cause
|
* Left hand and wrist [[radiograph]] for [[bone age]]
|-
![[Primary adrenal insufficiency]]/[[Addison's disease]]
|Chronic
|<nowiki>-</nowiki>
| -
|<nowiki>-</nowiki>
|
* [[Hypoglycemia]]
* [[Hypotension]]
|
* [[Dehydration]]
* [[Hyperpigmentation]]
* loss of [[pubic]] and [[axillary]] hair
|
* [[Hyponatremia]] with/without [[hyperkalemia]]
* [[Plasma renin activity]] to [[Aldosterone|aldosterone ratio]]
|
* Abdominal [[Computed tomography|CT]]
|
* Abdominal [[Computed tomography|CT]]
|
* Serum [[cortisol]] testing
* Serum [[ACTH]] testing
* Anti-adrenal [[Antibody|Ab]] testing
|-
![[Menopause]]
|Chronic
|<nowiki>-</nowiki>
|<nowiki>+/-</nowiki>
|[[Oligomenorrhea|Oligo]]/[[amenorrhea]]
|
* [[Hot flashes]]
* [[Insomnia]]
* [[Weight gain]] and [[bloating]]
* Mood changes
|
* [[Vaginal atrophy]]
* Loss of pelvic [[muscle tone]]
|
* ↑ [[FSH]]
* ↓ [[Estradiol]] and [[inhibin]]
|
* [[FSH]] > [[LH]]
|Normal
|
* [[Endometrial biopsy]]
|}
<small>


==References==
==References==

Latest revision as of 19:30, 25 February 2019

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 antidiuretic 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, muscle weakness and abdominal pain which include myopathies, celiac disease, Peutz-Jeghers syndrome, anorexia nervosa, syndrome of inappropriate antidiuretic 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

Addison's disease should be differentiated from other diseases causing secondary adrenal insufficiency due to hypopituitarism.[6][7][8][9][10][11][12]

Diseases Onset Manifestations Diagnosis
History and Symptoms Physical examination Laboratory findings Gold standard Imaging Other investigation findings
Trumatic delivery Lactation failure Menstrual irregularities Other features
Sheehan's syndrome Acute ++ ++ Oligo/amenorrhea Symptoms of:
  • Clinical diagnosis
  • Most senitive test: Low baseline prolactin levels w/o response to TRH
 CT/MRI:
  • Sequential changes of pituitary enlargement followed by:
  • Shrinkage and necrosis leading to decreased sellar volume or empty sella
Lymphocytic hypophysitis Acute +/- + Oligo/amenorrhea
  • Retro-orbital or Bitemporal pain
  • Diffuse and homogeneous contrast enhancement
 Assays for:
  • Anti-TPO
  • Anti-Tg Ab
Pituitary apoplexy Acute +/- ++ Oligo/amenorrhea Severe headache
  • Decreased levels of anterior pituitary hormones in blood.
  • CT scan without contrast: Hemorrhage on CT presents as a hyperdense lesion

Blood tests may be done to check:

Empty sella syndrome Chronic - + Oligo/amenorrhea
  • Decreased levels of pituitary hormones in blood.
Simmonds' disease/Pituitary cachexia Chronic +/- + Oligo/amenorrhea
  • Loss of body hair
  • Decreased levels of anterior pituitary hormones in blood.
  • Done to rule out any pituitary cause
Hypothyroidism Chronic +/- - Oligomenorrhea/menorrhagia
  • Dry skin
  • Hair loss
  • Normal/ low TSH
  • Rest of pituitary hormone levels WNL
  • Done to rule out any pituitary cause
  • Assays for anti-TPO and anti-Tg Ab
  • FNA biopsy
Hypogonadotropic hypogonadism Chronic - - Oligo/amenorrhea
  • Energy and mood changes
  • Done to rule out any pituitary cause
Hypoprolactinemia Chronic - + -
  • Puerperal agalactogenesis
  • No workup is necessary
  • Decreased prolactin levels
  • Done to rule out any pituitary cause
Panhypopituitarism Chronic - + Oligo/amenorrhea
  • All pituitary hormones decreased
  • Done to rule out any pituitary cause
Primary adrenal insufficiency/Addison's disease Chronic - - -
  • Abdominal CT
  • Abdominal CT
  • Anti-adrenal Ab testing
Menopause Chronic - +/- Oligo/amenorrhea Normal

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.
  6. ↑ Sato N, Sze G, Endo K (1998). "Hypophysitis: endocrinologic and dynamic MR findings". AJNR Am J Neuroradiol. 19 (3): 439–44. PMID 9541295.
  7. ↑ Powrie JK, Powell M, Ayers AB, Lowy C, Sönksen PH (1995). "Lymphocytic adenohypophysitis: magnetic resonance imaging features of two new cases and a review of the literature". Clin. Endocrinol. (Oxf). 42 (3): 315–22. PMID 7758238.
  8. ↑ Honegger J, Schlaffer S, Menzel C, Droste M, Werner S, Elbelt U, Strasburger C, Störmann S, Küppers A, Streetz-van der Werf C, Deutschbein T, Stieg M, Rotermund R, Milian M, Petersenn S (2015). "Diagnosis of Primary Hypophysitis in Germany". J. Clin. Endocrinol. Metab. 100 (10): 3841–9. doi:10.1210/jc.2015-2152. PMID 26262437.
  9. ↑ Thodou E, Asa SL, Kontogeorgos G, Kovacs K, Horvath E, Ezzat S (1995). "Clinical case seminar: lymphocytic hypophysitis: clinicopathological findings". J. Clin. Endocrinol. Metab. 80 (8): 2302–11. doi:10.1210/jcem.80.8.7629223. PMID 7629223.
  10. ↑ Imura H, Nakao K, Shimatsu A, Ogawa Y, Sando T, Fujisawa I, Yamabe H (1993). "Lymphocytic infundibuloneurohypophysitis as a cause of central diabetes insipidus". N. Engl. J. Med. 329 (10): 683–9. doi:10.1056/NEJM199309023291002. PMID 8345854.
  11. ↑ Hsieh CY, Liu BY, Yang YN, Yin WH, Young MS (2011). "Massive pericardial effusion with diastolic right ventricular compression secondary to hypothyroidism in a 73-year-old woman". Emerg Med Australas. 23 (3): 372–5. doi:10.1111/j.1742-6723.2011.01425.x. PMID 21668725.
  12. ↑ Dejager S, Gerber S, Foubert L, Turpin G (1998). "Sheehan's syndrome: differential diagnosis in the acute phase". J. Intern. Med. 244 (3): 261–6. PMID 9747750.

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