Cushing's syndrome differential diagnosis: Difference between revisions

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


{{CMG}} {{AE}} {{MMF}}
{{CMG}} {{AE}} {{MMF}}
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Cushing's syndrome must be differentiated from other diseases that cause [[hypertension]], [[obesity]], and [[hyperandrogenism]], such as [[Metabolic syndrome X]] and pseudo-Cushing's syndrome.
Cushing's syndrome must be differentiated from other diseases that cause [[hypertension]], [[obesity]], and [[hyperandrogenism]], such as [[Metabolic syndrome X]] and pseudo-Cushing's syndrome.


==Differentiating Cushing's syndrome from Other Diseases==
==Differentiating Cushing's Syndrome From Other Diseases==
The table below summarizes the findings that differentiate Cushing's disease from other conditions that may cause [[Hypertension|hypertensio]]<nowiki/>n, [[hyperandrogenism]], and [[obesity]]. Facial plethora, skin changes, [[osteoporosis]], [[nephrolithiasis]] and neuropsychiatric conditions should raise the concern for Cushing's syndrome.<ref name="pmid11253984">{{cite journal |vauthors=Boscaro M, Barzon L, Fallo F, Sonino N |title=Cushing's syndrome |journal=Lancet |volume=357 |issue=9258 |pages=783–91 |year=2001 |pmid=11253984 |doi=10.1016/S0140-6736(00)04172-6 |url=}}</ref><ref name="pmid11571938">{{cite journal |vauthors=Findling JW, Raff H |title=Diagnosis and differential diagnosis of Cushing's syndrome |journal=Endocrinol. Metab. Clin. North Am. |volume=30 |issue=3 |pages=729–47 |year=2001 |pmid=11571938 |doi= |url=}}</ref><ref name="pmid9793762">{{cite journal |vauthors=Newell-Price J, Trainer P, Besser M, Grossman A |title=The diagnosis and differential diagnosis of Cushing's syndrome and pseudo-Cushing's states |journal=Endocr. Rev. |volume=19 |issue=5 |pages=647–72 |year=1998 |pmid=9793762 |doi=10.1210/edrv.19.5.0346 |url=}}</ref><ref name="urlHow Is Metabolic Syndrome Diagnosed? - NHLBI, NIH">{{cite web |url=https://www.nhlbi.nih.gov/health/health-topics/topics/ms/diagnosis |title=How Is Metabolic Syndrome Diagnosed? - NHLBI, NIH |format= |work= |accessdate=}}</ref>
 
=== Differentials based on hypertension, hyperandrogenism and obesity ===
The table below summarizes the findings that differentiate Cushing's disease from other conditions that may cause [[Hypertension|hypertensio]]<nowiki/>n, [[hyperandrogenism]], and [[obesity]]. Facial [[plethora]], [[skin changes]], [[osteoporosis]], [[nephrolithiasis]] and [[neuropsychiatric]] conditions should raise the concern for Cushing's syndrome.<ref name="pmid11253984">{{cite journal |vauthors=Boscaro M, Barzon L, Fallo F, Sonino N |title=Cushing's syndrome |journal=Lancet |volume=357 |issue=9258 |pages=783–91 |year=2001 |pmid=11253984 |doi=10.1016/S0140-6736(00)04172-6 |url=}}</ref><ref name="pmid11571938">{{cite journal |vauthors=Findling JW, Raff H |title=Diagnosis and differential diagnosis of Cushing's syndrome |journal=Endocrinol. Metab. Clin. North Am. |volume=30 |issue=3 |pages=729–47 |year=2001 |pmid=11571938 |doi= |url=}}</ref><ref name="pmid9793762">{{cite journal |vauthors=Newell-Price J, Trainer P, Besser M, Grossman A |title=The diagnosis and differential diagnosis of Cushing's syndrome and pseudo-Cushing's states |journal=Endocr. Rev. |volume=19 |issue=5 |pages=647–72 |year=1998 |pmid=9793762 |doi=10.1210/edrv.19.5.0346 |url=}}</ref><ref name="urlHow Is Metabolic Syndrome Diagnosed? - NHLBI, NIH">{{cite web |url=https://www.nhlbi.nih.gov/health/health-topics/topics/ms/diagnosis |title=How Is Metabolic Syndrome Diagnosed? - NHLBI, NIH |format= |work= |accessdate=}}</ref>
<br>
<br>
{| align="center"
{| align="center"
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|-
|-
| align="center" style="background:#DCDCDC;" |[[Cushing's syndrome]]
| style="background:#DCDCDC;" align="center" |[[Cushing's syndrome]]
| style="padding: 5px 5px; background: #F5F5F5;" align="left" |
| style="padding: 5px 5px; background: #F5F5F5;" align="left" |
*Iatrogenic
*[[Iatrogenic]]
*Pituitary adenoma
*[[Pituitary adenoma]]
*Adrenal tumor
*[[Adrenal tumor]]
*Adrenal hyperplasia
*[[Adrenal hyperplasia]]
*Ectopic ACTH secretion
*[[Ectopic ACTH Syndrome|Ectopic ACTH secretion]]
| style="padding: 5px 5px; background: #F5F5F5;" align="left" |
| style="padding: 5px 5px; background: #F5F5F5;" align="left" |
* [[Obesity]]
* [[Obesity]]
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*[[Osteoporosis]]
*[[Osteoporosis]]
*[[Myopathy]]/cutaneous wasting
*[[Myopathy]]/cutaneous wasting
*Neuropsychiatric problems
*[[Neuropsychiatric]] problems
*[[Kidney stone|Kidney stones]]
*[[Kidney stone|Kidney stones]]
| style="padding: 5px 5px; background: #F5F5F5;" align="left" |
| style="padding: 5px 5px; background: #F5F5F5;" align="left" |
*24-hour urine cortisol
*24-hour urine [[cortisol]]
*Midnight salivary cortisol
*Midnight salivary [[cortisol]]
*Low dose dexamethasone challenge test
*[[Dexamethasone Oral|Low dose dexamethasone]] challenge test
*CRH stimulation
*[[CRH]] stimulation
*High dose dexamethasone test
*[[Dexamethasone Oral|High dose dexamethasone]] test
*MRI brain
*[[MRI|MRI brain]]
*CT/MRI adrenals
*CT/MRI [[adrenals]]


|-
|-
|-
|-
| align="center" style="background:#DCDCDC;" |[[Pseudo-Cushing's syndrome]]
| style="background:#DCDCDC;" align="center" |[[Pseudo-Cushing's syndrome]]
| style="padding: 5px 5px; background: #F5F5F5;" align="left" |
| style="padding: 5px 5px; background: #F5F5F5;" align="left" |
*Obesity
*[[Obesity]]
*Alcoholism
*[[Alcoholism]]
*Depression
*[[Depression]]
*HIV
*[[HIV]]
| style="padding: 5px 5px; background: #F5F5F5;" align="left" |
| style="padding: 5px 5px; background: #F5F5F5;" align="left" |
* [[Obesity]]
* [[Obesity]]
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*[[Oligomenorrhea]]/[[hypogonadism]]
*[[Oligomenorrhea]]/[[hypogonadism]]
| style="padding: 5px 5px; background: #F5F5F5;" align="left" |
| style="padding: 5px 5px; background: #F5F5F5;" align="left" |
*Urinary free cortisol
*Urinary free [[cortisol]]
*Midnight salivary cortisol
*Midnight salivary [[cortisol]]
*Low dose dexamethasone challenge test
*Low dose [[dexamethasone]] challenge test
*[[Glucose tolerance test]]
*[[Glucose tolerance test]]
*Loperamide test
*[[Loperamide]] test
|-
|-
| align="center" style="background:#DCDCDC;" |[[Metabolic syndrome X]]
| style="background:#DCDCDC;" align="center" |[[Metabolic syndrome X]]
| style="padding: 5px 5px; background: #F5F5F5;" align="left" |
| style="padding: 5px 5px; background: #F5F5F5;" align="left" |
*Familial/genetic
*Familial/[[genetic]]
*Obesity
*[[Obesity]]
*Insulin resistance
*[[Insulin]] resistance
| style="padding: 5px 5px; background: #F5F5F5;" align="left" |
| style="padding: 5px 5px; background: #F5F5F5;" align="left" |
* [[Obesity]]
* [[Obesity]]
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|}
|}
===Differentials based on virilization and hirsutism===
Cushing's syndrome must be differentiated from diseases that cause [[virilization]] and [[hirsutism]] in female:<ref name="pmid24830586">{{cite journal |vauthors=Hohl A, Ronsoni MF, Oliveira Md |title=Hirsutism: diagnosis and treatment |journal=Arq Bras Endocrinol Metabol |volume=58 |issue=2 |pages=97–107 |year=2014 |pmid=24830586 |doi= |url=}}</ref><ref name="pmid10857554">{{cite journal |vauthors=White PC, Speiser PW |title=Congenital adrenal hyperplasia due to 21-hydroxylase deficiency |journal=Endocr. Rev. |volume=21 |issue=3 |pages=245–91 |year=2000 |pmid=10857554 |doi=10.1210/edrv.21.3.0398 |url=}}</ref><ref name="ISBN:978-0323297387">{{cite book | last = Melmed | first = Shlomo | title = Williams textbook of endocrinology | publisher = Elsevier | location = Philadelphia, PA | year = 2016 | isbn = 978-0323297387 }}=</ref>
{| class="wikitable"
! align="center" style="background:#4479BA; color: #FFFFFF;" + |Disease name
! align="center" style="background:#4479BA; color: #FFFFFF;" + |Steroid status
! align="center" style="background:#4479BA; color: #FFFFFF;" + |Other laboratory
! align="center" style="background:#4479BA; color: #FFFFFF;" + |Important clinical findings
|-
|[[Cushing's syndrome]]
|
* Increase [[cortisol]] & metabolites
* Variable other [[steroids]]
|
* Variable [[mineralocorticoid]] excess
|
* [[Cushingoid appearance]]
|-
|Non-classic type of [[21-hydroxylase deficiency]]
|Increased:
* [[17-Hydroxyprogesterone|17-hydroxyprogesterone]]
* Exaggerated [[Androstenedione]], [[DHEA]], and [[17-Hydroxyprogesterone|17-hydroxyprogesterone]] in response to [[ACTH]]
|
* Low [[testosterone]] levels
|
* No symptoms in infancy and male
* [[Virilization]] in females
|-
|[[11β-hydroxylase deficiency|11-β hydroxylase deficiency]]
|Increased:
* DOC
* 11-Deoxy-[[Cortisol]]
Decreased:
* [[Cortisol]]
* [[Corticosterone]]
* [[Aldosterone]]
|
* Low [[testosterone]] levels
|
* [[Hypertension]] and [[hypokalemia]]
* [[Virilization]]
|-
|[[3 beta-hydroxysteroid dehydrogenase deficiency]]
|Increased:
* [[DHEA]]
* [[17-hydroxypregnenolone]]
* [[Pregnenolone]]
Decreased:
* [[Cortisol]]
* [[Aldosterone]]
|
* Low [[testosterone]] levels
|
* Salt-wasting [[adrenal crisis]] in infancy
* Mild [[virilization]] of genetically female infants
* [[Undervirilization]] of genetically male infants, making it the only form of [[CAH]] which can cause [[ambiguous genitalia]] in both genetic sexes.
|-
|[[Polycystic ovary syndrome ]]
|
* High [[DHEAS]] and [[androstenedione]] levels
|
* Low [[testosterone]] levels
|
* [[Polycystic ovaries]] in sonography
* [[Obesity]]
* [[PCOS]] is the most common cause of [[hirsutism]] in women
* No evidence another diagnosis
|-
|[[Adrenal tumors]]
|
* Variable levels depends on [[tumor]] type
|
* Low [[testosterone]] level
|
* Older age
* Rapidly progressive symptoms
|-
|Ovarian [[virilizing]] tumor
|
* Variable levels depends on [[tumor]] type
|
* [[Testosterone]] is high
|
* Older age
* Rapidly progressive symptoms
|-
|[[Hyperprolactinemia]]
|
* Normal levels of most of [[steroids]]
|
* Increased [[prolactin]]
|
* [[Infertility]], [[galactorrhea]]
|}
=== Differentials based on galactorrhea, amenorrhea and infertility ===
Cushing's syndrome should also be differentiated from other causes of [[hyperprolactinemia]] that may present as [[galactorrhea]], [[amenorrhea]], (in females) and [[infertility]] (in both males and females) including:
*'''Physiological:'''
**Normal [[pregnancy]]<ref name="pmid910825">{{cite journal| author=Rigg LA, Lein A, Yen SS| title=Pattern of increase in circulating prolactin levels during human gestation. | journal=Am J Obstet Gynecol | year= 1977 | volume= 129 | issue= 4 | pages= 454-6 | pmid=910825 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=910825  }} </ref>
*'''Pathological:'''
**[[Pituitary tumors]] (other than [[prolactinoma]]):<ref name="pmid15316045">{{cite journal| author=Levy A| title=Pituitary disease: presentation, diagnosis, and management. | journal=J Neurol Neurosurg Psychiatry | year= 2004 | volume= 75 Suppl 3 | issue=  | pages= iii47-52 | pmid=15316045 | doi=10.1136/jnnp.2004.045740 | pmc=1765669 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15316045  }} </ref>
***[[Somatotroph adenoma]]: [[Acromegaly]]
***[[ACTH-secreting tumor|Corticotroph adenoma]]: [[Cushing's syndrome]]
**[[Suprasellar tumors]] ([[tumors]] present in the region of the [[pituitary stalk]])
**[[Hypothyroidism]]<ref name="pmid4199418">{{cite journal| author=Snyder PJ, Jacobs LS, Utiger RD, Daughaday WH| title=Thyroid hormone inhibition of the prolactin response to thyrotropin-releasing hormone. | journal=J Clin Invest | year= 1973 | volume= 52 | issue= 9 | pages= 2324-9 | pmid=4199418 | doi=10.1172/JCI107421 | pmc=333037 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=4199418  }} </ref>
**[[Chronic renal failure]]<ref name="pmid7372775">{{cite journal| author=Sievertsen GD, Lim VS, Nakawatase C, Frohman LA| title=Metabolic clearance and secretion rates of human prolactin in normal subjects and in patients with chronic renal failure. | journal=J Clin Endocrinol Metab | year= 1980 | volume= 50 | issue= 5 | pages= 846-52 | pmid=7372775 | doi=10.1210/jcem-50-5-846 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=7372775  }} </ref>
**[[Hepato-biliary diseases|Liver disease]]<ref name="pmid26958514">{{cite journal| author=Jha SK, Kannan S| title=Serum prolactin in patients with liver disease in comparison with healthy adults: A preliminary cross-sectional study. | journal=Int J Appl Basic Med Res | year= 2016 | volume= 6 | issue= 1 | pages= 8-10 | pmid=26958514 | doi=10.4103/2229-516X.173984 | pmc=4765284 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=26958514  }} </ref>
***[[Cirrhosis]] (with or without [[encephalopathy]])
***[[Viral hepatitis]] (with [[encephalopathy]])
**[[Seizure|Seizure disorder]]<ref name="Ben-Menachem2006">{{cite journal|last1=Ben-Menachem|first1=Elinor|title=Is Prolactin a Clinically Useful Measure of Epilepsy?|journal=Epilepsy Currents|volume=6|issue=3|year=2006|pages=78–79|issn=1535-7597|doi=10.1111/j.1535-7511.2006.00104.x}}</ref><ref name="pmid737437">{{cite journal| author=Trimble MR| title=Serum prolactin in epilepsy and hysteria. | journal=Br Med J | year= 1978 | volume= 2 | issue= 6153 | pages= 1682 | pmid=737437 | doi= | pmc=1608938 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=737437  }} </ref>
*'''Medication-induced:'''
**[[Antipsychotic]] medications:<ref name="pmid11048906">{{cite journal| author=David SR, Taylor CC, Kinon BJ, Breier A| title=The effects of olanzapine, risperidone, and haloperidol on plasma prolactin levels in patients with schizophrenia. | journal=Clin Ther | year= 2000 | volume= 22 | issue= 9 | pages= 1085-96 | pmid=11048906 | doi=10.1016/S0149-2918(00)80086-7 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11048906  }} </ref>
***[[Haloperidol]]
***[[Risperidone]]
**[[Antiemetic]] medications:
***[[Metoclopramide]]<ref name="pmid777023">{{cite journal| author=McCallum RW, Sowers JR, Hershman JM, Sturdevant RA| title=Metoclopramide stimulates prolactin secretion in man. | journal=J Clin Endocrinol Metab | year= 1976 | volume= 42 | issue= 6 | pages= 1148-52 | pmid=777023 | doi=10.1210/jcem-42-6-1148 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=777023  }} </ref>
***[[Domperidone]]<ref name="pmid7037817">{{cite journal| author=Sowers JR, Sharp B, McCallum RW| title=Effect of domperidone, an extracerebral inhibitor of dopamine receptors, on thyrotropin, prolactin, renin, aldosterone, and 18-hydroxycorticosterone secretion in man. | journal=J Clin Endocrinol Metab | year= 1982 | volume= 54 | issue= 4 | pages= 869-71 | pmid=7037817 | doi=10.1210/jcem-54-4-869 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=7037817  }} </ref>
**[[Antihypertensive]] medications:
***[[Methyldopa]]<ref name="pmid1268617">{{cite journal| author=Steiner J, Cassar J, Mashiter K, Dawes I, Fraser TR, Breckenridge A| title=Effects of methyldopa on prolactin and growth hormone. | journal=Br Med J | year= 1976 | volume= 1 | issue= 6019 | pages= 1186-8 | pmid=1268617 | doi= | pmc=1639736 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=1268617  }} </ref>
***[[Verapamil]]<ref name="pmid6682619">{{cite journal| author=Fearrington EL, Rand CH, Rose JD| title=Hyperprolactinemia-galactorrhea induced by verapamil. | journal=Am J Cardiol | year= 1983 | volume= 51 | issue= 8 | pages= 1466-7 | pmid=6682619 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=6682619  }} </ref>
{| class="wikitable"
! align="center" style="background:#4479BA; color: #FFFFFF;" + |Disease
! align="center" style="background:#4479BA; color: #FFFFFF;" + |Clinical Findings
! align="center" style="background:#4479BA; color: #FFFFFF;" + |Laboratory findings
! align="center" style="background:#4479BA; color: #FFFFFF;" + |Management
|-
|[[Somatotroph adenoma]]:
[[Acromegaly]]
|Clinical features of [[acromegaly]] are due to high level of [[Growth hormone|human growth hormone]] ([[Growth hormone|hGH]]):
* [[Soft tissue]] [[swelling]] of the hands and feet
* Brow and lower jaw protrusion
* Enlarged hands
* Enlarged feet
* [[Arthritis]] and [[carpal tunnel syndrome]]
* Increase in teeth spacing
* [[Macroglossia]] (enlarged tongue)
* [[Heart failure]]
* [[Kidney failure]]
* Compression of the [[optic chiasm]] leading to loss of [[vision]] in the outer [[visual fields]] (typically [[bitemporal hemianopia]])
* [[Headache]]
* [[Diabetes mellitus]]
* [[Hypertension]]
* [[Cardiomegaly]]
|
* Elevated [[insulin-like growth factor-1]] ([[Insulin-like growth factor-I|IGF-1]]) levels
* Elevated [[growth hormone]] levels
|
* Medical management:
** [[Octreotide]]
** [[Bromocriptine]]
* Surgical management:
** Endonasal transsphenoidal surgery
* [[Radiation therapy]]
|-
|[[ACTH-secreting tumor|Corticotroph adenoma]]: [[Cushing's syndrome]]
|Clinical features of [[Cushing's syndrome]] are due to increased levels of [[cortisol]]:
* Rapid [[Obesity|weight gain]], particularly of the [[trunk]] and face with sparing of the [[limbs]] ([[central obesity]])
* Proximal [[muscle weakness]]
* A round face often referred to as a "[[moon face]]"
* Excess [[sweating]]
* [[Headache]]
* The excess [[cortisol]] may also affect other endocrine systems and cause, for example:
** [[Insomnia]]
** Reduced [[libido]]
** [[Impotence]]
** [[Amenorrhea]]
** [[Infertility]]
* Patients frequently suffer various [[psychological]] disturbances, ranging from [[Euphoria (emotion)|euphoria]] to [[psychosis]]. [[Clinical depression|Depression]] and [[anxiety]] are also common.
|
* [[Dexamethasone suppression test]]
* 24 hour urinary measurement of [[cortisol]]
|
* Medical management:
** [[Pasireotide]]
** [[Cabergoline]]
** [[Ketoconazole]]
** [[Metyrapone]]
** [[Mitotane]]
** [[Mifepristone]]
* Surgical management:
** Transsphenoidal [[Pituitary gland|pituitary]] resection
|-
|[[Hypothyroidism]]
|Clinical features of [[hypothyroidism]] are due to deficiency of [[thyroxine]]:
* [[Fatigue]]
* Cold intolerance
* Decreased [[sweating]]
* [[Hypothermia]]
* Coarse [[skin]]
* [[Weight gain]]
* [[Hoarseness]]
* [[Goiter]]
* Fullness in the throat and neck
* [[Depression]]
* [[Emotional lability]]
* [[Attention deficit]]
|
* Elevated [[Thyroid-stimulating hormone|TSH]]
* Low [[Thyroxine|T4]]
* Low [[Triiodothyronine|T3]]
* Elevated anti-thyroid [[antibodies]](anti-TPO)
|[[Levothyroxine]]
|-
|[[Chronic renal failure]]
|There are no [[pathognomonic]] symptoms associated with [[chronic renal failure]]. Common non-specific symptoms of [[chronic renal failure]] include:
* [[Malaise]]
* [[Nausea]]
* Unintentional [[weight loss]]
* [[Pruritus]]
* [[Lower extremity edema]]
* [[Sleep disorders]]
|[[Urinalysis]]:
* [[Albuminuria]]
* [[Hematuria]]
* [[Pyuria]]
* [[Red blood cell|Red cell]] or [[White blood cells|white cell]] [[casts]] and crystals
[[Fluid and electrolytes|Fluid and electrolyte]] disturbances:
* [[Hyponatremia]]
* [[Hyperkalemia]]
* [[Hyperphosphatemia]]
* [[Hyperchloremia]]
* [[Metabolic acidosis]]
* [[Hypocalcemia]]
[[Endocrine system|Endocrine]] and [[metabolic]] disturbances:
* [[Hyperuricemia]]
* [[Hypertriglyceridemia]]
* Decreased [[HDL]] levels
* [[Vitamin D deficiency]]
* Increased [[Parathyroid hormone]] levels
[[Hematologic]] abnormalities:
* [[Normocytic normochromic anemia]]
* [[Lymphocytopenia]]
* [[Leukopenia]]
* [[Thrombocytopenia]]
|
* Medical management:
** [[Blood pressure medication|Blood pressure management]]
** Control of [[Blood sugar|blood glucose]]
** [[Protein]] restriction
** Management of [[anemia]]
** Management of [[electrolyte disturbance]]
** [[Dialysis]]
* Surgical management
** [[Kidney transplant]]
|-
|[[Cirrhosis|Liver disease: Cirrhosis]]
|The clinical features of liver [[cirrhosis]] are very nonspecific. These include:
* [[Right upper quadrant (abdomen)|Right upper quadrant]] [[abdominal pain]]
* [[Fever]]
* [[Fatigue]] and [[weakness]]
* [[Loss of appetite]]
* [[Diarrhea]]
* [[Nausea]] and [[vomiting]]
* [[Weight loss]]
* [[Abdominal pain]] and [[bloating]] when fluid accumulates in the [[abdomen]]
* [[Itching]]
* [[Menstrual cycle|Menstrual]] irregularities
|
*Elevated [[aminotransferases]] ([[Aspartate transaminase|AST]] & [[Alanine transaminase|ALT]])
*Elevated [[alkaline phosphatase]] ([[Alkaline phosphatase|ALP]])
*Elevated [[gamma-glutamyl transpeptidase]]
*Elevated [[bilirubin]]
*Low [[albumin]]
*Elevated [[prothrombin time]]
*Elevated [[globulin]]
*[[Hyponatremia]]
*[[Anemia]]
*[[Leukopenia]] and [[neutropenia]]
*[[Thrombocytopenia]]
|
* Medical management:
** Treatment is usually directed towards the treatment of complications like [[ascites]], [[esophageal varices]], [[hepatic encephalopathy]], [[hepatorenal syndrome]], and [[spontaneous bacterial peritonitis]].
*** Some chronic constitutional [[symptoms]] that should be treated include:
**** [[Pruritis]]: [[Cholestyramine]] is the drug of choice
**** [[Hypogonadism]]: Topical [[testosterone]] preparations
**** [[Osteoporosis]]: [[Calcium]] and [[vitamin D]]
**** Pain management: [[Non-steroidal anti-inflammatory drug|NSAIDS]], [[celecoxib]], [[opioids]]
**** Nutrition: Adequate [[Calories|caloric]] and [[protein]] intake, and [[multivitamin]] supplementation
* Surgical management: [[Liver transplantation]]
|-
|[[Seizure|Seizure disorder]]
|The clinical features of [[seizure disorder]] may include:
* Change in [[alertness]], orientation and time perception
* Mood changes, such as unexplainable fear, panic, joy, or laughter
* Changes in sensation of the [[skin]], usually spreading over the [[arm]], [[Leg (anatomy)|leg]], or [[trunk]]
* [[Vision]] changes, including seeing flashing lights
* Rarely, [[Hallucination|hallucinations]] (seeing things that aren't there)
* Falling, loss of [[muscle]] control, occurs very suddenly
* [[Muscle twitching]] that may spread up or down an [[arm]] or [[leg]]
* [[Muscle]] tension or tightening that causes twisting of the body, [[head]], [[Arm|arms]], or [[legs]]
* Shaking of the entire body
* Tasting a bitter or metallic flavor
|[[Electroencephalogram]]
|
* Medical management:
** [[Antiepileptics|Antiepileptic]] medications
|-
|[[Medication-induced]]
|Clinical features of [[hyperprolactinemia]] after a specific period of regular medication ingestion
|Discontinuation of the medication for 3 days and remeasurement of [[prolactin]] levels<ref name="pmid21296991">{{cite journal| author=Melmed S, Casanueva FF, Hoffman AR, Kleinberg DL, Montori VM, Schlechte JA et al.| title=Diagnosis and treatment of hyperprolactinemia: an Endocrine Society clinical practice guideline. | journal=J Clin Endocrinol Metab | year= 2011 | volume= 96 | issue= 2 | pages= 273-88 | pmid=21296991 | doi=10.1210/jc.2010-1692 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21296991  }}</ref>
|Change to alternate medication
|}
===Differentials based on irregular menstruation and hirsutism===
Cushing's syndrome must be differentiated from other causes of irregular menses and hirsutism. The differentials include:


{| class="wikitable"
{| class="wikitable"
!Disease
! align="center" style="background:#4479BA; color: #FFFFFF;" + |Disease
!Differentiating Features
! align="center" style="background:#4479BA; color: #FFFFFF;" + |Differentiating Features
|-
|-
|[[Pregnancy]]
|[[Pregnancy]]
|
|
* Pregnancy always should be excluded in a patient with a history of amenorrhea
* Pregnancy should always be excluded in a patient with a history of [[amenorrhea]]


* Features include amenorrhea or oligomenorrhea, abnormal uterine bleeding, nausea/vomiting, cravings, weight gain (although not in the early stages and not if vomiting), polyuria, abdominal cramps and constipation, fatigue, dizziness/lightheadedness, and increased pigmentation (moles, nipples)
* Features include [[amenorrhea]] or [[oligomenorrhea]], abnormal [[uterine]] bleeding, nausea/[[vomiting]], cravings, weight gain (although not in the early stages and not if vomiting), [[polyuria]], abdominal cramps and constipation, fatigue, dizziness/lightheadedness, and increased [[pigmentation]] (moles, nipples)


* Uterine enlargement is detectable on abdominal examination at approximately 14 weeks of gestation
* [[Uterine]] enlargement is detectable on [[abdominal]] examination at approximately 14 weeks of gestation


* Ectopic pregnancy may cause oligomenorrhea, amenorrhea, or abnormal uterine bleeding with abdominal pain and sometimes subtle or absent physical symptoms and signs of pregnancy
* [[Ectopic]] pregnancy may cause [[oligomenorrhea]], [[amenorrhea]], or abnormal [[uterine]] bleeding with abdominal pain and sometimes subtle or absent physical symptoms and signs of pregnancy
|-
|-
|Hypothalamic amenorrhea
|[[Hypothalamic]] [[amenorrhea]]
|
|
* Diagnosis of exclusion
* Diagnosis of exclusion
* Seen in athletes, people on crash diets, patients with significant systemic illness, and those experiencing undue stress or anxiety  
* Seen in athletes, people on crash diets, patients with significant [[systemic]] illness, and those experiencing undue stress or anxiety  
* Predisposing features are as follows weight loss, particularly if features of anorexia nervosa are present or the BMI is <19 kg/m2
* Predisposing features are as follows weight loss, particularly if features of anorexia nervosa are present or the BMI is <19 kg/m2
* Recent administration of depot medroxyprogesterone, which may suppress ovarian activity for 6 months to a year
* Recent administration of depot [[Medroxyprogesterone (patient information)|medroxyprogesterone]], which may suppress [[ovarian]] activity for 6 months to a year
* Use of dopamine agonists (eg, antidepressants) and major tranquilizers
* Use of [[dopamine]] [[agonists]] (eg, [[antidepressants]]) and major tranquilizers
* Hyperthyroidism  
* [[Hyperthyroidism]]
* In patients with weight loss related to anorexia nervosa, fine hair growth (lanugo) may occur all over the body, but it differs from hirsutism in its fineness and wide distribution
* In patients with weight loss related to [[anorexia nervosa]], fine hair growth (lanugo) may occur all over the body, but it differs from [[hirsutism]] in its fineness and wide distribution
|-
|-
|[[Primary amenorrhea]]
|[[Primary amenorrhea]]
|
|
* Causes include reproductive system abnormalities, chromosomal abnormalities, or delayed puberty
* Causes include reproductive system abnormalities, [[chromosomal]] abnormalities, or delayed [[puberty]]
* If secondary sexual characteristics are present, an anatomic abnormality (eg, imperforate hymen, which is rare) should be considered
* If [[secondary sexual characteristics]] are present, an anatomic abnormality (eg, imperforate [[hymen]], which is rare) should be considered
* If secondary sexual characteristics are absent, a chromosomal abnormality (eg, Turner syndrome ) or delayed puberty should be considered
* If [[secondary sexual characteristics]] are absent, a [[chromosomal]] abnormality (eg, Turner syndrome ) or delayed puberty should be considered
|-
|-
|[[Cushing's syndrome|Cushing syndrome]]
|[[Cushing's syndrome|Cushing syndrome]]
|
|
* Cushing syndrome is due to excessive glucocorticoid secretion from the adrenal glands, either primarily or secondary to stimulation from pituitary or ectopic hormones; can also be caused by exogenous steroid use
* Cushing syndrome is due to excessive [[glucocorticoid]] secretion from the [[adrenal glands]], either primarily or secondary to stimulation from [[pituitary]] or [[ectopic]] hormones; can also be caused by [[exogenous]] [[steroid]] use


* Features include hypertension, weight gain (central distribution), acne, and abdominal striae Patients have low plasma sodium levels and elevated plasma cortisol levels on dexamethasone suppression testing
* Features include [[hypertension]], weight gain (central distribution), [[acne]], and abdominal striae. Patients have low plasma sodium levels and elevated plasma [[Cortisol level|cortisol]] levels on [[Dexamethasone suppression test|dexamethasone suppression testing]]
|-
|-
|[[Hyperprolactinemia]]
|[[Hyperprolactinemia]]
Line 130: Line 459:
* Physical examination findings are usually normal
* Physical examination findings are usually normal
* As in patients with PCOS, hyperprolactinemia may be associated with mild galactorrhea and oligomenorrhea or amenorrhea; however, galactorrhea also can occur with nipple stimulation and/or stress when prolactin levels are within normal ranges
* As in patients with PCOS, hyperprolactinemia may be associated with mild galactorrhea and oligomenorrhea or amenorrhea; however, galactorrhea also can occur with nipple stimulation and/or stress when prolactin levels are within normal ranges
* A large prolactinoma may cause headaches and visual field disturbance due to pressure on the optic chiasm, classically a gradually increasing bitemporal hemianopsia
* A large prolactinoma may cause headaches and visual field disturbance due to pressure on the optic chiasm, classically a gradually increasing bi-temporal hemianopsia
|-
|-
|Ovarian or adrenal tumor
|Ovarian or adrenal tumor
|
|
* Benign ovarian tumors and ovarian cancer are rarely causes of excessive androgen secretion; adrenocortical tumors also can increase the production of sex hormones
* Benign ovarian tumors and ovarian cancer are rare causes of excessive androgen secretion; adrenocortical tumors also can increase the production of sex hormones
* Abdominal swelling or mass, abdominal pain due to fluid leakage or torsion, dyspareunia, abdominal ascites, and features of metastatic disease may be present
* Abdominal swelling or mass, abdominal pain due to fluid leakage or torsion, dyspareunia, abdominal ascites, and features of metastatic disease may be present
* Features of androgenization include hirsutism, weight gain, oligomenorrhea or amenorrhea, acne, clitoral hypertrophy, deepening of the voice, and high serum androgen (eg, testosterone, other androgens) levels
* Features of androgenization include hirsutism, weight gain, oligomenorrhea or amenorrhea, acne, clitoral hypertrophy, deepening of the voice, and high serum androgen (eg, testosterone, other androgens) levels
Line 163: Line 492:
* When the cause is genetic, the excessive hair, especially on the face (upper lip), is present throughout adulthood, and there is no virilization
* When the cause is genetic, the excessive hair, especially on the face (upper lip), is present throughout adulthood, and there is no virilization
* When secondary to medications, the excessive hair is of new onset, and other features of virilization, such as acne and deepened voice, may be present
* When secondary to medications, the excessive hair is of new onset, and other features of virilization, such as acne and deepened voice, may be present
|}
===Less common differentials===
Cushing's syndrome must be differentiated from other adrenal tumors such as [[adrenocortical adenoma]], adrenal [[metastasis]], and [[Pheochromocytoma|adrenal medullary tumors]]:
{| style="border: 0px; font-size: 90%; margin: 3px; width: 1000px" align="center"
|+
! style="background: #4479BA; width: 200px;" | {{fontcolor|#FFF|Differential Diagnosis}}
! style="background: #4479BA; width: 300px;" | {{fontcolor|#FFF|Clinical picture}}
! style="background: #4479BA; width: 300px;" | {{fontcolor|#FFF|Imagings}}
! style="background: #4479BA; width: 300px;" | {{fontcolor|#FFF|Laboratory tests}}
|-
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold; text-align:center;" |'''Adrenocortica'''l carcinoma
| style="padding: 5px 5px; background: #F5F5F5;" |
* Mass effect symptoms
* Symptoms related to  excess [[glucocorticoid]]
* Symptoms related to  excess [[mineralocorticoid]]
* Symptoms related to  excess [[androgen]] or [[estrogen]] secretion
|
* Irregular shape
* Non-[[homogeneous]] density because of central areas of low attenuation due to [[tumor]] [[necrosis]]
* [[Tumor]] [[calcification]]
* Diameter usually >4 cm
* Unilateral location
* High unenhanced [[Computed tomography|CT]] attenuation values (>20 HU)
* Non-[[homogeneous]] enhancement on [[Computed tomography|CT]] with [[intravenous]] [[Contrast medium|contrast]]
* Delay in [[contrast medium]] washout (10 minutes after administration of [[contrast]], an absolute [[contrast medium]] washout of less than 50 percent)
* Hypointensity compared with [[liver]] on T1 weighted [[Magnetic resonance imaging|MRI]] and high to intermediate signal intensity on T2 weighted [[Magnetic resonance imaging|MRI]]
* High standardized uptake value (SUV) on [[FDG-PET|FDG]]-[[PET scan|PET-CT]] study
* Evidence of local [[invasion]] or [[Metastasis|metastases]]
|
* [[Androgen|Adrenal androgens]] ([[DHEAS|DHEAS)]]
* [[Androstenedione]]
* Bioavailable [[testosterone]] should be measured in every patient.
* [[17-Hydroxyprogesterone|17-hydroxyprogesterone]]
* Serum [[estradiol]] in men and postmenopausal women
* [[Cortisol level]]
* Fasting serum [[cortisol]] at 8 AM following a 1 mg dose of [[dexamethasone]] at bedtime
|-
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold; text-align:center;" |[[Adrenal adenoma]]
| style="padding: 5px 5px; background: #F5F5F5;" |
* Symptoms related to  excess [[glucocorticoid]]
* Symptoms related to  excess [[mineralocorticoid]]
|
* Round, [[homogeneous]] with sharp margination
* Unilateral with diameter less than 4 cm
* Low unenhanced [[Computed tomography|CT]] attenuation values (<10 HU)
* Rapid [[contrast medium]] washout after administration of contrast
* An absolute [[contrast medium]] washout of more than 50 percent
* [[Chemical shift]]: evidence of [[lipid]] on [[Magnetic resonance imaging|MRI]]
* Isointensity with [[liver]] on both T1 and T2 weighted [[Magnetic resonance imaging|MRI]] sequences
|
* [[Cortisol level]]
* Fasting [[serum]] [[cortisol]] at 8 AM following a 1 mg dose of [[dexamethasone]] at bedtime
* [[Renin]] ([[Plasma renin activity|PRA]]) or plasma renin concentration (PRC): very low in patients with [[primary aldosteronism]], usually less than 1 ng/mL per hour for [[Plasma renin activity|PRA]] and usually undetectable for PRC<ref name="pmid26372319">{{cite journal| author=Manolopoulou J, Fischer E, Dietz A, Diederich S, Holmes D, Junnila R et al.| title=Clinical validation for the aldosterone-to-renin ratio and aldosterone suppression testing using simultaneous fully automated chemiluminescence immunoassays. | journal=J Hypertens | year= 2015 | volume= 33 | issue= 12 | pages= 2500-11 | pmid=26372319 | doi=10.1097/HJH.0000000000000727 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=26372319  }}</ref>
|-
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold; text-align:center;" |[[Cushing's syndrome]]
| style="padding: 5px 5px; background: #F5F5F5;" |
* Rapid [[Obesity|weight gain]], particularly of the [[trunk]] and [[face]] with [[limbs]] sparing ([[central obesity]])
* Proximal [[muscle weakness]]
* A [[round face]] often referred to as a "[[moon face]]"
* Excess [[sweating]]
* [[Headache]]
|
* Imaging may show [[mass]] if presents
|
* 24-hour [[urine]] [[cortisol]]
* Midnight salivary [[cortisol]]
* Low-dose [[dexamethasone]] suppression test; high [[cortisol]] level after the [[dexamethasone]] test is suggestive of [[hypercortisolism]].
|-
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold; text-align:center;" |[[Pheochromocytoma]]
| style="padding: 5px 5px; background: #F5F5F5;" |
* [[Palpitations]] especially in [[Epinephrine|epinephrine-]]<nowiki/>producing [[Tumor|tumors]].
* [[Anxiety]] often resembling that of a [[panic attack]]
* [[Sweating]]
* [[Headaches]] occur in 90 % of patients.
* Paroxysmal attacks of [[hypertension]] but some patients have normal [[blood pressure]].
* It may be [[asymptomatic]] and discovered incidentally after [[Screening (medicine)|screening]] for [[MEN, type 2|MEN]] patients.
|
* Increased [[attenuation]] on non-enhanced [[Computed tomography|CT]] (>20 HU)
* Increased [[mass]] [[vascularity]]
* Delay in [[contrast medium]] washout (10 minutes after administration of [[contrast]], an absolute [[contrast medium]] washout of less than 50 percent)
* High signal intensity on T2 weighted [[Magnetic resonance imaging|MRI]]
* [[Cystic]] and [[hemorrhagic]] changes
* Variable size and may be [[bilateral]]
|
* [[Plasma]] fractionated [[Metanephrine|metanephrines]] 
* 24-hour [[urinary]] fractionated [[Metanephrine|metanephrines]]
|-
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold; text-align:center;" |[[Adrenal metastasis]]
| style="padding: 5px 5px; background: #F5F5F5;" |
* [[Symptoms]] and [[signs]] of primary [[malignancy]] especially [[lung cancer]]
* General constitutional symptoms:
**[[Fever]]
**[[Fatigue]]
**[[Weight loss]]
|
* Irregular shape and non-[[homogeneous]] nature
* Tendency to be [[bilateral]]
* High un-enhanced [[Computed tomography|CT]] [[attenuation]] values (>20 HU) and enhancement with [[Contrast medium|intravenous contrast]] on [[Computed tomography|CT]]
* Delay in [[contrast medium]] washout (10 minutes after administration of contrast, an absolute [[contrast medium]] washout of less than 50 percent)
* Isointensity or slightly less intense than the [[liver]] on T1 weighted [[Magnetic resonance imaging|MRI]] and high to intermediate signal intensity on T2 weighted [[Magnetic resonance imaging|MRI]] (representing an increased water content)
* Elevated standardized uptake value on [[FDG-PET|FDG]]-[[PET scan]]
|
|}
|}



Latest revision as of 19:25, 25 February 2019

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

Overview

Cushing's syndrome must be differentiated from other diseases that cause hypertension, obesity, and hyperandrogenism, such as Metabolic syndrome X and pseudo-Cushing's syndrome.

Differentiating Cushing's Syndrome From Other Diseases

Differentials based on hypertension, hyperandrogenism and obesity

The table below summarizes the findings that differentiate Cushing's disease from other conditions that may cause hypertension, hyperandrogenism, and obesity. Facial plethora, skin changes, osteoporosis, nephrolithiasis and neuropsychiatric conditions should raise the concern for Cushing's syndrome.[1][2][3][4]

Conditions Causes Associated features Diagnostic approach
Cushing's syndrome
Pseudo-Cushing's syndrome
Metabolic syndrome X

Differentials based on virilization and hirsutism

Cushing's syndrome must be differentiated from diseases that cause virilization and hirsutism in female:[5][6][7]

Disease name Steroid status Other laboratory Important clinical findings
Cushing's syndrome
Non-classic type of 21-hydroxylase deficiency Increased:
  • No symptoms in infancy and male
11-β hydroxylase deficiency Increased:

Decreased:

3 beta-hydroxysteroid dehydrogenase deficiency Increased:

Decreased:

Polycystic ovary syndrome
Adrenal tumors
  • Variable levels depends on tumor type
  • Older age
  • Rapidly progressive symptoms
Ovarian virilizing tumor
  • Variable levels depends on tumor type
  • Older age
  • Rapidly progressive symptoms
Hyperprolactinemia

Differentials based on galactorrhea, amenorrhea and infertility

Cushing's syndrome should also be differentiated from other causes of hyperprolactinemia that may present as galactorrhea, amenorrhea, (in females) and infertility (in both males and females) including:

Disease Clinical Findings Laboratory findings Management
Somatotroph adenoma:

Acromegaly

Clinical features of acromegaly are due to high level of human growth hormone (hGH):
Corticotroph adenoma: Cushing's syndrome Clinical features of Cushing's syndrome are due to increased levels of cortisol:
Hypothyroidism Clinical features of hypothyroidism are due to deficiency of thyroxine:
  • Fullness in the throat and neck
Levothyroxine
Chronic renal failure There are no pathognomonic symptoms associated with chronic renal failure. Common non-specific symptoms of chronic renal failure include: Urinalysis:

Fluid and electrolyte disturbances:

Endocrine and metabolic disturbances:

Hematologic abnormalities:

Liver disease: Cirrhosis The clinical features of liver cirrhosis are very nonspecific. These include:
Seizure disorder The clinical features of seizure disorder may include:
  • Change in alertness, orientation and time perception
  • Mood changes, such as unexplainable fear, panic, joy, or laughter
  • Changes in sensation of the skin, usually spreading over the arm, leg, or trunk
  • Vision changes, including seeing flashing lights
  • Rarely, hallucinations (seeing things that aren't there)
  • Falling, loss of muscle control, occurs very suddenly
  • Muscle twitching that may spread up or down an arm or leg
  • Muscle tension or tightening that causes twisting of the body, head, arms, or legs
  • Shaking of the entire body
  • Tasting a bitter or metallic flavor
Electroencephalogram
Medication-induced Clinical features of hyperprolactinemia after a specific period of regular medication ingestion Discontinuation of the medication for 3 days and remeasurement of prolactin levels[20] Change to alternate medication

Differentials based on irregular menstruation and hirsutism

Cushing's syndrome must be differentiated from other causes of irregular menses and hirsutism. The differentials include:

Disease Differentiating Features
Pregnancy
  • Pregnancy should always be excluded in a patient with a history of amenorrhea
  • Uterine enlargement is detectable on abdominal examination at approximately 14 weeks of gestation
Hypothalamic amenorrhea
  • Diagnosis of exclusion
  • Seen in athletes, people on crash diets, patients with significant systemic illness, and those experiencing undue stress or anxiety
  • Predisposing features are as follows weight loss, particularly if features of anorexia nervosa are present or the BMI is <19 kg/m2
  • Recent administration of depot medroxyprogesterone, which may suppress ovarian activity for 6 months to a year
  • Use of dopamine agonists (eg, antidepressants) and major tranquilizers
  • Hyperthyroidism
  • In patients with weight loss related to anorexia nervosa, fine hair growth (lanugo) may occur all over the body, but it differs from hirsutism in its fineness and wide distribution
Primary amenorrhea
Cushing syndrome
Hyperprolactinemia
  • Mild hyperprolactinemia may occur as part of PCOS-related hormonal dysfunction
  • Other causes include stress, lactation, and use of dopamine antagonists
  • A prolactinoma of the pituitary gland is an uncommon cause and should be suspected if prolactin levels are very high (>200 ng/mL)
  • Physical examination findings are usually normal
  • As in patients with PCOS, hyperprolactinemia may be associated with mild galactorrhea and oligomenorrhea or amenorrhea; however, galactorrhea also can occur with nipple stimulation and/or stress when prolactin levels are within normal ranges
  • A large prolactinoma may cause headaches and visual field disturbance due to pressure on the optic chiasm, classically a gradually increasing bi-temporal hemianopsia
Ovarian or adrenal tumor
  • Benign ovarian tumors and ovarian cancer are rare causes of excessive androgen secretion; adrenocortical tumors also can increase the production of sex hormones
  • Abdominal swelling or mass, abdominal pain due to fluid leakage or torsion, dyspareunia, abdominal ascites, and features of metastatic disease may be present
  • Features of androgenization include hirsutism, weight gain, oligomenorrhea or amenorrhea, acne, clitoral hypertrophy, deepening of the voice, and high serum androgen (eg, testosterone, other androgens) levels
  • In patients with an androgen-secreting tumor, serum testosterone is not suppressed by dexamethasone
Congenital adrenal hyperplasia
  • Congenital adrenal hyperplasia is a rare genetic condition resulting from 21-hydroxylase deficiency
  • The late-onset form presents at or around menarche Patients have features of androgenization and subfertility
  • Affects approximately 1% of hirsute patients More common in Ashkenazi Jews (19%), inhabitants of the former Yugoslavia (12%), and Italians (6%)
  • Associated with high levels of 17-hydroxyprogesterone
  • A short adrenocorticotropic hormone stimulation test with measurement of serum17-hydroxyprogesterone confirms the diagnosis Assays of a variety of androgenic hormones help define other rare adrenal enzyme deficiencies, which present similarly to 21-hydroxylase deficiency
Anabolic steroid abuse
  • Anabolic steroids are synthetic hormones that imitate the actions of testosterone by increasing muscle bulk and strength
  • Should be considered if the patient is a serious sportswoman or bodybuilder
  • Features include virilization (including acne and hirsutism), often increased muscle bulk in male pattern, oligomenorrhea or amenorrhea, clitoromegaly, gastritis, hepatic enlargement, alopecia, and aggression
  • Altered liver function test results are seen
Hirsutism
  • Hirsutism is excessive facial and body hair, usually coarse and in a male pattern of distribution
  • Approximately 10% of women report unwanted facial hair
  • There is often a family history and typically some Mediterranean or Middle Eastern ancestry
  • May also result from use of certain medications, both androgens, and others including danazol, glucocorticoids, cyclosporine, and phenytoin
  • Menstrual history is normal
  • When the cause is genetic, the excessive hair, especially on the face (upper lip), is present throughout adulthood, and there is no virilization
  • When secondary to medications, the excessive hair is of new onset, and other features of virilization, such as acne and deepened voice, may be present

Less common differentials

Cushing's syndrome must be differentiated from other adrenal tumors such as adrenocortical adenoma, adrenal metastasis, and adrenal medullary tumors:

Differential Diagnosis Clinical picture Imagings Laboratory tests
Adrenocortical carcinoma
Adrenal adenoma
Cushing's syndrome
  • Imaging may show mass if presents
Pheochromocytoma
Adrenal metastasis

References

  1. Boscaro M, Barzon L, Fallo F, Sonino N (2001). "Cushing's syndrome". Lancet. 357 (9258): 783–91. doi:10.1016/S0140-6736(00)04172-6. PMID 11253984.
  2. Findling JW, Raff H (2001). "Diagnosis and differential diagnosis of Cushing's syndrome". Endocrinol. Metab. Clin. North Am. 30 (3): 729–47. PMID 11571938.
  3. Newell-Price J, Trainer P, Besser M, Grossman A (1998). "The diagnosis and differential diagnosis of Cushing's syndrome and pseudo-Cushing's states". Endocr. Rev. 19 (5): 647–72. doi:10.1210/edrv.19.5.0346. PMID 9793762.
  4. "How Is Metabolic Syndrome Diagnosed? - NHLBI, NIH".
  5. Hohl A, Ronsoni MF, Oliveira M (2014). "Hirsutism: diagnosis and treatment". Arq Bras Endocrinol Metabol. 58 (2): 97–107. PMID 24830586. Vancouver style error: initials (help)
  6. White PC, Speiser PW (2000). "Congenital adrenal hyperplasia due to 21-hydroxylase deficiency". Endocr. Rev. 21 (3): 245–91. doi:10.1210/edrv.21.3.0398. PMID 10857554.
  7. Melmed, Shlomo (2016). Williams textbook of endocrinology. Philadelphia, PA: Elsevier. ISBN 978-0323297387.=
  8. Rigg LA, Lein A, Yen SS (1977). "Pattern of increase in circulating prolactin levels during human gestation". Am J Obstet Gynecol. 129 (4): 454–6. PMID 910825.
  9. Levy A (2004). "Pituitary disease: presentation, diagnosis, and management". J Neurol Neurosurg Psychiatry. 75 Suppl 3: iii47–52. doi:10.1136/jnnp.2004.045740. PMC 1765669. PMID 15316045.
  10. Snyder PJ, Jacobs LS, Utiger RD, Daughaday WH (1973). "Thyroid hormone inhibition of the prolactin response to thyrotropin-releasing hormone". J Clin Invest. 52 (9): 2324–9. doi:10.1172/JCI107421. PMC 333037. PMID 4199418.
  11. Sievertsen GD, Lim VS, Nakawatase C, Frohman LA (1980). "Metabolic clearance and secretion rates of human prolactin in normal subjects and in patients with chronic renal failure". J Clin Endocrinol Metab. 50 (5): 846–52. doi:10.1210/jcem-50-5-846. PMID 7372775.
  12. Jha SK, Kannan S (2016). "Serum prolactin in patients with liver disease in comparison with healthy adults: A preliminary cross-sectional study". Int J Appl Basic Med Res. 6 (1): 8–10. doi:10.4103/2229-516X.173984. PMC 4765284. PMID 26958514.
  13. Ben-Menachem, Elinor (2006). "Is Prolactin a Clinically Useful Measure of Epilepsy?". Epilepsy Currents. 6 (3): 78–79. doi:10.1111/j.1535-7511.2006.00104.x. ISSN 1535-7597.
  14. Trimble MR (1978). "Serum prolactin in epilepsy and hysteria". Br Med J. 2 (6153): 1682. PMC 1608938. PMID 737437.
  15. David SR, Taylor CC, Kinon BJ, Breier A (2000). "The effects of olanzapine, risperidone, and haloperidol on plasma prolactin levels in patients with schizophrenia". Clin Ther. 22 (9): 1085–96. doi:10.1016/S0149-2918(00)80086-7. PMID 11048906.
  16. McCallum RW, Sowers JR, Hershman JM, Sturdevant RA (1976). "Metoclopramide stimulates prolactin secretion in man". J Clin Endocrinol Metab. 42 (6): 1148–52. doi:10.1210/jcem-42-6-1148. PMID 777023.
  17. Sowers JR, Sharp B, McCallum RW (1982). "Effect of domperidone, an extracerebral inhibitor of dopamine receptors, on thyrotropin, prolactin, renin, aldosterone, and 18-hydroxycorticosterone secretion in man". J Clin Endocrinol Metab. 54 (4): 869–71. doi:10.1210/jcem-54-4-869. PMID 7037817.
  18. Steiner J, Cassar J, Mashiter K, Dawes I, Fraser TR, Breckenridge A (1976). "Effects of methyldopa on prolactin and growth hormone". Br Med J. 1 (6019): 1186–8. PMC 1639736. PMID 1268617.
  19. Fearrington EL, Rand CH, Rose JD (1983). "Hyperprolactinemia-galactorrhea induced by verapamil". Am J Cardiol. 51 (8): 1466–7. PMID 6682619.
  20. Melmed S, Casanueva FF, Hoffman AR, Kleinberg DL, Montori VM, Schlechte JA; et al. (2011). "Diagnosis and treatment of hyperprolactinemia: an Endocrine Society clinical practice guideline". J Clin Endocrinol Metab. 96 (2): 273–88. doi:10.1210/jc.2010-1692. PMID 21296991.
  21. Manolopoulou J, Fischer E, Dietz A, Diederich S, Holmes D, Junnila R; et al. (2015). "Clinical validation for the aldosterone-to-renin ratio and aldosterone suppression testing using simultaneous fully automated chemiluminescence immunoassays". J Hypertens. 33 (12): 2500–11. doi:10.1097/HJH.0000000000000727. PMID 26372319.


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