Cushing's syndrome resident survival guide: Difference between revisions

Jump to navigation Jump to search
 
(39 intermediate revisions by one other user not shown)
Line 2: Line 2:
{{Resident survival guide project}}
{{Resident survival guide project}}


{{WikiDoc CMG}}; {{AE}}
{{WikiDoc CMG}}; {{AE}} {{MSJ}}


==Overview==
==Overview==
This section provides a short and straight to the point overview of the disease or symptom.  The first sentence of the overview must contain the name of the disease.
[[Cushing’s syndrome]] is characterized by elevated circulating levels of [[glucocorticoid]] (i.e. [[cortisol]]) in [[blood]]. It presents with a wide range of clinical spectrum ranging from mild to severe. The clinical symptoms are characterized by central [[obesity]], facial [[edema]], buffalo hump, proximal [[myopathy]], [[hypertension]], [[hyperglycemia]], mood changes, skin thinning, abdominal [[striae]], and easy [[Bruise|bruising]]. The [[physician]] should aim to diagnose the cause of [[Cushing’s syndrome]] and treat it accordingly. This section provides a short and straight to the point overview of the [[Cushing's syndrome]].


==Causes==
==Causes==
Line 14: Line 14:
===Common Causes===
===Common Causes===
* Iatrogenic or factitious [[Cushing's syndrome]] due to administration of exogenous [[glucocorticoids]].
* Iatrogenic or factitious [[Cushing's syndrome]] due to administration of exogenous [[glucocorticoids]].
*[[Cushing's disease]] (due to excess secretion of [[Adrenocorticotropic hormone]] [ACTH] from [[anterior pituitary]]).
*[[Cushing's disease]] (due to excess secretion of [[Adrenocorticotropic hormone]] from [[anterior pituitary]]).
* Paraneoplastic: due to ectopic secretion of [[Adrenocorticotropic hormone|ACTH]] (includes, [[small cell  lung cancer]], benign [[Carcinoid syndrome|carcinoid tumor]]<nowiki/>s, [[Ewing's sarcoma]]).
* Paraneoplastic: due to ectopic secretion of ACTH (includes, [[small cell  lung cancer]], benign [[Carcinoid syndrome|carcinoid tumor]]<nowiki/>s, [[Ewing's sarcoma]]). <ref name="pmid11134141">{{cite journal| author=White A, Ray DW, Talbot A, Abraham P, Thody AJ, Bevan JS| title=Cushing's syndrome due to phaeochromocytoma secreting the precursors of adrenocorticotropin. | journal=J Clin Endocrinol Metab | year= 2000 | volume= 85 | issue= 12 | pages= 4771-5 | pmid=11134141 | doi=10.1210/jcem.85.12.7047 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11134141  }} </ref><ref name="pmid21346064">{{cite journal| author=More J, Young J, Reznik Y, Raverot G, Borson-Chazot F, Rohmer V | display-authors=etal| title=Ectopic ACTH syndrome in children and adolescents. | journal=J Clin Endocrinol Metab | year= 2011 | volume= 96 | issue= 5 | pages= 1213-22 | pmid=21346064 | doi=10.1210/jc.2010-2276 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21346064  }} </ref><ref name="pmid15914534">{{cite journal| author=Ilias I, Torpy DJ, Pacak K, Mullen N, Wesley RA, Nieman LK| title=Cushing's syndrome due to ectopic corticotropin secretion: twenty years' experience at the National Institutes of Health. | journal=J Clin Endocrinol Metab | year= 2005 | volume= 90 | issue= 8 | pages= 4955-62 | pmid=15914534 | doi=10.1210/jc.2004-2527 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15914534  }} </ref>
* Ectopic secretion of [[Corticotropin-releasing hormone]] (CRH).
* Ectopic secretion of [[Corticotropin-releasing hormone]] (CRH).
*[[Adenoma]] and [[carcinoma]] in the [[adrenal cortex]]
*[[Adenoma]] and [[carcinoma]] in the [[adrenal cortex]]
* Primary pigmented nodular adrenocortical disease (PPNAD)
* Primary pigmented nodular adrenocortical disease (PPNAD)<ref name="pmid3010718">{{cite journal| author=Larsen JL, Cathey WJ, Odell WD| title=Primary adrenocortical nodular dysplasia, a distinct subtype of Cushing's syndrome. Case report and review of the literature. | journal=Am J Med | year= 1986 | volume= 80 | issue= 5 | pages= 976-84 | pmid=3010718 | doi=10.1016/0002-9343(86)90648-0 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=3010718  }} </ref>
* Bilateral macronodular adrenal hyperplasia (BMAH)
* Bilateral macronodular adrenal hyperplasia (BMAH)<ref name="pmid11159817">{{cite journal| author=Lacroix A, Ndiaye N, Tremblay J, Hamet P| title=Ectopic and abnormal hormone receptors in adrenal Cushing's syndrome. | journal=Endocr Rev | year= 2001 | volume= 22 | issue= 1 | pages= 75-110 | pmid=11159817 | doi=10.1210/edrv.22.1.0420 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11159817  }} </ref>


==Diagnosis==
==Diagnosis==
Shown below is an algorithm summarizing the diagnosis of [[Cushing's syndrome]] according to the [[Endocrine Society]] clinical guidelines.
Shown below is an algorithm summarizing the diagnosis of [[Cushing's syndrome]] according to the [[Endocrine Society]] clinical guidelines.<ref name="pmid18334580">{{cite journal| author=Nieman LK, Biller BM, Findling JW, Newell-Price J, Savage MO, Stewart PM | display-authors=etal| title=The diagnosis of Cushing's syndrome: an Endocrine Society Clinical Practice Guideline. | journal=J Clin Endocrinol Metab | year= 2008 | volume= 93 | issue= 5 | pages= 1526-40 | pmid=18334580 | doi=10.1210/jc.2008-0125 | pmc=2386281 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18334580  }} </ref><ref name="pmid26004339">{{cite journal| author=Lacroix A, Feelders RA, Stratakis CA, Nieman LK| title=Cushing's syndrome. | journal=Lancet | year= 2015 | volume= 386 | issue= 9996 | pages= 913-27 | pmid=26004339 | doi=10.1016/S0140-6736(14)61375-1 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=26004339  }} </ref><ref name="pmid15251475">{{cite journal| author=Weber SL| title=Cushing'S syndrome attributable to topical use of lotrisone. | journal=Endocr Pract | year= 1997 | volume= 3 | issue= 3 | pages= 140-4 | pmid=15251475 | doi=10.4158/EP.3.3.140 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15251475  }} </ref><ref name="pmid14671138">{{cite journal| author=Arnaldi G, Angeli A, Atkinson AB, Bertagna X, Cavagnini F, Chrousos GP | display-authors=etal| title=Diagnosis and complications of Cushing's syndrome: a consensus statement. | journal=J Clin Endocrinol Metab | year= 2003 | volume= 88 | issue= 12 | pages= 5593-602 | pmid=14671138 | doi=10.1210/jc.2003-030871 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=14671138  }} </ref><ref name="pmid13761950">{{cite journal| author=LIDDLE GW| title=Tests of pituitary-adrenal suppressibility in the diagnosis of Cushing's syndrome. | journal=J Clin Endocrinol Metab | year= 1960 | volume= 20 | issue=  | pages= 1539-60 | pmid=13761950 | doi=10.1210/jcem-20-12-1539 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=13761950  }} </ref><ref name="pmid225638">{{cite journal| author=Crapo L| title=Cushing's syndrome: a review of diagnostic tests. | journal=Metabolism | year= 1979 | volume= 28 | issue= 9 | pages= 955-77 | pmid=225638 | doi=10.1016/0026-0495(79)90097-0 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=225638  }} </ref><ref name="pmid6316418">{{cite journal| author=Doppman JL, Oldfield E, Krudy AG, Chrousos GP, Schulte HM, Schaaf M | display-authors=etal| title=Petrosal sinus sampling for Cushing syndrome: anatomical and technical considerations. Work in progress. | journal=Radiology | year= 1984 | volume= 150 | issue= 1 | pages= 99-103 | pmid=6316418 | doi=10.1148/radiology.150.1.6316418 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=6316418  }} </ref><ref name="pmid8154641">{{cite journal| author=Hall WA, Luciano MG, Doppman JL, Patronas NJ, Oldfield EH| title=Pituitary magnetic resonance imaging in normal human volunteers: occult adenomas in the general population. | journal=Ann Intern Med | year= 1994 | volume= 120 | issue= 10 | pages= 817-20 | pmid=8154641 | doi=10.7326/0003-4819-120-10-199405150-00001 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8154641  }} </ref>
{{familytree/start |summary=PE diagnosis Algorithm.}}
{{familytree/start |summary=PE diagnosis Algorithm.}}
{{familytree | | | | A01 | | | A01= <div style="float: center; text-align: left;"> Symptoms suggestive of Cushing’s syndrome:
{{familytree | | | | A01 | | | A01= <div style="float: center; text-align: left;"> Symptoms suggestive of [[Cushing’s syndrome]]:
* Osteoporosis unusual for the age
* [[Osteoporosis]] unusual for the age
* Refractory hypertension
* Refractory [[hypertension]]
* Facial edema resulting in Moon-like face
* Facial [[edema]] resulting in Moon-like face
* Central obesity
* Central [[obesity]]
* Proximal muscle weakness
* Proximal muscle weakness
* Abdominal striae
* Abdominal [[striae]]
* Easy bruising
* Easy [[bruising]]
* Menstrual abnormalities: oligomenorrhea
* Menstrual abnormalities: [[oligomenorrhea]]
* Mood disorders, depression
* [[Mood disorder|Mood disorders]], [[depression]]
* Hirtuism }}
* [[Hirtuism]] }}
{{familytree | | | | |!| | | | }}
{{familytree | | | | |!| | | | }}
{{familytree | | | | B01 | | | B01= Take a detailed history of the patient including medication history. Rule out the use of any exogenous topical, oral, parenteral, or inhaled glucocorticoid and synthetic progesterone. }}
{{familytree | | | | B01 | | | B01= Take a detailed history of the patient including medication history. Rule out the use of any exogenous topical, oral, parenteral, or inhaled [[glucocorticoid]] and synthetic [[progesterone]]. }}
{{familytree | | | | |!| | | | }}
{{familytree | | | | |!| | | | }}
{{familytree | | | | C01 | | | C01= <div style="float: center; text-align: left;"> Perform any two of the following three laboratory investigations:
{{familytree | | | | C01 | | | C01= <div style="float: center; text-align: left;"> Perform any two of the following three laboratory investigations:
* Measure late-night levels of salivary cortisol (twice)
* Measure late-night levels of salivary [[cortisol]] (twice)
* Measure 24 hours urinary free cortisol (UFC) excretion (twice)
* Measure 24 hours urinary free [[cortisol]] (UFC) excretion (twice)
* Perform low-dose (1mg) overnight dexamethasone suppression test (DST)}}
* Perform low-dose (1mg) overnight [[dexamethasone suppression test]] (DST)}}
{{familytree | | | |,|-|^|-|-|.| }}
{{familytree | | | |,|-|^|-|-|.| }}
{{familytree | | | D01 | | |D02 | D01= <div style="float: center; text-align: left;"> Two of the following abnormal results:
{{familytree | | | D01 | | |D02 | D01= <div style="float: center; text-align: left;"> Two of the following abnormal results:
* Elevated levels of late-night salivary cortisol
* Elevated levels of late-night salivary [[cortisol]]
* 24 hours UFC threefold greater than the upper reference range.
* 24 hours UFC threefold greater than the upper reference range.
* Early morning (8 am) sample having serum cortisol 1.8 mcg/dL or higher after overnight DST| D02= Any one abnormal result }}
* Early morning (8 am) sample having serum cortisol 1.8 mcg/dL or higher after overnight DST| D02= Any one abnormal result }}
Line 59: Line 59:
{{familytree |!| | |!| | |!| | | |!| }}
{{familytree |!| | |!| | |!| | | |!| }}
{{familytree |!| | |!| | |!| | | |!| }}
{{familytree |!| | |!| | |!| | | |!| }}
{{familytree |J01|'| | |`|-|-|-|J02| J01= ACTH independent Cushing's syndrome| J02= ACTH dependent Cushing's syndrome }}
{{familytree |J01|'| | |`|-|-|-|J02| J01= ACTH independent [[Cushing's syndrome]] | J02= ACTH dependent [[Cushing's syndrome]] }}
{{familytree |!| | | | | | | | | |!| }}
{{familytree |!| | | | | | | | | |!| }}
{{familytree |K01| | | | | | | |K02| K01= CT scan/ MRI of adrenal glands to look for adrenal tumors or hyperplasia. | K02= <div style="float: center; text-align: left;"> Perform both tests:
{{familytree |K01| | | | | | | |K02| K01= CT scan/ MRI of [[Adrenal gland|adrenal glands]] to look for adrenal tumors or [[hyperplasia]]. | K02= <div style="float: center; text-align: left;"> Perform both tests:
* CRH or desmopressin stimulation test
* CRH or desmopressin stimulation test
* High dose (8mg) overnight DST }}
* High dose (8mg) overnight DST }}
{{familytree | | | | | | | |,|-|-|^|-|-|.| }}
{{familytree | | | | | | | |,|-|-|^|-|-|.| }}
{{familytree | | | | | | | |L01| | | |L02| L01= Adequate suppresion of early morning serum cortisol (with levels less than 5 mcg/dL) and stimulation with CRH | L02= Negative or equivocal response }}
{{familytree | | | | | | | |L01| | | |L02| L01= Adequate suppresion of early morning serum [[cortisol]] (with levels less than 5 mcg/dL) and stimulation with CRH | L02= Negative or equivocal response }}
{{familytree | | | | | | | |!| | | | | | |!| }}
{{familytree | | | | | | | |!| | | | | | |!| }}
{{familytree | | | | | | | |M01| | | | |!| M01= MRI of the pituitary }}  
{{familytree | | | | | | | |M01| | | | |!| M01= MRI of the [[Pituitary gland|pituitary]] }}  
{{familytree | | | | |,|-|-|^|-|.| | | | |!| }}
{{familytree | | | | |,|-|-|^|-|.| | | | |!| }}
{{familytree | | | | |N01| | |N02| | |!| | N01= Tumor >6mm | N02= Tumor <6mm or no mass lesion }}   
{{familytree | | | | |N01| | |N02| | |!| | N01= Tumor >6mm | N02= Tumor <6mm or no mass lesion }}   
{{familytree | | | | |!| | | | |!| | | | |!| | }}
{{familytree | | | | |!| | | | |!| | | | |!| | }}
{{familytree | | | | |O01| | |`|-|-|-|-|O02| O01= Cushing's disease | O02= Perform  Inferior petrosal sinus sampling. }}
{{familytree | | | | |O01| | |`|-|-|-|-|O02| O01= [[Cushing's disease]] | O02= Perform  [[Inferior petrosal sinus]] sampling. }}
{{familytree | | | | |!| | | | | | |,|-|-|^|-|.| | }}
{{familytree | | | | |!| | | | | | |,|-|-|^|-|.| | }}
{{familytree | | | | |!| | | | | | |!| | | | |!| | }}
{{familytree | | | | |!| | | | | | |!| | | | |!| | }}
Line 80: Line 80:


==Treatment==
==Treatment==
Shown below is an algorithm summarizing the treatment of [[Cushing's syndrome]] according the the Endocrine Society clinical practice guidelines.
Shown below is an algorithm summarizing the treatment of [[Cushing's syndrome]] according the the Endocrine Society clinical practice guidelines.<ref name="pmid26222757">{{cite journal| author=Nieman LK, Biller BM, Findling JW, Murad MH, Newell-Price J, Savage MO | display-authors=etal| title=Treatment of Cushing's Syndrome: An Endocrine Society Clinical Practice Guideline. | journal=J Clin Endocrinol Metab | year= 2015 | volume= 100 | issue= 8 | pages= 2807-31 | pmid=26222757 | doi=10.1210/jc.2015-1818 | pmc=4525003 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=26222757  }} </ref><ref name="pmid17970770">{{cite journal| author=Chow JT, Thompson GB, Grant CS, Farley DR, Richards ML, Young WF| title=Bilateral laparoscopic adrenalectomy for corticotrophin-dependent Cushing's syndrome: a review of the Mayo Clinic experience. | journal=Clin Endocrinol (Oxf) | year= 2008 | volume= 68 | issue= 4 | pages= 513-9 | pmid=17970770 | doi=10.1111/j.1365-2265.2007.03082.x | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17970770  }} </ref><ref name="pmid11572035">{{cite journal| author=Aniszewski JP, Young WF, Thompson GB, Grant CS, van Heerden JA| title=Cushing syndrome due to ectopic adrenocorticotropic hormone secretion. | journal=World J Surg | year= 2001 | volume= 25 | issue= 7 | pages= 934-40 | pmid=11572035 | doi=10.1007/s00268-001-0032-5 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11572035  }} </ref>
{{familytree/start |summary=PE diagnosis Algorithm.}}
{{familytree/start}}
{{familytree | | | | | | | | A01 |A01= The treatment depends upon the underlying etiology }}  
{{familytree | | | | | | | | | A01 | | | | | |A01= The treatment depends upon the underlying etiology }}
{{familytree | | |,|-|-|-|-|-|+|-|-|-|-|-|-|-|-|.| }}
{{familytree | | |,|-|-|-|-|-|-|+|-|-|-|-|-|-|-|-|.| }}
{{familytree | |B01| | | |B02| | | | | | |B03| |B01= [[Cushing's disease]] |B02= Paraneoplastic [[Cushing's syndrome]] |B03= ACTH-independent [[Cushing's syndrome]] }}
{{familytree | | B01 | | | | | B02 | | | | | | | B03 |B01= [[Cushing's disease]] |B02= Paraneoplastic [[Cushing's syndrome]] |B03= ACTH-independent [[Cushing's syndrome]] }}
{{familytree | |!| | | |,|-|^|-|-|.| | | | |,|-|^|-|.| }}
{{familytree | |!| | | | |,|-|^|-|-|.| | | |,|-|^|-|-|.| }}
{{familytree | |C01| |C02| | |C03| | |C04| |C05| C01= Transsphenoidal surgery: Treatment of choice in patients with [[pituitary]] adenoma with distinct margins. | C02= Resectable tumor | C03= Nonresectable tumor | C04= Adrenal adenomas | C05= Bilateral adrenal hyperplasia }}
{{familytree | |C01| | |C02| | |C03| |C04| | |C05| | C01= Transsphenoidal surgery: Treatment of choice in patients with [[pituitary]] [[adenoma]] with distinct margins. | C02= Resectable [[tumor]] | C03= Nonresectable [[tumor]] | C04= Adrenal [[adenoma]] | C05= Bilateral adrenal [[hyperplasia]] }}
{{familytree | |,|-|^|.| | |!| | |!| | |!| | | }}
{{familytree | |!| | | | |!| | | | |!| | | |!| | | | |!| }}
{{familytree |D01| | |D02| |D03| |D04| |D05| |D01= Pituitary irradiation carried out in patients with:  
{{familytree |D01| | | |D02| | |D03| |D04| | |D05| D01= <div style="float: left; text-align: left;">  [[Pituitary]] irradiation carried out in patients with:  
* Failure to resect tumor completely by surgery.
* Failure to resect [[tumor]] completely by surgery.
* The location of the tumor cannot be determined.
* The location of the [[tumor]] cannot be determined.
* The patient wishes to conceive in the future. | D02= Bilateral adrenalectomy is carried out in patients with severe refractory hypercortisolism. | D03= Resection of the primary tumor | D04= Medical therapy:   
* The patient wishes to conceive in the future. | D02= Resection of the primary [[tumor]] | D03= <div style="float: left; text-align: left;">  Medical therapy:   
* Inhibit the synthesis of adrenocortical enzymes: ketoconazole, metyrapone, and etomidate.  
* Inhibit the synthesis of adrenocortical enzymes: [[ketoconazole]], [[metyrapone]], and [[etomidate]].  
* Inhibits the secretion of ACTH from the ectopic site: Octreotide
* Inhibits the secretion of ACTH from the ectopic site: [[Octreotide]]
* Inhibits hyperglycemia secondary to hypercortisolism: Mifepristone | D04= Unilateral adrenalectomy | D05= Bilateral adrenalectomy }}        
* Inhibits hyperglycemia secondary to hypercortisolism: [[Mifepristone]] | D04= Unilateral [[adrenalectomy]] | D05= Bilateral [[adrenalectomy]] }}
{{familytree/end}
{{familytree | |!| | | | | | | | | | | | | | }}
{{familytree |E01| | | | | | | | | | | | | | E01= Bilateral [[adrenalectomy]] is performed in patients with severe refractory hypercortisolism despite surgical and radiation therapy. }}
{{familytree/end}}


==Do's==
==Do's==
* The content in this section is in bullet points.
* In ACTH-independent [[Cushing's syndrome|Cushing’s syndrome]], [[glucocorticoid]] therapy should be given to patients post-operatively due to suppression of the hypothalamic-pituitary axis. Patients with medication-induced [[Cushing's syndrome|Cushing’s syndrome]] should taper the dose of [[glucocorticoid]] instead of sudden withdrawal of the medications.
* Thromboprophylaxis should be initiated preoperatively in patients with [[Cushing's syndrome|Cushing’s syndrome]]<ref name="pmid26222757">{{cite journal| author=Nieman LK, Biller BM, Findling JW, Murad MH, Newell-Price J, Savage MO | display-authors=etal| title=Treatment of Cushing's Syndrome: An Endocrine Society Clinical Practice Guideline. | journal=J Clin Endocrinol Metab | year= 2015 | volume= 100 | issue= 8 | pages= 2807-31 | pmid=26222757 | doi=10.1210/jc.2015-1818 | pmc=4525003 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=26222757  }} </ref>. There is a hypercoagulable state in patients with [[Cushing's syndrome|Cushing’s syndrome]] due to impaired fibrinolysis and activation of the [[Coagulation|coagulation cascade]]. These patients have an increased risk of developing [[Deep vein thrombosis|deep venous thrombosis]] compared to the normal [[patient]] population<ref name="pmid19454584">{{cite journal| author=Van Zaane B, Nur E, Squizzato A, Dekkers OM, Twickler MT, Fliers E | display-authors=etal| title=Hypercoagulable state in Cushing's syndrome: a systematic review. | journal=J Clin Endocrinol Metab | year= 2009 | volume= 94 | issue= 8 | pages= 2743-50 | pmid=19454584 | doi=10.1210/jc.2009-0290 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19454584  }} </ref>.
* Rebound thymic [[hyperplasia]] can occur in [[Patient|patients]] whose [[Cushing's syndrome|hypercortisolism]] is controlled.  On the [[chest]] imaging, it is seen as a mass in the anterior [[mediastinum]] and can be misinterpreted as [[tumor]] recurrence, or [[metastasis]]<ref name="pmid7704966">{{cite journal| author=Tabarin A, Catargi B, Chanson P, Hieronimus S, Corcuff JB, Laurent F | display-authors=etal| title=Pseudo-tumours of the thymus after correction of hypercortisolism in patients with ectopic ACTH syndrome: a report of five cases. | journal=Clin Endocrinol (Oxf) | year= 1995 | volume= 42 | issue= 2 | pages= 207-13 | pmid=7704966 | doi=10.1111/j.1365-2265.1995.tb01865.x | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=7704966  }} </ref>.


==Don'ts==
==Don'ts==
* The content in this section is in bullet points.
* The 24 hours urinary free [[cortisol]] measurement should not be used for diagnosis in subclinical [[Cushing's syndrome|hypercortisolism]] (mild [[Cushing's syndrome|hypercortisolism]] in adrenal [[incidentaloma]]) as it can yield false-negative results<ref name="pmid18334580">{{cite journal| author=Nieman LK, Biller BM, Findling JW, Newell-Price J, Savage MO, Stewart PM | display-authors=etal| title=The diagnosis of Cushing's syndrome: an Endocrine Society Clinical Practice Guideline. | journal=J Clin Endocrinol Metab | year= 2008 | volume= 93 | issue= 5 | pages= 1526-40 | pmid=18334580 | doi=10.1210/jc.2008-0125 | pmc=2386281 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18334580  }} </ref>. False-positive results are present in patients with physiological [[Cushing's syndrome|hypercortisolism]] (patients with a [[Polycystic ovary syndrome|polycystic ovarian syndrome]] or [[Clinical depression|major depressive disorder]])<ref name="pmid8855803">{{cite journal| author=Cizza G, Nieman LK, Doppman JL, Passaro MD, Czerwiec FS, Chrousos GP | display-authors=etal| title=Factitious Cushing syndrome. | journal=J Clin Endocrinol Metab | year= 1996 | volume= 81 | issue= 10 | pages= 3573-7 | pmid=8855803 | doi=10.1210/jcem.81.10.8855803 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8855803  }} </ref><ref name="pmid935296">{{cite journal| author=Carroll BJ, Curtis GC, Davies BM, Mendels J, Sugerman AA| title=Urinary free cortisol excretion in depression. | journal=Psychol Med | year= 1976 | volume= 6 | issue= 1 | pages= 43-50 | pmid=935296 | doi=10.1017/s0033291700007480 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=935296  }} </ref>. High fluid intake can result in an increased fraction of excretion of free [[cortisol]] yielding false-positive results.<ref name="pmid9467592">{{cite journal| author=Mericq MV, Cutler GB| title=High fluid intake increases urine free cortisol excretion in normal subjects. | journal=J Clin Endocrinol Metab | year= 1998 | volume= 83 | issue= 2 | pages= 682-4 | pmid=9467592 | doi=10.1210/jcem.83.2.4555 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9467592  }} </ref>
* MRI is not a cost-effective diagnostic test. CT scan of the [[abdomen]] and [[Adrenal gland|adrenal glands]] is preferred as an imaging test to localize adrenal [[adenoma]] or [[carcinoma]] compared to MRI. On the Ct scan adrenal carcinoma has a bigger size along with hemorrhage, necrosis and calcification in the lesion<ref name="pmid16371582">{{cite journal| author=Blake MA, Kalra MK, Sweeney AT, Lucey BC, Maher MM, Sahani DV | display-authors=etal| title=Distinguishing benign from malignant adrenal masses: multi-detector row CT protocol with 10-minute delay. | journal=Radiology | year= 2006 | volume= 238 | issue= 2 | pages= 578-85 | pmid=16371582 | doi=10.1148/radiol.2382041514 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16371582  }} </ref>.


==References==
==References==

Latest revision as of 13:30, 20 August 2020

Resident Survival Guide
Introduction
Team
Guide
Page Template
Examine the Patient Template
Navigation Bar Template
Checklist
Topics

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Mydah Sajid, MD[2]

Overview

Cushing’s syndrome is characterized by elevated circulating levels of glucocorticoid (i.e. cortisol) in blood. It presents with a wide range of clinical spectrum ranging from mild to severe. The clinical symptoms are characterized by central obesity, facial edema, buffalo hump, proximal myopathy, hypertension, hyperglycemia, mood changes, skin thinning, abdominal striae, and easy bruising. The physician should aim to diagnose the cause of Cushing’s syndrome and treat it accordingly. This section provides a short and straight to the point overview of the Cushing's syndrome.

Causes

Life Threatening Causes

Life-threatening causes include conditions that may result in death or permanent disability within 24 hours if left untreated.

  • Does not include any known cause.

Common Causes

Diagnosis

Shown below is an algorithm summarizing the diagnosis of Cushing's syndrome according to the Endocrine Society clinical guidelines.[6][7][8][9][10][11][12][13]

 
 
 
Symptoms suggestive of Cushing’s syndrome:
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Take a detailed history of the patient including medication history. Rule out the use of any exogenous topical, oral, parenteral, or inhaled glucocorticoid and synthetic progesterone.
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Perform any two of the following three laboratory investigations:
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Two of the following abnormal results:
  • Elevated levels of late-night salivary cortisol
  • 24 hours UFC threefold greater than the upper reference range.
  • Early morning (8 am) sample having serum cortisol 1.8 mcg/dL or higher after overnight DST
 
 
Any one abnormal result
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
High suspicion for Cushing's syndrome
 
 
Low suspicion for Cushing's syndrome
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Measure late night plasma ACTH levels
 
 
Refer to endocrinologist
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Low value plasma ACTH <5 pg/mL
 
Indeterminate values of plasma ACTH between 5 to 20 pg/mL
 
High value plasma ACTH >20 pg/mL
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
CRH or desmopressin stimulation test
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
No ACTH response
 
+ ACTH response
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
ACTH independent Cushing's syndrome
 
 
 
 
 
 
 
 
 
ACTH dependent Cushing's syndrome
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
CT scan/ MRI of adrenal glands to look for adrenal tumors or hyperplasia.
 
 
 
 
 
 
 
Perform both tests:
  • CRH or desmopressin stimulation test
  • High dose (8mg) overnight DST
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Adequate suppresion of early morning serum cortisol (with levels less than 5 mcg/dL) and stimulation with CRH
 
 
 
Negative or equivocal response
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
MRI of the pituitary
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Tumor >6mm
 
 
Tumor <6mm or no mass lesion
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Cushing's disease
 
 
 
 
 
 
 
 
Perform Inferior petrosal sinus sampling.
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Central step-up
 
 
 
No Central step-up
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Ectopic ACTH production

Treatment

Shown below is an algorithm summarizing the treatment of Cushing's syndrome according the the Endocrine Society clinical practice guidelines.[14][15][16]

 
 
 
 
 
 
 
 
The treatment depends upon the underlying etiology
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Cushing's disease
 
 
 
 
Paraneoplastic Cushing's syndrome
 
 
 
 
 
 
ACTH-independent Cushing's syndrome
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Transsphenoidal surgery: Treatment of choice in patients with pituitary adenoma with distinct margins.
 
 
Resectable tumor
 
 
Nonresectable tumor
 
Adrenal adenoma
 
 
Bilateral adrenal hyperplasia
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Pituitary irradiation carried out in patients with:
  • Failure to resect tumor completely by surgery.
  • The location of the tumor cannot be determined.
  • The patient wishes to conceive in the future.
 
 
 
Resection of the primary tumor
 
 
Medical therapy:
  • Inhibit the synthesis of adrenocortical enzymes: ketoconazole, metyrapone, and etomidate.
  • Inhibits the secretion of ACTH from the ectopic site: Octreotide
  • Inhibits hyperglycemia secondary to hypercortisolism: Mifepristone
  •  
    Unilateral adrenalectomy
     
     
    Bilateral adrenalectomy
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
    Bilateral adrenalectomy is performed in patients with severe refractory hypercortisolism despite surgical and radiation therapy.
     
     
     
     
     
     
     
     
     
     
     
     
     

    Do's

    Don'ts

    References

    1. White A, Ray DW, Talbot A, Abraham P, Thody AJ, Bevan JS (2000). "Cushing's syndrome due to phaeochromocytoma secreting the precursors of adrenocorticotropin". J Clin Endocrinol Metab. 85 (12): 4771–5. doi:10.1210/jcem.85.12.7047. PMID 11134141.
    2. More J, Young J, Reznik Y, Raverot G, Borson-Chazot F, Rohmer V; et al. (2011). "Ectopic ACTH syndrome in children and adolescents". J Clin Endocrinol Metab. 96 (5): 1213–22. doi:10.1210/jc.2010-2276. PMID 21346064.
    3. Ilias I, Torpy DJ, Pacak K, Mullen N, Wesley RA, Nieman LK (2005). "Cushing's syndrome due to ectopic corticotropin secretion: twenty years' experience at the National Institutes of Health". J Clin Endocrinol Metab. 90 (8): 4955–62. doi:10.1210/jc.2004-2527. PMID 15914534.
    4. Larsen JL, Cathey WJ, Odell WD (1986). "Primary adrenocortical nodular dysplasia, a distinct subtype of Cushing's syndrome. Case report and review of the literature". Am J Med. 80 (5): 976–84. doi:10.1016/0002-9343(86)90648-0. PMID 3010718.
    5. Lacroix A, Ndiaye N, Tremblay J, Hamet P (2001). "Ectopic and abnormal hormone receptors in adrenal Cushing's syndrome". Endocr Rev. 22 (1): 75–110. doi:10.1210/edrv.22.1.0420. PMID 11159817.
    6. 6.0 6.1 Nieman LK, Biller BM, Findling JW, Newell-Price J, Savage MO, Stewart PM; et al. (2008). "The diagnosis of Cushing's syndrome: an Endocrine Society Clinical Practice Guideline". J Clin Endocrinol Metab. 93 (5): 1526–40. doi:10.1210/jc.2008-0125. PMC 2386281. PMID 18334580.
    7. Lacroix A, Feelders RA, Stratakis CA, Nieman LK (2015). "Cushing's syndrome". Lancet. 386 (9996): 913–27. doi:10.1016/S0140-6736(14)61375-1. PMID 26004339.
    8. Weber SL (1997). "Cushing'S syndrome attributable to topical use of lotrisone". Endocr Pract. 3 (3): 140–4. doi:10.4158/EP.3.3.140. PMID 15251475.
    9. Arnaldi G, Angeli A, Atkinson AB, Bertagna X, Cavagnini F, Chrousos GP; et al. (2003). "Diagnosis and complications of Cushing's syndrome: a consensus statement". J Clin Endocrinol Metab. 88 (12): 5593–602. doi:10.1210/jc.2003-030871. PMID 14671138.
    10. LIDDLE GW (1960). "Tests of pituitary-adrenal suppressibility in the diagnosis of Cushing's syndrome". J Clin Endocrinol Metab. 20: 1539–60. doi:10.1210/jcem-20-12-1539. PMID 13761950.
    11. Crapo L (1979). "Cushing's syndrome: a review of diagnostic tests". Metabolism. 28 (9): 955–77. doi:10.1016/0026-0495(79)90097-0. PMID 225638.
    12. Doppman JL, Oldfield E, Krudy AG, Chrousos GP, Schulte HM, Schaaf M; et al. (1984). "Petrosal sinus sampling for Cushing syndrome: anatomical and technical considerations. Work in progress". Radiology. 150 (1): 99–103. doi:10.1148/radiology.150.1.6316418. PMID 6316418.
    13. Hall WA, Luciano MG, Doppman JL, Patronas NJ, Oldfield EH (1994). "Pituitary magnetic resonance imaging in normal human volunteers: occult adenomas in the general population". Ann Intern Med. 120 (10): 817–20. doi:10.7326/0003-4819-120-10-199405150-00001. PMID 8154641.
    14. 14.0 14.1 Nieman LK, Biller BM, Findling JW, Murad MH, Newell-Price J, Savage MO; et al. (2015). "Treatment of Cushing's Syndrome: An Endocrine Society Clinical Practice Guideline". J Clin Endocrinol Metab. 100 (8): 2807–31. doi:10.1210/jc.2015-1818. PMC 4525003. PMID 26222757.
    15. Chow JT, Thompson GB, Grant CS, Farley DR, Richards ML, Young WF (2008). "Bilateral laparoscopic adrenalectomy for corticotrophin-dependent Cushing's syndrome: a review of the Mayo Clinic experience". Clin Endocrinol (Oxf). 68 (4): 513–9. doi:10.1111/j.1365-2265.2007.03082.x. PMID 17970770.
    16. Aniszewski JP, Young WF, Thompson GB, Grant CS, van Heerden JA (2001). "Cushing syndrome due to ectopic adrenocorticotropic hormone secretion". World J Surg. 25 (7): 934–40. doi:10.1007/s00268-001-0032-5. PMID 11572035.
    17. Van Zaane B, Nur E, Squizzato A, Dekkers OM, Twickler MT, Fliers E; et al. (2009). "Hypercoagulable state in Cushing's syndrome: a systematic review". J Clin Endocrinol Metab. 94 (8): 2743–50. doi:10.1210/jc.2009-0290. PMID 19454584.
    18. Tabarin A, Catargi B, Chanson P, Hieronimus S, Corcuff JB, Laurent F; et al. (1995). "Pseudo-tumours of the thymus after correction of hypercortisolism in patients with ectopic ACTH syndrome: a report of five cases". Clin Endocrinol (Oxf). 42 (2): 207–13. doi:10.1111/j.1365-2265.1995.tb01865.x. PMID 7704966.
    19. Cizza G, Nieman LK, Doppman JL, Passaro MD, Czerwiec FS, Chrousos GP; et al. (1996). "Factitious Cushing syndrome". J Clin Endocrinol Metab. 81 (10): 3573–7. doi:10.1210/jcem.81.10.8855803. PMID 8855803.
    20. Carroll BJ, Curtis GC, Davies BM, Mendels J, Sugerman AA (1976). "Urinary free cortisol excretion in depression". Psychol Med. 6 (1): 43–50. doi:10.1017/s0033291700007480. PMID 935296.
    21. Mericq MV, Cutler GB (1998). "High fluid intake increases urine free cortisol excretion in normal subjects". J Clin Endocrinol Metab. 83 (2): 682–4. doi:10.1210/jcem.83.2.4555. PMID 9467592.
    22. Blake MA, Kalra MK, Sweeney AT, Lucey BC, Maher MM, Sahani DV; et al. (2006). "Distinguishing benign from malignant adrenal masses: multi-detector row CT protocol with 10-minute delay". Radiology. 238 (2): 578–85. doi:10.1148/radiol.2382041514. PMID 16371582.


    Template:WikiDoc Sources