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| | {{Infobox_Disease | |
| | Name = {{PAGENAME}} | |
| | Image = Kone_med_stor_struma.jpg | |
| | Caption = A woman with a goiter. | |
| | DiseasesDB = 5332 | |
| | ICD10 = {{ICD10|E|01|0|e|00}}-{{ICD10|E|01|2|e|00}} | |
| | ICD9 = {{ICD9|240.9}} | |
| | ICDO = | |
| | OMIM = | |
| | MedlinePlus = 001178 | |
| | eMedicineSubj = | |
| | eMedicineTopic = | |
| | MeshID = Goiter | |
| | }} |
| {{SI}} | | {{SI}} |
| {{CMG}} | | {{CMG}} |
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| ==Overview== | | ==Overview== |
| | '''Goiter''' is defined as an enlargement of the [[thyroid gland]]. |
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| '''Cushing's disease''' (also known as '''Cushing disease''', '''tertiary or secondary hypercortisolism''', '''tertiary or secondary hypercorticism''', '''Itsenko-Cushing disease''')<ref>[http://www.whonamedit.com/doctor.cfm/1520.html "Whonamedit - Nikolai Mikhailovich Itsenko"]. "Nikolai Mikhailovich Itsenko investigated neural infections, vegetative nervous system diseases and cerebral tumors. In 1926 he was the first one who described Itsenko-Cushing's disease, six years before Cushing."</ref><ref name="gozhenko">{{cite book|author=A.I. Gozhenko, I.P. Gurkalova, W. Zukow, Z. Kwasnik, B. Mroczkowska |title =Pathology: Medical Student's Library|chapter =Trematoda|publisher =Radomska Szkola Wyžsza uk. Zubrzyckiego|year =2009|page=280|isbn =978-83-61047-18-6|url =http://books.google.com.ph/books?id=Pvk0MoLNjgYC&lpg=PA280&dq=Itsenko-Cushing's%20disease%20and%20Itsenko-Cushing's%20syndrome%5C&pg=PA280#v=onepage&q=Itsenko-Cushing's%20disease%20and%20Itsenko-Cushing's%20syndrome%5C&f=false}}</ref> is a cause of [[Cushing's syndrome]] characterised by increased secretion of [[adrenocorticotropic hormone]] (ACTH) from the [[anterior pituitary]] ('''secondary''' [[hypercortisolism]]). This is most often as a result of a pituitary [[adenoma]] (specifically pituitary basophilism) or due to excess production of hypothalamus CRH ([[Corticotropin releasing hormone]]) ('''tertiary''' hypercortisolism/hypercorticism) that stimulates the synthesis of cortisol by the adrenal glands. Pituitary adenomas are responsible for 80% of endogenous Cushing's syndrome,<ref name="cushing's" /> when excluding Cushing's syndrome from exogenously administered [[corticosteroid]]s.
| | ==Etymology== |
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| This should not be confused with [[Cushing's syndrome#Pathophysiology|ectopic Cushing syndrome]] or exogenous steroid use.<ref>http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0001443/</ref>
| | A '''goitre''' (BrE), or '''goiter''' (AmE) ([[Latin]] ''struma''), also called a '''bronchocele''', is a swelling in the neck (just below [[Adam's apple]] or [[larynx]]) due to an enlarged [[thyroid|thyroid gland]]. |
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| == Signs and symptoms == | | ==Classification== |
| | They are classified in different ways: |
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| The symptoms of Cushing's disease are similar to those seen in other causes of [[Cushing's syndrome]].<ref>{{cite web|title=Cushing's Syndrome Information Page|url=http://www.ninds.nih.gov/disorders/cushings/cushings.htm|accessdate=August 26, 2013}}</ref>
| | * A "diffuse goitre" is a goitre that has spread through all of the thyroid (and can be a "simple goitre", or a "multinodular goitre"). |
| Patients with Cushing's disease usually present with one or more signs and symptoms secondary to the presence of excess [[cortisol]] or [[ACTH]].<ref>{{cite journal|last=Kirk|first=Lawrence F., Jr |author2=Robert B. Hash |author3=Harold P. Katner |author4=Tom Jones |title=Cushing's Disease: Clinical Manifestations and Diagnostic Evaluation |journal=American Family Physician |date=September 2000|volume=62|page=1119; 1127|url=http://www.aafp.org/afp/2000/0901/p1119.html|accessdate=2013-08-26}}</ref>
| | * "Toxic goitre" refers to goitre with [[hyperthyroidism]]. These most commonly due to [[Graves disease]], but can be caused by [[inflammation]] or a multinodular goitre. |
| Although uncommon, some patients with Cushing's disease have large pituitary tumors (macroadenomas). In addition to the severe hormonal effects related to increase blood cortisol levels, the large tumor can compress adjacent structures. {{citation needed|date=April 2013}} These tumors can compress the nerves that carry information from the eyes, causing a decrease in peripheral vision.{{citation needed|date=April 2013}} Glaucoma and cataracts also may occur in Cushing's syndrome. In children, the two main symptoms are obesity and decreased linear growth.<ref name="newell-price" />
| | * "Nontoxic goitre" (associated with normal or low thyroid levels) refers to all other types (such as that caused by [[lithium]] or certain other [[autoimmune]] diseases). |
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| The clinical diagnosis must be based on the presence of one or more of the symptoms listed below, because the syndrome itself has no true pathognomonic signs or symptoms.{{citation needed|date=April 2013}} The most common symptoms seen in male patients are [[stretch marks|purple striae]], [[muscle atrophy]], [[osteoporosis]], and [[kidney stone]]s.<ref name="newell-price" />
| | == Epidemiology and Demographics == |
| | * Sporadic form more common in women: 8:1 (female:male) |
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| ===Common symptoms=== | | == Causes == |
| Symptoms include:
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| * weight gain
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| * high blood pressure <ref name="symptoms">{{cite journal|last=Wilson|first=P.J. |author2=Williams, J.R. |author3=Smee, R.I.|title=Cushing's disease: A single centre's experience using the linear accelerator (LINAC) for stereotactic radiosurgery and fractionated stereotactic radiotherapy|journal=Journal of Clinical Neuroscience|year=2014|volume=21|issue=1|pages=100–106|pmid=24074805|url=http://www.ncbi.nlm.nih.gov/pubmed/24074805|doi=10.1016/j.jocn.2013.04.007}}</ref>
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| * poor short-term memory
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| * irritability
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| * excess hair growth (women)<ref name="cushing's" />
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| * Impaired immunological function <ref name="symptoms" />
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| * red, ruddy face {{ns|35}}
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| * extra fat around neck
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| * [[moon face]]
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| * fatigue
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| * red stretch marks
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| * poor concentration
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| * irregular menstruation.<ref name="newell-price">{{cite journal|last=Newell-Price|first=J.|author2=Bertagna, X. |author3=Grossman, A.B. |author4= Nieman, L.K. |title=Cushing's syndrome|journal=The Lancet|year=2006|volume=367|issue=9522|pages=1605–1617|doi=10.1016/S0140-6736(08)61345-8|url=http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(06)68699-6/abstract|accessdate=30 January 2014}}</ref>
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| |}
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| ===Less common symptoms===
| | Other causes are: |
| The less-common symptoms include:
| | * [[Hashimoto's thyroiditis]] (E06.3) |
| * [[insomnia]] | | * [[Graves-Basedow disease]] (E05.0) |
| * recurrent infection | | * [[inborn errors]] of thyroid hormone synthesis, causing [[congenital hypothyroidism]] (E03.0) |
| * thin skin and stretch marks <ref name="symptoms" /> | | * [[Thyroiditis]] (acute, chronic) (E06) |
| * easy bruising
| | * [[Adverse drug reaction|Side-effects]] of pharmacological therapy (E03.2) |
| * weak bones {{ns|39}}
| | * [[Thyroid cancer]] |
| * [[acne]] | |
| * balding (women)
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| * depression | |
| * hip and shoulder weakness
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| * swelling of feet/legs
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| * [[diabetes mellitus]].<ref name="symptoms"/> | |
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| ==History== | | == Occurrence == |
| In 1924, the Soviet neurologist Nikolai Mikhailovich Itsenko reported two patients with [[pituitary adenoma]]. The resulting excessive adrenocorticotropic hormone secretion led to the production of large amounts of [[cortisol]] by the [[adrenal glands]]. The disease associated with this increased secretion of cortisol was described by [[Harvey Cushing]] in 1932, after Cushing was presented with a unique case of the disease<ref>{{cite book|last=Laws Jr., E.R., Ezzat, S., Asa, S.L., Rio, L.M., Michel, L. & Knutzen, R.|title=Pituitary Disorders: Diagnosis and Management|year=2013|publisher=Wiley-blackwell|location=United Kingdom|isbn=978-0-470-67201-3|page=xiv}}</ref> In 1910, the American neurosurgeon [[Harvey Cushing]] (1869-1939) was presented with a case of a 23-year-old woman called Minnie G.. Minnie’s symptoms included painful [[obesity]], [[amenorrhea]], [[hypertrichosis]] (abnormal hair growth), underdevelopment of secondary sexual characteristics, [[hydrocephalus]] and cerebral tension.<ref name="cushing's">{{cite journal|last=Lanzino|first=Giuseppe|author2=Maartens, Niki F. |author3=Laws, Edward R. |title=Cushing's case XLV: Minnie G.|journal=Journal of Neurosurgery|year=2002|volume=97|issue=1|pages=231–234|accessdate=January 30, 2014|pmid=12134925|doi=10.3171/jns.2002.97.1.0231}}</ref> This combination of symptoms was not yet described by any medical disorder at the time.<ref name="cushing's" /> However, Cushing was confident that Minnie’s symptoms were due to dysfunction of the pituitary gland, and resembled those associated with an [[adrenal tumor]]. Given this conviction, and his knowledge of the three [[anterior pituitary]] cell types, Cushing hypothesized that if acidophil [[hyperpituitarism]] (excess secretion from the acidophil cells) caused [[acromegaly]], then an excess of [[basophil cell]]s must be involved in another pituitary disorder that involves sexual dysfunction ([[amenorrhea]] in females and [[erectile dysfunction]] in males) and could explain Minnie's symptoms.<ref name="cushing's" /> Experimental evidence and case reports by Cushing led to his publication in 1932 on pituitary basophilism as the cause of Cushing's disease. In this publication, the clinical symptoms of the disease, named after [[Harvey Cushing]], were described.<ref>{{cite journal|first=Harvey|last=Cushing|title=The basophil adenomas of the pituitary body and their clinical manifestations (pituitary basophilism)|journal=[[Bulletin of the Johns Hopkins Hospital]]|volume=50|pages=137–95|year=1932|pmc=2387613|pmid=19310569|issue=4}}</ref><ref>{{cite news|title=Dr. Cushing Dead; Brain Surgeon, 70. A Pioneer Who Won Fame as Founder of New School of Neuro-Surgery. Discovered Malady Affecting Pituitary dre. Was Noted Teacher and Author|url=http://select.nytimes.com/gst/abstract.html?res=F30915F73C5A177A93CAA9178BD95F4D8385F9|work=[[New York Times]]|date=8 October 1939|accessdate=2010-03-21}}</ref> Out of the 12 cases with [[hypercortisolism]] described in Cushing’s monograph on the pituitary body, 67% died within a few years after symptom presentation, whereas Minnie G. survived for more than 40 years after symptom presentation, despite the fact that she did not receive any treatments for a pituitary tumor.<ref name="cushing's" /> The prolonged survival led to the uniqueness of Minnie's case. The reason behind this survival remains a mystery, since an [[autopsy]] of Minnie was refused after her death.<ref name="cushing's" /> However, the most likely explanation, proposed by J. Aidan Carney and based on statistical evidence, was that the [[basophil]] [[adenoma]] Minnie might have harbored underwent partial [[infarction]], leading to symptom regression.<ref name="cushing's" /> The other hypothesis was that Minnie might have suffered from Primary Pigmented Nodular Adrenocortical Disease (PPNAD), which when associated with Cushing's syndrome ([[Carney complex]]) can infrequently cause spontaneous symptom regression of the latter.<ref name="cushing's" />
| | Iodine is necessary for the synthesis of the thyroid [[hormone]]s [[triiodothyronine]] and [[thyroxine]] (T3 and T4). In conditions producing endemic goitre, when iodine is not available, these hormones cannot be made. In response to low thyroid hormones, the [[pituitary gland]] releases [[thyroid stimulating hormone]] (TSH). Thyroid stimulating hormone acts to increase synthesis of T3 and T4, but it also causes the thyroid gland to grow in size by increasing cell division. |
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| == Diagnosis ==
| | Goitre is more common among women, but this includes the many types of goitre caused by autoimmune problems, and not only those caused by simple lack of iodine. |
| Diagnosis is made first by diagnosing Cushing's Syndrome, which can be difficult to do clinically since the most characteristic symptoms only occur in a minority of patients.<ref name="nieman">{{cite journal|last=Nieman|first=L.K.|author2=Ilias, I.|title=Evaluation and treatment of Cushing’s syndrome|journal=The American Journal of Medicine|year=2005|volume=118|issue=12|pages=1340–1346|doi=10.1016/j.amjmed.2005.01.059|url=http://www.amjmed.com/article/S0002-9343(05)00160-9/abstract|accessdate=30 January 2014|pmid=16378774}}</ref> Some of the biochemical diagnostic tests used include [[saliva testing|salivary]] and blood serum cortisol testing, 24-hour urinary free cortisol (UFC) testing, the [[dexamethasone suppression test]] (DST), and bilateral [[inferior petrosal sinus sampling]] (BIPSS). No single test is perfect and multiple tests should always be used to achieve a proper diagnosis.<ref name="newell-price" /> Diagnosing Cushing's disease is a multidisciplinary process involving doctors, endocrinologists, radiologists, surgeons, and chemical pathologists.<ref name="newell-price" />
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| Once Cushing's syndrome has been diagnosed, the first step towards finding the cause is measuring plasma corticotropin concentrations. A concentration consistently below 1.1 pmol/L is classified as corticotropin-independent and does not lead to a diagnosis of Cushing's disease. In such cases, the next step is adrenal imaging with X-ray computed tomography|CT. If plasma corticotropin concentrations are consistently above 3.3 pmol/L, then corticotropin-dependent Cushing's syndrome is most likely. Any intermediate values need to be cautiously interpreted and a corticotropin-releasing hormone (CRH) test is advised in order to confirm corticotropin dependency. If corticotropin-dependent Cushing's syndrome is determined then the next step is to distinguish between Cushing's disease and ectopic corticotropin syndrome. This is done via a combination of techniques including CRH, high-dose DST, BIPSS, and pituitary [[Magnetic resonance imaging|MRI]].
| | ==Diagnosis== |
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| Two dexamethasone suppression tests (DSTs) are generally used, the overnight and 48-h DSTs.<ref name="newell-price" /> For both tests, a plasma cortisol level above 50 nmol/L is indicative of Cushing's disease.<ref name="newell-price" /> However, 3-8% of patients with Cushing's disease will test negative due to a retention of dexamethasone suppression abilities.<ref name="newell-price" /> For non-Cushing or healthy patients, the false-positive rate is 30%.<ref name="newell-price" /> The 48-h DST is advantageous since it is more specific and can be done by outpatients upon proper instruction.<ref name="newell-price" /> In the high-dose 48-h DST, 2 mg of dexamethasone is given every 6 hours for 48 hours or a single dose of 8 mg is given.<ref name="newell-price" /> This test is not needed if the 48-h low-dose DST has shown suppression of cortisol by over 30%.<ref name="newell-price" /> These tests are based on the glucocorticoid sensitivity of pituitary adenomas compared to non-pituitary tumors.<ref name="newell-price" />
| | ===Physical examination=== |
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| Administration of [[corticotropin releasing hormone]] (CRH) can differentiate this condition from ectopic ACTH secretion. In a patient with Cushing's disease, the tumor cells will be stimulated to release corticotropin and elevated plasma corticotropin levels will be detected.<ref name="newell-price" /> This rarely occurs with ectopic corticotropin syndrome and thus is quite useful for distinguishing between the two conditions.<ref name="newell-price" /> If ectopic, the plasma ACTH and [[cortisol]] levels should remain unchanged; if this is pituitary related, levels of both would rise. The CRH test uses recombinant human or ovine-sequence CRH, which is administered via a 100μg intravenous [[Bolus (medicine)|bolus]] dose. The sensitivity of the CRH test for detecting Cushing's disease is 93% when plasma levels are measured after fifteen and thirty minutes.<ref name="newell-price" /> However, this test is used only as a last resort due to its high cost and complexity.<ref name="nieman" />
| | * Inspection |
| | * Palpation |
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| A CT or MRI of the pituitary may also show the ACTH secreting tumor if present. However, in 40% of Cushing's disease patients MRI is unable to detect a tumor.<ref name="newell-price" /> In one study of 261 patients with confirmed pituitary Cushing's Disease, only 48% of pituitary lesions were identified using MRI prior to surgery. The average size of tumor, both those that were identified on MRI and those that were only discovered during surgery, was 6 mm.<ref>Jagannathan, J. et al, [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2945523/ Outcome of using the histological pseudocapsule as a surgical capsule in Cushing disease], ''Journal of Neurosurgery'', 25 September 2010, Retrieved 2014-01-27</ref>
| | (Images courtesy of Charlie Goldberg, M.D., UCSD School of Medicine and VA Medical Center, San Diego, CA) |
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| A more accurate but invasive test used to differentiate pituitary from ectopic or adrenal Cushing's syndrome is [[inferior petrosal sinus sampling]].<ref>{{cite journal|last=Deipolyi|first=A|author2=Karaosmanoglu, A|author3=Habito, C|author4=Brannan, S|author5=Wicky, S|author6=Hirsch, J|author7=Oklu, R|title=The role of bilateral inferior petrosal sinus sampling in the diagnostic evaluation of Cushing disease.|journal=Diagnostic and interventional radiology (Ankara, Turkey)|date=2011-02-23|pmid=21348009|doi=10.4261/1305-3825.DIR.4279-11.0|volume=18|issue=1|pages=132–8}}</ref> A corticotropin gradient sample via BIPSS is required to confirm diagnosis when pituitary MRI imaging and biochemical diagnostic tests have been inconclusive.<ref name="newell-price" /> A basal central:peripheral ratio of over 3:1 when CRH is administered is indicative of Cushing’s disease.<ref name="newell-price" /> This test has been the gold standard for distinguishing between Cushing's disease and ectopic corticotropin syndrome.<ref name="newell-price" /> The BIPSS has a sensitivity and specificity of 94% for Cushing's disease but it is usually used as a last resort due to its invasiveness, rare but serious complications, and the expertise required to perform it.<ref name="nieman" />
| | <div align="left"> |
| | <gallery heights="175" widths="175"> |
| | Image:thyromegaly.jpg|Thyromegaly |
| | Image:head_goiter2.jpg|Thyromegaly |
| | Image:head_goiter1.jpg|Thyromegaly |
| | </gallery> |
| | </div> |
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| Another diagnostic test used is the urinary free cortisol (UFC) test, which measures the excess cortisol excreted by the kidneys into the urine. Results of 4x higher cortisol levels than normal are likely to be Cushing's disease.<ref name="newell-price" /><ref name="nieman" /> This test should be repeated three times in order to exclude any normally occurring periods of hypercortisolism.<ref name="nieman" /> The UFC test has a specificity of 81% and thus has a high rate of false-positives that are due to [[Pseudo-Cushing's syndrome|pseudo-Cushing states]], [[sleep apnea]], [[polycystic ovary syndrome]], familial glucocorticoid resistance, and [[hyperthyroidism]].<ref name="nieman" />
| | ===Laboratory tests=== |
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| The late-night or midnight Saliva testing#Cortisol and melatonin aberrations|salivary cortisol test has been gaining support due to its ease of collection and stability at room temperature, therefore it can be assigned to outpatients.<ref name="newell-price" /> The test measures free circulating cortisol and has both a sensitivity and specificity of 95-98%.<ref name="newell-price" /><ref name="nieman" /> This test is especially useful for diagnosing children.<ref name="newell-price" />
| | * [[T3]] |
| | * [[T4]] |
| | * [[TSH]] |
| | * [[FT3]] |
| | * [[FT4]] |
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| == Treatment == | | === Thyroid ultrasound=== |
| The first-line treatment of Cushing's disease is surgical resection of ACTH-secreting [[pituitary adenoma]]; this surgery involves removal of the tumor via transsphenoidal surgery (TSS).<ref>{{cite journal|last=Ding|first=Dale |author2=Robert M. Starke |author3=Jason P. Sheehan |title=Treatment paradigms for pituitary adenomas: defining the roles of radiosurgery and radiation therapy|journal=J Neurooncol|year=2013|doi=10.1007/s11060-013-1262-8|volume=117|pages=445–457}}</ref>
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| There are two possible options for access to sphenoidal sinus including of endonosal approach (through the nostril) or sublabial approach (through an incision under the top lip); many factors such as the size of nostril, the size of the lesion, and the preferences of the surgeon cause the selection of one access route over the other.<ref>{{cite book|last=Laws|first=Edward R|title=Transsphenoidal Surgery|year=2010|publisher=Elsevier Inc.|url=http://www.expertconsultbook.com/expertconsult/ob/book.do?method=display&type=bookPage&decorator=none&eid=4-u1.0-B978-1-4160-0292-5..00017-6--s0080&isbn=978-1-4160-0292-5#lpState=opened&lpTab=contentsTab&content=4-u1.0-B978-1-4160-0292-5..00032-2%3Bfrom%3Dtoc%3Btype%3DbookPage%3Bisbn%3D978-1-4160-0292-5&search=none}}</ref>
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| Some tumors do not contain a discrete border between tumor and pituitary gland; therefore, careful sectioning through pituitary gland may be required to identify the location of tumor.<ref name=TREATMENT>{{cite journal |vauthors=Biller BM, Grossman AB, Stewart PM, Melmed S, Bertagna X, Bertherat J, Buchfelder M, Colao A, Hermus AR, Hofland LJ, Klibanski A, Lacroix A, Lindsay JR, Newell-Price J, Nieman LK, Petersenn S, Sonino N, Stalla GK, Swearingen B, Vance ML, Wass JA, Boscaro M |title=Treatment of adrenocorticotropin-dependent Cushing's syndrome: a consensus statement.|journal=J Clin Endocrinol Metab|year=2008|volume=93|issue=7|pages=2454–2462|pmid=18413427|doi=10.1210/jc.2007-2734|pmc=3214276}}</ref> The probability of successful resection is higher in patients where the tumor was identified at initial surgery in compare to patients where no tumor was found initially; the overall remission rates in patients with microadenomas undergoing TSS are in range of 65%-90%, and the remission rate in patients with macroadenomas are lower than 65%.<ref name=TREATMENT/> patients with persistent disease after initial surgery are treated with repeated pituitary surgery as soon as the active persistent disease is evident; however, reoperation has lower success rate and increases the risk of pituitary insufficiency.<ref name=TREATMENT/>
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| Pituitary [[radiation therapy]] is another option for treatment of postoperative persisting hypercortisolemia following unsuccessful [[transsphenoidal surgery]].<ref name=RT>{{cite journal|last=Storr|first=HL|author2=Plowman PN |author3=Carroll PV |author4=François I |author5=Krassas GE |author6=Afshar F |author7=Besser GM |author8=Grossman AB |author9=Savage MO. |title=Clinical and Endocrine Responses to Pituitary Radiotherapy in Pediatric Cushing’s Disease: An Effective Second-Line Treatment|journal=J Clin Endocrinol Metab|year=2003|volume=88|issue=1|pages=34–37|doi=10.1210/jc.2002-021032}}</ref> External-beam pituitary RT is more effective treatment for pediatric CD in children with cure rates of 80%-88%. [[Hypopituitarism]] specifically [[growth hormone deficiency]] has been reported as the only most common late morbidity of this treatment; GHD has been reported in 36% and 68% of the patients undergoing post pituitary RT for Cushing's disease.<ref name=RT/>
| | == Differential Diagnosis == |
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| Bilateral adrenalectomy is another treatment which provides immediate reduction of cortisol level and control of hypercortisolism. However, it requires education of patients, because lifelong [[glucocorticoid]] and [[mineralocorticoid]] replacement therapy is needed for these patients. One of the major complications of this treatment is progression of Nelson's syndrome which is caused by enhance level of tumor growth and ACTH secretion post adrenalectomy in 8%-29% of patients with CD.<ref>{{cite journal|last=Gadelha|first=Mônica R. |author2=Leonardo Vieira Neto |title=Efficacy of medical treatment in Cushing's disease: a systematic review|journal=Clinical Endocrinology|year=2014|volume=80|pages=1–12|doi=10.1111/cen.12345}}</ref>
| | In alphabetical order. <ref>Sailer, Christian, Wasner, Susanne. Differential Diagnosis Pocket. Hermosa Beach, CA: Borm Bruckmeir Publishing LLC, 2002:77 ISBN 1591032016</ref> <ref>Kahan, Scott, Smith, Ellen G. In A Page: Signs and Symptoms. Malden, Massachusetts: Blackwell Publishing, 2004:68 ISBN 140510368X</ref> |
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| During post surgical recovery, patients collect 24-hour urine sample and blood sample for detecting the level of cortisol with the purpose of cure test; level of cortisol near the detection limit assay, corresponds to cure. Hormonal replacement such as [[steroid]] is given to patients because of steroid withdrawal. After the completion of collecting urine and blood samples, patients are asked to switch to glucocorticoid such as [[prednisone]] to decrease symptoms associated with adrenal withdrawal.<ref>{{cite news|last=Fairfield|first=Wesley P.|title=Cushing's Disease after Successful Transsphenoidal Surgery - What to Expect and How to Manage|url=http://csrf.net/doctors-articles/recovery/cushings-disease-after-successful-transphenoidal-surgery-what-to-expect-and-how-to-manage/|accessdate=Jan 31, 2014|year=2003}}</ref>
| | === Diffuse Goiter === |
| | |
| | * [[Acromegaly]] |
| | * [[Acute thyroiditis]] |
| | * [[Adenoma of the thyroid]] |
| | * [[Amyloidosis]] |
| | * [[Anaplastic carcinoma of the thyroid]] |
| | * Benign and malignant thyroid gland tumors |
| | * Calcium and fluorides in water |
| | * [[Carcinosarcoma of the thyroid]] |
| | * Chemicals |
| | * [[Colloid nodule of the thyroid]] |
| | * Compensatory hyperplasia after hemithyroidectomy |
| | * [[Cyst]] |
| | * Defects in thyroid hormone synthesis |
| | * [[DeQuervain's Thyroiditis]] |
| | * [[Drugs]] |
| | * Excess [[thyroid stimulating hormone]] ([[TSH]]) |
| | * Focal [[thyroiditis]] |
| | * [[Follicular carcinoma of the Thyroid]] |
| | * Goitrogenic vegetables (bamboo shoots, broccoli, cabbage, cassava, cauliflower, brussels sprouts, turnips) |
| | * [[Grave's Disease]] |
| | * [[Hashimoto's Thyroiditis]] |
| | * [[Hematoma]] |
| | * [[Hyperthyroidism]] |
| | * [[Hypothyroidism]] |
| | * Impairment of the thyroid hormone synthesis/enzyme defect |
| | * [[Insulin-like growth factor]] |
| | * [[Iodine deficiency]] |
| | * [[Lymphoma]] |
| | * Maternal antithyroid drug therapy |
| | * Maternal iodine therapy |
| | * [[Medullary carcinoma of the thyroid]] |
| | * [[Menopause]] |
| | * [[Metastases of extrathyroidal tumors]] |
| | * [[Mixed papillary-follicular carcinoma of the thyroid]] |
| | * [[Multiple adenomas]] |
| | * [[Nontoxic nodular goiter]] |
| | * [[Papillary carcinoma of the thyroid]] |
| | * [[Paraneoplastic production of thyroid stimulating hormone]] ([[TSH]]) |
| | * [[Parasite]] |
| | * Parathyroid tumoral tissue |
| | * [[Pregnancy]] |
| | * [[Puberty]] |
| | * [[Reidel's Thyroiditis]] |
| | * Resistance to thyroid hormone |
| | * [[Sarcoidosis]] |
| | * [[Sarcoma]] |
| | * [[Selenium deficiency]] |
| | * [[Silent thyroiditis]] |
| | * [[Squamous Cell Carcinoma of the thyroid]] |
| | * [[Toxic multinodular goiter]] |
| | * Thymic tumoral tissue |
| | * Thyroid gland autonomy |
| | * Thyroid growth immunoglobulins |
| | * [[Thyroiditis]] |
| | |
| | === Hyperthyroid === |
| | * [[Chloriocarcinoma of the thyroid]] |
| | * [[Embrional cell carcinoma of the testis]] |
| | * Gestational stimulation by human chorionic gonadotropin |
| | * [[Grave's Disease]] |
| | * [[Hydatiform mole]] |
| | * Pituitary resistence to thyroid hormone |
| | * [[Thyroid stimulating hormone (TSH)-secreting pituitary gland tumor]] |
| | * [[Thyroiditis]] |
| | |
| | === Other === |
| | * [[Carotid]] [[aneurysm]] |
| | * [[Cystic hygroma]] |
| | * [[Dermoid]] |
| | * [[Hemangioma]] |
| | * [[Lipoma]] |
| | * [[Lymph node]] |
| | * [[Parathyroid]] [[adenoma]] |
| | * [[Teratoma]] |
| | * [[Thyroglossal duct cyst]] |
| | |
| | ==Treatment== |
| | Treatment for goitre may not be necessary if the goitre is small. [[Hypothyroidism]] should be treated, and this treatment often leads to a substantial reduction in the size of the goitre. Removal of the goitre may be necessary if it causes difficulty with breathing or swallowing. There is now an alternative to surgery in large goitres. Radioiodine therapy with or without the pre-injection of a synthetic thyroid stimulating hormone, TSH, can relieve obstruction and reduce the size of the goitre by 30-65%. But removal of a goitre requires removing the thyroid. The complete removal of the thyroid gland removes the body's ability to produce thyroid hormone. In this case, supplements of oral [[thyroxine]] are necessary to avoid harm from [[hypothyroidism]]. |
| | |
| | == History and future == |
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| A study of 3,525 cases of TSS for Cushing's disease in the nationally representative
| | Goitre was previously common in many areas that were deficient in iodine in the [[soil]]. For example, in the English Midlands, the condition was known as '''Derbyshire Neck'''. In the United States, goitre was found in the Midwest, and Intermountain regions. The condition now is practically absent in affluent nations, where [[Sodium chloride|table salt]] is [[Iodized salt|supplemented with iodine]]. However, it is still prevalent in India,<ref>[http://www.nytimes.com/2006/12/16/health/16iodine.html "In Raising the World’s I.Q., the Secret’s in the Salt"], article by Donald G. McNeil, Jr., December 16, 2006, ''New York Times''</ref> Central Asia and Central Africa. |
| sample of US hospitals between 1993 and 2002 was conducted and revealed the following results: the in-hospital mortality rate was 0.7%; the complication rate was 42.1%. [[Diabetes insipidus]] (15%), fluid and [[electrolyte]] abnormalities (12.5%), and neurological deficits (5.6%) were the most common complications reported. The analyses of the study show that complications were more likely in patients with pre-operative [[comorbidities]]. Patients older than 64 years were more likely to have an adverse outcome and prolonged hospital stay. Women were 0.3 times less likely to have adverse outcomes in comparison to men.<ref name="pmid17961019">{{cite journal|last=Patil|first=CG|author2=Lad, SP |author3=Harsh, GR |author4=Laws ER, Jr |author5=Boakye, M |title=National trends, complications, and outcomes following transsphenoidal surgery for Cushing's disease from 1993 to 2002.|journal=Neurosurgical focus|year=2007|volume=23|issue=3|pages=E7|pmid=17961019|doi=10.3171/foc.2007.23.3.9}}</ref>
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| ==Epidemiology==
| | Some health workers fear that a resurgence of goitre might occur because of the trend to use rock salt and/or sea salt, which has not been fortified with [[iodine]]. |
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| Cases of Cushing's disease are rare, and few epidemiological data is available on the disease. An 18 year study conducted on the population of Vizcaya, Spain reported a 0.004% [[prevalence]] of Cushing's disease.<ref name=Epidemiology>{{cite journal|last=Etxabe|first=J.|author2=J. A. Vazquez|title=Morbidity and mortality in Cushing’s disease: an epidemiological approach|journal=Clinical endocrinology|year=1994|volume=40|issue=4|pages=479–484|accessdate=January 31, 2014|pmid=8187313|doi=10.1111/j.1365-2265.1994.tb02486.x}}</ref> The average [[incidence (epidemiology)|incidence]] of newly diagnosed cases was 2.4 cases per million inhabitants per year. The disease is often diagnosed 3–6 years after the onset of illness.<ref name=Epidemiology />
| | New research indicates that there may in fact be a tendency to inherit an increased vulnerability to goitre. |
| Several studies have shown that Cushing's disease is more prevalent in women than men at a ratio of 3-6:1, respectively.<ref>{{cite journal|last=Boggan|first=J.E |author2=Tyrell, J.B |author3=Wilson C.B|title=Transsphenoidal microsurgical management of Cushing’s disease: report of 100 cases.|journal=Journal of neurosurgery|year=1983|volume=95|issue=2|pages=195–200|url=http://thejns.org/doi/abs/10.3171/jns.1983.59.2.0195|doi=10.3171/jns.1983.59.2.0195}}</ref><ref>{{cite journal|last=Howlet|first=T.A|author2=Perry L. |author3=Doniach I. |author4=Rees LH. |author5=Besser G.M |title=Diagnosis and management of ACTHdependent Cushing’s syndrome: comparison of the features in ectopic and pituitary ACTH production.|journal=Clinical endocrinology|year=1986|volume=24|issue=6|pages=699–713|pmid=3024870|url=http://www.ncbi.nlm.nih.gov/pubmed/3024870|accessdate=January 31, 2014 |doi=10.1111/j.1365-2265.1986.tb01667.x}}</ref> Moreover, most women affected were between the ages of 50 and 60 years.
| |
| The prevalence of [[hypertension]], and abnormalities in [[glucose metabolism]] are major predictors of [[Case fatality rate|mortality]] and [[morbidity]] in untreated cases of the disease.<ref name=Epidemiology /> The mortality rate of Cushing's disease was reported to be 10-11%,<ref name=Epidemiology /><ref>{{cite journal|last=Lindholm|first=J. |author2=Juul, S. |author3=Jørgensen, J.O.L. |author4=Astrup, J. |author5=Bjerre, P. |author6=Feldt-Rasmussen, U. |author7=Hagen, C. |author8=Jørgensen, J. |author9=Kosteljanetz, M. |author10=Kristensen, L.Ø. |author11=Laurberg, P. |author12=Schmidt, K. |author13=Weeke, J|title=Incidence and late prognosis of Cushing's syndrome: A population-based study|journal=Journal of Clinical Endocrinology and Metabolism|year=2001|volume=86|issue=1|pages=117–123|pmid=11231987|url=http://www.ncbi.nlm.nih.gov/pubmed/11231987|accessdate=January 31, 2014|doi=10.1210/jc.86.1.117}}</ref> with the majority of deaths due to vascular disease <ref name="symptoms" /><ref name=Epidemiology /> Women aged 45–70 years have a significantly higher mortality rate than men.<ref name=Epidemiology />
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| Moreover, the disease shows a progressive increase with time. Reasons for the trend are unknown, but better diagnostic tools, and a higher incidence rate are two possible explanations.<ref name=Epidemiology/>
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| == See also == | | ==See also== |
| * [[Cushing's syndrome]] | | *[[Struma ovarii]] (a kind of [[teratoma]]) |
| * [[Hyperpituitarism]]
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| ==References== | | ==References== |
| {{reflist|2}} | | {{reflist|2}} |
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| ==External links== | | == External links == |
| * [http://www.aboutcushings.com/understanding-cushings-disease/causes-and-differences.jsp The difference between Cushing’s disease and other forms of Cushing’s syndrome] | | * [http://www.nhsdirect.nhs.uk/articles/article.aspx?articleId=179 National Health Services, UK] |
| * [http://pituitary.asn.au/Adults/ConditionsIntroduction/Cushingssyndrome.aspx Australian Pituitary Foundation]
| | * [http://www.iodinenetwork.net Network for Sustained Elimination of Iodine Deficiency] |
| * [http://csrf.net/ Cushing's Support & Research Foundation] | | * [http://www.sph.emory.edu/PAMM/sang/partnership/ Network for Sustained Elimination of Iodine Deficiency] - alternate site at [[Emory University]]'s School of [[Public Health]] |
| * [http://www.eje-online.org/content/early/2012/06/22/EJE-11-1095.full.pdf The burden of Cushing’s disease (CD): clinical and health-related quality of life aspects (RA Feelders, SJ Pulgar, A Kempel, and AM Pereira)] | | |
| | == References == |
| | {{reflist|2}} |
| | |
| | == Suggested Reading and Key General References == |
| | |
| | == Suggested Links and Web Resources == |
| | |
| | == For Patients == |
| | |
| | {{endocrine_system}} |
| | {{Endocrinology}} |
| | {{Endocrine pathology}} |
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| | [[ar:تورم درقي]] |
| | [[bs:Strume]] |
| | [[da:Struma]] |
| | [[de:Struma]] |
| | [[es:Bocio]] |
| | [[eu:Bozio]] |
| | [[fr:Goitre]] |
| | [[id:Gondok]] |
| | [[it:Gozzo endemico]] |
| | [[he:זפקת]] |
| | [[no:Struma]] |
| | [[pt:Bócio]] |
| | [[sv:Struma]] |
| | [[ta:முன்கழுத்துக் கழலை]] |
| | [[pl:Wole (tarczyca)]] |
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| [[Category:Medical conditions related to obesity]] | | [[Category:Disease]] |
| | [[Category:Signs and symptoms]] |
| | [[Category:Endocrinology]] |
| | [[Category:Physical Examination]] |
