Sandbox:Mazia: Difference between revisions

Latest revision as of 19:11, 16 February 2018

Overview

History Patients with Pancoast syndrome may present with referred pain over the scapula to the shoulder as the result of damage to the afferent pain fibers of the sympathetic trunk. The symptoms are typical of the location of the tumor in the superior sulcus or thoracic inlet adjacent to the eighth cervical nerve roots, the first and second thoracic trunk distribution, the sympathetic chain, and the stellate ganglion.

Initially, localized pain occurs in the shoulder and vertebral border of the scapula. Pain may later extend along an ulnar nerve distribution of the arm to the elbow and, ultimately, to the ulnar surface of the forearm and to the small and ring fingers of the hand (C8). If the tumor extends to the sympathetic chain and stellate ganglion, Horner syndrome and anhidrosis develop on the ipsilateral side of the face and upper extremity.

The pain is frequently relentless and unremitting, and adequate relief often requires administration of narcotics. The patient usually supports the elbow of the affected arm in the hand of the opposite upper extremity to ease the tension on the shoulder and upper arm.

The hand muscles may become weak and atrophic, and the triceps reflex may be absent. The first or second rib or vertebrae may be involved by tumor extension and intensify the severity of pain. The spinal canal and spinal cord may be invaded or compressed, with subsequent symptoms of spinal cord tumor or cervical disk disease.

Many patients are initially treated for presumed local musculoskeletal conditions such as bursitis and vertebral osteoarthritis with radicular pain. Symptoms may persist for many months before evaluation for progression reveals the cause. In a 1994 series by Maggi et al, symptoms lasted 2-36 months, with a mean of 9.7 months. [7] In 1997, Muscolino described plexopathy or radicular symptoms in 53% of 15 patients. [24]

Historical Perspective

[Disease name] was first discovered by [scientist name], a [nationality + occupation], in [year] during/following [event].
In [year], [gene] mutations were first identified in the pathogenesis of [disease name].
In [year], the first [discovery] was developed by [scientist] to treat/diagnose [disease name].

Classification

[Disease name] may be classified according to [classification method] into [number] subtypes/groups:

[group1]
[group2]
[group3]

Other variants of [disease name] include [disease subtype 1], [disease subtype 2], and [disease subtype 3].

Pathophysiology

The pathogenesis of [disease name] is characterized by [feature1], [feature2], and [feature3].
The [gene name] gene/Mutation in [gene name] has been associated with the development of [disease name], involving the [molecular pathway] pathway.
On gross pathology, [feature1], [feature2], and [feature3] are characteristic findings of [disease name].
On microscopic histopathological analysis, [feature1], [feature2], and [feature3] are characteristic findings of [disease name].

Causes

[Disease name] may be caused by either [cause1], [cause2], or [cause3].
[Disease name] is caused by a mutation in the [gene1], [gene2], or [gene3] gene[s].
There are no established causes for [disease name].

Differentiating [disease name] from other Diseases

[Disease name] must be differentiated from other diseases that cause [clinical feature 1], [clinical feature 2], and [clinical feature 3], such as:

[Differential dx1]
[Differential dx2]
[Differential dx3]

Epidemiology and Demographics

The prevalence of [disease name] is approximately [number or range] per 100,000 individuals worldwide.
In [year], the incidence of [disease name] was estimated to be [number or range] cases per 100,000 individuals in [location].

Age

Patients of all age groups may develop [disease name].

[Disease name] is more commonly observed among patients aged [age range] years old.
[Disease name] is more commonly observed among [elderly patients/young patients/children].

Gender

[Disease name] affects men and women equally.

[Gender 1] are more commonly affected with [disease name] than [gender 2].
The [gender 1] to [Gender 2] ratio is approximately [number > 1] to 1.

Race

There is no racial predilection for [disease name].

[Disease name] usually affects individuals of the [race 1] race.
[Race 2] individuals are less likely to develop [disease name].

Risk Factors

Common risk factors in the development of [disease name] are [risk factor 1], [risk factor 2], [risk factor 3], and [risk factor 4].

Natural History, Complications and Prognosis

The majority of patients with [disease name] remain asymptomatic for [duration/years].
Early clinical features include [manifestation 1], [manifestation 2], and [manifestation 3].
If left untreated, [#%] of patients with [disease name] may progress to develop [manifestation 1], [manifestation 2], and [manifestation 3].
Common complications of [disease name] include [complication 1], [complication 2], and [complication 3].
Prognosis is generally [excellent/good/poor], and the [1/5/10year mortality/survival rate] of patients with [disease name] is approximately [#%].

Diagnosis

Diagnostic Criteria

The diagnosis of [disease name] is made when at least [number] of the following [number] diagnostic criteria are met:

[criterion 1]
[criterion 2]
[criterion 3]
[criterion 4]

Symptoms

[Disease name] is usually asymptomatic.
Symptoms of [disease name] may include the following:

[symptom 1]
[symptom 2]
[symptom 3]
[symptom 4]
[symptom 5]
[symptom 6]

Physical Examination

Patients with [disease name] usually appear [general appearance].
Physical examination may be remarkable for:

[finding 1]
[finding 2]
[finding 3]
[finding 4]
[finding 5]
[finding 6]

Laboratory Findings

There are no specific laboratory findings associated with [disease name].

A [positive/negative] [test name] is diagnostic of [disease name].
An [elevated/reduced] concentration of [serum/blood/urinary/CSF/other] [lab test] is diagnostic of [disease name].
Other laboratory findings consistent with the diagnosis of [disease name] include [abnormal test 1], [abnormal test 2], and [abnormal test 3].

Imaging Findings

There are no [imaging study] findings associated with [disease name].

[Imaging study 1] is the imaging modality of choice for [disease name].
On [imaging study 1], [disease name] is characterized by [finding 1], [finding 2], and [finding 3].
[Imaging study 2] may demonstrate [finding 1], [finding 2], and [finding 3].

Other Diagnostic Studies

[Disease name] may also be diagnosed using [diagnostic study name].
Findings on [diagnostic study name] include [finding 1], [finding 2], and [finding 3].

Treatment

Medical Therapy

There is no treatment for [disease name]; the mainstay of therapy is supportive care.

The mainstay of therapy for [disease name] is [medical therapy 1] and [medical therapy 2].
[Medical therapy 1] acts by [mechanism of action 1].
Response to [medical therapy 1] can be monitored with [test/physical finding/imaging] every [frequency/duration].

Surgery

Surgery is the mainstay of therapy for [disease name].
[Surgical procedure] in conjunction with [chemotherapy/radiation] is the most common approach to the treatment of [disease name].
[Surgical procedure] can only be performed for patients with [disease stage] [disease name].

Prevention

There are no primary preventive measures available for [disease name].

Effective measures for the primary prevention of [disease name] include [measure1], [measure2], and [measure3].

Once diagnosed and successfully treated, patients with [disease name] are followed-up every [duration]. Follow-up testing includes [test 1], [test 2], and [test 3].

References

Pancoast syndrome (Pancoast’s syndrome) typically results when a malignant neoplasm of the superior sulcus of the lung (lung cancer) leads to destructive lesions of the thoracic inlet and involvement of the brachial plexus and cervical sympathetic nerves (stellate ganglion). [1, 2, 3] This is accompanied by the following:

Severe pain in the shoulder region radiating toward the axilla and scapula, with later extension along the ulnar aspect of the arm to the hand Atrophy of hand and arm muscles Horner syndrome ( ptosis, miosis, hemianhidrosis, enophthalmos) Compression of the blood vessels with edema Most Pancoast tumors are squamous cell carcinomas (SCCs) or adenocarcinomas; only 3-5% are small cell carcinomas. Squamous cell carcinoma occurs more frequently, although large cell and undifferentiated types are also common. Adenocarcinoma is sometimes found in this location and can even be metastatic. Involvement of the phrenic or recurrent laryngeal nerve or superior vena cava obstruction is not representative of the classic Pancoast tumor.

Once universally fatal, Pancoast tumors are currently treatable with outcomes similar to those of other stage-matched non–small cell lung cancers. [4] Careful assessment and appropriate staging are performed before surgery, and selected patients are administered preoperative irradiation of 30 Gy over 2 weeks. After an interval of 2-4 weeks, surgical resection of the chest wall and lower brachial plexus and en bloc lung resection produces a 5-year survival rate of 30%. Contraindications to surgical management include the following:

Extension of the tumor into the neck or vertebrae Presence of substantial mediastinal lymph nodes Peripheral tumor dissemination Protocols that use combinations of radiation therapy, chemotherapy, and surgery are currently being studied to determine the best therapy.

Pathophysiology Pancoast tumors are a subset of lung cancers that invade the apical chest wall. Because of their location in the pleural apex, they invade adjoining tissue. Although other tumors may have a similar clinical presentation because of their location at the thoracic inlet, the most common cause is believed to be a bronchogenic carcinoma arising in or near the superior sulcus and invading adjacent extrathoracic structures by direct extension. Location, rather than pathology or histology of origin, is significant in producing the tumor’s characteristic clinical pattern. [5]

The bulk of a true Pancoast tumor is extrathoracic, originating in an extreme peripheral location with a plaquelike extension over the lung apex and principally involving the chest wall structures rather than the underlying lung parenchyma. Bronchogenic carcinomas occurring in the narrow confines of the thoracic inlet invade the lymphatic vessels in the endothoracic fascia and include, by direct extension, the following structures:

Intercostal nerves Lower roots of the brachial plexus Stellate ganglion Sympathetic chain Adjacent ribs and vertebrae. Carcinomas in the superior pulmonary sulcus produce Pancoast syndrome, thus causing pain in the shoulder and along the ulnar nerve distribution of the arm and hand. [6] (These carcinomas also cause Horner syndrome.) These apical lung tumors tend to be locally invasive early. In the absence of metastases and regional nodal involvement, these apical cancers can be successfully treated.

The tumor may invade the bony structures of the chest, including the first or second thoracic vertebra or the first, second, or third rib. In a review of 60 patients with Pancoast tumors, Maggi et al found radiographic evidence of rib erosion in 50%; an almost equal percentage demonstrated involvement of the first or second rib, and 20% had involvement of the third rib. One patient had involvement of all 3 ribs. [7]

The tumor can also invade the first or second thoracic vertebral bodies or intervertebral foramina. From this point, it can extend to the spinal cord and result in cord compression. The subclavian vein or artery may also be invaded.

Etiology The overwhelming majority of cases of Pancoast syndrome are non–small cell lung carcinoma (NSCLC), with more than 95% located in the superior sulcus. The most common varieties are SCC and adenocarcinoma; large cell carcinoma has also been reported.

Although quite rare (responsible for fewer than 5% percent of cases in most series), small cell carcinoma is also observed. Maggi et al reported small cell carcinoma in only 3 of the 60 patients in their series. [7] More typically, small cell carcinoma manifests in a central rather than a peripheral location.

Although NSCLC is by far the most common cause of Pancoast syndrome, the list of differential diagnoses is broad. Because of the wide variety of diseases that can produce Pancoast syndrome, a histologic diagnosis is mandatory before definitive treatment is initiated.

Rare causes include the following:

Desmoid tumors [8] Hemangiopericytoma [9] Adenoid cystic carcinoma [10] Metastatic carcinoma [11] Lymphoma [12] Thyroid carcinoma [13] Bacterial [14, 15] and fungal infections [16, 17] Lymphomatoid granulomatosis Vascular aneurysms Amyloid nodules Cervical rib syndrome Inflammatory pseudotumor (plasma cell granuloma) Mycotic subclavian artery aneurysm Carotid pseudoaneurysm in a child (caused by a hydatid cyst) Risk factors are similar for almost all lung cancers and include the following:

Prolonged asbestos exposure Exposure to industrial elements (eg, gold, nickel) Tobacco smoking Secondary smoke exposure Epidemiology Overall, Pancoast tumors are much less common than other lung cancers, accounting for fewer than 5% of these cancers (1-3% in various previous series). [18, 19] Originally deemed universally fatal, Pancoast tumors are now amenable to curative treatment because of improvements in combined modality therapy and development of new techniques for resection.

Prognosis The prognosis for patients with Pancoast syndrome is stage dependent. Adverse prognostic factors include the following:

Presence of Horner syndrome Involvement of mediastinal lymph nodes Incomplete resection Involvement of supraclavicular lymph node Vertebral body invasion To date, no patient with the first 3 prognostic factors has survived for 5 years.

Distant disease limits survival. Treatment failure is especially frequent in patients with involvement of the brain. The authors recommend careful surveillance for brain metastasis during and after the therapy. The authors also recommend obtaining brain imaging prior to surgery in patients receiving induction therapy for the primary tumor.

Mortality and survival Attar et al reported a median survival of 36.8 months in patients with T3 lesions undergoing combined modality treatment; median survival was only 6.4 months if the patient had T4 disease. [20]

Overall survival data were summarized by Detterbeck, who noted that 5-year survival rates ranged from 15% to 56%. [21] Of the 104 patients treated by Attar and coworkers, 7 (~7%) were 5-year survivors and 3 (~3%) were 10-year survivors. [20] Another study demonstrated surgical morbidity rates of 7-38%, with mortality ranging from 5% to 10%. [22]

For neoplastic causes, predictors of 5-year survival are weight loss, supraclavicular fossa or vertebral body involvement, disease stage, and surgical treatment. A study by an MD Anderson group reported the following findings [23] :

For patients with stage IIB disease, the 5-year survival rate was 47%, whereas for those with stage IIIA and IIIB disease, it was 14% and 16%, respectively In patients with stage IIB disease, surgical treatment and weight loss were significant independent predictors of 5-year survival Among patients with stage IIIA disease, the only predictor of survival was the Karnofsky performance score In patients with stage IIIB disease, the only independent predictor of survival was a right superior sulcus location, which was associated with a worse 5-year survival rate than a left superior sulcus location Compared with patients who had squamous cell tumors, more patients with adenocarcinoma had cerebral metastases within 5 years Relapse Locoregional relapse is common despite preoperative or postoperative radiation therapy. Muscolino et al found locoregional recurrence in 60% of patients treated with a combined radiosurgical approach. Ginsberg et al found that 94 of their 124 patients had recurrence of disease, with 72% of these cases being locoregional at initial recurrence. In two thirds of patients who underwent complete resection, local recurrences were the first site of relapse. [18]

This distribution of relapses was noted in several studies reviewed by Detterbeck. In many of these studies, patients received preoperative radiation therapy. [21] In the Memorial Sloan-Kettering experience, additional postoperative brachytherapy was administered to achieve maximal possible local control; despite these measures, local relapses and, ultimately, distant relapses were frequent. [18]

Pancoast syndrome (Pancoast’s syndrome) typically results when a malignant neoplasm of the superior sulcus of the lung (lung cancer) leads to destructive lesions of the thoracic inlet and involvement of the brachial plexus and cervical sympathetic nerves (stellate ganglion). [1, 2, 3] This is accompanied by the following:

Severe pain in the shoulder region radiating toward the axilla and scapula, with later extension along the ulnar aspect of the arm to the hand Atrophy of hand and arm muscles Horner syndrome ( ptosis, miosis, hemianhidrosis, enophthalmos) Compression of the blood vessels with edema Most Pancoast tumors are squamous cell carcinomas (SCCs) or adenocarcinomas; only 3-5% are small cell carcinomas. Squamous cell carcinoma occurs more frequently, although large cell and undifferentiated types are also common. Adenocarcinoma is sometimes found in this location and can even be metastatic. Involvement of the phrenic or recurrent laryngeal nerve or superior vena cava obstruction is not representative of the classic Pancoast tumor.

Once universally fatal, Pancoast tumors are currently treatable with outcomes similar to those of other stage-matched non–small cell lung cancers. [4] Careful assessment and appropriate staging are performed before surgery, and selected patients are administered preoperative irradiation of 30 Gy over 2 weeks. After an interval of 2-4 weeks, surgical resection of the chest wall and lower brachial plexus and en bloc lung resection produces a 5-year survival rate of 30%. Contraindications to surgical management include the following:

Extension of the tumor into the neck or vertebrae Presence of substantial mediastinal lymph nodes Peripheral tumor dissemination Protocols that use combinations of radiation therapy, chemotherapy, and surgery are currently being studied to determine the best therapy. Pathophysiology Pancoast tumors are a subset of lung cancers that invade the apical chest wall. Because of their location in the pleural apex, they invade adjoining tissue. Although other tumors may have a similar clinical presentation because of their location at the thoracic inlet, the most common cause is believed to be a bronchogenic carcinoma arising in or near the superior sulcus and invading adjacent extrathoracic structures by direct extension. Location, rather than pathology or histology of origin, is significant in producing the tumor’s characteristic clinical pattern. [5]

The bulk of a true Pancoast tumor is extrathoracic, originating in an extreme peripheral location with a plaquelike extension over the lung apex and principally involving the chest wall structures rather than the underlying lung parenchyma. Bronchogenic carcinomas occurring in the narrow confines of the thoracic inlet invade the lymphatic vessels in the endothoracic fascia and include, by direct extension, the following structures:

Intercostal nerves Lower roots of the brachial plexus Stellate ganglion Sympathetic chain Adjacent ribs and vertebrae. Carcinomas in the superior pulmonary sulcus produce Pancoast syndrome, thus causing pain in the shoulder and along the ulnar nerve distribution of the arm and hand. [6] (These carcinomas also cause Horner syndrome.) These apical lung tumors tend to be locally invasive early. In the absence of metastases and regional nodal involvement, these apical cancers can be successfully treated.

The tumor may invade the bony structures of the chest, including the first or second thoracic vertebra or the first, second, or third rib. In a review of 60 patients with Pancoast tumors, Maggi et al found radiographic evidence of rib erosion in 50%; an almost equal percentage demonstrated involvement of the first or second rib, and 20% had involvement of the third rib. One patient had involvement of all 3 ribs. [7]

The tumor can also invade the first or second thoracic vertebral bodies or intervertebral foramina. From this point, it can extend to the spinal cord and result in cord compression. The subclavian vein or artery may also be invaded.

@@ Line 1: / Line 1: @@
 __NOTOC__
+==Overview==
+History
+Patients with Pancoast syndrome may present with referred pain over the scapula to the shoulder as the result of damage to the afferent pain fibers of the sympathetic trunk. The symptoms are typical of the location of the tumor in the superior sulcus or thoracic inlet adjacent to the eighth cervical nerve roots, the first and second thoracic trunk distribution, the sympathetic chain, and the stellate ganglion.
-{{CMG}}; {{AE}} {{Mazia}}
+Initially, localized pain occurs in the shoulder and vertebral border of the scapula. Pain may later extend along an ulnar nerve distribution of the arm to the elbow and, ultimately, to the ulnar surface of the forearm and to the small and ring fingers of the hand (C8). If the tumor extends to the sympathetic chain and stellate ganglion, Horner syndrome and anhidrosis develop on the ipsilateral side of the face and upper extremity.
+The pain is frequently relentless and unremitting, and adequate relief often requires administration of narcotics. The patient usually supports the elbow of the affected arm in the hand of the opposite upper extremity to ease the tension on the shoulder and upper arm.
-==Pseudohypoparathyroidism==
+The hand muscles may become weak and atrophic, and the triceps reflex may be absent. The first or second rib or vertebrae may be involved by tumor extension and intensify the severity of pain. The spinal canal and spinal cord may be invaded or compressed, with subsequent symptoms of spinal cord tumor or cervical disk disease.
-__NOTOC__
-==Overview==
+Many patients are initially treated for presumed local musculoskeletal conditions such as bursitis and vertebral osteoarthritis with radicular pain. Symptoms may persist for many months before evaluation for progression reveals the cause. In a 1994 series by Maggi et al, symptoms lasted 2-36 months, with a mean of 9.7 months. [7] In 1997, Muscolino described plexopathy or radicular symptoms in 53% of 15 patients. [24]
-Pseudohypoparathyroidism (PHP) refers to a group of rare [[endocrine]] disorders characterized by end organ resistance to the action of [[parathyroid hormone]] (PTH), manifestations include [[hypocalcemia]], [[hyperphosphatemia]], and increased serum concentration of [[PTH]].
-Development of pseudohypoparathyroidism is the result from multiple genetic mutations involving mainly the [[GNAS1|GNAS]] gene.
 ==Historical Perspective==
-*In 1942, Fuller albright, an American endocrinologist, first discovered pseudohypoparathyroidim. Pseudohypoparathyoroidism is the first hormone resistance syndrome to be discovered.<ref>{{cite journal |vauthors=Albright F, Burnett CH, Smith PH, Parson |date=1942 |title=Pseudohypoparathyroidism- An example of ‘Seabright-Bantam syndrome’ |url= |journal= Endocrinology |volume=30 |issue= |pages=922–32 |doi= |access-date= }}</ref>
+*[Disease name] was first discovered by [scientist name], a [nationality + occupation], in [year] during/following [event].
+*In [year], [gene] mutations were first identified in the pathogenesis of [disease name].
-*In the same year, Albright hereditary osteodystrophy was clinically described together with pseudohypoparathyroidism. <ref name="pmid5002252">{{cite journal |vauthors=Eyre WG, Reed WB |title=Albright's hereditary osteodystrophy with cutaneous bone formation |journal=Arch Dermatol |volume=104 |issue=6 |pages=634–42 |year=1971 |pmid=5002252 |doi= |url=}}</ref>
+*In [year], the first [discovery] was developed by [scientist] to treat/diagnose [disease name].
 ==Classification==
-*Pseudohypoparathyroidism is classified based on the measurement of serum and urinary [[cAMP]] and [[phosphate]] excretion levels after the injection of biologically active [[PTH|parathyroid hormone]] into following types:<ref name="pmid11117980">{{cite journal |vauthors=Marx SJ |title=Hyperparathyroid and hypoparathyroid disorders |journal=N. Engl. J. Med. |volume=343 |issue=25 |pages=1863–75 |year=2000 |pmid=11117980 |doi=10.1056/NEJM200012213432508 |url=}}</ref>
+*[Disease name] may be classified according to [classification method] into [number] subtypes/groups:
-**Pseudohypoparathyroidism type I
+:*[group1]
-**Pseudohypoparathyroidism type II
+:*[group2]
+:*[group3]
-*Pseudohypoparathyroidism type 1 is further classified into following subtype:<ref name="pmid11117980">{{cite journal |vauthors=Marx SJ |title=Hyperparathyroid and hypoparathyroid disorders |journal=N. Engl. J. Med. |volume=343 |issue=25 |pages=1863–75 |year=2000 |pmid=11117980 |doi=10.1056/NEJM200012213432508 |url=}}</ref>
+*Other variants of [disease name] include [disease subtype 1], [disease subtype 2], and [disease subtype 3].
-**Pseudohypoparathyroidism type 1a
-**Pseudohypoparathyroidism type 1b
-**Pseudohypoparathyroidism type 1c.
-**Pseudopseudohypoparathyroidism
-*Other forms of [[PTH|parathyroid hormone]] resistance include :
-**Blomstrand Syndrome
-**Acrodysostosis type 1
-**Acrodysostosis type 2
 ==Pathophysiology==
-*Pseudohypoparathyroidism is characterized by end organ resistance to [[parathyroid hormone]].
+*The pathogenesis of [disease name] is characterized by [feature1], [feature2], and [feature3].
-*[[Parathyroid hormone]] effect is mediated by the [[parathyroid hormone receptor type 1]], which acts on a stimulatory [[guanine-nucleotide–binding (Gs) protein]], which is composed of three subunits (α, β, and γ). The [[GNAS1]] gene encodes Gsα subunit that mediates [[cyclic AMP]] stimulation by [[parathyroid hormone]] and by several other peptide hormones, including [[thyrotropin]].<ref name="pmid17986833">{{cite journal |vauthors=Spiegel AM |title=Inherited endocrine diseases involving G proteins and G protein-coupled receptors |journal=Endocr Dev |volume=11 |issue= |pages=133–44 |year=2007 |pmid=17986833 |doi=10.1159/0000111069 |url=}}</ref>
+*The [gene name] gene/Mutation in [gene name] has been associated with the development of [disease name], involving the [molecular pathway] pathway.
-*Gene mutation results in failure of signal transduction through  Gsα inability to activate [[Adenylate cyclase|adenyl cyclase]] that results in resistance of target tissues to [[parathyroid hormone]] evidenced by [[hypocalcemia]] and [[hyperphosphatemia]], in the presence of high plasma [[Parathyroid hormone|PTH]] level.<ref name="pmid4309802">{{cite journal |vauthors=Chase LR, Melson GL, Aurbach GD |title=Pseudohypoparathyroidism: defective excretion of 3',5'-AMP in response to parathyroid hormone |journal=J. Clin. Invest. |volume=48 |issue=10 |pages=1832–44 |year=1969 |pmid=4309802 |pmc=322419 |doi=10.1172/JCI106149 |url=}}</ref>
+*On gross pathology, [feature1], [feature2], and [feature3] are characteristic findings of [disease name].
-*Blomstrand's Chondrodystrophy is lethal prenatally characterized by abnormal [[Endochondral ossification|endochondral]] bone formation with prematurely occurring [[mineralization]] of the [[cartilaginous]] bone templates.
+*On microscopic histopathological analysis, [feature1], [feature2], and [feature3] are characteristic findings of [disease name].
-*Acrodysostosis patients have resistance to [[parathormone]] with normal [[calcium]] and [[phosphorus]], in addition to resistance [[thyroid-stimulating hormone]] and [[growth hormone releasing hormone]].
-Genetic mutations associated with parathyroid hormone resistance are discussed below <ref name="pmid23076042">{{cite journal |vauthors=Levine MA |title=An update on the clinical and molecular characteristics of pseudohypoparathyroidism |journal=Curr Opin Endocrinol Diabetes Obes |volume=19 |issue=6 |pages=443–51 |year=2012 |pmid=23076042 |pmc=3679535 |doi=10.1097/MED.0b013e32835a255c |url=}}</ref><ref name="pmid21816789">{{cite journal |vauthors=Mantovani G |title=Clinical review: Pseudohypoparathyroidism: diagnosis and treatment |journal=J. Clin. Endocrinol. Metab. |volume=96 |issue=10 |pages=3020–30 |year=2011 |pmid=21816789 |doi=10.1210/jc.2011-1048 |url=}}</ref><ref name="pmid25891861">{{cite journal |vauthors=Lee S, Mannstadt M, Guo J, Kim SM, Yi HS, Khatri A, Dean T, Okazaki M, Gardella TJ, Jüppner H |title=A Homozygous [Cys25]PTH(1-84) Mutation That Impairs PTH/PTHrP Receptor Activation Defines a Novel Form of Hypoparathyroidism |journal=J. Bone Miner. Res. |volume=30 |issue=10 |pages=1803–13 |year=2015 |pmid=25891861 |pmc=4580526 |doi=10.1002/jbmr.2532 |url=}}</ref><ref name="pmid9649554">{{cite journal |vauthors=Jobert AS, Zhang P, Couvineau A, Bonaventure J, Roume J, Le Merrer M, Silve C |title=Absence of functional receptors for parathyroid hormone and parathyroid hormone-related peptide in Blomstrand chondrodysplasia |journal=J. Clin. Invest. |volume=102 |issue=1 |pages=34–40 |year=1998 |pmid=9649554 |pmc=509062 |doi=10.1172/JCI2918 |url=}}</ref><ref name="pmid22464250">{{cite journal |vauthors=Michot C, Le Goff C, Goldenberg A, Abhyankar A, Klein C, Kinning E, Guerrot AM, Flahaut P, Duncombe A, Baujat G, Lyonnet S, Thalassinos C, Nitschke P, Casanova JL, Le Merrer M, Munnich A, Cormier-Daire V |title=Exome sequencing identifies PDE4D mutations as another cause of acrodysostosis |journal=Am. J. Hum. Genet. |volume=90 |issue=4 |pages=740–5 |year=2012 |pmid=22464250 |pmc=3322219 |doi=10.1016/j.ajhg.2012.03.003 |url=}}</ref><ref name="pmid21651393">{{cite journal |vauthors=Linglart A, Menguy C, Couvineau A, Auzan C, Gunes Y, Cancel M, Motte E, Pinto G, Chanson P, Bougnères P, Clauser E, Silve C |title=Recurrent PRKAR1A mutation in acrodysostosis with hormone resistance |journal=N. Engl. J. Med. |volume=364 |issue=23 |pages=2218–26 |year=2011 |pmid=21651393 |doi=10.1056/NEJMoa1012717 |url=}}</ref>
-{| class="wikitable"
-! colspan="2" |Type of pseudohyoparathyroidism
-!Molecular Defect
-!Origin Of Mutation
-!Inheritence
-|-
-| rowspan="4" |Pseudohypoparathyroidism type I
-|Type 1a
-|[[Heterozygous]] ''[[GNAS1|GNAS]]'' inactivating mutations that reduce expression or function of Gα<sub>s</sub>
-|Maternal
-|[[Autosomal dominant]]
-|-
-| rowspan="2" |Type 1b
-|[[Familial]]- [[heterozygous]] deletions in ''[[STX16|STX]]16'', NESP55, and/or AS exons or loss of [[methylation]] at ''[[GNAS1|GNAS]]''
-|Maternal
-|[[Autosomal dominant]]
-|-
-|Sporadic- paternal [[Uniparental disomy]] of chromosome 20q in some or [[methylation]] defect affecting all four ''[[GNAS1|GNAS]]'' DMRs
-|Maternal
-|[[Genomic imprinting]]
-|-
-|Type 1c
-|[[Heterozygous]] ''[[GNAS1|GNAS]]'' inactivating mutations that reduce expression or function of Gα<sub>s</sub>
-|Maternal
-|[[Autosomal dominant]]
-|-
-| colspan="2" |Pseudopseudohypoparathyroidism
-|Combination of inactivating mutations of ''[[GNAS1]]'' and [[Albright's hereditary osteodystrophy|Albright's osteodystrophy]]
-|Paternal
-|[[Genomic imprinting]]
-|-
-| colspan="2" |Pseudohypoparathyroidism type II
-|Insufficient data to suggest genetic or familial source
-|N/A
-|N/A
-|-
-| colspan="2" |Blomstrand chondrodysplasia
-|Homozygous or heterozygous mutations in both alleles encoding the type 1 parathyroid hormone receptor
-|N/A
-|[[Autosomal recessive]]
-|-
-| colspan="2" |Acrodysostosis type 1
-|''PRKAR1A'' germ-line mutation in the encoding gene
-|N/A
-|[[Autosomal dominant]]
-|-
-| colspan="2" |Acrodysostosis type 2
-|''Phosphodiesterase 4D (PDE4D) gene''
-|N/A
-|[[Autosomal dominant]]
-|}
 ==Causes==
-Pseudohypoparathyroidism is caused by mutations involving primarily the [[GNAS1|GNAS]] gene that results in end organ resistance to [[parathyroid hormone]].For a complete review of genes involved in pseudohypoparathyroidism and associated parathyroid hormone resistance click here.
+* [Disease name] may be caused by either [cause1], [cause2], or [cause3].
+* [Disease name] is caused by a mutation in the [gene1], [gene2], or [gene3] gene[s].
-==Differentiating ((Page name)) from Other Diseases==
+* There are no established causes for [disease name].
-[Disease name] must be differentiated from other diseases that cause [clinical feature 1], [clinical feature 2], and [clinical feature 3], such as [differential dx1], [differential dx2], and [differential dx3].
+==Differentiating [disease name] from other Diseases==
-OR
+*[Disease name] must be differentiated from other diseases that cause [clinical feature 1], [clinical feature 2], and [clinical feature 3], such as:
+:*[Differential dx1]
-[Disease name] must be differentiated from [[differential dx1], [differential dx2], and [differential dx3].
+:*[Differential dx2]
+:*[Differential dx3]
 ==Epidemiology and Demographics==
+* The prevalence of [disease name] is approximately [number or range] per 100,000 individuals worldwide.
-===Prevalence===
+* In [year], the incidence of [disease name] was estimated to be [number or range] cases per 100,000 individuals in [location].
-*In Japan, the [[prevalence]] of pseudohypoparathyroidism ranges from a low of 0.26 per 100,000 persons to a high of 0.42 per 100,000 persons with an average [[prevalence]] of 0.34 per 100,000 persons.<ref name="pmid10695258">{{cite journal |vauthors=Nakamura Y, Matsumoto T, Tamakoshi A, Kawamura T, Seino Y, Kasuga M, Yanagawa H, Ohno Y |title=Prevalence of idiopathic hypoparathyroidism and pseudohypoparathyroidism in Japan |journal=J Epidemiol |volume=10 |issue=1 |pages=29–33 |year=2000 |pmid=10695258 |doi= |url=https://www.jstage.jst.go.jp/article/jea1991/10/1/10_1_29/_pdf}}</ref>
-*In Italy, the estimated [[prevalence]] of PHP type 1a, type1b, and PPHP is 1 per 150,000.<ref name="urlOrphanet: Pseudohypoparat">{{cite web |url=http://www.orpha.net/consor/cgi-bin/Disease_Search.php?lng=EN&data_id=12935&Disease_Disease_Search_diseaseGroup=Pseudohypoparathyroidism&Disease_Disease_Search_diseaseType=Pat&Disease(s)/group%20of%20diseases=Pseudohypoparathyroidism&title=Pseudohypoparat |title=Orphanet: Pseudohypoparat |format= |work= |accessdate=}}</ref>
+===Age===
+*Patients of all age groups may develop [disease name].
+*[Disease name] is more commonly observed among patients aged [age range] years old.
+*[Disease name] is more commonly observed among [elderly patients/young patients/children].
+===Gender===
+*[Disease name] affects men and women equally.
+*[Gender 1] are more commonly affected with [disease name] than [gender 2].
+* The [gender 1] to [Gender 2] ratio is approximately [number > 1] to 1.
+===Race===
+*There is no racial predilection for [disease name].
+*[Disease name] usually affects individuals of the [race 1] race.
+*[Race 2] individuals are less likely to develop [disease name].
 ==Risk Factors==
-The most potent risk factor in the development of pseudohypoparathyroidism is a positive family history for [[GNAS1|GNAS]] mutation.
+*Common risk factors in the development of [disease name] are [risk factor 1], [risk factor 2], [risk factor 3], and [risk factor 4].
+== Natural History, Complications and Prognosis==
+*The majority of patients with [disease name] remain asymptomatic for [duration/years].
+*Early clinical features include [manifestation 1], [manifestation 2], and [manifestation 3].
+*If left untreated, [#%] of patients with [disease name] may progress to develop [manifestation 1], [manifestation 2], and [manifestation 3].
+*Common complications of [disease name] include [complication 1], [complication 2], and [complication 3].
+*Prognosis is generally [excellent/good/poor], and the [1/5/10year mortality/survival rate] of patients with [disease name] is approximately [#%].
+== Diagnosis ==
+===Diagnostic Criteria===
+*The diagnosis of [disease name] is made when at least [number] of the following [number] diagnostic criteria are met:
+:*[criterion 1]
+:*[criterion 2]
+:*[criterion 3]
+:*[criterion 4]
+=== Symptoms ===
+*[Disease name] is usually asymptomatic.
+*Symptoms of [disease name] may include the following:
+:*[symptom 1]
+:*[symptom 2]
+:*[symptom 3]
+:*[symptom 4]
+:*[symptom 5]
+:*[symptom 6]
+=== Physical Examination ===
+*Patients with [disease name] usually appear [general appearance].
+*Physical examination may be remarkable for:
+:*[finding 1]
+:*[finding 2]
+:*[finding 3]
+:*[finding 4]
+:*[finding 5]
+:*[finding 6]
+=== Laboratory Findings ===
+*There are no specific laboratory findings associated with [disease name].
-==Screening==
+*A  [positive/negative] [test name] is diagnostic of [disease name].
-There is insufficient evidence to recommend routine screening for pseudohypoparathyroidism.
+*An [elevated/reduced] concentration of [serum/blood/urinary/CSF/other] [lab test] is diagnostic of [disease name].
+*Other laboratory findings consistent with the diagnosis of [disease name] include [abnormal test 1], [abnormal test 2], and [abnormal test 3].
+===Imaging Findings===
+*There are no [imaging study] findings associated with [disease name].
+*[Imaging study 1] is the imaging modality of choice for [disease name].
+*On [imaging study 1], [disease name] is characterized by [finding 1], [finding 2], and [finding 3].
+*[Imaging study 2] may demonstrate [finding 1], [finding 2], and [finding 3].
+=== Other Diagnostic Studies ===
+*[Disease name] may also be diagnosed using [diagnostic study name].
+*Findings on [diagnostic study name] include [finding 1], [finding 2], and [finding 3].
+== Treatment ==
+=== Medical Therapy ===
+*There is no treatment for [disease name]; the mainstay of therapy is supportive care.
+*The mainstay of therapy for [disease name] is [medical therapy 1] and [medical therapy 2].
+*[Medical therapy 1] acts by [mechanism of action 1].
+*Response to [medical therapy 1] can be monitored with [test/physical finding/imaging] every [frequency/duration].
+=== Surgery ===
+*Surgery is the mainstay of therapy for [disease name].
+*[Surgical procedure] in conjunction with [chemotherapy/radiation] is the most common approach to the treatment of [disease name].
+*[Surgical procedure] can only be performed for patients with [disease stage] [disease name].
+=== Prevention ===
+*There are no primary preventive measures available for [disease name].
+*Effective measures for the primary prevention of [disease name] include [measure1], [measure2], and [measure3].
-==Complications==
+*Once diagnosed and successfully treated, patients with [disease name] are followed-up every [duration]. Follow-up testing includes [test 1], [test 2], and [test 3].
-Complications that can develop as a result of pseudohypoparathyroidism are
+==References==
-*[[Seizures]] (children).
+Pancoast syndrome (Pancoast’s syndrome) typically   results when a malignant neoplasm of the superior sulcus of the lung (lung cancer) leads to destructive lesions of the thoracic inlet and involvement of the brachial plexus and cervical sympathetic nerves (stellate ganglion). [1, 2, 3] This is accompanied by the following:
-*[[Hypothyroidism]] due to associated resistance to [[thyrotropin]].
-*[[Gonadotropin]] or [[GHRH]] resistance.
-*Patients may develop [[hypocalcemia]] resulting in<ref name="pmid18663313">{{cite journal |vauthors=Shalitin S, Davidovits M, Lazar L, Weintrob N |title=Clinical heterogeneity of pseudohypoparathyroidism: from hyper- to hypocalcemia |journal=Horm. Res. |volume=70 |issue=3 |pages=137–44 |year=2008 |pmid=18663313 |doi=10.1159/000137658 |url=}}</ref>
-**[[Paresthesias]]
-** Muscular cramping
-**[[Tetany]]
-**[[Carpopedal spasm]]
-*Subcutaneous [[calcification]] in [[neonatal]] period.<ref name="pmid20011056">{{cite journal |vauthors=Adachi M, Muroya K, Asakura Y, Kondoh Y, Ishihara J, Hasegawa T |title=Ectopic calcification as discernible manifestation in neonates with pseudohypoparathyroidism type 1a |journal=Int J Endocrinol |volume=2009 |issue= |pages=931057 |year=2009 |pmid=20011056 |pmc=2778176 |doi=10.1155/2009/931057 |url=}}</ref>
+Severe pain in the shoulder region radiating toward the axilla and scapula, with later extension along the ulnar aspect of the arm to the hand
+Atrophy of hand and arm muscles
+Horner syndrome ( ptosis, miosis, hemianhidrosis, enophthalmos)
+Compression of the blood vessels with edema
+Most Pancoast tumors are squamous cell carcinomas (SCCs) or adenocarcinomas; only 3-5% are small cell carcinomas. Squamous cell carcinoma occurs more frequently, although large cell and undifferentiated types are also common. Adenocarcinoma is sometimes found in this location and can even be metastatic. Involvement of the phrenic or recurrent laryngeal nerve or superior vena cava obstruction is not representative of the classic Pancoast tumor.
-*Reproductive dysfunction is seen in patients with pseudohypoparathyroidism 1a. Women may experience delayed [[puberty]], [[oligomenorrhea]], and [[infertility]].In men decreased [[Fertility]]  may present with maturation arrest of [[Testes]] and [[cryptorchidism]].
+Once universally fatal, Pancoast tumors are currently treatable with outcomes similar to those of other stage-matched non–small cell lung cancers. [4] Careful assessment and appropriate staging are performed before surgery, and selected patients are administered preoperative irradiation of 30 Gy over 2 weeks. After an interval of 2-4 weeks, surgical resection of the chest wall and lower brachial plexus and en bloc lung resection produces a 5-year survival rate of 30%. Contraindications to surgical management include the following:
-*Pseudohypoparathyroidism type 1b patients are at risk of developing tertiary [[hyperparathyroidism]] and [[hyperparathyroid]] bone disease. <ref name="pmid22736772">{{cite journal |vauthors=Neary NM, El-Maouche D, Hopkins R, Libutti SK, Moses AM, Weinstein LS |title=Development and treatment of tertiary hyperparathyroidism in patients with pseudohypoparathyroidism type 1B |journal=J. Clin. Endocrinol. Metab. |volume=97 |issue=9 |pages=3025–30 |year=2012 |pmid=22736772 |pmc=3431579 |doi=10.1210/jc.2012-1655 |url=}}</ref>
+Extension of the tumor into the neck or vertebrae
+Presence of substantial mediastinal lymph nodes
+Peripheral tumor dissemination
+Protocols that use combinations of radiation therapy, chemotherapy, and surgery are currently being studied to determine the best therapy.
-*[[Osteopenia]] and [[rickets]] in peudohypoparathyroidism-1a  is associated with variable [[osteoclast]] responsiveness to [[parathyroid]] hormone.<ref name="pmid18805917">{{cite journal |vauthors=Balavoine AS, Ladsous M, Velayoudom FL, Vlaeminck V, Cardot-Bauters C, d'Herbomez M, Wemeau JL |title=Hypothyroidism in patients with pseudohypoparathyroidism type Ia: clinical evidence of resistance to TSH and TRH |journal=Eur. J. Endocrinol. |volume=159 |issue=4 |pages=431–7 |year=2008 |pmid=18805917 |doi=10.1530/EJE-08-0111 |url=}}</ref>
+Pathophysiology
+Pancoast tumors are a subset of lung cancers that invade the apical chest wall. Because of their location in the pleural apex, they invade adjoining tissue. Although other tumors may have a similar clinical presentation because of their location at the thoracic inlet, the most common cause is believed to be a bronchogenic carcinoma arising in or near the superior sulcus and invading adjacent extrathoracic structures by direct extension. Location, rather than pathology or histology of origin, is significant in producing the tumor’s characteristic clinical pattern. [5]
-==Prognosis==
+The bulk of a true Pancoast tumor is extrathoracic, originating in an extreme peripheral location with a plaquelike extension over the lung apex and principally involving the chest wall structures rather than the underlying lung parenchyma. Bronchogenic carcinomas occurring in the narrow confines of the thoracic inlet invade the lymphatic vessels in the endothoracic fascia and include, by direct extension, the following structures:
-Insufficient data is available to determine the long term outcomes of pseudohypoparathyroidism. In some patients [[calcium]] [[homeostasis]] adapts to [[parathyroid]] hormone resistance resulting in resolution of [[hypocalcemia]] while others who do not adapt to [[parathyroid hormone]] resistance are managed with lifelong [[calcium]] supplementation. Long term [[levothyroxine]] is used in patients with associated [[Hypothyroidism|hypothyroidism.]]
-==Diagnosis==
+Intercostal nerves
+Lower roots of the brachial plexus
+Stellate ganglion
+Sympathetic chain
+Adjacent ribs and vertebrae.
+Carcinomas in the superior pulmonary sulcus produce Pancoast syndrome, thus causing pain in the shoulder and along the ulnar nerve distribution of the arm and hand. [6] (These carcinomas also cause Horner syndrome.) These apical lung tumors tend to be locally invasive early. In the absence of metastases and regional nodal involvement, these apical cancers can be successfully treated.
-===Diagnostic Criteria===
+The tumor may invade the bony structures of the chest, including the first or second thoracic vertebra or the first, second, or third rib. In a review of 60 patients with Pancoast tumors, Maggi et al found radiographic evidence of rib erosion in 50%; an almost equal percentage demonstrated involvement of the first or second rib, and 20% had involvement of the third rib. One patient had involvement of all 3 ribs. [7]
-The diagnosis of pseudohypoparathyroidism Type 1a patients includes:
-*Clinical features of [[Albright's hereditary osteodystrophy]]
-*[[Parathyroid]] hormone resistance evidenced by
-**[[Hypocalcemia]]
-**[[Hyperphosphatemia]]
-**Elevated serum concentration of [[parathyroid]] hormone
-**Diminished urinary [[cAMP]] response after administration of the biosynthetic N-terminal fragment of [[parathyroid]] hormone.
-===History and Symptoms===
+The tumor can also invade the first or second thoracic vertebral bodies or intervertebral foramina. From this point, it can extend to the spinal cord and result in cord compression. The subclavian vein or artery may also be invaded.
-*A positive family history of pseudohypoparathyroidism is suggestive of the [[autosomal dominant]] inheritance.
-*The most common symptoms of pseudohypoparathyroidism type 1a include [[short stature]],[[mental retardation]] associated with [[Albright's hereditary osteodystrophy|Albright hereditary Osteodystrophy]] [[phenotype]].
+Etiology
+The overwhelming majority of cases of Pancoast syndrome are non–small cell lung carcinoma (NSCLC), with more than 95% located in the superior sulcus. The most common varieties are SCC and adenocarcinoma; large cell carcinoma has also been reported.
-*Common symptoms due to associated [[hypocalcemia]] include
+Although quite rare (responsible for fewer than 5% percent of cases in most series), small cell carcinoma is also observed. Maggi et al reported small cell carcinoma in only 3 of the 60 patients in their series. [7] More typically, small cell carcinoma manifests in a central rather than a peripheral location.
-**[[Paresthesia|Paresthesias]] (peri-oral, extremities)
-**[[Muscle twitching]]
-**[[Carpopedal spasm]]
-**[[Seizures]]
-**[[Prolonged QT interval]]
-**[[Hypotension]]
-**[[Arrhythmia]].
-===Physical Examination===
+Although NSCLC is by far the most common cause of Pancoast syndrome, the list of differential diagnoses is broad. Because of the wide variety of diseases that can produce Pancoast syndrome, a histologic diagnosis is mandatory before definitive treatment is initiated.
-*Patients with pseudohypoparathyroidism type1A , type 1c and pseudopseudohypoparathyroidism presents by the second decade of life with characteristic physical features of [[Albright's hereditary osteodystrophy]] like:
-**Subcutaneous ossifications
-**Shortening of third, fourth, and fifth [[metacarpals]] and [[metatarsals]]
-**Round face
-**Obesity
-**Frontal bossing
-**Dental [[hypoplasia]]
-*Pseudohypoparathyroidism Type 1B isolated resistance to [[parathyroid hormone]] without the associated clinical features of [[Albright's hereditary osteodystrophy|Albright's osteodystrophy]]. Mild [[brachydactyly]] is seen in some cases.
+Rare causes include the following:
-*Blomstrand's chondrodystrophy presents with short limbs due to characteristic growth impairment.Secondary [[hyperplasia]] of the [[parathyroid glands]] occurs as a result of associated [[hypocalcemia]].
+Desmoid tumors [8]
+Hemangiopericytoma [9]
+Adenoid cystic carcinoma [10]
+Metastatic carcinoma [11]
+Lymphoma [12]
+Thyroid carcinoma [13]
+Bacterial [14, 15] and fungal infections [16, 17]
+Lymphomatoid granulomatosis
+Vascular aneurysms
+Amyloid nodules
+Cervical rib syndrome
+Inflammatory pseudotumor (plasma cell granuloma)
+Mycotic subclavian artery aneurysm
+Carotid pseudoaneurysm in a child (caused by a hydatid cyst)
+Risk factors are similar for almost all lung cancers and include the following:
-*Acrodysostosis characteristic physical findings include<ref name="pmid5551869">{{cite journal |vauthors=Robinow M, Pfeiffer RA, Gorlin RJ, McKusick VA, Renuart AW, Johnson GF, Summitt RL |title=Acrodysostosis. A syndrome of peripheral dysostosis, nasal hypoplasia, and mental retardation |journal=Am. J. Dis. Child. |volume=121 |issue=3 |pages=195–203 |year=1971 |pmid=5551869 |doi= |url=}}</ref>
+Prolonged asbestos exposure
-**Short hands;
+Exposure to industrial elements (eg, gold, nickel)
-**Small, flat, upturned nose;
+Tobacco smoking
-**Mild to moderate intellectual disability.
+Secondary smoke exposure
-**Hypoplastic genitalia
+Epidemiology
-**[[Cryptorchidism]]
+Overall, Pancoast tumors are much less common than other lung cancers, accounting for fewer than 5% of these cancers (1-3% in various previous series). [18, 19] Originally deemed universally fatal, Pancoast tumors are now amenable to curative treatment because of improvements in combined modality therapy and development of new techniques for resection.
-===Laboratory Findings===
+Prognosis
-*The diagnosis of pseudohypoparathyroidism is made by measurement of variations in serum [[calcium]], [[phosphorus]], [[cAMP]] and [[calcitriol]] and in urinary [[Cyclic adenosine monophosphate|cAMP]] and [[phosphorus]] excretion helps in assessment of skeletal and renal responsiveness to [[parathyroid]] hormone.
+The prognosis for patients with Pancoast syndrome is stage dependent. Adverse prognostic factors include the following:
-*Laboratory findings consistent with the diagnosis of pseudohypoparathyroidism include
-**[[Hypocalcemia]]
-**[[Hyperphosphatemia]]
-**Elevated serum concentration of [[parathyroid hormone]]
-**Diminished urinary [[cAMP]] response after administration of the biosynthetic N-terminal fragment of [[parathyroid]] hormone
-**[[Secondary hyperparathyroidism]] and [[hyperparathyroid]] bone disease due to the [[parathyroid]] hormone resistance .
-*Immunoradiometric assay (IRMA) can be used to measure serum [[parathyroid]] hormone concentration.<ref name="pmid18663313">{{cite journal |vauthors=Shalitin S, Davidovits M, Lazar L, Weintrob N |title=Clinical heterogeneity of pseudohypoparathyroidism: from hyper- to hypocalcemia |journal=Horm. Res. |volume=70 |issue=3 |pages=137–44 |year=2008 |pmid=18663313 |doi=10.1159/000137658 |url=}}</ref>
+Presence of Horner syndrome
+Involvement of mediastinal lymph nodes
+Incomplete resection
+Involvement of supraclavicular lymph node
+Vertebral body invasion
+To date, no patient with the first 3 prognostic factors has survived for 5 years.
-*Assessment of [[thyroid function tests]], [[gonadotropin]], [[testosterone]], [[estrogen]] and insulin like growth factor will help in identification of any associated underlying hormonal dysfunction
+Distant disease limits survival. Treatment failure is especially frequent in patients with involvement of the brain. The authors recommend careful surveillance for brain metastasis during and after the therapy. The authors also recommend obtaining brain imaging prior to surgery in patients receiving induction therapy for the primary tumor.
-===Electrocardiogram===
+Mortality and survival
-An [[ECG]] may be helpful in the diagnosis of cardiac dysfunction associated with the pseudohypoparathyroidism. Findings on an ECG suggestive of cardiac dysfunction due to  [[hypocalcemia]] associated with pseudohypoparathyroidism include [[prolonged QT]] interval.
+Attar et al reported a median survival of 36.8 months in patients with T3 lesions undergoing combined modality treatment; median survival was only 6.4 months if the patient had T4 disease. [20]
-===X-ray===
+Overall survival data were summarized by Detterbeck, who noted that 5-year survival rates ranged from 15% to 56%. [21] Of the 104 patients treated by Attar and coworkers, 7 (~7%) were 5-year survivors and 3 (~3%) were 10-year survivors. [20] Another study demonstrated surgical morbidity rates of 7-38%, with mortality ranging from 5% to 10%. [22]
-An [[x-ray]] of the hand may be helpful in the diagnosis of [[pseudohypoparathyroidism]]. Findings on an x-ray include short distal phalanx of thumb and short third to fifth metacarpals associated with features of [[Albright's hereditary osteodystrophy|albright hereditary osteodystrophy.]]
-An [[x-ray]] of the hand may be helpful in the diagnosis of acrodysostosis. Findings on an x-ray of hand include shortened [[metacarpals]] with cone [[epiphyses]]. The spine may also be affected with loss of [[caudal]] widening of interpedicular distance, which may correlate with stenosis of the spinal canal<ref name="pmid5551869">{{cite journal |vauthors=Robinow M, Pfeiffer RA, Gorlin RJ, McKusick VA, Renuart AW, Johnson GF, Summitt RL |title=Acrodysostosis. A syndrome of peripheral dysostosis, nasal hypoplasia, and mental retardation |journal=Am. J. Dis. Child. |volume=121 |issue=3 |pages=195–203 |year=1971 |pmid=5551869 |doi= |url=}}</ref>
+For neoplastic causes, predictors of 5-year survival are weight loss, supraclavicular fossa or vertebral body involvement, disease stage, and surgical treatment. A study by an MD Anderson group reported the following findings [23] :
-===Echocardiography or Ultrasound===
+For patients with stage IIB disease, the 5-year survival rate was 47%, whereas for those with stage IIIA and IIIB disease, it was 14% and 16%, respectively
-There are no [[echocardiography]]/[[ultrasound]]  findings associated with pseudohypoparathyroidism.
+In patients with stage IIB disease, surgical treatment and weight loss were significant independent predictors of 5-year survival
+Among patients with stage IIIA disease, the only predictor of survival was the Karnofsky performance score
+In patients with stage IIIB disease, the only independent predictor of survival was a right superior sulcus location, which was associated with a worse 5-year survival rate than a left superior sulcus location
+Compared with patients who had squamous cell tumors, more patients with adenocarcinoma had cerebral metastases within 5 years
+Relapse
+Locoregional relapse is common despite preoperative or postoperative radiation therapy. Muscolino et al found locoregional recurrence in 60% of patients treated with a combined radiosurgical approach. Ginsberg et al found that 94 of their 124 patients had recurrence of disease, with 72% of these cases being locoregional at initial recurrence. In two thirds of patients who underwent complete resection, local recurrences were the first site of relapse. [18]
-===CT scan===
+This distribution of relapses was noted in several studies reviewed by Detterbeck. In many of these studies, patients received preoperative radiation therapy. [21] In the Memorial Sloan-Kettering experience, additional postoperative brachytherapy was administered to achieve maximal possible local control; despite these measures, local relapses and, ultimately, distant relapses were frequent. [18]
-Findings on [[CT scan]] suggestive of pseudohypoparathyroidism in some patients includes include symmetric calcifications in [[basal ganglia]], perivascular calcifications in soft tissues. <ref name="pmid1638002">{{cite journal |vauthors=Nekula J, Urbanek K, Buresova J |title=[Radiological findings in pseudohypoparathyroidism] |language=German |journal=Rofo |volume=157 |issue=1 |pages=34–6 |year=1992 |pmid=1638002 |doi=10.1055/s-2008-1032961 |url=}}</ref>
-===MRI===
+Pancoast syndrome (Pancoast’s syndrome) typically   results when a malignant neoplasm of the superior sulcus of the lung (lung cancer) leads to destructive lesions of the thoracic inlet and involvement of the brachial plexus and cervical sympathetic nerves (stellate ganglion). [1, 2, 3] This is accompanied by the following:
-Findings on brain [[MRI]] in pseudohypoparathyroidism Ia patients, particularly those with abnormal [[neurological examination]] or [[developmental delay]] include [[Arnold-Chiari malformation|Chiari Malformation-Type I]] .
-===Other Imaging Findings===
+Severe pain in the shoulder region radiating toward the axilla and scapula, with later extension along the ulnar aspect of the arm to the hand
-There are no other imaging findings associated with psuedohypoparathyroidism.
+Atrophy of hand and arm muscles
+Horner syndrome ( ptosis, miosis, hemianhidrosis, enophthalmos)
+Compression of the blood vessels with edema
+Most Pancoast tumors are squamous cell carcinomas (SCCs) or adenocarcinomas; only 3-5% are small cell carcinomas. Squamous cell carcinoma occurs more frequently, although large cell and undifferentiated types are also common. Adenocarcinoma is sometimes found in this location and can even be metastatic. Involvement of the phrenic or recurrent laryngeal nerve or superior vena cava obstruction is not representative of the classic Pancoast tumor.
-===Other Diagnostic Studies===
+Once universally fatal, Pancoast tumors are currently treatable with outcomes similar to those of other stage-matched non–small cell lung cancers. [4] Careful assessment and appropriate staging are performed before surgery, and selected patients are administered preoperative irradiation of 30 Gy over 2 weeks. After an interval of 2-4 weeks, surgical resection of the chest wall and lower brachial plexus and en bloc lung resection produces a 5-year survival rate of 30%. Contraindications to surgical management include the following:
-*Genetic testing may be helpful in the diagnosis of pseudohypoparathyroidism. Analysis of the [[GNAS1|''GNAS1'' gene]] can confirm diagnosis and identify the different variants of PHP. Testing for paternal uniparental isodisomy of chromosome 20q or deletions in [[STX16|STX]]16 can also help in diagnosis of pseudohypoparathyroidism 1b. <ref name="pmid26943720">{{cite journal |vauthors=Clarke BL, Brown EM, Collins MT, Jüppner H, Lakatos P, Levine MA, Mannstadt MM, Bilezikian JP, Romanischen AF, Thakker RV |title=Epidemiology and Diagnosis of Hypoparathyroidism |journal=J. Clin. Endocrinol. Metab. |volume=101 |issue=6 |pages=2284–99 |year=2016 |pmid=26943720 |pmc=5393595 |doi=10.1210/jc.2015-3908 |url=}}</ref>
-*Gsα defects can be diagnosed by assessment of variations in [[platelet aggregation]] responses reflecting a patient's [[genotype]].<ref name="pmid18812479">{{cite journal |vauthors=Freson K, Izzi B, Labarque V, Van Helvoirt M, Thys C, Wittevrongel C, Bex M, Bouillon R, Godefroid N, Proesmans W, de Zegher F, Jaeken J, Van Geet C |title=GNAS defects identified by stimulatory G protein alpha-subunit signalling studies in platelets |journal=J. Clin. Endocrinol. Metab. |volume=93 |issue=12 |pages=4851–9 |year=2008 |pmid=18812479 |doi=10.1210/jc.2008-0883 |url=}}</ref>
+Extension of the tumor into the neck or vertebrae
+Presence of substantial mediastinal lymph nodes
+Peripheral tumor dissemination
+Protocols that use combinations of radiation therapy, chemotherapy, and surgery are currently being studied to determine the best therapy.
+Pathophysiology
+Pancoast tumors are a subset of lung cancers that invade the apical chest wall. Because of their location in the pleural apex, they invade adjoining tissue. Although other tumors may have a similar clinical presentation because of their location at the thoracic inlet, the most common cause is believed to be a bronchogenic carcinoma arising in or near the superior sulcus and invading adjacent extrathoracic structures by direct extension. Location, rather than pathology or histology of origin, is significant in producing the tumor’s characteristic clinical pattern. [5]
-*Psuedohypoparathyroidism type 1b associated bone disease can be evaluated with [[bone mineral density]] (BMD) testing.
+The bulk of a true Pancoast tumor is extrathoracic, originating in an extreme peripheral location with a plaquelike extension over the lung apex and principally involving the chest wall structures rather than the underlying lung parenchyma. Bronchogenic carcinomas occurring in the narrow confines of the thoracic inlet invade the lymphatic vessels in the endothoracic fascia and include, by direct extension, the following structures:
-==Treatment==
+Intercostal nerves
-===Medical Therapy===
+Lower roots of the brachial plexus
-*The mainstay of treatment for pseudohypoparathyroidism is oral [[calcium]] and 1alpha-hydroxylated vitamin D metabolites, such as [[calcitriol]]. Other forms of Vitamin D cannot be used as [[parathyroid]] hormone resistance in the [[proximal tubule]] decreases the efficiency of production of 1,25(OH)2 vitamin D from 25-hydroxyvitamin D.
+Stellate ganglion
-*The majority of cases of pseudohypoparathyroidism are self-limited and require only supportive care.
+Sympathetic chain
-* The goal is to maintain serum [[calcium]] within the normal range to prevent [[hypercalciuria]] and to maintain [[parathyroid]] hormone levels within reference range which helps prevent bone remodeling and [[hyperparathyroid]] bone disease that can result from elevated [[parathyroid hormone]] level.
+Adjacent ribs and vertebrae.
-*Intravenous calcium is recommended for all patients who develop severe symptomatic [[hypocalcemia]]. Adult dosage is started 100 mg of elemental [[calcium]] (either [[calcium chloride]] or [[calcium gluconate]]) over 10 to 20 minutes. An additional dose of 100 mg/hr of [[elemental calcium]] can be infused if symptoms do not resolve, with close monitoring of [[calcium]] levels.Cardiac monitoring may help to guide therapy as rapid infusion of [[calcium]] can cause cardiac conduction defects;
+Carcinomas in the superior pulmonary sulcus produce Pancoast syndrome, thus causing pain in the shoulder and along the ulnar nerve distribution of the arm and hand. [6] (These carcinomas also cause Horner syndrome.) These apical lung tumors tend to be locally invasive early. In the absence of metastases and regional nodal involvement, these apical cancers can be successfully treated.
-* [[Parenteral|Parentera]]<nowiki/>l formulations available are [[calcium chloride]] and [[calcium gluconate]]; a 10-mL ampule of 10% [[calcium chloride]] contains 360 mg of [[elemental calcium]], and a 10-mL ampule of 10% [[calcium gluconate]] contains 93 mg of elemental [[calcium]].
-*For [[neonates]], [[infants]], and [[children]], the recommended initial dose is 0.5-1 mL/kg of 10% [[calcium gluconate]] administered over 5 minutes.
+The tumor may invade the bony structures of the chest, including the first or second thoracic vertebra or the first, second, or third rib. In a review of 60 patients with Pancoast tumors, Maggi et al found radiographic evidence of rib erosion in 50%; an almost equal percentage demonstrated involvement of the first or second rib, and 20% had involvement of the third rib. One patient had involvement of all 3 ribs. [7]
-===Surgery===
-*Surgery is not the first-line treatment option for patients with psuedohypoparathyroidism.
-*Surgical resection of enlarged [[parathyroid glands]] is usually reserved for patients that develop [[tertiary hyperparathyroidism]] in pseudohypoparathyroidism 1b. Rarely,  excision of extraskeletal [[osteomas]] is done to relieve associated pressure symptoms in patients.  <ref name="pmid22736772" />
-===Primary Prevention===
-Effective measures for the primary prevention of pseudohypoparathyroidism include [[genetic counseling]] in inherited cases.
-===Secondary Prevention===
-Monitor therapy with regular serum and urinary [[calcium]] measurements.Pseudohypoparathyroidism type 1b patients at an increased risk of developing [[hyperparathyroidism]] and [[hyperparathyroid]] bone disease should be maintained at sufficient doses of [[calcium]] and [[vitamin D]] to maintain serum [[calcium]] and [[PTH]] levels within the normal range. Monitor therapy with regular serum and urinary [[calcium]] measurements.
-==References==
-{{reflist|2}}
-{{WikiDoc Help Menu}}
+The tumor can also invade the first or second thoracic vertebral bodies or intervertebral foramina. From this point, it can extend to the spinal cord and result in cord compression. The subclavian vein or artery may also be invaded.
-{{WikiDoc Sources}}

Sandbox:Mazia: Difference between revisions

Latest revision as of 19:11, 16 February 2018

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