Acromegaly: Difference between revisions

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== Definition/Description 
==
== Definition/Description 
==


肢端肥大症是一种罕见的系统性疾病的影响s the entire body.1. Vance M. Acromegaly: a fascinating pituitary disorder. Neurosurg Focus 2010;29(4):1. It is characterized by a hypersecretion of growth hormone (GH) which the body is unable to regulate.2. Cordero RA, Barkan AL. Current diagnosis of acromegaly. Rev Endocr Metab Disord 2008;9:13-19. GH facilitates growth of muscles, internal organs, and bones, as well as stimulating secretion of its target hormone insulin-like growth factor 1 (IGF-1).>1.</ref> ,3.Merck Manual Home Edition. Acromegaly and gigantism: pituitary gland disorders. http://www.merckmanuals.com/home/print/sec13/ch162e.html (Accessed March 11 2011). The extremely high levels of GH and IGF-1 which typify acromegaly cause tissue enlargement and metabolic changes that result in visible deformity as well as an increase in mortality.>2.</ref>4.Fleseriu M, Delashaw JB, Cook DM. Acromegaly: a review of current medical therapy and new drugs on the horizon. Neurosurg Focus 2010;29(4):E15. The disease often begins between the ages of 30 and 50, and has an insidious onset and slow progression, often delaying diagnosis until later stages of the disease.>2.</ref>>3.</ref>
肢端肥大症是一种罕见的系统性疾病的影响s the entire body.1. Vance M. Acromegaly: a fascinating pituitary disorder. Neurosurg Focus 2010;29(4):1. It is characterized by a hypersecretion of growth hormone (GH) which the body is unable to regulate.2. Cordero RA, Barkan AL. Current diagnosis of acromegaly. Rev Endocr Metab Disord 2008;9:13-19. GH facilitates growth of muscles, internal organs, and bones, as well as stimulating secretion of its target hormone insulin-like growth factor 1 (IGF-1). ,3.Merck Manual Home Edition. Acromegaly and gigantism: pituitary gland disorders. http://www.merckmanuals.com/home/print/sec13/ch162e.html (Accessed March 11 2011). The extremely high levels of GH and IGF-1 which typify acromegaly cause tissue enlargement and metabolic changes that result in visible deformity as well as an increase in mortality.4.Fleseriu M, Delashaw JB, Cook DM. Acromegaly: a review of current medical therapy and new drugs on the horizon. Neurosurg Focus 2010;29(4):E15. The disease often begins between the ages of 30 and 50, and has an insidious onset and slow progression, often delaying diagnosis until later stages of the disease.


[[Image:Acromegaly classic woman.gif|Serial photos of woman with acromegaly]]
[[Image:Acromegaly classic woman.gif|Serial photos of woman with acromegaly]]
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== Prevalence ==
== Prevalence ==


*,肢端肥大症患病率is  approximately 40-70 cases per million persons.>2.</ref>>4.</ref> 
*,肢端肥大症患病率is  approximately 40-70 cases per million persons. 
*However, new research suggests that the prevalence may be as high as 77 cases per million persons.>4.</ref>
*However, new research suggests that the prevalence may be as high as 77 cases per million persons.
*The annual incidence of acromegaly is approximately is 3-4 new cases per million persons.>4.</ref>
*The annual incidence of acromegaly is approximately is 3-4 new cases per million persons.


== Characteristics/Clinical Presentation ==
== Characteristics/Clinical Presentation ==


Acromegaly affects many of the body's systems, and various signs and symptoms develop over a period of several years.5. Reid TJ, Post KD, Bruce JN, Kanibir MN, Reyes-Vidal CM, Freda PU. Features at diagnosis of 324 patients with acromegaly did not change from 1981 to 2006: acromegaly remains under-recognized and under-diagnosed. Clinical Endocrinology 2010;72:203-208. They range from subtle changes to notable disfigurement.>2.</ref>
Acromegaly affects many of the body's systems, and various signs and symptoms develop over a period of several years.5. Reid TJ, Post KD, Bruce JN, Kanibir MN, Reyes-Vidal CM, Freda PU. Features at diagnosis of 324 patients with acromegaly did not change from 1981 to 2006: acromegaly remains under-recognized and under-diagnosed. Clinical Endocrinology 2010;72:203-208. They range from subtle changes to notable disfigurement.


Clinical Presentation>2.</ref>>3.</ref>>5.</ref>6.Melmed S. Acromegaly pathogenesis and treatment. J. Clin. Invest 2009;119:3189-3202.:
Clinical Presentation6.Melmed S. Acromegaly pathogenesis and treatment. J. Clin. Invest 2009;119:3189-3202.:


*Hand and foot enlargement
*Hand and foot enlargement
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== Associated Co-morbidities ==
== Associated Co-morbidities ==


IGF-1, the target molecule of GH, enables many of the growth-promoting actions of GH; GH itself is also a regulator of mineral, lipid, and carbohydrate metabolism.>6.</ref> Therefore the elevated levels of GH and IGF-1 which are characteristic of acromegaly excessive soft tissue growth, swelling of internal organs, and musculoskeletal, neurological, and metabolic comorbidities.>6.</ref> 
IGF-1, the target molecule of GH, enables many of the growth-promoting actions of GH; GH itself is also a regulator of mineral, lipid, and carbohydrate metabolism. Therefore the elevated levels of GH and IGF-1 which are characteristic of acromegaly excessive soft tissue growth, swelling of internal organs, and musculoskeletal, neurological, and metabolic comorbidities. 


Cardiovascular:>1.</ref>>2.</ref>>5.</ref>>6.</ref>
Cardiovascular:


*Hypertension
*Hypertension
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Pulmonary:>1.</ref>>2.</ref>>5.</ref>>6.</ref>
Pulmonary:


*Obstructive sleep apnea
*Obstructive sleep apnea
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Metabolic:>1.</ref>>2.</ref>>6.</ref>
Metabolic:


*Insulin resistance
*Insulin resistance
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Visceral:>1.</ref>>6.</ref>
Visceral:


*Organ enlargement
*Organ enlargement
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Musculoskeletal:>2.</ref>
Musculoskeletal:


*Arthropathy/osteoarthritis
*Arthropathy/osteoarthritis
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== Medications ==
== Medications ==


*Somatostatin analogs- somatostatin inhibits endocrine cells, including GH-secreting cells of the pituitary gland.  Somatostatin analogs (SSAs) mimic the GH-suppressing effects of the body's own somatostatin.>4.</ref>  SSAs are one of the most common medications prescribed for acromegaly.  There are currently three SSAs approved in the US: short-acting octreotride, octreotride LAR, and Somatuline Depot.>2.</ref> Most common adverse events are glucose intolerance, and gallbladder and sludge stones.>4.</ref>
*Somatostatin analogs- somatostatin inhibits endocrine cells, including GH-secreting cells of the pituitary gland.  Somatostatin analogs (SSAs) mimic the GH-suppressing effects of the body's own somatostatin.  SSAs are one of the most common medications prescribed for acromegaly.  There are currently three SSAs approved in the US: short-acting octreotride, octreotride LAR, and Somatuline Depot. Most common adverse events are glucose intolerance, and gallbladder and sludge stones.
*Dopamine agonists- leads to GH suppression in a portion of acromegaly patients.  Interestingly, this medication stimulates GH release in healthy patients.>4.</ref>  Advantages of this medication are relatively low cost, oral administration, and no hypopituitarism associated with medication.  However,  the medication is only effective at lowering GH and IGF-1 to safe levels in approximately 10% of patients, and potentially causes cardiac valvular damage.>4.</ref>
*Dopamine agonists- leads to GH suppression in a portion of acromegaly patients.  Interestingly, this medication stimulates GH release in healthy patients.  Advantages of this medication are relatively low cost, oral administration, and no hypopituitarism associated with medication.  However,  the medication is only effective at lowering GH and IGF-1 to safe levels in approximately 10% of patients, and potentially causes cardiac valvular damage.
*Growth hormone receptor agonists- blocks the GH signal for IGF-1 production.  More effective for patients with higher levels of IGF-1, and demonstrated a more favorable influence on glycemic control.>4.</ref> Adverse events often associated with growth hormone receptor agonists are compromised liver function and reactions at the injection site.>4.</ref> < ref name = " Del波尔图“> 7。德尔·波尔图拉,Liubinas SV, Kaye AH. Treatment of persistent acromegaly. J Clin Neurosci 2011; 18:181-190.
*Growth hormone receptor agonists- blocks the GH signal for IGF-1 production.  More effective for patients with higher levels of IGF-1, and demonstrated a more favorable influence on glycemic control. Adverse events often associated with growth hormone receptor agonists are compromised liver function and reactions at the injection site.7.Del Porto LA, Liubinas SV, Kaye AH. Treatment of persistent acromegaly. J Clin Neurosci 2011; 18:181-190.


[[Image:Acromegaly-GHRA 4-7-.jpg|left|300px]]
[[Image:Acromegaly-GHRA 4-7-.jpg|left|300px]]
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Diagnostic Tests:
Diagnostic Tests:


Oral Glucose Tolerance Test (OGTT)- glucose has a neuroendocrine suppressive signal that lowers GH.>6.</ref>  In this test, 75 g of glucose is administered with GH measurements at different points over a period of 120 minutes.>2.</ref> The failure to suppress GH secretion to less than 1 microgram/liter is currently the standard for diagnosis of acromegaly.>6.</ref>
Oral Glucose Tolerance Test (OGTT)- glucose has a neuroendocrine suppressive signal that lowers GH.  In this test, 75 g of glucose is administered with GH measurements at different points over a period of 120 minutes. The failure to suppress GH secretion to less than 1 microgram/liter is currently the standard for diagnosis of acromegaly.


Magnetic Resonance Imaging (MRI)- the preferred imaging method when diagnosing acromegaly.>2.</ref>  An MRI of the pituitary gland is taken in order to look for any abnormal growth.>3.</ref> It can help determine the tumor size, as well as compression of surrounding structures.>2.</ref>
Magnetic Resonance Imaging (MRI)- the preferred imaging method when diagnosing acromegaly.  An MRI of the pituitary gland is taken in order to look for any abnormal growth. It can help determine the tumor size, as well as compression of surrounding structures.


Blood tests- blood may be used to measure serum levels of IGF-1 in addition to GH.>2.</ref>>4.</ref>>6.</ref> High levels of IGF-1 have been used as a marker for acromegaly; IGF-1 is correlated with GH levels as well as the clinical manifestations of acromegaly.>2.</ref>>6.</ref> IGF-1 levels also tend to remain stable throughout the day, making IGF-1 testing a fairly reliable diagnostic tool.>2.</ref>>4.</ref> Generally, a diagnosis of acromegaly can be excluded if IGF-1 levels are within the normal range.>7.</ref>
Blood tests- blood may be used to measure serum levels of IGF-1 in addition to GH. High levels of IGF-1 have been used as a marker for acromegaly; IGF-1 is correlated with GH levels as well as the clinical manifestations of acromegaly. IGF-1 levels also tend to remain stable throughout the day, making IGF-1 testing a fairly reliable diagnostic tool. Generally, a diagnosis of acromegaly can be excluded if IGF-1 levels are within the normal range.


Radiographs- an x-ray of the skull can show bone thickening as well as enlargement of the nasal sinuses.>3.</ref> Thickening of the carpal phalanges can be seen in x-rays of the hands.>3.</ref>
Radiographs- an x-ray of the skull can show bone thickening as well as enlargement of the nasal sinuses. Thickening of the carpal phalanges can be seen in x-rays of the hands.


Computed tomography (CT)- this imaging method can be used to identify abnormal growths in the pituitary gland.>3.</ref> 
Computed tomography (CT)- this imaging method can be used to identify abnormal growths in the pituitary gland. 


Lab Values:
Lab Values:


Growth Hormone (GH)- in individuals without acromegaly, GH values are typically 0.1-0.2 micrograms/liter.  There are, however, 6-10 bursts of GH secretion where levels of the hormone are 5-30 micrograms/liter.>2.</ref> This may overlap with the values seen in patients with acromegaly.>2.</ref> Growth hormone concentrations of less than 2.5 ng/ml are associated with mortality rates similar to the normal population.>4.</ref> Thus normalization of GH levels is currently defined as below 2.5 ng/ml.>7.</ref>
Growth Hormone (GH)- in individuals without acromegaly, GH values are typically 0.1-0.2 micrograms/liter.  There are, however, 6-10 bursts of GH secretion where levels of the hormone are 5-30 micrograms/liter. This may overlap with the values seen in patients with acromegaly. Growth hormone concentrations of less than 2.5 ng/ml are associated with mortality rates similar to the normal population. Thus normalization of GH levels is currently defined as below 2.5 ng/ml.


[[Image:Acromegalic hand x-ray.jpg]][[Image:Acromegalic skull x-ray.jpg]]
[[Image:Acromegalic hand x-ray.jpg]][[Image:Acromegalic skull x-ray.jpg]]
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== Etiology/Causes ==
== Etiology/Causes ==


*绝大多数(99%)引起的肢端肥大症病例by the proliferation of somatotroph cells in the pituitary which leads to a pituitary adenoma.>2.</ref>>6.</ref> Somatotroph cells make up more than half of the hormone-secreting cells in the ptuitary.>6.</ref>
*绝大多数(99%)引起的肢端肥大症病例by the proliferation of somatotroph cells in the pituitary which leads to a pituitary adenoma. Somatotroph cells make up more than half of the hormone-secreting cells in the ptuitary.
*The pituitary tumor causes an increase in circulating levels of GH.>2.</ref>  GH mediates anabolic reactions by binding to growth hormone receptors, creating docking sites for cell signaling proteins, and initiating the synthesis of target genes like IGF-1.>7.</ref>  This in turn increases the production of insulin-like growth factor 1 (IGF-1)>2.</ref>>4.</ref>>7.</ref>.  IGF-1 causes metabolic changes and somatic growth, stimulating proliferation of cartilage, skeletal muscle and bone which ultimately lead to tissue enlargement.>2.</ref>>7.</ref>
*The pituitary tumor causes an increase in circulating levels of GH.  GH mediates anabolic reactions by binding to growth hormone receptors, creating docking sites for cell signaling proteins, and initiating the synthesis of target genes like IGF-1.  This in turn increases the production of insulin-like growth factor 1 (IGF-1).  IGF-1 causes metabolic changes and somatic growth, stimulating proliferation of cartilage, skeletal muscle and bone which ultimately lead to tissue enlargement.
*Enlargement of tissues and metabolic abnormalities cause the two to three-fold increase in mortality seen in acromegaly.>1.</ref>>2.</ref>>4.</ref>>6.</ref>>7.</ref>
*Enlargement of tissues and metabolic abnormalities cause the two to three-fold increase in mortality seen in acromegaly.


[[Image:Acromegaly fig.jpg|GH secretion and IGF-1 production]]
[[Image:Acromegaly fig.jpg|GH secretion and IGF-1 production]]
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*Acromegalic cordiomyopathy- common features include biventricular hypertrophy, thickening of cardiac walls, diastolic dysfunction, limited systolic function, and heart failure with signs of dilative cardiomyopathy.8.Colao A, Ferone D, Marzullo P, Lombardi G. Systemic complications of acromegaly: epidemiology, pathogenesis, and management. Endocrine Reviews. 2004; 25(1):102-152
*Acromegalic cordiomyopathy- common features include biventricular hypertrophy, thickening of cardiac walls, diastolic dysfunction, limited systolic function, and heart failure with signs of dilative cardiomyopathy.8.Colao A, Ferone D, Marzullo P, Lombardi G. Systemic complications of acromegaly: epidemiology, pathogenesis, and management. Endocrine Reviews. 2004; 25(1):102-152
*Mitral and aortic valve dysfunction.>8.</ref>
*Mitral and aortic valve dysfunction.
*Arrhythmia- linked to a combination of factors, including increased left ventricle wall thickness as well as late action potentials in the heart.>8.</ref>>2.</ref>
*Arrhythmia- linked to a combination of factors, including increased left ventricle wall thickness as well as late action potentials in the heart.
*Hypertension- due in part to increased plasma volume.>2.</ref>>8.</ref>
*Hypertension- due in part to increased plasma volume.
*Atherosclerosis and endothelial dysfunction>8.</ref>
*Atherosclerosis and endothelial dysfunction




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Metabolic Involvement
Metabolic Involvement


*Impaired glucose tolerance and diabetes mellitus- growth hormone counteracts the effects of insulin on glucose metabolism.>8.</ref> GH also regulates the response of tissues to insulin; as a result excessive GH may be a causative factor in insulin resistance.>8.</ref>
*Impaired glucose tolerance and diabetes mellitus- growth hormone counteracts the effects of insulin on glucose metabolism. GH also regulates the response of tissues to insulin; as a result excessive GH may be a causative factor in insulin resistance.
*受损的脂质代谢,肢端肥大症是correlated with lipid metabolism abnormalities.>8.</ref>Studies have found serum triglyceride levels to be higher in patients with acromegaly.>8.</ref>
*受损的脂质代谢,肢端肥大症是correlated with lipid metabolism abnormalities.Studies have found serum triglyceride levels to be higher in patients with acromegaly.




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Pulmonary Involvement
Pulmonary Involvement


*Mortality associated with repiratory disorders increased in patients with acromegaly.>8.</ref>
*Mortality associated with repiratory disorders increased in patients with acromegaly.
*Increased incidence of sleep apnea.>2.</ref>>8.</ref>
*Increased incidence of sleep apnea.
由于morpholo变化*桶状胸发达gy of vertebra and ribs.>8.</ref> Ribs become elongated and vertebral bodies become enlarged and elongated, which impair inspiration.>8.</ref>
由于morpholo变化*桶状胸发达gy of vertebra and ribs. Ribs become elongated and vertebral bodies become enlarged and elongated, which impair inspiration.


== Medical Management (current best evidence) ==
== Medical Management (current best evidence) ==


The goal of currrent medical management is to reduce the effects of the pituitary tumor by surgical resection, regulate the hypersecretion of GH and IGF-1 with medication, attempt to improve the numerous comorbidities associated with the disease, reduce the mortality risk, and maintain normal function of the pituitary gland.>4.</ref>
The goal of currrent medical management is to reduce the effects of the pituitary tumor by surgical resection, regulate the hypersecretion of GH and IGF-1 with medication, attempt to improve the numerous comorbidities associated with the disease, reduce the mortality risk, and maintain normal function of the pituitary gland.




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Surgery
Surgery


*Pituitary surgery is often the first choice in acromegaly management because it can reduce hypersecretion of GH and IGF-1 and reduce the effects of the tumor on surrounding brain structures.>7.</ref>
*Pituitary surgery is often the first choice in acromegaly management because it can reduce hypersecretion of GH and IGF-1 and reduce the effects of the tumor on surrounding brain structures.
*The goal of surgical debulking is to resect as much of the tumor as possible while still maintaining normal function of the pituitary gland.>4.</ref>>6.</ref>
*The goal of surgical debulking is to resect as much of the tumor as possible while still maintaining normal function of the pituitary gland.
*Resection of adenomas in the pituitary gland is difficult due to the location of the pituitary gland and its proximity to important vascular and neural structures.>6.</ref> As a result, surgery is most successful with an experienced surgeon; numerous studies have demonstrated that the outcome of surgical treatment of acromegaly is correlated with the level of experience of the surgeon.>7.</ref>
*Resection of adenomas in the pituitary gland is difficult due to the location of the pituitary gland and its proximity to important vascular and neural structures. As a result, surgery is most successful with an experienced surgeon; numerous studies have demonstrated that the outcome of surgical treatment of acromegaly is correlated with the level of experience of the surgeon.


[[Image:Acromegaly pre post.jpg|MRI of brain pre- and post surgery]]
[[Image:Acromegaly pre post.jpg|MRI of brain pre- and post surgery]]


Drug Therapy>4.</ref>
Drug Therapy


*Somatostatin Analogs
*Somatostatin Analogs
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Radiation Therapy
Radiation Therapy


*Involves the use of supervoltage irradiation.>3.</ref>
*Involves the use of supervoltage irradiation.
*少比传统手术创伤.>3.</ref>
*少比传统手术创伤.
*The radiation therapy is delivered in weekly doses spread over a period of six weeks.>6.</ref>
*The radiation therapy is delivered in weekly doses spread over a period of six weeks.
*Approximately 50% of patients with acromegaly experience biochemical remission after radiation therapy.>6.</ref>
*Approximately 50% of patients with acromegaly experience biochemical remission after radiation therapy.
*The radiation treatment may take years to have its full effect.>3.</ref>
*The radiation treatment may take years to have its full effect.


== Physical Therapy Management (current best evidence) ==
== Physical Therapy Management (current best evidence) ==


Acromegaly is a disease which affects several systems in the body.>1.</ref>>2.</ref>>6.</ref> Therapists may be called on to provide a program addressing the musculoskeletal and neurological manifestations of the disease. 9.Goodman CC, Fuller KS. Pathology: implications for the physical therapist. 3rd ed. St.Louis: Saunders-Elsevier, 2009.
Acromegaly is a disease which affects several systems in the body. Therapists may be called on to provide a program addressing the musculoskeletal and neurological manifestations of the disease. 9.Goodman CC, Fuller KS. Pathology: implications for the physical therapist. 3rd ed. St.Louis: Saunders-Elsevier, 2009.


Preferred Practice Patterns:>9.</ref>
Preferred Practice Patterns:


*4D: Impaired joint mobility, motor function, muscle performance, and range of motion associated with connective tissue dysfunction.>9.</ref>
*4D: Impaired joint mobility, motor function, muscle performance, and range of motion associated with connective tissue dysfunction.
*4E: Impaired joint mobility, motor function, muscle performance, and range of motion associated with localized inflammation.>9.</ref>
*4E: Impaired joint mobility, motor function, muscle performance, and range of motion associated with localized inflammation.
*4F: Impaired joint mobility, motor function, muscle performance, range of motion, and reflex integrity associated with spinal disorders.>9.</ref>
*4F: Impaired joint mobility, motor function, muscle performance, range of motion, and reflex integrity associated with spinal disorders.
*5F: Impaired peripheral nerve integrity and muscle performance associated with peripheral nerve injury.>9.</ref>
*5F: Impaired peripheral nerve integrity and muscle performance associated with peripheral nerve injury.




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Screening
Screening


*Individuals with acromegaly should be screened for changes in joint mobility, decreased exercise tolerance, and weakness.>9.</ref>
*Individuals with acromegaly should be screened for changes in joint mobility, decreased exercise tolerance, and weakness.
*If an acromegalic client presents to physical therapy with unusual muscle weakness, they should be referred to a physician for a complete workup to look for neuropathies and inflammatory myopathies.  This will help identify underlying causes which can be treated.>9.</ref>
*If an acromegalic client presents to physical therapy with unusual muscle weakness, they should be referred to a physician for a complete workup to look for neuropathies and inflammatory myopathies.  This will help identify underlying causes which can be treated.




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Orthopedic Intervention
Orthopedic Intervention


*Arthritis of several joints is often present in patients with acromegaly.>9.</ref> In addition, carpal tunnel syndrome is seen in approximately 50% of patients with acromegaly, and there is a similar incidence of thoracic and lumbar pain in acromegalic patients.>9.</ref>
*Arthritis of several joints is often present in patients with acromegaly. In addition, carpal tunnel syndrome is seen in approximately 50% of patients with acromegaly, and there is a similar incidence of thoracic and lumbar pain in acromegalic patients.
*X-ray studies have demonstrated large osteophytes in the anterior longitudinal ligament and increased intervertebral space.>9.</ref>
*X-ray studies have demonstrated large osteophytes in the anterior longitudinal ligament and increased intervertebral space.
*A physical therapy program would work to promote muscle strength, mobility of the joints, and independence with functional activities.>9.</ref>  Adaptive equipment for assistance with activities of daily living may be considered depending on the severity of the disease.>9.</ref>
*A physical therapy program would work to promote muscle strength, mobility of the joints, and independence with functional activities.  Adaptive equipment for assistance with activities of daily living may be considered depending on the severity of the disease.




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Postoperative Intervention
Postoperative Intervention


*Exercise and ambulation are encouraged within the first 24 hours after removal of the pituitary tumor.>9.</ref>
*Exercise and ambulation are encouraged within the first 24 hours after removal of the pituitary tumor.
*Breathing exercises are indicated.  However, coughing, sneezing, and blowing the nose are contraindicated.>9.</ref>
*Breathing exercises are indicated.  However, coughing, sneezing, and blowing the nose are contraindicated.
*Monitor vital signs closely. Any change in vision, dropping pulse rate, or rising blood pressure could indicate an increase in intracranial pressure and should be reported immediately.>9.</ref>
*Monitor vital signs closely. Any change in vision, dropping pulse rate, or rising blood pressure could indicate an increase in intracranial pressure and should be reported immediately.
*The physical therapist should consult with the nursing staff to determine if blood glucose monitoring is needed during exercise.  GH levels may drop rapidly after removal of the tumor and result in hypoglycemia.>9.</ref>
*The physical therapist should consult with the nursing staff to determine if blood glucose monitoring is needed during exercise.  GH levels may drop rapidly after removal of the tumor and result in hypoglycemia.


== Differential Diagnosis ==
== Differential Diagnosis ==


Several of the comorbidities of acromegaly overlap common disorders; as a result, the acromegaly may be misdiagnosed.>5.</ref> The comorbidities which may lead to improper diagnosis include:
Several of the comorbidities of acromegaly overlap common disorders; as a result, the acromegaly may be misdiagnosed. The comorbidities which may lead to improper diagnosis include:


*Arthritis>5.</ref>
*Arthritis
*Hypertension>5.</ref>
*Hypertension
*Diabetes mellitus>5.</ref>>6.</ref>
*Diabetes mellitus
*Carpal tunnel syndrome>5.</ref>
*Carpal tunnel syndrome
*Respiratory dysfunction>8.</ref>
*Respiratory dysfunction
*Cardiac involvement>8.</ref>
*Cardiac involvement
*未能抑制生长激素也可以en in patients with diabetes, renal failure, hepatic failure, and patients with obesity or those on estrogen replacement.>6.</ref>  This could potentially lead to misdiagnosis.
*未能抑制生长激素也可以en in patients with diabetes, renal failure, hepatic failure, and patients with obesity or those on estrogen replacement.  This could potentially lead to misdiagnosis.


== Case Reports/ Case Studies  ==
== Case Reports/ Case Studies  ==

Revision as of 15:26, 6 June 2017

Original Editors- Alex Kentfrom Bellarmine University's Pathophysiology of Complex Patient Problems project.

Top Contributors-Alex Kent,Admin,Gayatri Jadav Upadhyay,Lucinda hampton,Elaine Lonnemann,WikiSysop,Kim Jackson,Chelsea Mclene,Wendy Walkerand127.0.0.1

Definition/Description
[edit|edit source]

肢端肥大症是一种罕见的系统性疾病的影响s the entire body.[1]It is characterized by a hypersecretion of growth hormone (GH) which the body is unable to regulate.[2]GH facilitates growth of muscles, internal organs, and bones, as well as stimulating secretion of its target hormone insulin-like growth factor 1 (IGF-1).[1],[3]The extremely high levels of GH and IGF-1 which typify acromegaly cause tissue enlargement and metabolic changes that result in visible deformity as well as an increase in mortality.[2][4]The disease often begins between the ages of 30 and 50, and has an insidious onset and slow progression, often delaying diagnosis until later stages of the disease.[2][3]

Serial photos of woman with acromegaly

Prevalence[edit|edit source]

  • 肢端肥大症的患病率大约是40-70 cases per million persons.[2][4]
  • However, new research suggests that the prevalence may be as high as 77 cases per million persons.[4]
  • The annual incidence of acromegaly is approximately is 3-4 new cases per million persons.[4]

Characteristics/Clinical Presentation[edit|edit source]

Acromegaly affects many of the body's systems, and various signs and symptoms develop over a period of several years.[5]They range from subtle changes to notable disfigurement.[2]

Clinical Presentation[2][3][5][6]:

  • Hand and foot enlargement
  • Hyperhydrosis- increased perspiration
  • Increased skin thickness
  • Darkening and thickening of body hair
  • Frontal skull bossing- an abnormally heavy brow and prominent forehead
  • Widening of the maxilla accompanied by separation of the teeth
  • Jaw malocclusion and overbite
  • Soft tissue enlargement
  • Skeletal overgrowth and thickening causing many areas to appear swollen
  • Deep and husky voice due to thickening of cartilage in the larynx
  • Ventilatory dysfunction
  • Weight gain
  • Joint pain
  • Sleep apnea
  • Acne
  • Vision problems
Image:Graphic-3_small.gif Acromegalic hands.gif

Associated Co-morbidities[edit|edit source]

IGF-1, the target molecule of GH, enables many of the growth-promoting actions of GH; GH itself is also a regulator of mineral, lipid, and carbohydrate metabolism.[6]Therefore the elevated levels of GH and IGF-1 which are characteristic of acromegaly excessive soft tissue growth, swelling of internal organs, and musculoskeletal, neurological, and metabolic comorbidities.[6]

Cardiovascular:[1][2][5][6]

  • Hypertension
  • Arrhythmias
  • Valvulopathy
  • Cardiomyopathy
  • Hypertrophy (biventricular or asymmetric septal)
  • Congestive heart failure


Pulmonary:[1][2][5][6]

  • Obstructive sleep apnea
  • Macroglossia
  • Upper airway obstruction
  • Ventilatory dysfunction
  • Upper airway obstruction


Metabolic:[1][2][6]

  • Insulin resistance
  • Impaired glucose metabolism
  • Diabetes mellitus


Visceral:[1][6]

  • Organ enlargement
  • Colon polyps
  • Fluid retention
  • Renal failure


Musculoskeletal:[2]

  • Arthropathy/osteoarthritis
  • Carpal tunnel syndrome
  • Osteopenia

Acromegaly comorbidities.jpg

Medications[edit|edit source]

  • Somatostatin analogs- somatostatin inhibits endocrine cells, including GH-secreting cells of the pituitary gland. Somatostatin analogs (SSAs) mimic the GH-suppressing effects of the body's own somatostatin.[4]SSAs are one of the most common medications prescribed for acromegaly. There are currently three SSAs approved in the US: short-acting octreotride, octreotride LAR, and Somatuline Depot.[4]Most common adverse events are glucose intolerance, and gallbladder and sludge stones.[4]
  • Dopamine agonists- leads to GH suppression in a portion of acromegaly patients. Interestingly, this medication stimulates GH release in healthy patients.[4]Advantages of this medication are relatively low cost, oral administration, and no hypopituitarism associated with medication. However, the medication is only effective at lowering GH and IGF-1 to safe levels in approximately 10% of patients, and potentially causes cardiac valvular damage.[4]
  • Growth hormone receptor agonists- blocks the GH signal for IGF-1 production. More effective for patients with higher levels of IGF-1, and demonstrated a more favorable influence on glycemic control.[4]Adverse events often associated with growth hormone receptor agonists are compromised liver function and reactions at the injection site.[4][7]
Acromegaly-GHRA 4-7-.jpg

Diagnostic Tests/Lab Tests/Lab Values[edit|edit source]

Diagnostic Tests:

Oral Glucose Tolerance Test (OGTT)- glucose has a neuroendocrine suppressive signal that lowers GH.[6]In this test, 75 g of glucose is administered with GH measurements at different points over a period of 120 minutes.[2]The failure to suppress GH secretion to less than 1 microgram/liter is currently the standard for diagnosis of acromegaly.[6]

Magnetic Resonance Imaging (MRI)- the preferred imaging method when diagnosing acromegaly.[2]An MRI of the pituitary gland is taken in order to look for any abnormal growth.[3]It can help determine the tumor size, as well as compression of surrounding structures.[2]

Blood tests- blood may be used to measure serum levels of IGF-1 in addition to GH.[2][4][6]High levels of IGF-1 have been used as a marker for acromegaly; IGF-1 is correlated with GH levels as well as the clinical manifestations of acromegaly.[2][6]IGF-1 levels also tend to remain stable throughout the day, making IGF-1 testing a fairly reliable diagnostic tool.[2][6]Generally, a diagnosis of acromegaly can be excluded if IGF-1 levels are within the normal range.[7]

Radiographs- an x-ray of the skull can show bone thickening as well as enlargement of the nasal sinuses.[3]Thickening of the carpal phalanges can be seen in x-rays of the hands.[3]

Computed tomography (CT)- this imaging method can be used to identify abnormal growths in the pituitary gland.[3]

Lab Values:

Growth Hormone (GH)- in individuals without acromegaly, GH values are typically 0.1-0.2 micrograms/liter. There are, however, 6-10 bursts of GH secretion where levels of the hormone are 5-30 micrograms/liter.[2]This may overlap with the values seen in patients with acromegaly.[2]Growth hormone concentrations of less than 2.5 ng/ml are associated with mortality rates similar to the normal population.[4]Thus normalization of GH levels is currently defined as below 2.5 ng/ml.[7]

Acromegalic hand x-ray.jpgAcromegalic skull x-ray.jpg

Etiology/Causes[edit|edit source]

  • The majority (99%) of acromegaly cases are caused by the proliferation of somatotroph cells in the pituitary which leads to a pituitary adenoma.[2][6]Somatotroph cells make up more than half of the hormone-secreting cells in the ptuitary.[6]
  • The pituitary tumor causes an increase in circulating levels of GH.[2]GH mediates anabolic reactions by binding to growth hormone receptors, creating docking sites for cell signaling proteins, and initiating the synthesis of target genes like IGF-1.[7]This in turn increases the production of insulin-like growth factor 1 (IGF-1)[2][4][7]. IGF-1 causes metabolic changes and somatic growth, stimulating proliferation of cartilage, skeletal muscle and bone which ultimately lead to tissue enlargement.[2][7]
  • Enlargement of tissues and metabolic abnormalities cause the two to three-fold increase in mortality seen in acromegaly.[1][2][4][6][7]

GH secretion and IGF-1 production

Systemic Involvement[edit|edit source]

Cardiovascular Involvement

  • Acromegalic cordiomyopathy- common features include biventricular hypertrophy, thickening of cardiac walls, diastolic dysfunction, limited systolic function, and heart failure with signs of dilative cardiomyopathy.[8]
  • Mitral and aortic valve dysfunction.[8]
  • Arrhythmia- linked to a combination of factors, including increased left ventricle wall thickness as well as late action potentials in the heart.[8][2]
  • Hypertension- due in part to increased plasma volume.[2][8]
  • Atherosclerosis and endothelial dysfunction[8]



Metabolic Involvement

  • Impaired glucose tolerance and diabetes mellitus- growth hormone counteracts the effects of insulin on glucose metabolism.[8]GH also regulates the response of tissues to insulin; as a result excessive GH may be a causative factor in insulin resistance.[8]
  • Impaired lipid metabolism- acromegaly is correlated with lipid metabolism abnormalities.[8]Studies have found serum triglyceride levels to be higher in patients with acromegaly.[8]


Pulmonary Involvement

  • Mortality associated with repiratory disorders increased in patients with acromegaly.[8]
  • Increased incidence of sleep apnea.[2][8]
  • Barrel chest developed due to changes in morphology of vertebra and ribs.[8]Ribs become elongated and vertebral bodies become enlarged and elongated, which impair inspiration.[8]

Medical Management (current best evidence)[edit|edit source]

The goal of currrent medical management is to reduce the effects of the pituitary tumor by surgical resection, regulate the hypersecretion of GH and IGF-1 with medication, attempt to improve the numerous comorbidities associated with the disease, reduce the mortality risk, and maintain normal function of the pituitary gland.[4]


Surgery

  • Pituitary surgery is often the first choice in acromegaly management because it can reduce hypersecretion of GH and IGF-1 and reduce the effects of the tumor on surrounding brain structures.[7]
  • The goal ofsurgical debulking is to resect as much of the tumor as possible while still maintaining normal function of the pituitary gland.[4][6]
  • Resection of adenomas in the pituitary gland is difficult due to the location of the pituitary gland and its proximity to important vascular and neural structures.[6]As a result, surgery is most successful with an experienced surgeon; numerous studies have demonstrated that the outcome of surgical treatment of acromegaly is correlated with the level of experience of the surgeon.[7]

MRI of brain pre- and post surgery

Drug Therapy[4]

  • Somatostatin Analogs
  • Dopamine Agonists
  • Growth hormone receptor agonists
  • The specific actions of these medications are described in the Medications section.

Radiation Therapy

  • Involves the use of supervoltage irradiation.[3]
  • Less traumatic than traditional surgery.[3]
  • The radiation therapy is delivered in weekly doses spread over a period of six weeks.[6]
  • Approximately 50% of patients with acromegaly experience biochemical remission after radiation therapy.[6]
  • The radiation treatment may take years to have its full effect.[3]

Physical Therapy Management (current best evidence)[edit|edit source]

Acromegaly is a disease which affects several systems in the body.[1][2][6]Therapists may be called on to provide a program addressing the musculoskeletal and neurological manifestations of the disease.[9]

Preferred Practice Patterns:[9]

  • 4 d:受损关节的灵活性、运动机能,muscle performance, and range of motion associated with connective tissue dysfunction.[9]
  • 4E: Impaired joint mobility, motor function, muscle performance, and range of motion associated with localized inflammation.[9]
  • 4F: Impaired joint mobility, motor function, muscle performance, range of motion, and reflex integrity associated with spinal disorders.[9]
  • 5F: Impaired peripheral nerve integrity and muscle performance associated with peripheral nerve injury.[9]


Screening

  • Individuals with acromegaly should be screened for changes in joint mobility, decreased exercise tolerance, and weakness.[9]
  • If an acromegalic client presents to physical therapy with unusual muscle weakness, they should be referred to a physician for a complete workup to look for neuropathies and inflammatory myopathies. This will help identify underlying causes which can be treated.[9]


Orthopedic Intervention

  • Arthritis of several joints is often present in patients with acromegaly.[9]In addition, carpal tunnel syndrome is seen in approximately 50% of patients with acromegaly, and there is a similar incidence of thoracic and lumbar pain in acromegalic patients.[9]
  • X-ray studies have demonstrated large osteophytes in the anterior longitudinal ligament and increased intervertebral space.[9]
  • A physical therapy program would work to promote muscle strength, mobility of the joints, and independence with functional activities.[9]Adaptive equipment for assistance with activities of daily living may be considered depending on the severity of the disease.[9]


Postoperative Intervention

  • Exercise and ambulation are encouraged within the first 24 hours after removal of the pituitary tumor.[9]
  • Breathing exercises are indicated. However, coughing, sneezing, and blowing the nose are contraindicated.[9]
  • Monitor vital signs closely. Any change in vision, dropping pulse rate, or rising blood pressure could indicate an increase in intracranial pressure and should be reported immediately.[9]
  • The physical therapist should consult with the nursing staff to determine if blood glucose monitoring is needed during exercise. GH levels may drop rapidly after removal of the tumor and result in hypoglycemia.[9]

Differential Diagnosis[edit|edit source]

Several of the comorbidities of acromegaly overlap common disorders; as a result, the acromegaly may be misdiagnosed.[5]The comorbidities which may lead to improper diagnosis include:

  • Arthritis[5]
  • Hypertension[5]
  • Diabetes mellitus[5][6]
  • Carpal tunnel syndrome[5]
  • Respiratory dysfunction[8]
  • Cardiac involvement[8]
  • Failure to suppress growth hormone can also be seen in patients with diabetes, renal failure, hepatic failure, and patients with obesity or those on estrogen replacement.[6]This could potentially lead to misdiagnosis.

Case Reports/ Case Studies[edit|edit source]

Resources
[edit|edit source]

Recent Related Research (from Pubmed)[edit|edit source]

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References[edit|edit source]

seeadding references tutorial.

  1. ↑1.01.11.21.31.41.51.61.71. Vance M. Acromegaly: a fascinating pituitary disorder. Neurosurg Focus 2010;29(4):1.
  2. ↑2.002.012.022.032.042.052.062.072.082.092.102.112.122.132.142.152.162.172.182.192.202.212.222.232.242.252.262. Cordero RA, Barkan AL. Current diagnosis of acromegaly. Rev Endocr Metab Disord 2008;9:13-19.
  3. ↑3.03.13.23.33.43.53.63.73.83.93.Merck Manual Home Edition. Acromegaly and gigantism: pituitary gland disorders.http://www.merckmanuals.com/home/print/sec13/ch162e.html(Accessed March 11 2011).
  4. ↑4.004.014.024.034.044.054.064.074.084.094.104.114.124.134.144.154.164.174.Fleseriu M, Delashaw JB, Cook DM. Acromegaly: a review of current medical therapy and new drugs on the horizon. Neurosurg Focus 2010;29(4):E15.
  5. ↑5.05.15.25.35.45.55.65.75.85. Reid TJ, Post KD, Bruce JN, Kanibir MN, Reyes-Vidal CM, Freda PU. Features at diagnosis of 324 patients with acromegaly did not change from 1981 to 2006: acromegaly remains under-recognized and under-diagnosed. Clinical Endocrinology 2010;72:203-208.
  6. ↑6.006.016.026.036.046.056.066.076.086.096.106.116.126.136.146.156.166.176.186.196.206.216.Melmed S. Acromegaly pathogenesis and treatment. J. Clin. Invest 2009;119:3189-3202.
  7. ↑7.07.17.27.37.47.57.67.77.87.Del Porto LA, Liubinas SV, Kaye AH. Treatment of persistent acromegaly. J Clin Neurosci 2011; 18:181-190.
  8. ↑8.008.018.028.038.048.058.068.078.088.098.108.118.128.138.148.Colao A, Ferone D, Marzullo P, Lombardi G. Systemic complications of acromegaly: epidemiology, pathogenesis, and management. Endocrine Reviews. 2004; 25(1):102-152
  9. ↑9.009.019.029.039.049.059.069.079.089.099.109.119.129.139.149.159.169.Goodman CC, Fuller KS. Pathology: implications for the physical therapist. 3rd ed. St.Louis: Saunders-Elsevier, 2009.
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