Acromegaly: Difference between revisions

m (Text replace - ''''Lead Editors'''' to ''''Top Contributors''' - {{Special:Contributors/{{FULLPAGENAME}}}}')
No edit summary
Line 1: Line 1:
 
<div class="editorbox">
<div class="noeditbox">Welcome to [[Pathophysiology of Complex Patient Problems|PT 635 Pathophysiology of Complex Patient Problems]] This is a wiki created by and for the students in the School of Physical Therapy at Bellarmine University in Louisville KY. Please do not edit unless you are involved in this project, but please come back in the near future to check out new information!!</div><div class="editorbox">
'''Original Editors '''- Alex Kent&nbsp;[[Pathophysiology of Complex Patient Problems|from Bellarmine University's&nbsp;Pathophysiology of Complex Patient Problems project.]]  
'''Original Editors '''- Alex Kent&nbsp;[[Pathophysiology of Complex Patient Problems|from Bellarmine University's&nbsp;Pathophysiology of Complex Patient Problems project.]]  


'''Top Contributors''' - {{Special:Contributors/{{FULLPAGENAME}}}} &nbsp;
'''Top Contributors''' - {{Special:Contributors/{{FULLPAGENAME}}}} &nbsp;  
</div>
</div>  
== Definition/Description&nbsp;<br> ==
== Definition/Description&nbsp;<br> ==


Acromegaly is a rare systemic disease which affects the entire body.<ref name="Vance">1. Vance M. Acromegaly: a fascinating pituitary disorder. Neurosurg Focus 2010;29(4):1.</ref> It is characterized by a hypersecretion of growth hormone (GH) which the body is unable to regulate.<ref name="Cordero">2. Cordero RA, Barkan AL. Current diagnosis of acromegaly. Rev Endocr Metab Disord 2008;9:13-19.</ref>&nbsp;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).<ref name="Vance">1.</ref> <sup>,</sup><ref name="Merck">3.Merck Manual Home Edition. Acromegaly and gigantism: pituitary gland disorders. http://www.merckmanuals.com/home/print/sec13/ch162e.html (Accessed March 11 2011).</ref> 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.<ref name="Cordero">2.</ref><ref name="Fleseriu">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.</ref> 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.<ref name="Cordero">2.</ref><ref name="Merck">3.</ref>  
Acromegaly is a rare systemic disease which affects the entire body.<ref name="Vance">1. Vance M. Acromegaly: a fascinating pituitary disorder. Neurosurg Focus 2010;29(4):1.</ref> It is characterized by a hypersecretion of growth hormone (GH) which the body is unable to regulate.<ref name="Cordero">2. Cordero RA, Barkan AL. Current diagnosis of acromegaly. Rev Endocr Metab Disord 2008;9:13-19.</ref>&nbsp;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).<ref name="Vance">1.</ref> <sup>,</sup><ref name="Merck">3.Merck Manual Home Edition. Acromegaly and gigantism: pituitary gland disorders. http://www.merckmanuals.com/home/print/sec13/ch162e.html (Accessed March 11 2011).</ref> 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.<ref name="Cordero">2.</ref><ref name="Fleseriu">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.</ref> 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.<ref name="Cordero">2.</ref><ref name="Merck">3.</ref>  


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


== Prevalence  ==
== Prevalence  ==


*The&nbsp;prevalence of acromegaly is&nbsp;approximately 40-70 cases&nbsp;per million persons.<ref name="Cordero">2.</ref><ref name="Fleseriu">4.</ref>&nbsp;
*The&nbsp;prevalence of acromegaly is&nbsp;approximately 40-70 cases&nbsp;per million persons.<ref name="Cordero">2.</ref><ref name="Fleseriu">4.</ref>&nbsp;  
*However, new research suggests that the prevalence may be as high as 77 cases per million persons.<ref name="Fleseriu">4.</ref>
*However, new research suggests that the prevalence may be as high as 77 cases per million persons.<ref name="Fleseriu">4.</ref>  
*The annual incidence of acromegaly is approximately is 3-4 new cases per million persons.<ref name="Fleseriu">4.</ref>
*The annual incidence of acromegaly is approximately is 3-4 new cases per million persons.<ref name="Fleseriu">4.</ref>


Line 40: Line 39:
*Vision problems
*Vision problems


&nbsp;<br>[[Image:Graphic-3 small.gif|Image:Graphic-3_small.gif]]&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; [[Image:Acromegalic_hands.gif]]
&nbsp;<br>[[Image:Graphic-3 small.gif|Image:Graphic-3_small.gif]]&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; [[Image:Acromegalic hands.gif]]  


== Associated Co-morbidities  ==
== Associated Co-morbidities  ==


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


Cardiovascular:<ref name="Vance">1.</ref><ref name="Cordero">2.</ref><ref name="Reid">5.</ref><ref name="Shlomo">6.</ref>  
Cardiovascular:<ref name="Vance">1.</ref><ref name="Cordero">2.</ref><ref name="Reid">5.</ref><ref name="Shlomo">6.</ref>  
Line 55: Line 54:
*Congestive heart failure
*Congestive heart failure


&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; <br>
&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; <br>  


Pulmonary:<ref name="Vance">1.</ref><ref name="Cordero">2.</ref><ref name="Reid">5.</ref><ref name="Shlomo">6.</ref>  
Pulmonary:<ref name="Vance">1.</ref><ref name="Cordero">2.</ref><ref name="Reid">5.</ref><ref name="Shlomo">6.</ref>  
Line 65: Line 64:
*Upper airway obstruction
*Upper airway obstruction


<br>
<br>  


Metabolic:<ref name="Vance">1.</ref><ref name="Cordero">2.</ref><ref name="Shlomo">6.</ref>  
Metabolic:<ref name="Vance">1.</ref><ref name="Cordero">2.</ref><ref name="Shlomo">6.</ref>  
Line 73: Line 72:
*Diabetes mellitus
*Diabetes mellitus


<br>
<br>  


Visceral:<ref name="Vance">1.</ref><ref name="Shlomo">6.</ref>  
Visceral:<ref name="Vance">1.</ref><ref name="Shlomo">6.</ref>  
Line 82: Line 81:
*Renal failure
*Renal failure


<br>
<br>  


Musculoskeletal:<ref name="Cordero">2.</ref>  
Musculoskeletal:<ref name="Cordero">2.</ref>  
Line 90: Line 89:
*Osteopenia
*Osteopenia


[[Image:Acromegaly_comorbidities.jpg]]
[[Image:Acromegaly comorbidities.jpg]]  


== Medications  ==
== Medications  ==
Line 98: Line 97:
*Growth hormone receptor agonists- blocks the GH signal for IGF-1 production.&nbsp; More effective for patients with higher levels of IGF-1, and demonstrated a more favorable influence on glycemic control.<ref name="Fleseriu">4.</ref>&nbsp;Adverse events often associated with growth hormone receptor agonists are compromised liver function and reactions at the injection site.<ref name="Fleseriu">4.</ref><ref name="Del Porto">7.Del Porto LA, Liubinas SV, Kaye AH. Treatment of persistent acromegaly. J Clin Neurosci 2011; 18:181-190.</ref>
*Growth hormone receptor agonists- blocks the GH signal for IGF-1 production.&nbsp; More effective for patients with higher levels of IGF-1, and demonstrated a more favorable influence on glycemic control.<ref name="Fleseriu">4.</ref>&nbsp;Adverse events often associated with growth hormone receptor agonists are compromised liver function and reactions at the injection site.<ref name="Fleseriu">4.</ref><ref name="Del Porto">7.Del Porto LA, Liubinas SV, Kaye AH. Treatment of persistent acromegaly. J Clin Neurosci 2011; 18:181-190.</ref>


[[Image:Acromegaly-GHRA_4-7-.jpg]]
[[Image:Acromegaly-GHRA 4-7-.jpg]]  


== Diagnostic Tests/Lab Tests/Lab Values  ==
== Diagnostic Tests/Lab Tests/Lab Values  ==


Diagnostic Tests:<br>
Diagnostic Tests:<br>  


Oral Glucose Tolerance Test (OGTT)- glucose has a neuroendocrine suppressive signal that lowers GH.<ref name="Shlomo">6.</ref>&nbsp; In this test, 75 g of glucose is administered with GH measurements&nbsp;at different points over a period of 120 minutes.<ref name="Cordero">2.</ref>&nbsp;The failure to suppress GH secretion to less than 1 microgram/liter is currently the standard for diagnosis of acromegaly.<ref name="Shlomo">6.</ref>  
Oral Glucose Tolerance Test (OGTT)- glucose has a neuroendocrine suppressive signal that lowers GH.<ref name="Shlomo">6.</ref>&nbsp; In this test, 75 g of glucose is administered with GH measurements&nbsp;at different points over a period of 120 minutes.<ref name="Cordero">2.</ref>&nbsp;The failure to suppress GH secretion to less than 1 microgram/liter is currently the standard for diagnosis of acromegaly.<ref name="Shlomo">6.</ref>  
Line 118: Line 117:
Growth Hormone (GH)- in individuals without acromegaly, GH values are typically 0.1-0.2 micrograms/liter.&nbsp; There are, however, 6-10 bursts of GH secretion where levels of the hormone are 5-30 micrograms/liter.<ref name="Cordero">2.</ref>&nbsp;This may overlap with the values seen in patients with acromegaly.<ref name="Cordero">2.</ref>&nbsp;Growth hormone concentrations of less than 2.5 ng/ml are associated with mortality rates similar to the normal population.<ref name="Fleseriu">4.</ref>&nbsp;Thus normalization of GH levels is currently defined as below 2.5 ng/ml.<ref name="Del Porto">7.</ref>  
Growth Hormone (GH)- in individuals without acromegaly, GH values are typically 0.1-0.2 micrograms/liter.&nbsp; There are, however, 6-10 bursts of GH secretion where levels of the hormone are 5-30 micrograms/liter.<ref name="Cordero">2.</ref>&nbsp;This may overlap with the values seen in patients with acromegaly.<ref name="Cordero">2.</ref>&nbsp;Growth hormone concentrations of less than 2.5 ng/ml are associated with mortality rates similar to the normal population.<ref name="Fleseriu">4.</ref>&nbsp;Thus normalization of GH levels is currently defined as below 2.5 ng/ml.<ref name="Del Porto">7.</ref>  


[[Image:Acromegalic_hand_x-ray.jpg]][[Image:Acromegalic_skull_x-ray.jpg]]
[[Image:Acromegalic hand x-ray.jpg]][[Image:Acromegalic skull x-ray.jpg]]  


== Etiology/Causes  ==
== Etiology/Causes  ==


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


[[Image:Acromegaly_fig.jpg|GH secretion and IGF-1 production]]
[[Image:Acromegaly fig.jpg|GH secretion and IGF-1 production]]  


== Systemic Involvement  ==
== Systemic Involvement  ==
Line 133: Line 132:


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


<br>


<br>


Metabolic Involvement


 
*Impaired glucose tolerance and diabetes mellitus- growth hormone counteracts the effects of insulin on glucose metabolism.<ref name="Annamaria">8.</ref>&nbsp;GH also regulates the response of tissues to insulin; as a result excessive GH may be a causative factor in insulin resistance.<ref name="Annamaria">8.</ref>  
Metabolic Involvement
 
*Impaired glucose tolerance and diabetes mellitus- growth hormone counteracts the effects of insulin on glucose metabolism.<ref name="Annamaria">8.</ref>&nbsp;GH also regulates the response of tissues to insulin; as a result excessive GH may be a causative factor in insulin resistance.<ref name="Annamaria">8.</ref>
*Impaired lipid metabolism- acromegaly is correlated with lipid metabolism abnormalities.<ref name="Annamaria">8.</ref>Studies have found serum triglyceride levels to be higher in patients with acromegaly.<ref name="Annamaria">8.</ref>
*Impaired lipid metabolism- acromegaly is correlated with lipid metabolism abnormalities.<ref name="Annamaria">8.</ref>Studies have found serum triglyceride levels to be higher in patients with acromegaly.<ref name="Annamaria">8.</ref>


<br>


Pulmonary Involvement


Pulmonary Involvement
*Mortality associated with repiratory disorders increased in patients with acromegaly.<ref name="Annamaria">8.</ref>  
 
*Increased incidence of sleep apnea.<ref name="Cordero">2.</ref><ref name="Annamaria">8.</ref>  
*Mortality associated with repiratory disorders increased in patients with acromegaly.<ref name="Annamaria">8.</ref>
*Increased incidence of sleep apnea.<ref name="Cordero">2.</ref><ref name="Annamaria">8.</ref>
*Barrel chest developed due to changes in morphology of vertebra and ribs.<ref name="Annamaria">8.</ref>&nbsp;Ribs become elongated and vertebral bodies become enlarged and elongated, which impair inspiration.<ref name="Annamaria">8.</ref>
*Barrel chest developed due to changes in morphology of vertebra and ribs.<ref name="Annamaria">8.</ref>&nbsp;Ribs become elongated and vertebral bodies become enlarged and elongated, which impair inspiration.<ref name="Annamaria">8.</ref>


Line 159: Line 158:
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&nbsp;comorbidities associated with the disease, reduce the mortality risk, and maintain normal function of the pituitary gland.<ref name="Fleseriu">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&nbsp;comorbidities associated with the disease, reduce the mortality risk, and maintain normal function of the pituitary gland.<ref name="Fleseriu">4.</ref>  


<br>
<br>  


Surgery  
Surgery  


*Pituitary surgery is often the first choice in acromegaly management&nbsp;because it can reduce hypersecretion of GH and IGF-1 and reduce the effects of the tumor on surrounding brain structures.<ref name="Del Porto">7.</ref>  
*Pituitary surgery is often the first choice in acromegaly management&nbsp;because it can reduce hypersecretion of GH and IGF-1 and reduce the effects of the tumor on surrounding brain structures.<ref name="Del Porto">7.</ref>  
*The goal of <span id="fck_dom_range_temp_1301858332531_320"></span>surgical debulking is to resect as much of the tumor as possible while still maintaining normal function of the pituitary gland.<ref name="Fleseriu">4.</ref><ref name="Shlomo">6.</ref>  
*The goal of <span id="fck_dom_range_temp_1301858332531_320" />surgical debulking is to resect as much of the tumor as possible while still maintaining normal function of the pituitary gland.<ref name="Fleseriu">4.</ref><ref name="Shlomo">6.</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.<ref name="Shlomo">6.</ref>&nbsp;As a result, surgery is most successful with an experienced surgeon; numerous studies have demonstrated that the outcome of surgical treatment of acromegaly&nbsp;is correlated with the level of experience of the surgeon.<ref name="Del Porto">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.<ref name="Shlomo">6.</ref>&nbsp;As a result, surgery is most successful with an experienced surgeon; numerous studies have demonstrated that the outcome of surgical treatment of acromegaly&nbsp;is correlated with the level of experience of the surgeon.<ref name="Del Porto">7.</ref>


[[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<ref name="Fleseriu">4.</ref>  
Drug Therapy<ref name="Fleseriu">4.</ref>  
Line 195: Line 194:
*5F: Impaired peripheral nerve integrity and muscle performance&nbsp;associated with peripheral nerve injury.<ref name="Goodman">9.</ref>
*5F: Impaired peripheral nerve integrity and muscle performance&nbsp;associated with peripheral nerve injury.<ref name="Goodman">9.</ref>


<br>
<br>  


Screening  
Screening  
Line 202: Line 201:
*If an acromegalic client presents to physical&nbsp;therapy&nbsp;with unusual muscle weakness, they should be referred to a physician for a complete workup to look for neuropathies and inflammatory myopathies.&nbsp; This will help identify underlying causes which can be treated.<ref name="Goodman">9.</ref>
*If an acromegalic client presents to physical&nbsp;therapy&nbsp;with unusual muscle weakness, they should be referred to a physician for a complete workup to look for neuropathies and inflammatory myopathies.&nbsp; This will help identify underlying causes which can be treated.<ref name="Goodman">9.</ref>


<br>
<br>  


Orthopedic Intervention
Orthopedic Intervention  


*Arthritis of&nbsp;several joints is often&nbsp;present in patients with acromegaly.<ref name="Goodman">9.</ref>&nbsp;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.<ref name="Goodman">9.</ref>  
*Arthritis of&nbsp;several joints is often&nbsp;present in patients with acromegaly.<ref name="Goodman">9.</ref>&nbsp;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.<ref name="Goodman">9.</ref>  
Line 210: Line 209:
*A physical therapy program would work to promote muscle strength, mobility of the joints, and independence with functional activities.<ref name="Goodman">9.</ref>&nbsp; Adaptive equipment for assistance with activities of daily living may be considered depending on the severity of the disease.<ref name="Goodman">9.</ref>
*A physical therapy program would work to promote muscle strength, mobility of the joints, and independence with functional activities.<ref name="Goodman">9.</ref>&nbsp; Adaptive equipment for assistance with activities of daily living may be considered depending on the severity of the disease.<ref name="Goodman">9.</ref>


<br>


Postoperative Intervention


Postoperative Intervention
*Exercise and ambulation are encouraged within the first 24 hours after removal of the pituitary tumor.<ref name="Goodman">9.</ref>  
 
*Breathing exercises are indicated.&nbsp; However, coughing, sneezing, and blowing the nose are contraindicated.<ref name="Goodman">9.</ref>  
*Exercise and ambulation are encouraged within the first 24 hours after removal of the pituitary tumor.<ref name="Goodman">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.<ref name="Goodman">9.</ref>  
*Breathing exercises are indicated.&nbsp; However, coughing, sneezing, and blowing the nose are contraindicated.<ref name="Goodman">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.<ref name="Goodman">9.</ref>
*The physical therapist should consult with the nursing staff to determine if blood glucose monitoring is needed during exercise.&nbsp; GH levels may drop rapidly after removal of the tumor and result in hypoglycemia.<ref name="Goodman">9.</ref>
*The physical therapist should consult with the nursing staff to determine if blood glucose monitoring is needed during exercise.&nbsp; GH levels may drop rapidly after removal of the tumor and result in hypoglycemia.<ref name="Goodman">9.</ref>


Line 225: Line 224:
== Differential Diagnosis  ==
== Differential Diagnosis  ==


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


*Arthritis<ref name="Reid">5.</ref>
*Arthritis<ref name="Reid">5.</ref>  
*Hypertension<ref name="Reid">5.</ref>
*Hypertension<ref name="Reid">5.</ref>  
*Diabetes mellitus<ref name="Reid">5.</ref><ref name="Shlomo">6.</ref>
*Diabetes mellitus<ref name="Reid">5.</ref><ref name="Shlomo">6.</ref>  
*Carpal tunnel syndrome<ref name="Reid">5.</ref>
*Carpal tunnel syndrome<ref name="Reid">5.</ref>  
*Respiratory dysfunction<ref name="Annamaria">8.</ref>
*Respiratory dysfunction<ref name="Annamaria">8.</ref>  
*Cardiac involvement<ref name="Annamaria">8.</ref>
*Cardiac involvement<ref name="Annamaria">8.</ref>  
*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.<ref name="Shlomo">6.</ref>&nbsp; This could potentially lead to misdiagnosis.
*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.<ref name="Shlomo">6.</ref>&nbsp; This could potentially lead to misdiagnosis.


Line 242: Line 241:
*Acromegalic axial arthropathy: a clinical case-control study.&nbsp;[http://highwire.stanford.edu/cgi/searchresults?sendit=Search&pubdate_year=2004&volume=89&author1=Scarpa+R&title=Acromegalic+axial+arthropathy%3A+a+clinical+case+control+study&firstpage=598&andorexacttitle=or http://highwire.stanford.edu/cgi/searchresults?sendit=Search&amp;pubdate_year=2004&amp;volume=89&amp;author1=Scarpa+R&amp;title=Acromegalic+axial+arthropathy%3A+a+clinical+case+control+study&amp;firstpage=598&amp;andorexacttitle=or] (Accessed April 5, 2011).
*Acromegalic axial arthropathy: a clinical case-control study.&nbsp;[http://highwire.stanford.edu/cgi/searchresults?sendit=Search&pubdate_year=2004&volume=89&author1=Scarpa+R&title=Acromegalic+axial+arthropathy%3A+a+clinical+case+control+study&firstpage=598&andorexacttitle=or http://highwire.stanford.edu/cgi/searchresults?sendit=Search&amp;pubdate_year=2004&amp;volume=89&amp;author1=Scarpa+R&amp;title=Acromegalic+axial+arthropathy%3A+a+clinical+case+control+study&amp;firstpage=598&amp;andorexacttitle=or] (Accessed April 5, 2011).


== Resources <br> ==
== Resources <br> ==


*The Pituitary Network Association. Acromegaly.org.&nbsp;[http://www.acromegaly.org/ http://www.acromegaly.org/]  
*The Pituitary Network Association. Acromegaly.org.&nbsp;[http://www.acromegaly.org/ http://www.acromegaly.org/]  
Line 257: Line 256:
&lt;divclass="researchbox"&gt;<rss>http://eutils.ncbi.nlm.nih.gov/entrez/eutils/erss.cgi?rss_guid=1z_pxc-9fhP4GP3q0wWQCYsnlVFM4agzcQ1rGpworXkUZUpgvo |charset=UTF-8|short|max=10</rss>&lt;/div&gt;  
&lt;divclass="researchbox"&gt;<rss>http://eutils.ncbi.nlm.nih.gov/entrez/eutils/erss.cgi?rss_guid=1z_pxc-9fhP4GP3q0wWQCYsnlVFM4agzcQ1rGpworXkUZUpgvo |charset=UTF-8|short|max=10</rss>&lt;/div&gt;  


<br>
<br>  


== References  ==
== References  ==
Line 263: Line 262:
see [[Adding References|adding references tutorial]].  
see [[Adding References|adding references tutorial]].  


<references />
<references />  


[[Category:Bellarmine_Student_Project]]
[[Category:Bellarmine_Student_Project]]

Revision as of 08:34, 23 June 2013

Original Editors - Alex Kent from 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, 127.0.0.1 and Wendy Walker  

Definition/Description 
[edit | edit source]

Acromegaly is a rare systemic disease which affects 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]

  • The prevalence of acromegaly is approximately 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           File: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]

File: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]

File:Acromegalic hand x-ray.jpgFile:Acromegalic 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 of surgical 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]

  • 4D: Impaired joint mobility, motor function, 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]

Alternative/Holistic Management (current best evidence)[edit | edit source]

add text here

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]

add appropriate resources here

== Recent Related Research (from Pubmed)

<divclass="researchbox">Extension:RSS -- Error: Not a valid URL: http://eutils.ncbi.nlm.nih.gov/entrez/eutils/erss.cgi?rss_guid=1z_pxc-9fhP4GP3q0wWQCYsnlVFM4agzcQ1rGpworXkUZUpgvo |charset=UTF-8|short|max=10</div>


References[edit | edit source]

see adding references tutorial.

  1. ↑ 1.0 1.1 1.2 1.3 1.4 1.5 1.6 1.7 1. Vance M. Acromegaly: a fascinating pituitary disorder. Neurosurg Focus 2010;29(4):1. Cite error: Invalid <ref> tag; name "Vance" defined multiple times with different content Cite error: Invalid <ref> tag; name "Vance" defined multiple times with different content Cite error: Invalid <ref> tag; name "Vance" defined multiple times with different content Cite error: Invalid <ref> tag; name "Vance" defined multiple times with different content Cite error: Invalid <ref> tag; name "Vance" defined multiple times with different content Cite error: Invalid <ref> tag; name "Vance" defined multiple times with different content Cite error: Invalid <ref> tag; name "Vance" defined multiple times with different content
  2. ↑ 2.00 2.01 2.02 2.03 2.04 2.05 2.06 2.07 2.08 2.09 2.10 2.11 2.12 2.13 2.14 2.15 2.16 2.17 2.18 2.19 2.20 2.21 2.22 2.23 2.24 2.25 2.26 2. Cordero RA, Barkan AL. Current diagnosis of acromegaly. Rev Endocr Metab Disord 2008;9:13-19. Cite error: Invalid <ref> tag; name "Cordero" defined multiple times with different content Cite error: Invalid <ref> tag; name "Cordero" defined multiple times with different content Cite error: Invalid <ref> tag; name "Cordero" defined multiple times with different content Cite error: Invalid <ref> tag; name "Cordero" defined multiple times with different content Cite error: Invalid <ref> tag; name "Cordero" defined multiple times with different content Cite error: Invalid <ref> tag; name "Cordero" defined multiple times with different content Cite error: Invalid <ref> tag; name "Cordero" defined multiple times with different content Cite error: Invalid <ref> tag; name "Cordero" defined multiple times with different content Cite error: Invalid <ref> tag; name "Cordero" defined multiple times with different content Cite error: Invalid <ref> tag; name "Cordero" defined multiple times with different content Cite error: Invalid <ref> tag; name "Cordero" defined multiple times with different content Cite error: Invalid <ref> tag; name "Cordero" defined multiple times with different content Cite error: Invalid <ref> tag; name "Cordero" defined multiple times with different content Cite error: Invalid <ref> tag; name "Cordero" defined multiple times with different content Cite error: Invalid <ref> tag; name "Cordero" defined multiple times with different content Cite error: Invalid <ref> tag; name "Cordero" defined multiple times with different content Cite error: Invalid <ref> tag; name "Cordero" defined multiple times with different content Cite error: Invalid <ref> tag; name "Cordero" defined multiple times with different content Cite error: Invalid <ref> tag; name "Cordero" defined multiple times with different content Cite error: Invalid <ref> tag; name "Cordero" defined multiple times with different content Cite error: Invalid <ref> tag; name "Cordero" defined multiple times with different content Cite error: Invalid <ref> tag; name "Cordero" defined multiple times with different content Cite error: Invalid <ref> tag; name "Cordero" defined multiple times with different content Cite error: Invalid <ref> tag; name "Cordero" defined multiple times with different content Cite error: Invalid <ref> tag; name "Cordero" defined multiple times with different content Cite error: Invalid <ref> tag; name "Cordero" defined multiple times with different content
  3. ↑ 3.0 3.1 3.2 3.3 3.4 3.5 3.6 3.7 3.8 3.9 3.Merck Manual Home Edition. Acromegaly and gigantism: pituitary gland disorders. http://www.merckmanuals.com/home/print/sec13/ch162e.html (Accessed March 11 2011). Cite error: Invalid <ref> tag; name "Merck" defined multiple times with different content Cite error: Invalid <ref> tag; name "Merck" defined multiple times with different content Cite error: Invalid <ref> tag; name "Merck" defined multiple times with different content Cite error: Invalid <ref> tag; name "Merck" defined multiple times with different content Cite error: Invalid <ref> tag; name "Merck" defined multiple times with different content Cite error: Invalid <ref> tag; name "Merck" defined multiple times with different content Cite error: Invalid <ref> tag; name "Merck" defined multiple times with different content Cite error: Invalid <ref> tag; name "Merck" defined multiple times with different content Cite error: Invalid <ref> tag; name "Merck" defined multiple times with different content
  4. ↑ 4.00 4.01 4.02 4.03 4.04 4.05 4.06 4.07 4.08 4.09 4.10 4.11 4.12 4.13 4.14 4.15 4.16 4.17 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. Cite error: Invalid <ref> tag; name "Fleseriu" defined multiple times with different content Cite error: Invalid <ref> tag; name "Fleseriu" defined multiple times with different content Cite error: Invalid <ref> tag; name "Fleseriu" defined multiple times with different content Cite error: Invalid <ref> tag; name "Fleseriu" defined multiple times with different content Cite error: Invalid <ref> tag; name "Fleseriu" defined multiple times with different content Cite error: Invalid <ref> tag; name "Fleseriu" defined multiple times with different content Cite error: Invalid <ref> tag; name "Fleseriu" defined multiple times with different content Cite error: Invalid <ref> tag; name "Fleseriu" defined multiple times with different content Cite error: Invalid <ref> tag; name "Fleseriu" defined multiple times with different content Cite error: Invalid <ref> tag; name "Fleseriu" defined multiple times with different content Cite error: Invalid <ref> tag; name "Fleseriu" defined multiple times with different content Cite error: Invalid <ref> tag; name "Fleseriu" defined multiple times with different content Cite error: Invalid <ref> tag; name "Fleseriu" defined multiple times with different content Cite error: Invalid <ref> tag; name "Fleseriu" defined multiple times with different content Cite error: Invalid <ref> tag; name "Fleseriu" defined multiple times with different content Cite error: Invalid <ref> tag; name "Fleseriu" defined multiple times with different content Cite error: Invalid <ref> tag; name "Fleseriu" defined multiple times with different content
  5. ↑ 5.0 5.1 5.2 5.3 5.4 5.5 5.6 5.7 5.8 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. Cite error: Invalid <ref> tag; name "Reid" defined multiple times with different content Cite error: Invalid <ref> tag; name "Reid" defined multiple times with different content Cite error: Invalid <ref> tag; name "Reid" defined multiple times with different content Cite error: Invalid <ref> tag; name "Reid" defined multiple times with different content Cite error: Invalid <ref> tag; name "Reid" defined multiple times with different content Cite error: Invalid <ref> tag; name "Reid" defined multiple times with different content Cite error: Invalid <ref> tag; name "Reid" defined multiple times with different content Cite error: Invalid <ref> tag; name "Reid" defined multiple times with different content
  6. ↑ 6.00 6.01 6.02 6.03 6.04 6.05 6.06 6.07 6.08 6.09 6.10 6.11 6.12 6.13 6.14 6.15 6.16 6.17 6.18 6.19 6.20 6.21 6.Melmed S. Acromegaly pathogenesis and treatment. J. Clin. Invest 2009;119:3189-3202. Cite error: Invalid <ref> tag; name "Shlomo" defined multiple times with different content Cite error: Invalid <ref> tag; name "Shlomo" defined multiple times with different content Cite error: Invalid <ref> tag; name "Shlomo" defined multiple times with different content Cite error: Invalid <ref> tag; name "Shlomo" defined multiple times with different content Cite error: Invalid <ref> tag; name "Shlomo" defined multiple times with different content Cite error: Invalid <ref> tag; name "Shlomo" defined multiple times with different content Cite error: Invalid <ref> tag; name "Shlomo" defined multiple times with different content Cite error: Invalid <ref> tag; name "Shlomo" defined multiple times with different content Cite error: Invalid <ref> tag; name "Shlomo" defined multiple times with different content Cite error: Invalid <ref> tag; name "Shlomo" defined multiple times with different content Cite error: Invalid <ref> tag; name "Shlomo" defined multiple times with different content Cite error: Invalid <ref> tag; name "Shlomo" defined multiple times with different content Cite error: Invalid <ref> tag; name "Shlomo" defined multiple times with different content Cite error: Invalid <ref> tag; name "Shlomo" defined multiple times with different content Cite error: Invalid <ref> tag; name "Shlomo" defined multiple times with different content Cite error: Invalid <ref> tag; name "Shlomo" defined multiple times with different content Cite error: Invalid <ref> tag; name "Shlomo" defined multiple times with different content Cite error: Invalid <ref> tag; name "Shlomo" defined multiple times with different content Cite error: Invalid <ref> tag; name "Shlomo" defined multiple times with different content Cite error: Invalid <ref> tag; name "Shlomo" defined multiple times with different content Cite error: Invalid <ref> tag; name "Shlomo" defined multiple times with different content
  7. ↑ 7.0 7.1 7.2 7.3 7.4 7.5 7.6 7.7 7.8 7.Del Porto LA, Liubinas SV, Kaye AH. Treatment of persistent acromegaly. J Clin Neurosci 2011; 18:181-190. Cite error: Invalid <ref> tag; name "Del Porto" defined multiple times with different content Cite error: Invalid <ref> tag; name "Del Porto" defined multiple times with different content Cite error: Invalid <ref> tag; name "Del Porto" defined multiple times with different content Cite error: Invalid <ref> tag; name "Del Porto" defined multiple times with different content Cite error: Invalid <ref> tag; name "Del Porto" defined multiple times with different content Cite error: Invalid <ref> tag; name "Del Porto" defined multiple times with different content Cite error: Invalid <ref> tag; name "Del Porto" defined multiple times with different content Cite error: Invalid <ref> tag; name "Del Porto" defined multiple times with different content
  8. ↑ 8.00 8.01 8.02 8.03 8.04 8.05 8.06 8.07 8.08 8.09 8.10 8.11 8.12 8.13 8.14 8.Colao A, Ferone D, Marzullo P, Lombardi G. Systemic complications of acromegaly: epidemiology, pathogenesis, and management. Endocrine Reviews. 2004; 25(1):102-152 Cite error: Invalid <ref> tag; name "Annamaria" defined multiple times with different content Cite error: Invalid <ref> tag; name "Annamaria" defined multiple times with different content Cite error: Invalid <ref> tag; name "Annamaria" defined multiple times with different content Cite error: Invalid <ref> tag; name "Annamaria" defined multiple times with different content Cite error: Invalid <ref> tag; name "Annamaria" defined multiple times with different content Cite error: Invalid <ref> tag; name "Annamaria" defined multiple times with different content Cite error: Invalid <ref> tag; name "Annamaria" defined multiple times with different content Cite error: Invalid <ref> tag; name "Annamaria" defined multiple times with different content Cite error: Invalid <ref> tag; name "Annamaria" defined multiple times with different content Cite error: Invalid <ref> tag; name "Annamaria" defined multiple times with different content Cite error: Invalid <ref> tag; name "Annamaria" defined multiple times with different content Cite error: Invalid <ref> tag; name "Annamaria" defined multiple times with different content Cite error: Invalid <ref> tag; name "Annamaria" defined multiple times with different content Cite error: Invalid <ref> tag; name "Annamaria" defined multiple times with different content
  9. ↑ 9.00 9.01 9.02 9.03 9.04 9.05 9.06 9.07 9.08 9.09 9.10 9.11 9.12 9.13 9.14 9.15 9.16 9.Goodman CC, Fuller KS. Pathology: implications for the physical therapist. 3rd ed. St.Louis: Saunders-Elsevier, 2009. Cite error: Invalid <ref> tag; name "Goodman" defined multiple times with different content Cite error: Invalid <ref> tag; name "Goodman" defined multiple times with different content Cite error: Invalid <ref> tag; name "Goodman" defined multiple times with different content Cite error: Invalid <ref> tag; name "Goodman" defined multiple times with different content Cite error: Invalid <ref> tag; name "Goodman" defined multiple times with different content Cite error: Invalid <ref> tag; name "Goodman" defined multiple times with different content Cite error: Invalid <ref> tag; name "Goodman" defined multiple times with different content Cite error: Invalid <ref> tag; name "Goodman" defined multiple times with different content Cite error: Invalid <ref> tag; name "Goodman" defined multiple times with different content Cite error: Invalid <ref> tag; name "Goodman" defined multiple times with different content Cite error: Invalid <ref> tag; name "Goodman" defined multiple times with different content Cite error: Invalid <ref> tag; name "Goodman" defined multiple times with different content Cite error: Invalid <ref> tag; name "Goodman" defined multiple times with different content Cite error: Invalid <ref> tag; name "Goodman" defined multiple times with different content Cite error: Invalid <ref> tag; name "Goodman" defined multiple times with different content Cite error: Invalid <ref> tag; name "Goodman" defined multiple times with different content
Retrieved from "https://www.physio-pedia.com/index.php?title=Acromegaly&oldid=74924"