Acromegaly: Difference between revisions
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== Physical Therapy Management (current best evidence) == | == Physical Therapy Management (current best evidence) == | ||
Acromegaly is a disease which affects several systems in the body.<ref name="Vance">1.</ref><ref name="Cordero">2.</ref><ref name="Shlomo">6.</ref> Therapists may be called on to provide a program addressing the musculoskeletal and neurological manifestations of the disease. | |||
== Alternative/Holistic Management (current best evidence) == | == Alternative/Holistic Management (current best evidence) == |
Revision as of 00:52, 5 April 2011
Original Editors - Alex Kent from Bellarmine University's Pathophysiology of Complex Patient Problems project.
Lead Editors - Your name will be added here if you are a lead editor on this page. Read more.
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]
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
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]
- Hypertension
- Arrhythmias
- Valvulopathy
- Cardiomyopathy
- Hypertrophy (biventricular or asymmetric septal)
- Congestive heart failure
- Obstructive sleep apnea
- Macroglossia
- Upper airway obstruction
- Ventilatory dysfunction
- Upper airway obstruction
- Insulin resistance
- Impaired glucose metabolism
- Diabetes mellitus
- Organ enlargement
- Colon polyps
- Fluid retention
- Renal failure
Musculoskeletal:[2]
- Arthropathy/osteoarthritis
- Carpal tunnel syndrome
- Osteopenia
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]
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]
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]
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]
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.
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]
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Resources
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Recent Related Research (from Pubmed)[edit | edit source]
add appropriate resources here
== Recent Related Research (from Pubmed)
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References[edit | edit source]
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- ↑ 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
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tag; name "Cordero" defined multiple times with different content - ↑ 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
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