In this update to the 2012 summary, the current diagnostic and therapeutic approaches to acromegaly are reviewed. The goals of therapy are
to control excess growth hormone (GH) secretion and tumor growth, and to limit, if not reverse, the long-term medical consequences and risk
for premature mortality associated with acromegaly. Surgery is the preferred primary therapeutic option because it can lead to rapid reductions
in GH levels and prevent mass effects from local tumor growth. Use of a somatostatin receptor ligand (SRL) preoperatively to improve surgical
outcomes has not been substantiated. Medical therapy, including SRLs, dopamine agonists, and the GH receptor antagonist pegvisomant, is
used most often in an adjuvant, secondary role for patients in whom surgery has been unsuccessful. Radiation therapy is most commonly
recommended in the setting of failed surgery and lack of adequate control with medical therapy. A role of primary medical therapy for de novo
patients has been proposed, particularly with SRLs. Using a multimodality approach, successful management of the disease and associated
consequences should be achieved in the majority of subjects.
Acromegaly, somatostatin, pegvisomant, pituitary adenoma, cabergoline
Laurence Katznelson, MD, has received research support from Novartis Pharmaceuticals, and is an advisor for Ipsen and Novartis. No funding was received for the
publication of this article
June 10, 2014 Accepted
November 26, 2014
Laurence Katznelson, MD, 875 Blake Wilbur Drive, Stanford, CA 94305-5821, US. E: LKatznelson@stanford.edu
Acromegaly is an uncommon disorder that, in the vast majority of cases, is the result of a growth hormone (GH)-secreting pituitary adenoma. Because tumors are often macroadenomas at the time of diagnosis, there may be a number of signs and symptoms related to local mass effects, including headache, visual field loss, ophthalmoplegia, and hypopituitarism. Chronic GH and insulin-like growth factor 1 (IGF-1) hypersecretion can lead to soft tissue and bone overgrowth manifestations, medical comorbidities, and accompanying clinical features. Medical comorbidites include arthropathy, cardiomegaly, type 2 diabetes, hypertension, sleep apnea syndrome, and colon polyps. In addition, acromegaly is associated with premature mortality, primarily owing to cardiovascular disease. Appropriate therapy of acromegaly can lead to improvement in these comorbidities and reversal of the premature mortality risk. This current review is an update to the 2012 summary.1
Diagnosis of Acromegaly
The diagnosis of acromegaly begins with a clinical suspicion by the physician that the patient has this disease. Typical physical examination findings include hand and foot enlargement or facial bone enlargement and acral/soft tissue changes. Of note, subjects usually do not present with a chief complaint related to acral growth. In women, the most common presenting complaint is amenorrhea.2
Biochemical testing involves measurement of GH and IGF-1. GH, produced by the somatotroph cells of the pituitary gland in a pulsatile fashion, circulates and stimulates hepatic secretion of IGF-1. In the recent Endocrine Society guidelines on the approach to acromegaly, it was recommended that a serum IGF-1 level be measured in subjects with acral manifestations. Owing to the lack of agreement between assays and the lack of validated normal ranges for IGF-1,3,4 the same assay should be used in the same patient for serial measurement.5 A random GH measurement was not considered useful in diagnosis because of the lack of a well-defined normal or safe range, although a markedly elevated random GH level is certainly consistent with the disease. Additionally, in subjects with elevated or equivocal serum IGF-1 concentrations, the recent acromegaly guidelines recommended confirmation of the diagnosis with a lack of suppression of GH to less than 1 mcg/l following an oral glucose load.6 In a patient with signs and symptoms of acromegaly and an elevated IGF-1 value, an oral glucose tolerance test (OGTT) may not be necessary for diagnosis. In the setting of a clinical suspicion but discordant values, such as an elevated IGF-1 and normal GH value (i.e., suppressible with OGTT), the subject likely has early stage acromegaly.7
After diagnosis of acromegaly, a magnetic resonance imaging (MRI) scan of the sella should be obtained to determine tumor size, location, and invasiveness.6 Visual field testing is performed if the tumor is touching or compressing the optic chiasm. A thorough ophthalmologic examination should be performed if the patient describes diplopia and the tumor is invading the cavernous sinus. Further endocrine testing should be performed to determine general pituitary function and need for hormone replacement therapy.
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Acromegaly, somatostatin, pegvisomant, pituitary adenoma, cabergoline