Diagnosis and Management of Acromegaly in 2012

Laurence Katznelson
European Endocrinology, 2012;8(1):48-52

Abstract

Acromegaly is an insidious disease that, in most cases, is a result of a pituitary adenoma that hypersecretes growth hormone (GH). The goals of therapy are to control excess GH secretion and tumor growth, and to limit, if not reverse, the long-term medical consequences and risk of 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. Medical therapy, including somatostatin analogs, 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 somatostatin analogs. Using a multimodality approach, successful management of the disease and associated consequences should be achieved in the majority of subjects.
Keywords
Acromegaly, somatostatin, pegvisomant, pituitary adenoma, cabergoline
Disclosure Laurence Katznelson, MD, has received research support from Novartis Pharmaceuticals, Ipsen, and Pfizer.
Received: November 03, 2011 Accepted December 12, 2011 Citation European Endocrinology, 2012;8(1):48-52
Correspondence: Laurence Katznelson, MD, 875 Blake Wilbur Drive, Stanford, CA 94305-5821. E: LKatznelson@stanford.edu
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Acromegaly is an uncommon disorder that, in the vast majority of cases, is the result of a growth hormone (GH)-secreting pituitary adenoma. There is an estimated prevalence of 40–125 per million and an incidence of three to four new cases per million, although a more recent study in Belgium suggested a higher incidence of approximately 13 cases per 100,000.1,2 Acromegaly is often diagnosed in patients in their early to mid-40s and has equal gender distribution.3–5 Because the features of acromegaly progress in an insidious fashion, there is often a delay in diagnosis of approximately seven to 10 years after the estimated onset of symptoms.6 Therefore, a pituitary macroadenoma (greater than 1 cm) is present in the majority of subjects.7 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, sleep apnea syndrome, type 2 diabetes, hypertension, 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.

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.4

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 general, IGF-1 levels correlate with GH concentrations, especially with serum GH levels less than 20 ng/ml.8 Because IGF-1 is an integrated measure of GH secretion and is subject to less serum variation than GH, a random IGF-1 measurement is highly useful for assessment of GH hypersecretion (see Table 1). Owing to the lack of agreement between assays and the lack of validated normal ranges for IGF-1,9,10 the same assay should be used in the same patient for serial measurement.11 A random GH measurement is not generally 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. In one consensus statement, the presence of a random GH less than 0.4 ng/ml and normal IGF-1 was considered sufficient to consider the diagnosis highly unlikely.12

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