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Pituary Disorders


Diagnosis and Management of Acromegaly in 2012 Laurence Katznelson


Professor of Medicine and Neurosurgery, Stanford University


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 tumour 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 analogues, 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 analogues. 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 has received research support from Novartis Pharmaceuticals, Ipsen and Pfizer. Received: 3 November 2011 Accepted: 12 December 2011 Citation: European Endocrinology, 2012;8(1):48–52 Correspondence: Laurence Katznelson, 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. 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


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


diagnosed in patients in their early to mid-40s and has equal gender distribution.3–5


1 cm) is present in the majority of subjects.7


Therefore, a pituitary macroadenoma (greater than Because tumours 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 co-morbidities and accompanying clinical features. Medical co-morbidites include arthropathy, cardiomegaly, sleep apnoea 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 co-morbidities 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


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usually do not present with a chief complaint related to acral growth. In women, the most common presenting complaint is amenorrhoea.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


same patient for serial measurement.11


the same assay should be used in the 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


An oral glucose tolerance test (OGTT) is considered the gold standard test for acromegaly, and the inability to suppress serum GH to less than 1 ng/ml after glucose administration (75 g is recommended) is consistent with the diagnosis.13–16


It is important to note that this


In a patient with signs and symptoms of acromegaly and an elevated IGF-1 value, an OGTT may not be necessary for diagnosis. In the setting of a clinical suspicion but discordant values, such as an


© TOUCH BRIEFINGS 2012


cut-off nadir GH value is controversial, particularly given the development of more sensitive GH assays that lead to lower serum GH levels.17


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