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Pituitary Disorders Are We Achieving Pharmacological Disease Control in Acromegaly? Annamaria Colao Professor of Endocrinology, Department of Molecular and Clinical Endocrinology and Oncology, ‘Federico II’ University of Naples, Naples, Italy Abstract Acromegaly is a rare endocrine disorder, associated with significant morbidity and mortality due to the harmful effects of prolonged exposure to increased levels of growth hormone (GH) and its effector, insulin-like growth factor-1 (IGF-1). The most common cause of acromegaly is a pituitary adenoma, for which surgical resection is usually the first choice treatment. In cases where surgical resection is not possible, or where the patient declines surgery, somatostatin analogues (SSAs) are used as first-line medical therapy. Other therapeutic options include dopamine antagonists and the GH receptor antagonist – pegvisomant. In addition, considerable current research is investigating the clinical utility of combined therapies. Disease control is defined in terms of reduction of GH and IGF-1 normalisation and reduction in mortality levels to those seen in the general population. Reported disease control rates of acromegaly are highly variable and it has been reported that treatment efficacy in clinical practice is considerably lower than the success rates reported by reference centres. There is therefore a substantial need for improved disease management strategies for acromegaly. Keywords Acromegaly, growth hormone, insulin-like growth factor, pegvisomant, somatostatin analogue Disclosure: Annamaria Colao is a member of the Novartis European advisory board and receives grants for neuroendocrine research and speaker fees from Novartis. Acknowledgements: Editorial assistance was provided by Janet Manson at Touch Medical Media and was funded by Novartis. Received: 24 October 2012 Accepted: 30 October 2012 Citation: European Endocrinology, 2012;8(2):105–11 Correspondence: Annamaria Colao, Professor of Endocrinology, Department of Molecular and Clinical Endocrinology and Oncology, ‘Federico II’ University of Naples, Via S. Pansini 5, 80131 Naples, Italy. E: colao@unina.it Support: The publication of this article was funded by Novartis. The views and opinions expressed are those of the author and not necessarily those of Novartis. Acromegaly is an endocrine disorder and is characterised by soft tissue enlargement and excessive skeletal growth with acral enlargement and coarse facial features. The incidence of acromegaly is approximately 3.3/1,000,000.0/year and the prevalence is 60/1,000,000. 1 Although a rare condition, the clinical, economic and health-related quality of life (HRQoL) burden associated with acromegaly is considerable owing to its broad spectrum of co-morbidities as well as the need for lifelong management. Acromegaly is diagnosed in approximately equal numbers of men and women, and the mean age at diagnosis for both sexes is in the early to mid-40s. 2 The features of acromegaly develop slowly over decades, and diagnosis can be delayed up to 10 years after the onset of symptoms. 3 Excessive levels of growth hormone (GH) and insulin-like growth factor-1 (IGF-1) cause major structural and functional cardiac changes, and as a result the disease has numerous clinical manifestations ranging from acral overgrowth to myocardial hypertrophy and diastolic heart failure (see Table 1). 4 One study found that the most common presenting symptoms are acral enlargement (in 86 % of patients), maxillofacial change (74 %), excessive perspiration (48 %), arthralgia (46 %), headache (40 %) and hypogonadal symptoms (38 %). 5 In young patients acromegaly occurring before the closure of epiphyseal bone results in accelerated growth and gigantism. However, this is very rare, in a review of 2,367 children and adolescents with pituitary adenomas, only 0.6 % had gigantism. 6 © TOUCH MEDICAL MEDIA 2012 Acromegaly is also associated with a high incidence of co-morbidities: one study (n=100) reported multiple co-morbidities in 40 % of patients. 7 GH excess in acromegaly negatively impacts glucose homeostasis, and is associated with hypertension, which are believed to be major contributors to the increased cardiovascular risk associated with the disease. 8 Acromegaly is associated with several abnormalities of the cardiovascular system and control of GH/IGF-1 secretion can reverse cardiovascular abnormalities. 9 An increased arterial intima-media thickness of both the carotid arteries has been observed in patients with acromegaly. However, the prevalence of well defined carotid plaques was not increased in both groups of patients with acromegaly as compared with controls, suggesting that cardiovascular risk resulting from GH and IGF-1 excess in acromegaly is associated with heart rather than vascular abnormalities. 10 Further co-morbidities include lipid abnormalities, arthritis, hypertension and sleep apnoea. 11 Although advances in the management of acromegaly have led to an increased number of patients achieving biochemical control over the long-term, elevated levels of GH and IGF-1 in acromegaly are associated with a twofold increase in mortality levels to those similar to the general population. 12,13 Causes of mortality are similar to those of the general population but with an excess of death from cardiovascular disease. 14 The most frequent cause of death in acromegaly is cardiomyopathy, the prevalence of which is 3.3–14.2 times higher in the acromegalic versus the non-acromegalic population. 15 105