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Saptarshi Bhattacharya, Sanjay Kalra, Lakshmi Nagendra

Very few trials in the history of medical science have altered the treatment landscape as profoundly as the UK Prospective Diabetes Study (UKPDS). Even 44 years after its inception, the trial and post-study follow-up findings continue to fascinate and enlighten the medical community. The study was conceived at a time when there was uncertainty about […]

Are We Achieving Pharmacological Disease Control in Acromegaly?

Annamaria Colao
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Published Online: Sep 12th 2012 European Endocrinology, 2012;8(2):105-111 DOI: http://doi.org/10.17925/EE.2012.08.02.105
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Abstract

Overview

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

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Article

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 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

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

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References

  1. Holdaway IM, Rajasoorya C, Epidemiology of acromegaly,
    Pituitary, 1999;2:29–41.

  2. Ezzat S, Forster MJ, Berchtold P, et al., Acromegaly. Clinical
    and biochemical features in 500 patients, Medicine (Baltimore),
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  3. Rajasoorya C, Holdaway IM, Wrightson P, et al., Determinants
    of clinical outcome and survival in acromegaly, Clin Endocrinol
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  4. Melmed S, Medical progress: Acromegaly, N Engl J Med,
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  5. Drange MR, Fram NR, Herman-Bonert V, Melmed S, Pituitary
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  6. Abe T, Tara LA, Lüdecke DK, Growth hormone-secreting
    pituitary adenomas in childhood and adolescence: features
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  7. Nachtigall L, Delgado A, Swearingen B, et al., Changing
    patterns in diagnosis and therapy of acromegaly over two
    decades, J Clin Endocrinol Metab, 2008;93:2035–41.

  8. Colao A, Ferone D, Marzullo P, Lombardi G, Systemic
    complications of acromegaly: epidemiology, pathogenesis,
    and management, Endocr Rev, 2004;25:102–52.

  9. Colao A, The GH-IGF-I axis and the cardiovascular system:
    clinical implications, Clin Endocrinol (Oxf), 2008;69:347–58.

  10. Colao A, Spiezia S, Cerbone G, et al., Increased arterial intimamedia
    thickness by B-M mode echodoppler ultrasonography in
    acromegaly, Clin Endocrinol (Oxf), 2001;54:515–24.

  11. Ben-Shlomo A, Sheppard MC, Stephens JM, et al., Clinical,
    quality of life, and economic value of acromegaly disease
    control, Pituitary, 2011;14:284–94.

  12. Holdaway IM, Excess mortality in acromegaly, Horm Res,
    2007;68(Suppl. 5):166–72.

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Article Information

Disclosure

Annamaria Colao is a member of the Novartis European advisory board and receives grants for neuroendocrine research and speaker fees from Novartis.

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.

Received

2012-10-24T00:00:00

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