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Diagnosis and Management of Acromegaly in 2012


Addition of cabergoline to patients with partial response to a somatostatin analogue may lead to IGF-1 normalisation in about half of subjects,63


although this benefit is generally noted in


subjects with modest IGF-1 elevations. Another option involves surgical debulking of macroadenomas to improve the subsequent response to somatostatin analogues.23


In a patient with full resistance


to a somatostatin analogue, substitution of pegvisomant for the somatostatin analogue may be considered.64


Finally, in a patient


with somatostatin analogue resistance, consideration of radiation therapy may be warranted.65


Radiation Therapy


Radiation therapy is usually considered as an adjunctive therapy in subjects with active disease despite surgery and/or medical therapy, or to limit the need for lifelong medical therapy.28,65,66


There are two


main types of radiotherapy for patients with acromegaly: conventional fractionated radiotherapy and stereotactic radiosurgery.


Fractionated radiotherapy is typically administered in daily doses of 160–180 cGray (cGy) over a five- to six-week period up to a total dose of 4,500–5,000 cGy. Using strict remission criteria, such as a glucose-suppressed GH value of less than 1 ng/ml and a normal IGF-1 value, conventional fractionated radiation therapy results in biochemical cure in 10–60 % of subjects.67–70


Stereotactic radiosurgery includes a number of modalities, such as Gamma Knife® (Elekta AB, Stockholm, Sweden), CyberKnife® (Accuray Incorporated, Sunnyvale, CA, US) and a linear accelerator that delivers high-energy photons. Another option is use of proton particles.71


In


acromegaly, most experience with stereotactic radiosurgery involves Gamma Knife radiosurgery, which is usually delivered by a cobalt-60 gamma radiation source as a single treatment. With Gamma Knife radiosurgery, biochemical remission rates (without the need for medical therapy) are reported to be 17–50 % over a five-year follow-up period.72–74


It has been suggested that time to remission is shorter with


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2. Daly AF, Rixhon M, Adam C, et al., High prevalence of pituitary adenomas: a cross-sectional study in the province of Liege, Belgium, J Clin Endocrinol Metab, 2006;91:4769–75.


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6. Rajasoorya C, Holdaway IM, Wrightson P, et l., Determinants of clinical outcome and survival in acromegaly, Clin Endocrinol (Oxf), 1994;41:95–102.


7. Mestron A, Webb SM, Astorga R, et al., Epidemiology, clinical characteristics, outcome, morbidity and mortality in acromegaly based on the Spanish Acromegaly Registry (Registro Espanol de Acromegalia, REA), Eur J Endocrinol, 2004;151:439–46.


8. Dobrashian RD, O’Halloran DJ, Hunt A, et al., Relationships between insulin-like growth factor-1 levels and growth hormone concentrations during diurnal profiles and following oral glucose in acromegaly, Clin Endocrinol (Oxf), 1993;38:589–93.


9. Frystyk J, Freda P, Clemmons DR, The current status of IGF-I assays – a 2009 update, Growth Horm IGF Res, 2010;20:8–18.


10. Pokrajac A, Wark G, Ellis AR, et al., Variation in GH and IGF-I assays limits the applicability of international consensus criteria to local practice, Clin Endocrinol (Oxf), 2007;67:65–70.


11. Katznelson L, Approach to the patient with persistent acromegaly after pituitary surgery, J Clin Endocrinol Metab, 2010;95:4114–23.


12. Giustina A, Melmed S, Acromegaly consensus: the next steps, J Clin Endocrinol Metab, 2003;88:1913–4.


13. Kirchengast S, Hartmann B, Huber J, Serum levels of sex


Managing Associated Medical Co-morbidities The long-term management of acromegaly should also include screening and intervention for the associated co-morbidities. For example, cardiovascular co-morbidities, including hyperlipidaemia, diabetes and hypertension, should be monitored and treated accordingly. Serial colonoscopy should be performed in patients with polyps found at the baseline colonoscopy and those with persistent acromegaly.82,83


somatostatin analogue may result in biochemical control in up to 58 % of subjects and, through dose reduction of both the pegvisomant and somatostatin analogue, this regimen may have a cost benefit.62


Gamma Knife radiosurgery than with conventional radiotherapy, although this is not entirely clear.72,74–76


Radiosurgery is generally considered if the tumour is a minimal distance from the optic chiasm, such as 5 mm, owing to concern about optic nerve injury.77


Periodic withdrawal of medical therapy


following radiotherapy should be performed for biochemical assessment. Somastatin analogues are often withheld at the time of radiation therapy because of concern that they may be radioprotective, although this finding is controversial, as it is not supported in all studies.72,74,75,78


The main limitation for radiotherapy is the development of hypopituitarism, which may occur in up to 50 % of patients after five to 10 years.67,79


radionecrosis have been reported in fewer than 2 % of patients undergoing conventional radiotherapy.80,81


Radiation-induced secondary tumours and


In a subject with sleep apnoea syndrome, biochemical control may lead to improvement in the sleep disorder, although sleep apnoea may persist. Therefore, repeat sleep apnoea assessments should be performed and appropriate treatment offered.84,85


Such monitoring should be performed in parallel with the


acromegaly management. Conclusion


Acromegaly is a multisystem disease that often requires multimodality therapy for control of the tumour, the GH hypersecretion and the medical consequences. With current therapeutic options, successful disease control should be achieved in the majority of patients. n


hormones, thyroid hormones, growth hormone, IGF I, and cortisol and their relations to body fat distribution in healthy women dependent on their menopausal status, Z Morphol Anthropol, 1996;81:223–34.


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16. Puder JJ, Nilavar S, Post KD, Freda PU, Relationship between disease-related morbidity and biochemical markers of activity in patients with acromegaly, J Clin Endocrinol Metab, 2005;90:1972–8.


17. Trainer PJ, Editorial: acromegaly – consensus, what consensus?, J Clin Endocrinol Metab, 2002;87:3534–6.


18. Dimaraki EV, Jaffe CA, DeMott-Friberg R, et al., Acromegaly with apparently normal GH secretion: implications for diagnosis and follow-up, J Clin Endocrinol Metab, 2002;87:3537–42.


19. Zirkzee EJ, Corssmit EP, Biermasz NR, et al., Pituitary magnetic resonance imaging is not required in the postoperative follow-up of acromegalic patients with long-term biochemical cure after transsphenoidal surgery, J Clin Endocrinol Metab, 2004;89:4320–4.


20. Bourdelot A, Coste J, Hazebroucq V, et al., Clinical, hormonal and magnetic resonance imaging (MRI) predictors of transsphenoidal surgery outcome in acromegaly, Eur J Endocrinol, 2004;150:763–71.


21. Jane JA, Jr, Starke RM, Elzoghby MA, et al., Endoscopic transsphenoidal surgery for acromegaly: remission using modern criteria, complications, and predictors of outcome, J Clin Endocrinol Metab, 2011;96:2732–40.


22. Nomikos P, Buchfelder M, Fahlbusch R, The outcome of surgery in 668 patients with acromegaly using current criteria of biochemical ‘cure’, Eur J Endocrinol, 2005;152:379–87.


23. Petrossians P, Borges-Martins L, Espinoza C, et al., Gross total resection or debulking of pituitary adenomas improves hormonal control of acromegaly by somatostatin analogs, Eur J Endocrinol, 2005;152:61–6.


24. Saeki N, Iuchi T, Isono S, et al., MRI of growth hormone-secreting pituitary adenomas: factors determining pretreatment hormone levels, Neuroradiology, 1999;41:765–71.


25. Shimon I, Cohen ZR, Ram Z, Hadani M, Transsphenoidal surgery for acromegaly: endocrinological follow-up of 98 patients, Neurosurgery, 2001;48:1239–43; discussion 1244–35.


26. Krieger MD, Couldwell WT, Weiss MH, Assessment of long-term remission of acromegaly following surgery, J Neurosurg, 2003;98:719–24.


27. Carmichael JD, Bonert VS, Mirocha JM, Melmed S, The utility of oral glucose tolerance testing for diagnosis and assessment of treatment outcomes in 166 patients with acromegaly, J Clin Endocrinol Metab, 2009;94:523–7.


28. Melmed S, Colao A, Barkan A, et al., Guidelines for acromegaly management: an update, J Clin Endocrinol Metab 2009;94:1509–17.


29. Giustina A, Chanson P, Bronstein MD, et al., A consensus on criteria for cure of acromegaly, J Clin Endocrinol Metab, 2010;95:3141–8.


30. Dina TS, Feaster SH, Laws ER, Jr, Davis DO, MR of the pituitary gland postsurgery: serial MR studies following transsphenoidal resection, AJNR Am J Neuroradiol, 1993;14:763–9.


31. Carlsen SM, Lund-Johansen M, Schreiner T, et al., Preoperative octreotide treatment in newly diagnosed acromegalic patients with macroadenomas increases cure short-term postoperative rates: a prospective, randomized trial, J Clin Endocrinol Metab, 2008;93:2984–90.


32. Mao ZG, Zhu YH, Tang HL, et al., Preoperative lanreotide treatment in acromegalic patients with macroadenomas increases short-term postoperative cure rates: a prospective, randomised trial, Eur J Endocrinol, 2010;162:661–6.


EUROPEAN ENDOCRINOLOGY 51


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