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Special Features: S. Melmed, A. Colao, A. Barkan, M. Molitch, A. B. Grossman, D. Kleinberg, D. Clemmons, P. Chanson, E. Laws, J. Schlechte, M. L. Vance, K. Ho, and A. Giustina Guidelines for Acromegaly Management: An Update J Clin Endocrinol Metab 2009; 94: 1509-1517 [Abstract] [Full text] [PDF]

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Guidelines for Acromegaly Management

Sebastian J.C.M.M. Neggers, Lely AJ   (20 May 2009)

Guidelines for Acromegaly Management 20 May 2009
Sebastian J.C.M.M. Neggers, MD Erasmus University MC Rotterdam, Lely AJ Send letter to journal: Re: Guidelines for Acromegaly Management s.neggers{at}erasmusmc.nl Sebastian J.C.M.M. Neggers, et al.	In a recent article Melmed et al. (1) discuss the current consensus on the approach to managing acromegaly the reference (2) to the report of Neggers et al., entitled “Quality of Life in Acromegalic Patients during Long-Term Somatostatin Analog Treatment with and without Pegvisomant” was slightly misinterpreted. Melmed et al. stated that “Pegvisomant is highly effective in acromegaly and significantly improves the quality of life in patients that require both somatostatin analog (SRL) treatment and pegvisomant to achieve biochemical control” (2). However the take-home messages of the quoted article are different with consequences for patient care. All of the 20 subjects in this randomized, double-blind, placebo-controlled, crossover study (2) had an IGF-I within the age-adjusted reference ranges during long-term SRL treatment, fulfilling criteria. Despite the fact that these biochemically cured acromegalics reported low quality of life, we observed that adding a weekly low dose of pegvisomant did not change serum IGF-I levels to the SRL treatment alone, significantly improves quality of life measures. Patients considered to be controlled might still have what might be termed ‘peripheral acromegaly’. Several reports suggest that somatostatin analogs make the liver GH resistant, probably by a decrease of portal insulin (3-5), thus leaving tissues other than liver still exposed to elevated GH levels. This is in line with a report by Segev and co-workers (6), who observed that lower concentrations of GH antagonist are needed to block the GH receptor on rodent kidney, than the ones that lower serum IGF-I levels or somatic growth. Understandably, the current consensus statements by Melmed et al. (1) seem to focus mainly on the normalization of IGF-I and GH, and are, therefore, linked to mortality and morbidity data, more than the important issue of quality of life in acromegaly patients (7-11). In our study, however, the total serum IGF-I level did not correlate with the improvement in quality of life. These observations question the concept that the approach if pegvisomant is indicated only when SRLs do not normalize serum IGF-I. More data are necessary to confirm the existence of ‘peripheral acromegaly,’ but the available data suggest its presence. References 1. Melmed S., Colao A, Barkan A, Molitch M, Grossman A. B, Kleinberg D, Clemmons D, Chanson P, Laws E, Schlechte J, Vance M. L, Ho K, and Giustina A. 2009 Guidelines for Acromegaly Management: An Update. J Clin Endocrinol Metab 94:1509–1517 2. Neggers SJ, van Aken MO, de Herder WW, Feelders RA, Janssen JA, Badia X, Webb SM, van der Lely AJ. 2008 Quality of life in acromegalic patients during long-term somatostatin analog treatment with and without pegvisomant. J Clin Endocrinol Metab 93:3853–3859 3. Wurzburger, M.I., Prelevic, G.M., Sonksen, P.H., Balint-Peric, L.A., Wheeler, M. 1993 The effect of recombinant human growth hormone on regulation of growth hormone secretion and blood glucose in insulin-dependent diabetes. J Clin Endocrinol Metab 77:267-272 4. Neggers, S., de Herder, W., Janssen, J., Feelders, R., Van der Lely, A. 2009 Combined treatment for acromegaly with long-acting somatostatin analogues and pegvisomant: Long-term safety up to 4.5 years (median 2.2 yrs) of follow-up in 86 patients. Eur J Endocrinol 160: 529-533 5. Shishko, P.I., Dreval, A.V., Abugova, I.A., Zajarny, I.U., Goncharov, V.C. 1994 Insulin-like growth factors and binding proteins in patients with recent-onset type 1 (insulin-dependent) diabetes mellitus: influence of diabetes control and intraportal insulin infusion. Diabetes Res Clin Pract 25:1-12 6. Segev Y, Landau D, Rasch R, Flyvbjerg A, Phillip M. 1999 Growth hormone receptor antagonism prevents early renal changes in nonobese diabetic mice. J Am Soc Nephrol 10:2374–2381 7. Hua SC, Yan YH, Chang TC. 2006 Associations of remission status and lanreotide treatment with quality of life in patients with treated acromegaly. Eur J Endocrinol 155:831–837 8. Biermasz NR, Pereira AM, Smit JW, Romijn JA, Roelfsema F 2005 Morbidity after long-term remission for acromegaly: persisting joint-related complaints cause reduced quality of life. J Clin Endocrinol Metab 90:2731–2739 9. Biermasz NR, van Thiel SW, Pereira AM, Hoftijzer HC, van Hemert AM, Smit JW, Romijn JA, Roelfsema F. 2004 Decreased quality of life in patients with acromegaly despite long-term cure of growth hormone excess. J Clin Endocrinol Metab 89:5369–5376 10. Bonapart IE, van Domburg R, ten Have SM, de Herder WW, Erdman RA, Janssen JA, van der Lely AJ. 2005 The ‘bio-assay’ quality of life might be a better marker of disease activity in acromegalic patients than serum total IGF-I concentrations. Eur J Endocrinol 152:217–224 11. Rowles SV, Prieto L, Badia X, Shalet SM, Webb SM, Trainer PJ. 2005 Quality of life (QOL) in patients with acromegaly is severely impaired: use of a novel measure of QOL: acromegaly quality of life questionnaire. J Clin Endocrinol Metab 90:3337–3341