Acromegaly Consensus: The Next Steps

Andrea Giustina and Shlomo Melmed

Endocrine Section, Department of Internal Medicine, University of Brescia, 25125 Brescia, Italy; and Cedars Sinai Medical Center, University of California Los Angeles School of Medicine, Los Angeles, California 90048

Address correspondence to: Prof. Andrea Giustina, Endocrine Section c/o 2a Medicina, Spedali Civili, 25125 Brescia, Italy. E-mail: a.giustina{at}libero.it.

To the editor:

We enjoyed reading the article published by Dimaraki et al. (1) in the August 2002 issue of JCEM as well as the accompanying editorial of Dr. P. Trainer (2). Both articles confirm the crucial need for biochemical criteria for establishing the diagnosis of acromegaly or defining control after acromegaly treatment. The fundamental importance of these criteria has been highlighted by recent reports of mild acromegaly (1) as well as the availability of powerful new medical tools, especially long-acting somatostatin analogs for disease control. Delays in somatostatin receptor ligand administration to patients not completely cured by what was heretofore considered the first-line therapeutic approach to the disease (i.e. neurosurgery) are now unacceptable (3). This approach avoids the subtle yet unacceptable exposure of peripheral tissues to excess GH and/or IGF-I secretion leading to enhanced mortality. The increasing perception of these concepts has been challenged for years by the lack of an internationally validated reference for evaluating the biochemical profile of acromegaly. Heterogeneous practice has been based on personal opinions, different clinical experiences, very variable hormone assay methodologies, and laboratory test precision and reproducibility. The goal of the Consensus Conference held in February 1999 was to overcome differences of opinion among leading world experts in this field by obtaining a consensus based on simple and worldwide relevant biochemical criteria for diagnosis and ascertainment of disease control. These consensus-driven criteria are well enunciated in the statement published in JCEM in February 2000 (4). This document serves as a current international reference not only for research but also, more importantly, for clinical endocrinologists. In his editorial titled "Acromegaly Consensus, What Consensus?", Dr. Trainer highlights the importance of biochemical assessment of acromegaly, therefore validating the reasons that prompted the organization of a Consensus Conference devoted to this critical issue. It is, however, puzzling to suggest that there is no consensus on the biochemical evaluation of acromegaly. The basis on which Dr. Trainer supports this contention can be challenged. The series of patients described by Dimaraki et al. (1) are clearly not representative of the bulk of patients harboring GH-secreting pituitary tumors displaying a very mild disease activity, and frequency estimates of 25% remain speculative; the purported discrepancy between IGF-I levels and the GH response to oral glucose tolerance test (OGTT) has only become evident because of the availability of accurate IGF-I assays. The assumption that "correct" information is provided solely by an elevated IGF-I is not supported in the literature, and therefore only concordant information from both of these two parameters allows a clear-cut diagnosis (4). Discordant information derived from IGF-I measurements and the GH nadir after OGTT require further evaluation, including measuring spontaneous GH secretion, or other dynamic testing (4). The 24-h GH profile is a costly and resource-requiring research tool, and it cannot be recommended for use in clinical practice. Therefore, it seems apparent that the paper by Dimaraki et al. (1) does not "challenge the diagnostic criteria proposed in the Consensus statement" but reports a series of particular cases in which the diagnosis of acromegaly may be difficult and to which the Consensus agrees that particular attention should be given. However, Dr. Trainer, in his analysis of the Consensus paper, discusses the GH cut-off for diagnosis of acromegaly and suggests lowering the cut-off of the GH nadir after OGTT to between 0.14 and 0.3 ng/ml based on the postoperative series by Freda et al. (5), obtained with a highly sensitive immunoradiometric assay with a detection limit of 0.05 ng/ml GH. It was agreed in the Consensus that the GH nadir after OGTT cut-off values would be lowered in the future due to refinement of assay techniques. At the time of the Consensus, the 1 ng/ml cut-off was an important advance with respect to the 5 or 2.5 ng/ml used previously. We, however, need to bear in mind that the accurate diagnosis of acromegaly should be enabled using criteria applicable throughout the world by clinical laboratories. Dr. Trainer also states, in agreement with the Consensus, that measurement of a 24-h GH profile is not applicable to routine acromegaly assessment, and multiple GH measurements should only be made when results of IGF-I and GH nadir after OGTT are discrepant. Dr. Trainer calls for a revision of the Consensus statement suggesting slight changes in absolute values for baseline (0.3 from 0.4 ng/ml) and post-OGTT nadir (0.3 from 1 ng/ml). Periodic revision of the consensus-driven criteria was already predicted (4) and will be undertaken in a forthcoming workshop. We appreciate the positive spirit of Dr. Trainer’s editorial and his acceptance of the method proposed for approaching the diagnosis of acromegaly. On a universal but controversial question like this, neither the opinion of single experts nor data reported from single research centers should set the standard. Careful integration of different clinical experiences and experimental data derived from scientists worldwide to produce an overall accepted consensus will provide consistent, cost-effective, and accurate guidelines for clinicians. Therefore, rather than saying "Acromegaly Consensus, What Consensus?", we suggest "Acromegaly Consensus: The Next Steps."

Received October 23, 2002.

References

  1. Dimaraki EV, Jaffe CA, DeMott-triberg R, Chandler WF, Barkan AL 2002 Acromegaly with apparently normal GH secretion: implications for diagnosis and follow-up. J Clin Endocrinol Metab 87:3537 3542[Abstract/Free Full Text]
  2. Trainer PS 2002 Acromegaly consensus, what consensus? J Clin Endocrinol Metab 87:3534–3536[Free Full Text]
  3. Melmed S, Casanueva FF, Cavagnini F, Chanson P, Frohman L, Grossman A, Ho K, Kleinberg D, Lamberts S, Laws E, Lombardi G, Vance ML, Von Werder K, Wass J, Giustina A 2002 Guidelines for acromegaly management. J Clin Endocrinol Metab 87:4054–4058[Free Full Text]
  4. Giustina A, Barkan A, Casanueva FF, Cavagnini F, Frohman L, Ho K, Veldhuis J, Wass J, Von Werder K, Melmed S 2000 Criteria for cure of acromegaly: a consensus statement. J Clin Endocrinol Metab 85:526–529[Abstract/Free Full Text]
  5. Freda PU, Post KD, Powell JS, Wardlaw SL 1998 Evaluation of disease status with sensitive measures of growth hormone secretion in 60 postoperative patients with acromegaly. J Clin Endocrinol Metab 83:3806–3816




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