Consensus on criteria for cure of acromegaly published

A consensus group has reviewed the criteria for cure of acromegaly, and updated guidelines detailing the latest management criteria were published in the Journal of Clinical Endocrinology & Metabolism.

The criteria were re-evaluated and updated last year by the Acromegaly Consensus Group, an international collaboration of endocrinologists and neurosurgeons.

In the 10 years since the Acromegaly Consensus Group defined the criteria for cure of acromegaly, significant progress has been made in the management of acromegaly, according to the experts.

“The previous guidelines created a decade ago were rigid, offered fewer clinical options and resulted in practically all patients submitted to the same type of follow-up independently of the treatment,” Andrea Giustina, MD, professor of internal medicine, University of Brescia, Italy, told Endocrine Today. “This updated consensus is more flexible, with different approaches in terms of biochemical evaluation for various treatment modalities such as surgery or different medical therapies.”

Review of criteria

The consensus group reviewed criteria for relevant assays, biochemical measures, clinical outcomes, definition of disease control, available published evidence and strength of consensus statements. The group made several significant changes to the 2000 guidelines.

“If managed appropriately by a multimodality team with specific experience of managing pituitary tumors, there is little justification for patients to have reduced life expectancy, frequent morbidity or uncontrolled disease,” the experts wrote in the report.

New drug therapies are the cornerstone of the criteria for disease control, particularly long-acting somatostatin analogues and a growth hormone receptor antagonist. Since the previous consensus, GH receptor antagonists such as pegvisomant (Somavert, Pfizer) have become integral components of acromegaly treatment.

“These medications have proven relatively safe and highly effective in achieving tighter control of GH and insulin-like growth factor I hypersecretion,” Shlomo Melmed, MD, Endocrine Today Editorial Board member and senior vice president of academic affairs and dean at Cedars-Sinai Medical Center, Los Angeles, said in an interview.

The first clinical trial of pegvisomant was published in 2000, making it substantially an experimental drug at the time the last criteria were established, according to Giustina.

“Now, after 10 years, we have a solid familiarity with the treatment,” he said. “Furthermore, we recognize that the GH assay is not useful in assessing the response to pegvisomant treatment.”

Long-acting somatostatin analogues have proved to be safe, potential alternatives to surgery.

“Emerging evidence now supports the notion of using somatostatin analogues as primary therapy to shrink tumor size in the appropriately selected patient,” Melmed said. “Medical, rather than surgical, therapy can be offered to those patients who exhibit no compressive tumor mass effects, those in whom surgery will invariably still require postoperative medical treatment, those who are too frail for anesthesia and those who decline surgery.”

The issues of unreliable GH and IGF-I assays, assay standardization and rigorous normative data have presented challenges in interpreting biochemical measures and have led to major discrepancies in values.

The updated criteria include the use of international units, the adoption of the highly purified recombinant IGF-I World Health Organization first international standard and the further development of mass spectroscopy-based technology.

Changes were also made to the levels defining disease control. Optimal control is now defined as age-adjusted normal IGF-I level, determined by a reliable standardized assay, and a GH level less than 1 mcg/L measured as a random GH using an ultrasensitive assay. In patients undergoing surgical management of GH-secreting tumors, the oral glucose tolerance test is recommended to assess the outcome.

The updated criteria also include further recommendations for assays, GH and IGF-I regulation, discrepant biochemical results, clinical outcomes and definition of disease control.

Future effect

The experts expect the guidelines to have a major effect on the treatment of acromegaly.

“It allows us to speak a common language. Clinicians all over the world will be able to approach acromegaly in a unified manner, and we believe that this is important for the standard of care and cure of the disease,” Giustina said.

More rigorous control of hormone hypersecretion will lead to improved management of comorbidities such as diabetes, hypertension, cardiovascular disease, arthritis and sleep disorders, Melmed said.

“Ultimately, these advances should improve the adverse mortality rates associated with uncontrolled acromegaly,” he said. – by Matthew Brannon

Giustina A. J Clin Endocrinol Metab. 2010;94:10.1210/jc.2009-2670.