Growth Disorder Tx Has Room for Improvement

By Kristina Fiore, Staff Writer, MedPage Today
Reviewed by Zalman S. Agus, MD; Emeritus Professor, Perelman School of Medicine at the University of Pennsylvania and Dorothy Caputo, MA, BSN, RN, Nurse

Although control of the disease has improved over the past few decades, about a quarter of patients with acromegaly aren't hitting treatment targets, British researchers found.

In a U.K. registry study, growth hormone levels were well controlled in about 75% of patients on either somatostatins or dopamine agonists -- leaving 25% of patients not well controlled, Trevor Howlett, MD, of the University Hospitals of Leicester in England, and colleagues reported online in Clinical Endocrinology.

"It seems we are not generally optimizing the dose of some drugs despite incomplete control," Howlett said in a statement. "This could be improved. As high growth hormone is associated with reduced life expectancy, we should perhaps also be more ready to consider additional surgery or radiotherapy if control is not achieved with drugs."

Baha Arafah, MD, chief of endocrinology at University Hospitals Case Medical Center, told MedPage Today that the findings confirms what endocrinologists already know -- that "we are not perfect in managing this disease and we still have a ways to go."

Arafah said the ideal way to improve outcomes for this population would be to recognize the disease earlier.

"The average time to presentation to medical care [for acromegaly patients] is 10 to 11 years," he said. "If we educate primary care doctors or orthodontists ... about the presentation of this disease, likely we can see these patients earlier and manage them earlier."

Those suggesting more demanding consensus criteria for treating acromegaly have advocated for normalization of both growth hormone levels (under 1 mcg/L) and insulin-like growth factor-1 (IGF-1) levels in order to dub patients as "cured," Howlett and colleagues wrote.

Standard treatment includes pituitary surgery and/or radiotherapy, as well as medical therapy with either dopamine agonists or the newer somatostatin analogs.

To assess changes in treatment over time, the researchers looked at data from the U.K. Acromegaly Registry, which includes information on 2,572 patients from 31 centers in the country: 70% had surgery, 45% had some form of radiotherapy, 40.6% took somatostatin analogs and 41.4% used dopamine agonists.

Overall, they found that control of growth hormone and IGF-1 improved over time, particularly for patients on drug therapy. These improvements are probably due to improvement in surgical outcomes and greater use of drug therapy, they wrote.

Still, among patients who were on long-term somatostatin analog or dopamine agonist therapy, 75% achieved growth hormone levels indicative of control -- leaving a quarter that were not well controlled, they reported.

Growth hormone also appeared easier to control than IGF-1 levels, they found. Among those on long-term somatostatins, IGF-1 levels were controlled in 69% of patients, and both growth hormone and IGF levels were controlled in 55%.

The numbers were even lower among patients on dopamine agonists, the researchers wrote. Just over half (55%) had well controlled IGF-1 levels, and only 45% had both their growth hormone and IGF levels controlled -- figures that Howell and colleagues called "disappointing."

They noted that clinicians appeared to fail at escalating the dose of somatostatin analogs in order to achieve the maximum effective dose -- one factor that may help improve control, they wrote. Other approaches include changing from dopamine agonist to somatostatin analog therapy, increasing use of growth hormone antagonists when indicated, using newer somatostatin analogs, and opting for pituitary surgery in patients who aren't controlled on medical therapy.

They added that their findings may call into question the achievability of consensus guidelines for "controlled" acromegaly, which push growth hormone levels to under 1 mcg/L and require a normalization of IGF-1.

Until 2009, the U.K. Acromegaly Registry was funded by Novartis. It is currently supported by Ipsen and the Clinical Endocrinology Trust.

The researchers reported no conflicts of interest.

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