Rare But Devastating: Keeping Track of Acromegaly Cases

Since acromegaly is such a rare disorder, when an endocrinologist is presented with a potential case, the most accurate and complete data available would be a helpful tool. Endocrine News takes a closer look at how the Mexican Acromegaly Registry has helped endocrinologists address the issues patients with acromegaly face, both physically and financially.  

Late last year, a paper appeared in The Journal of Clinical Endocrinology and Metabolism, which aimed to examine long-term outcomes of pharmacological and surgical treatments in patients with acromegaly, the rare but often devastating disease can carry a high cost, both financially and physically.

In fact, the authors of the JCEM paper, led by Moises Mercado, MD, FRCP, of the Endocrinology Service and Research Unit in Endocrine Diseases at the Hospital de Especialdades in Mexico City, Mexico, refer to acromegaly as a “low-prevalence, high-cost” disease. Mercado tells Endocrine News that a general endocrinologist in private practice would probably only see about 40 or 50 patients with acromegaly during his or her lifetime, which means these physicians would need the most accurate and complete data to start a cost-effective workup of these patients.

The Mexican Acromegaly Registry (MAR) was founded in 2009 as an official program of the Mexican Society for Nutrition and Endocrinology and it has been continuously gathering information ever since, growing to become the largest acromegaly registry published in literature, with more than 2,700 patients registered from more than 20 centers distributed throughout Mexico.

In 2016, JCEM published the first international report of the MAR, describing the general epidemiology of acromegaly in the country, particularly focusing on the frequency of the different symptoms, signs, and comorbidities of the disease. That group studied date from more than 2,000 patients with acromegaly and concluded that their findings highlight important within-country differences in treatment choice due to variations in the availability of resources.

“We believe that this real-life information, albeit retrospective, should be the basis of the diagnostic and therapeutic recommendations for patients with acromegaly. The data has been very valuable in negotiating with official authorities the coverage of high-cost medications used to treat acromegaly.” – Moises Mercado, MD, FRCP, Endocrinology Service and Research Unit in Endocrine Diseases, Hospital de Especialdades, Mexico City, Mexico

“Registries such as the MAR provide very valuable information about the clinical behavior of a disease, particularly when it comes to relatively rare diseases like acromegaly,” says Mercado, who was a co-author of the 2016 JCEM paper. “In the first paper we describe the differences and similarities among institutions in the way acromegaly is diagnosed and treated.”

Now, Mercado and his team have returned to the MAR to evaluate long-term therapeutic outcomes in patients with acromegaly, pointing out that the information from national registries like these provide a better reflection of what occurs in real life with these patients, outside of controlled clinical trials.

Taking a Toll

Again, acromegaly is not only rare, but slow-moving, and comorbidities are usually present before the patient is even diagnosed with acromegaly. And while treatment options have improved over the years, surgery techniques refined, Mercado and his team write that active acromegaly is still associated with significant morbidity and mortality from neoplastic and cardiovascular causes.

Patients with acromegaly of course have a diminished quality of life due to the prolonged exposure to excessive growth hormones – headaches, sleep apnea, development of diabetes, even changes to their face, all of which can take a toll.

The primary treatment is resecting the GH-secreting adenoma, but as Mercado and his co-authors point out, the outcomes of these surgeries vary with the surgeon’s expertise. As for pharmacological treatments, first-generation somatostatin analogs (SSAs) have shown promise in numerous controlled, prospective clinical trials, but Mercado says that achievement of stringent biochemical goals occurs in only 25% to 40% of patients.

Reflecting Real Life

For the most recent JCEM study, the researchers extracted data from the from the four main MAR participating centers: Hospital de Especialidades, Centro Médico Nacional Siglo XXI, Centro Hospitalario “20 de noviembre,” Instituto Nacional de Neurología y Neurocirugía, and Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, all located in Mexico City, to analyze surgical outcomes in 650 patients, as well as pharmacological outcomes in 395 patients.

For those patients who underwent surgery, 261 patients (40.15%) achieved biochemical remission, 287 (44.2%) remained biochemically active, 44 (6.8%) were categorized as GH discordant, and 58 (8.9%) as IGF-1 discordant. Out of 267 patients with acromegaly who took SSAs, only about 28% achieved remission, and of the 100 patients who took a combination of SSAs and cabergoline, 19% achieved remission and 44% remained active. The authors found that in both groups, persistently active acromegaly was associated with harboring an invasive macroadenoma.

“We decided to look at therapeutic outcomes in the four main contributing centers, because the information from these centers is more complete,” Mercado says. “We are convinced that the information derived from studies based on epidemiological registries reflects what actually occurs in real life, that is, out of the context of a controlled clinical study.”

Reducing the Burdens

For Mercado and his team, their data not only led them to conclude that therapeutic outcomes in acromegaly vary with tumor size and invasiveness, it also confirmed information previously generated in local and international single-center studies. The work could also lead to less burden on patients who suffer from acromegaly, physically as well as financially.

“We decided to look at therapeutic outcomes in the four main contributing centers, because the information from these centers is more complete. We are convinced that the information derived from studies based on epidemiological registries reflects what actually occurs in real life, that is, out of the context of a controlled clinical study.” – Moises Mercado, MD, FRCP, Endocrinology Service and Research Unit in Endocrine Diseases, Hospital de Especialdades, Mexico City, Mexico

“We believe that this real-life information, albeit retrospective, should be the basis of the diagnostic and therapeutic recommendations for patients with acromegaly,” Mercado says. “The data has been very valuable in negotiating with official authorities the coverage of high-cost medications used to treat acromegaly.”

Caring for patients with acromegaly, easing their pain any way possible, is of the utmost concern for physicians and researchers treating and studying this complex disease. Mercado says that optimal care requires a multidisciplinary approach, including neuroendocrinologist, neurosurgeons, ENT specialists, among other specialists. “We hope our study helps all these specialists that are involved in the care of acromegaly patients,” he says.

Bagley is the senior editor of Endocrine News. In the August issue, he wrote about how newly discovered mutations could hold the key to treating adrenal cancer.