Acromegaly: Addressing a Rare Endocrine Disorder

At a Glance

  • Though scientists estimate fewer than 20,000 people in the US develop acromegaly each year, clinical diagnosis is often missed, so rates may be higher.
  • Early recognition is crucial because acromegaly is associated with many comorbidities that can significantly reduce survival.
  • In cases when surgery does not relieve symptoms, NewYork-Presbyterian offers medical approaches, including therapy with somatostatin analogues.

“Even though acromegaly is rare, its progression is insidious. Increased clinical vigilance and earlier diagnosis can make a real difference in the lives of patients.”

— Dr. Pamela U. Freda

While small pituitary adenomas are common, affecting about 17 percent of the U.S. population, research suggests that most of these tumors do not cause symptoms and rarely produce excess growth hormone. According to the National Institutes of Health (NIH), scientists estimate that three to four out of every million people develop acromegaly each year.

“In almost all cases, acromegaly is due to a growth hormone-producing tumor of the pituitary gland,” says Pamela U. Freda, MD, Clinical Director of the Neuroendocrine Unit in the Division of Endocrinology and Co-Director of The Pituitary Center at NewYork-Presbyterian/Columbia University Medical Center.

Because the clinical diagnosis of acromegaly is often missed, these numbers likely don’t reflect the true frequency of this rare and often disfiguring disease — the most common features being abnormal growth of the hands and feet. Overgrowth of bone and cartilage often leads to arthritis; body organs, including the heart, may also enlarge. Acromegaly is currently under-recognized and under-diagnosed, notes Dr. Freda, who for much of her career has specialized in the diagnosis, treatment, and research of this disease.

“The diagnosis of acromegaly is typically not made until patients experience signs and symptoms of the disease for an average of seven to eight years,” she says. “As acromegaly cannot be detected on routine laboratory testing, the diagnosis needs to be first considered based on history and physical examination findings and then confirmed bio-chemically by measurement of a serum IGF-1 level and measurement of GH suppression during an oral glucose tolerance test. Early recognition is crucial because acromegaly is associated with many comorbidities, including hypertension, diabetes, and arthritis, that can significantly reduce survival. The diagnosis should be suspected in a patient with the characteristic clinical findings.”

Dr. Freda is one of four endocrinologists in Columbia’s Neuroendocrine Unit. Under the direction of Sharon L. Wardlaw, MD, the Unit treats patients with the full range of disorders of the pituitary gland. These include nonfunctioning pituitary tumors, Cushing’s disease, prolactinomas, and other types of tumors in the region such as craniopharyngiomas, as well as hypopituitarism, diabetes insipidus, lymphocytic hypophysitis, and other diseases that affect the pituitary or hypothalamus. “Ours is very much a multidisciplinary team approach to these neuroendocrine disorders and we work very closely with neurosurgery, neuroradiology, neuro-oncology, and radiation oncology in the care of our patients,” says Dr. Freda.

Integrated Clinical and Research Endeavors

According to Dr. Freda, the main goal of therapy for acromegaly is to achieve biochemical control, including suppression of GH and IGF-1 normalization. “Transsphenoidal surgery is the most effective treatment for relieving the signs and symptoms of the tumor mass effect and can be curative in many patients,” explains Dr. Freda. “In selected patients, medical therapy can be used initially. In patients who are not successfully treated by surgery alone, we institute medical approaches that include therapy with somatostatin analogues and a growth hormone-receptor antagonist. Some patients also undergo radiotherapy, which can take many years to take effect. So in the interim, medical therapy is also begun.”

MRI of a pituitary tumor

MRI of a pituitary tumor.

Complementing the Neuroendocrine Unit’s clinical programs is a robust research program funded by the National Institutes of Health and industry. The Unit has the only NIH-funded research program for acromegaly in the country and the only NIH-funded research program for pituitary disease in the New York area. These programs offer patients the opportunity for novel diagnostic and therapeutic options for their pituitary tumors beyond those routinely available.

“For the past 20 years my research has focused on acromegaly,” says Dr. Freda, who is internationally recognized for her clinical and research program. “Our Neuroendocrine team at Columbia is widely known for our rigorous acromegaly research program and high quality clinical care of pituitary tumor patients.”

Dr. Freda and her colleagues have established and followed prospectively a uniquely large cohort of patients with acromegaly that has grown considerably over the years. “We have undertaken many studies based on this cohort,” she says. “Much of our research has aimed to determine how best to diagnose the disease and to determine whether or not patients are cured after treatment.”

Dr. Freda’s major research interests focus on clinical and translational investigations. In one series of studies of newly diagnosed and postoperative patients with acromegaly, she examined serum IGF-1 levels relative to the upper normal limit related to insulin sensitivity, serum cardiovascular risk markers, and body composition.

The researchers found that active acromegaly presents a unique combination of features associated with cardiovascular risk, reduced insulin sensitivity, yet lower body fat and lower levels of some serum cardiovascular risk markers, a pattern that is reversed in remission. “The percentage of the upper limit of normal of IGF-1 levels strongly predicts these features,” says Dr. Freda. “Our findings suggest that of all the factors insulin resistance is the most strongly related to disease activity and potentially to the increased cardiovascular risk in active acromegaly.”

In another study, the results of which were published in Endocrine Practice, the Columbia researchers took part in ACROSTUDY, an observational registry intended to collect safety and efficacy data on pegvisomant, a growth hormone receptor antagonist, in the treatment of acromegaly. The global safety surveillance study, which was set in 14 countries and 373 sites, analyzed safety, MRI readings, and treatment outcomes in 710 subjects who received at least one pegvisomant dose during and up to five years of follow-up. The ACROSTUDY data indicate that pegvisomant used as the sole medical therapy is a safe and effective medical treatment for this disease. The reported low incidence of pituitary tumor size increase and liver enzyme elevations support the positive benefit-risk of pegvisomant.

“Even though acromegaly is rare, its progression is insidious,” says Dr. Freda. “Increased clinical vigilance and earlier diagnosis can make a real difference in the lives of patients.”

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