Biochemical Control Now Possible in Nearly All Patients with Acromegaly

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For the management of patients with persistent or recurrent acromegaly after transsphenoidal surgery, medical therapies, such as with somatostatin analogs, dopamine agonists and growth hormone receptor antagonists, have been widely studied. However, there are few reports on the outcomes of multimodality therapy over the long term.

In a study spanning nearly 40 years, Lisa B. Nachtigall, MD, clinical director of the Neuroendocrine and Pituitary Tumor Clinical Center in the Department of Medicine, and Brooke Swearingen, MD, neurosurgeon in the Department of Neurosurgery at the Massachusetts General Hospital, and colleagues determined that in the modern era, the vast majority of patients with acromegaly achieve biochemical control. They published their results in The Journal of Clinical Endocrinology & Metabolism.

Study Methods

The researchers retrospectively studied 266 patients with acromegaly who were seen at Mass General between January 1980 and July 2019 and were followed for at least one year and/or two office visits after treatment initiation. Control of insulin-like growth factor 1 (IGF-1) was judged as normalization of the IGF-1 index (IGF-1 level/upper level of normal).

Types of Management

Patients were categorized into those diagnosed before or after 2006, around the time new medical therapies became available. 98% of all patients underwent first-line transsphenoidal surgery, with similar percentages in the two groups. 30% needed no further therapy after surgery and maintained a normal IGF-1 index at the time of last follow-up (median follow-up, 10 years).

For patients who did not achieve biochemical remission after initial surgery, a second surgery and/or radiation therapy were used more frequently before 2006, whereas medical therapy was more commonly used in the recent era.

Time to Biochemical Remission

The median time to normalization of the IGF-1 index was 14 months among patients diagnosed after 2006 versus 28 months among those diagnosed before (P =.002).

Recurrence:

• Twenty-four patients (9%) had the recurrent disease at some point after initial remission. The median time to recurrence was 48 months (range, 24–96 months)
• At the time of recurrence, 33% of the 24 patients had tumor growth in the pituitary gland, 29% had stable remnant tumor tissue and 38% had biochemical recurrence with no tumor detected
• Six patients with recurrent disease underwent repeat surgery, seven received radiation and 20 had medical therapy
• At last follow-up, 88% of the patients with recurrent disease had a normal IGF-1 index
• No factor could be found that predicted high IGF-1 after a period of normalization

Long-Term Outcomes

At last follow-up:

• 248 patients (93%) had achieved normalization of the IGF-1 index, with similar results in those diagnosed before and after 2006
• No patient with normal IGF-1 had evidence of tumor growth
• IGF-1 was abnormal in 18 patients (7%) because of noncompliance (n=8), lack of access to medication or insurance coverage (n=4), side effects/intolerance (n=3) and therapy still being adjusted (n=2). The remaining patient had no symptoms and IGF-1 was only mildly elevated
• 6% of patients had died at an average age of 67

The Importance of Monitoring

The potential for the recurrence of high IGF-1 many years after achieving control, sometimes with stable or absent tumor remnant, suggests the need for ongoing long-term monitoring of IGF-1 levels in patients with acromegaly.

Nevertheless, since no patient with a normal IGF-1 index had evidence of tumor growth at last follow-up, the vast majority of patients who have long-term normalization of IGF-1 and stable structural disease do not seem to require routine pituitary imaging.

Instead, pituitary MRI could be reserved for patients who exhibit elevated IGF-1 after some period of tumoral stability. This strategy would help prevent unnecessary exposure to gadolinium, a topic of increasing concern because of the potential long-term retention of the compound.

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Learn more about the Neuroendocrine & Pituitary Tumor Clinical Center at Mass General

Refer a patient to the Department of Neurosurgery