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Best Practices in Acromegaly
Timely Recognition and Management of Acromegaly: Updates and Best Practices

Released: September 20, 2024

Expiration: September 19, 2025

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Key Takeaways
  • Understanding the similarities and differences between oral and injectable somatostatin receptor analogs like octreotide, lanreotide, and pasireotide is key for providing optimal care in acromegaly.
  • With an expanding treatment armamentarium, it is important for healthcare professionals to know the ideal place in therapy for each available agent to individualize treatment plans.

In this commentary, Julie M. Silverstein, MD, answers frequently asked and compelling questions from a series of live webinars on diagnosing and effectively treating acromegaly. 

Do the oral and injectable formulations of octreotide exhibit similar safety and efficacy profiles?
Based on clinical studies involving patients who were treated with and controlled on somatostatin analogs—either long-acting octreotide or lanreotide—most patients maintained biochemical control after switching to oral octreotide, suggesting injectable and oral octreotide have similar efficacy. The safety profile of both octreotide formulations is similar between the two, with the biggest difference of no injection-site reactions with oral octreotide. Oral octreotide should be taken on an empty stomach twice daily. In addition, certain medications, such as levothyroxine, should not be taken at the same time because this can decrease absorption.

If a patient prefers oral therapy, which would you recommend: cabergoline or octreotide?
Cabergoline is a good option for patients with mild to moderate elevations in insulin-like growth factor 1 (IGF-1) levels. It is very easy to take, cost-effective, and typically prescribed twice weekly.

For patients with more severe disease, where cabergoline may not be sufficiently effective, oral octreotide could be an option. Although oral octreotide is indicated for patients with acromegaly who are well-controlled on standard-of-care somatostatin receptor ligands, it may be considered as a first-line option.

When is it appropriate to switch or add pegvisomant into a patient’s treatment regimen?
If patients’ acromegaly is not adequately controlled on somatostatin receptor ligands, it is reasonable to consider adding pegvisomant to their treatment plan. However, it is important to note that pegvisomant will require additional injections and can be costly. It is also reasonable to switch a patient to pegvisomant monotherapy.

Why do some patients with acromegaly exhibit suppression on the oral glucose tolerance test (OGTT)?
The OGTT suppression is likely because of the mild nature of their disease. Although the exact mechanism is not fully understood, it appears that patients with less severe forms are able to suppress their growth hormone (GH) levels during the OGTT.

Can the results of the OGTT be affected in patients with type 2 diabetes?
Recent studies suggest that the OGTT is accurate in patients without poorly controlled type 2 diabetes when using sensitive GH assays. If a patient with uncontrolled or poorly controlled type 2 diabetes does not suppress appropriately on an OGTT, it might be reasonable to repeat the test when the diabetes is better controlled.

What is the role of pasireotide in the treatment of acromegaly?
Pasireotide is primarily indicated for patients with acromegaly whose disease remains uncontrolled despite treatment with first-generation somatostatin analogs. However, because the risk of diabetes and hyperglycemia is higher with pasireotide, I tend not to use it. Pasireotide is also approved by the FDA for the treatment of Cushing’s disease. In my practice, I have prescribed pasireotide for patients with aggressive adenomas and Cushing’s disease.

What is the recommended frequency for monitoring IGF-1 in patients undergoing medical therapy?
When initiating treatment with injectable octreotide or lanreotide, we typically measure IGF-1 levels before the third dose, and then I check every 3 months while adjusting the dose. Once the patient is stable, it is reasonable to monitor levels and symptoms every 6-12 months. For patients receiving oral octreotide, I recommend checking an IGF-1 4 weeks after starting therapy, every 4 weeks while adjusting the dose, and then every 6-12 months.

How quickly can we expect IGF-1 to normalize with radiotherapy?
Radiation therapy is generally considered second line or third line in patients not controlled with surgery and/or medication. Response to radiotherapy can be a slow process. The mean time to biochemical control with stereotactic radiosurgery is 2 years compared with 3 years with fractionated radiotherapy.  Patients will need treatment with medical therapy as a bridge. Overall, we consider radiotherapy to be effective approximately 50% to 70% of the time.

Can radiation therapy shrink the size of a tumor?
Yes, radiation therapy is associated with tumor shrinkage. However, we currently tend to do less radiation because of the availability of good medical therapies. It may be the best option for patients with large tumors for oncologic control. Patients with small pretreatment tumors may see complete tumor resolution after radiation therapy.

Is there a difference in effectiveness between lanreotide and octreotide?
No, both lanreotide and octreotide are equally effective in terms of biochemical control and tumor shrinkage. The reason to choose one or the other would depend on factors such as ease of administration, potentially, but in terms of efficacy, they are just as effective as each other. 

If a patient’s IGF-1 levels increase after switching from injectable to oral octreotide, how should this be managed? Would you switch back to the injectable form?  
Assuming patients had well-controlled disease on the injectable form of octreotide and not controlled on the maximum dose of oral octreotide, I would recommend just switching them back to injectable form.

What are your follow-up protocols for your patients, especially those receiving pegvisomant or other therapies? Do you have any recommendations for follow-up care? 
Pegvisomant is a GH receptor antagonist, so follow-up involves monitoring IGF-1 levels. GH levels may increase, and some assays might inaccurately detect pegvisomant. It is important to regularly monitor liver enzymes levels and MRI scans because of the risk for tumor growth. 

For patients receiving somatostatin receptor ligands, we monitor IGF-1 and GH levels. Our goal is to maintain the patient’s IGF-1 levels within the normal range based on the reference range appropriate for the patient’s age and gender. We aim to keep GH levels <1 mcg/L, as this level is associated with normalized mortality. The frequency of monitoring really depends on how the patient is doing. When initiating treatment with an injectable, I usually recheck the levels before the third dose and continue this interval until the patient is stable. After that, the interval can be extended to 6 months or even 1 year. 

When would you choose pasireotide over a first-generation somatostatin receptor analogs?
I would consider using pasireotide for patients who are not controlled on maximum dose of octreotide or lanreotide.

Do you find it difficult to navigate patients who initially resist using injectables, or do you find that many of your patients prefer oral medications? 
Of interest, when patients are presented with both options, many patients express a preference for a monthly treatment, such as an injection, over daily oral medication. I have encountered some patients who have needle phobias, and in that scenario, I might consider starting them on oral octreotide first. In my experience, patients who are knowledgeable about their disease and comorbidities often are able to overcome their fear of needles. The main challenge I find patients face is access to a healthcare professional. I am in St Louis, Missouri, and we have a lot of patients who live hours away in the middle of nowhere. In these patients, an oral option is often preferred over injectables. 

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