Strategies to improve management of patients with acromegaly
Acromegaly is a rare disease characterized by the overproduction of growth hormone primarily from benign tumors in the pituitary gland. This leads to the hypersecretion of insulin-like growth factor I, a hormone responsible for the clinicopathologic features of acromegaly.
Continued exposure to high levels of GH and IGF-I increases the risk for morbidity and mortality in patients with acromegaly. Early diagnosis, effective treatment and frequent monitoring are critical for improving clinical symptoms and outcomes of disease. Thus, a primary goal of treatment in acromegaly is to achieve biochemical control, defined as GH levels less than 1 µg/mL and IGF-I levels within the normal range, through surgical or pharmacologic interventions.
Current treatment options
Surgery is recommended as first-line treatment and provides biochemical control to many patients with acromegaly. However, some patients will be ineligible for or will not experience adequate control of disease with surgery. In these patients, further treatment with medical therapy is recommended.
Michael H. Shanik
Somatostatin analogues (SSAs), dopamine agonists and GH receptor antagonists are three classes of medical therapy that are currently available, with each having varying success rates for biochemical control. Endocrine Society acromegaly clinical guidelines recommend use of SSAs — Sandostatin (octreotide, Novartis), Somatuline Depot (lanreotide, Ipsen) and Signifor (pasireotide, Novartis) — or a GH receptor antagonist, Somavert (pegvisomant, Pfizer), in patients with acromegaly who have moderate to severe signs and symptoms of disease after surgery, whereas a dopamine agonist is suggested for those with mild disease.
SSAs are well tolerated and are considered the mainstay of medical therapy, providing both tumor volume reduction and biochemical control to many patients. Despite the reported success rates of surgical or medical intervention, 45% of patients will continue to have persistent disease or develop recurrent disease. For these patients, combination medical therapies could be considered, but this approach carries an added risk for side effects and increased cost because of the use of multiple drugs. Alternatively, radiotherapy is suggested as a third-line treatment; however, it is accompanied by a high risk for adverse effects and long-term side effects.
Improved management, treatment options needed
There are several patient subpopulations in need of improved treatment and management, including patients with acromegaly who have experienced incorrect or delayed diagnoses, which are a barrier for timely implementation of proper treatment. Nonspecific symptoms, such as headaches, joint pain, fatigue and carpal tunnel syndrome, may be the first signs of acromegaly. However, connecting these initial symptoms with acromegaly can be challenging for the treating physician because it is a rare disease, and physical findings are frequently subtle until the disease is more advanced. Therefore, it is imperative to increase awareness of the disease among health care professionals so that patients can be directed to appropriate treatment programs.
Another patient population in need of better treatment includes those who are not suitable for surgery or those with persistent or recurrent disease after surgery or medical therapy. In these cases, it will be important to identify strategies that are individualized for the patient and provide higher rates of sustainable biochemical control with available treatment over the long term. This could involve use of SSAs for patients for whom surgery is not suitable, or switching or increasing doses of medical therapy, combination therapy or radiotherapy for those with persistent or recurrent disease.
Patients with acromegaly often experience a long journey of multiple doctors’ visits and debilitating symptoms that can last for years before the correct diagnosis is made. By the time acromegaly is diagnosed and treated, long-term uncontrolled acromegaly may have had a substantial effect on the patient’s quality of life and associated comorbidities. Many patients experience substantial pain and discomfort, which affects sleep, family life, and their ability to work, and can cause depression and anxiety. When patients are successfully treated and achieve biochemical control, there are substantial improvements to their overall physical and emotional health, such that patients are often willing to tolerate transient side effects or inconvenient dosing regimens.
From a physician perspective, being aware of treatment options, understanding the burden of treatment, and being able to evaluate the wide-ranging symptoms and appropriately treat comorbidities are critical. Regular monitoring is vital because current therapies may only be effective if continued care and compliance to treatment are maintained. Some patients do not adhere to follow-up visits, particularly those achieving biochemical control and those in disease remission, and are in need of improved management. Absence of reported symptoms, lack of improvement of symptoms with current therapy, and lack of understanding that follow-up visits are necessary are some of the reasons that patients fail to follow-up with their physician. Patients lost to follow-up are without optimal monitoring and adequate medical treatment and are, thus, at increased risk for experiencing active disease. Therefore, it is critical to provide treatment options that improve symptoms, which will motivate adherence to therapy.
Expanding treatment options
There is a need for alternative therapeutic options for patients with acromegaly who do not achieve biochemical control with current therapies. In 2014, the FDA approved pasireotide long-acting release for the treatment of patients with acromegaly who do not achieve control of disease with surgery or for those who cannot undergo surgery.
In recent years, several novel medical therapies have been under investigation in clinical trials. These agents include somatoprim (Strongbridge Biopharma) and Temodar (temozolomide, Merck), which could be effective in patients who do not achieve long-term control with current therapies. Additionally, octreotide subcutaneous depot (Camurus AB) and oral octreotide (Chiasma) are investigational agents that potentially not only increase the rate of biochemical control, but also provide different modes of administration that may reduce loss to follow-up or treatment discontinuation in patients with acromegaly.
- Katznelson L, et al. Endocr Pract. 2011; 17:636-646.
- Katznelson L, et al. J Clin Endocrinol Metab. 2014;doi:10.1210/jc.2014-2700.
- For more information:
- Michael H. Shanik, MD, FACP, FACE, is an endocrinologist at Endocrine Associates of Long Island, P.C. He can be reached at: firstname.lastname@example.org.
Disclosure: Shanik reports receiving research funding from Novartis Pharmaceuticals.