Despite successful medical intervention, people with acromegaly don’t always share their clinician’s optimistic outlook. Eliza B. Geer, MD, director of Memorial Sloan Kettering’s Multidisciplinary Pituitary & Skull Base Tumor Center, takes us through a holistic approach to treating this often-confounding condition and how a team-based methodology is frequently the key to success.
Recently, I was reviewing an acromegaly patient’s test results in preparation for her upcoming visit. I was pleased with our treatment plan: her tumor had been successfully surgically debulked and the remnant was stable and not encroaching on surrounding critical structures; and her recent IGF-1 levels were within the normal range on ongoing monthly somatostatin receptor ligand injections.
I was looking forward to sharing the good news with her, but when I walked in the exam room, the expression on her face did not match my optimistic perspective. As we talked about her symptoms, she reported that she had ongoing joint pain that was impacting her ability to go hiking, which was one of her favorite hobbies, and the monthly clinic injections were painful and challenging to schedule with her work and family obligations. While she was pleased to hear about her reassuring test results, she still struggled with ongoing symptoms and concerns that were impacting her quality of life.
This discrepancy between objective markers of successful treatment for acromegaly, and the acromegaly patient’s daily experience living with this chronic condition, is dishearteningly common.
A Diagnostic Challenge
Acromegaly typically results from a growth hormone (GH)-secreting pituitary adenoma, causing excess circulating GH and resulting high insulin-like growth factor-1 (IGF-1) levels. The insidious onset and slow progression of associated signs, including facial changes and enlargement of the hands and feet, coupled with non-specific symptoms such as headaches and joint pain that may be attributed to stress, aging, or other conditions, creates a challenge for achieving a timely diagnosis.
Diagnosis is often delayed by several years and, as a result, patients often present with significant disease burden and advanced comorbidities including sleep apnea, type 2 diabetes, and cardiovascular disease.
Psychological symptoms are also an important aspect of acromegaly. These can include depression and functional deficits resulting from both psychological and somatic symptoms, such as difficulties in social situations or maintaining relationships due to self-consciousness surrounding visible body changes.
A Multidisciplinary Approach
Effective treatment of acromegaly requires a multidisciplinary team of specialists who work together to manage the many aspects of this disorder, including reducing tumor volume, normalizing GH and/or IGF-1 levels, minimizing associated comorbidities, addressing symptoms, and improving quality of life.
First-line treatment for acromegaly typically consists of surgery to debulk the pituitary tumor. Overall, approximately half of patients have persistent disease after surgery and require ongoing medical therapy to achieve biochemical remission. Medical therapy options include somatostatin receptor ligands (SRLs) such as octreotide, lanreotide, or pasireotide; the GH-antagonist pegvisomant; or a dopamine agonist like cabergoline. Radiation therapy may be indicated particularly for aggressive tumors.
As with many endocrine disorders, the treatment burden in acromegaly can be significant. For instance, pituitary tumor resection may result in hypopituitarism, and injectable SRL use commonly requires administration in a healthcare setting and carries the inherent challenges of injection treatment (including pain, swelling, bruising, and nodules). Even monitoring the disorder with blood draws, MRIs, and other appointments can cause anxiety and discomfort, and require the patient to spend time away from work and family — all obvious burdens that should not be discounted.
A multi-disciplinary team of physicians developing an optimal treatment and management plan for each patient must consider both the burden of acromegaly itself, as well as the burden of the treatment.
Assess Patient-Reported Symptoms
After patients receive a diagnosis and begin a course of treatment, many quickly experience improved or resolved symptoms — soft tissue swelling decreases, and headaches may subside. However, certain phenotypic changes, symptoms, and comorbidities, especially musculoskeletal disorders, may be irreversible or difficult to manage even with treatment. Joint pain, for instance, often remains difficult to address with current therapies, as well as sleep apnea.
In the context of patient-centered care, it is important to remember that physicians must not only emphasize biochemical control — which is typically measured as normalization of serum IGF-1 levels — but also consider patient-reported symptom control. Biochemical control is, of course, a valuable and critical marker, as IGF-1 normalization has been shown to correlate with reduced mortality and improved long-term patient outcomes. However, established normal ranges of IGF-1 levels are based on population-level statistics that don’t always reflect individual variability. IGF-1 normalization is also not an ideal proxy for qualitative well-being at the level of individual patients, as it does not strongly correlate with improvement in patient symptoms.
If physicians focus solely on achieving normal IGF-1 levels, they may unintentionally fail to capture a complete picture of the ongoing symptom burden their patients may experience day to day. Physicians must take into consideration their patients’ characterizations of their symptoms and overall well-being alongside biochemical control to determine treatment plans.
Understanding Symptom Burden
As it stands, there is a documented discrepancy between how acromegaly patients report the nature and severity of their symptoms and how their physicians perceive those symptoms. As part of my recent research into the dynamics between physicians and their acromegaly patients, relative to patients’ self-reported symptoms, physicians tended to report fewer instances of several symptoms (including mental fog, joint pain, and headache), reported fatigue and weakness more often, and rated symptoms as “severe” less often than patients did for most of the symptoms surveyed.
In addition to the need for a better understanding of patients’ overall symptom burden, some studies have documented fluctuating degrees of symptom control in patients receiving once monthly or less frequent injectable SRLs. In these cases, different (e.g., oral octreotide or pegvisomant) or additional agents (e.g., supplemental injections, cabergoline, pegvisomant) may provide more consistent control of acromegaly symptoms.
In addition, virtual education programming has been shown to have positive effects on acromegaly patients’ perceptions of their disease and should be incorporated as part of a multi-disciplinary model of long-term care for this condition. Physicians should have a thorough discussion with their patients about their treatment options to ensure the patient’s adherence and comfort, followed by regular follow-up conversations to gather honest assessments of their patient’s symptoms.
Given the complexities of acromegaly’s impact on quality of life, our multidisciplinary care teams must not lose sight of each patient’s well-being and symptom burden. Providers should maintain open two-way communication and consideration of all available treatment options as part of a patient-centered approach.