Acromegaly is an endocrine disorder characterized by excessive soft tissue and bone growth, and is caused by excessive levels of growth hormone secreted by the pituitary gland. These excessive hormone levels are usually secreted by pituitary adenomas, which are benign.
Because the body changes are slow, diagnosis is usually delayed despite symptoms manifesting earlier. Correct diagnosis and treatment of acromegaly are complicated and often misunderstood—even by specialists. If left untreated, this disease can lead to severe illness and death.
Medscape spoke with Laurence Katznelson, MD, endocrinologist and medical director of the Pituitary Center at Stanford Hospital and Clinics, Stanford, California, about the diagnosis and treatment of patients with acromegaly.
Medscape: What are the keys to diagnosing acromegaly?
Katznelson: For pituitary adenomas, the basis of diagnosis is the determination of growth hormone (GH) hypersecretion. The vast majority of patients with acromegaly have a pituitary tumor. Rarely do these patients have neuroendocrine tumors elsewhere in the body.
The assessment of GH levels is done in two ways. First, we measure levels of insulin-like growth factor–1 (IGF-1), which is an integrated marker of GH levels, over the preceding weeks. IGF-1 is secreted by the liver in response to GH, so the higher the GH, the higher the IGF-1. There are cutoff ranges for IGF-1 on the basis of age and gender. This is an easy and useful test that can be done at any time of day regardless of food intake.
Second, if there is any question following the measurement of IGF-1—for instance, if the levels are borderline or the patient has clinical findings with borderline levels—then the next test would be a glucose tolerance test, where we give glucola and then measure the nadir GH levels.
We look for a cutoff of 1 ng/mL, as suppression to less than this number is normal. If the level is higher than 1 ng/mL, that is consistent with acromegaly.
But with early disease—and this is part of the problem because we're increasingly picking up this disease earlier—the GH levels can be low and the patient may have a suppressible GH after glucola, so we rely more on the clinical features as well as the elevated IGF-1 values.
Medscape: Do you see any misconceptions about diagnosis among specialists?
Katznelson: One is the use of a random GH level to diagnose the disease, which is still done pretty commonly. The problem with a random GH level is that it's useful if the value is very high, but the value usually isn't. GH levels can fluctuate depending on food, diet, exercise, activity level, and nutrition status.
Thus, random GH levels are not terribly useful. We urge physicians to do the other tests. Not that they can't do a random GH level, but it's not useful for diagnostic purposes.
Medscape: What are your preferences for evidence-based treatment of acromegaly?
Katznelson: On the basis of the guidelines of the Endocrine Society and the American Association of Clinical Endocrinologists, the majority of patients with acromegaly should have surgery. The surgery involves a transsphenoidal approach, which has gotten much better over the years, particularly with the advent of intraoperative endoscopy as part of the procedure.
The surgery is successful for patients whose tumors are located within the sella turcica and have not extended to the cavernous sinus, adjacent to the sella. If the tumors extend into the cavernous sinus, there will likely be residual disease following surgery.
In general, most patients should have surgery upfront to resect all that is potentially resectable. Rarely do we go right to medical therapy [and would consider this strategy only] for patients whose tumors are exclusively in the cavernous sinus, patients who are not good surgical candidates, or patients who prefer this approach.
Starting with surgery is important because if the patient needs adjuvant medical therapy, which many do, then the smaller the tumor and the lower the GH levels, the better the chances that medical therapy will be successful. In general, surgery is effective in 40%-50% of patients with normalization of IGF-1 levels, and that is because the majority of tumors are large and often do invade the surrounding areas.
For patients who have residual disease after surgery, medical therapy should be started. Most patients start on somatostatin analogues, which are effective and well tolerated. Some also start on a GH antagonist called pegvisomant, which is a medication that bypasses the pituitary adenoma and blocks GH systemically.
If a patient has adenoma resection and it is successful, then that's the end of the story and we monitor annually.
Medscape: Are there any contentious aspects to the treatment of acromegaly?
Katznelson: There is a question about whether medical therapy should be given upfront. There are no studies that have clearly shown that medical therapy will improve surgical outcomes.
In general, medical therapy is used upfront for patients who are poor surgical candidates. Medical therapy may also be considered for candidates who have an edematous pharynx, which makes intubation difficult and may be associated with significant sleep apnea syndrome that would be problematic post-op.
Or, a patient may have significant cardiovascular disease, thus increasing the risk for cardiomyopathy and heart failure. So there are situations where we may want to treat medically upfront to minimize surgical risk.
Medscape: How is the quality of life for patients with acromegaly?
Katznelson: Quality of life is a big issue with these patients. Patients with acromegaly have multiple comorbidities. They develop cardiac disease and they have sleep apnea syndrome. One of the most debilitating parts of the disease is skeletal problems, including arthropathy.
The joint aches are problematic. If you see patients years out who are in remission and ask them what the biggest residual problem is from their acromegaly, it is joint pains.
What physicians need to understand is that even if the patient's GH levels are normal, there are comorbidities that need to be monitored and treated aggressively in parallel, including joint pains and heart disease.
For example, diabetes and heart disease do not melt away after surgery. Sleep apnea syndrome often improves but may also persist, so we recommend that patients have sleep studies after surgery, particularly if they have morning fatigue or snoring. These patients very commonly have continued sleep apnea syndrome.
Medscape: Is depression a factor in acromegaly?
Katznelson: There have been studies looking at the psychological outcomes of acromegaly, some of which are based on the fact that these patients are often disfigured. They have dysmorphic facies, which can lead to depression or anxiety. In addition, these patients often have low pituitary function because of the surgery and tumor size, which may also lead to depression. Depression has several different causes. We recommend that patients seek counseling if they show any evidence of depression.
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Cite this: Understanding the Nuanced Management of Acromegaly - Medscape - Dec 12, 2018.