Acromegaly

Diagnosis

Since the pathologic effects of increased GH secretion tend to be progressive over time, early detection is an important step in the management of acromegaly.

• The Difficulty of Diagnosis
• Tests Used in Diagnosing Acromegaly
• Importance of Measuring GH Levels
• Confirming a Diagnosis of Acromegaly
• The Role of Imaging in Diagnosis

The Difficulty of Diagnosis

The difficulty of early diagnosis results from several challenges:

• Since symptoms develop gradually, time is required for them to be recognized by patients and physicians.
• Patients may exhibit a variety of different clinical signs and symptoms since they may have any combination of the common symptoms.
• Other conditions can produce the signs and symptoms of acromegaly and must, therefore, be ruled out.

For these reasons, most cases of acromegaly are not diagnosed until about 10 years (range: 5-15 years) after the onset of increased GH secretion.

Acromegaly is initially detected by different types of health care professionals who observe different signs and symptoms:

Tests Used in Diagnosing Acromegaly

Several tests are useful in diagnosing and monitoring acromegaly. The most important are laboratory tests that measure the levels of GH and IGF-1 in the blood. Because these levels vary naturally depending on the patient's age, the time of day, and time since the last meal, there are two main approaches to measuring GH and IGF-1 levels.

• Multiple tests. To compensate for the variation in levels, the values may be averaged from a series of "random" blood tests.
• Oral glucose tolerance test (OGTT). Alternatively, a way to get an accurate reading in a single measurement is to take the blood sample after an overnight fast, followed by an early morning drink of concentrated glucose solution.

The Importance of Measuring GH Levels

Since GH is secreted sporadically throughout the day and has a short half-life, a single random GH testing is considered to be of little value in diagnosing acromegaly. However, since elevation in GH is a basic abnormality in acromegaly, basal GH levels may be examined during the diagnostic phase, as well as during the ongoing monitoring of acromegalic patients. When acromegaly is suspected, an oral glucose tolerance test (OGTT) is used to evaluate the response of GH to "glucose challenge." In this test, 75 or 100 g of glucose are administered in an oral solution to a patient who has fasted overnight. Blood samples are obtained from the patient 30 minutes before ingestion of the glucose, then every 30 minutes afterwards for a total of 2 hours. The following results are observed (1):

• In normal individuals, administration of glucose suppresses GH levels to <1 µ/mL for 1 to 2 hours.
• In most acromegalic patients, GH levels remain elevated in the presence of glucose.

Confirming a Diagnosis of Acromegaly

On the other hand, IGF-1 is maintained at relatively stable levels in plasma, but normal concentrations vary as a function of gender and age. IGF-1 becomes elevated as a result of excessive GH secretion.

• Normal levels of IGF-1 depend on gender and age.
• Elevated IGF-1 generally confirms a diagnosis of acromegaly.

The following steps are carried out in reaching a diagnosis of acromegaly (1):

• Acromegaly suspected
• Initiate GH and IGF-1 assays
• If GH and IGF-1 assays are normal, then conduct glucose tolerance test
• If GH, IGF-1 assays and glucose tolerance test are normal, this excludes a diagnosis of acromegaly
• If any of these results are abnormal, then perform a magnetic resonance imaging (MRI) of the pituitary
• If MRI is normal, then conduct tests for other causes
• If MRI is abnormal and reveals the presence of an adenoma, then a diagnosis of acromegaly is confirmed

Role of Imaging in Diagnosis

When it is established that a patient has elevated GH and IGF-1 levels, MRI or computed tomography (CT) imaging is used to examine the pituitary.

• Imaging studies are used to determine the site and the size of the tumor, which aid in the planning of treatment options.
• Images may also be obtained to detect potential enlargement of the heart, liver or other organs that may be affected by acromegaly.
• If no pituitary tumor is detected, scans of other body areas may be performed to identify the source of excessive GH and/or IGF-1.

In addition to MRI or CT imaging, somatostatin receptor scintigraphy (SRS) may be used to obtain images of pituitary adenomas. In this procedure, radiolabeled octreotide is injected into the systemic circulation. Since pituitary adenomas frequently contain elevated numbers of somatostatin receptors, the radioactive octreotide binds to these receptors and can be detected subsequently as bright spots in the resulting images.

SRS Whole-Body Scan (OctreoScan®*)