In this section, you will find information about:
- The Difficulty of Diagnosis
- Tests Used in Diagnosing Acromegaly
- The 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 challenges1:
- 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 after the onset of increased GH secretion2.
Acromegaly is initially detected by different types of healthcare professionals who observe different signs and symptoms:
| Detecting the Signs and Symptoms of Acromegaly | |
|---|---|
| Presenting Symptoms | Referring Specialist |
| Backache | Chiropractor |
| Colonic polyps | Gastroenterologist |
| Loosening of teeth, prognathia | Dentist |
| Amenorrhea | Ob-Gyn |
| Diabetes | Primary Care MD/Internist |
| Increased sweating | Primary Care MD |
| Excessive increase in shoe size | Podiatrist |
| Carpal tunnel syndrome | Surgeon |
| Arrhythmias | Cardiologist |
| Sleep apnea, headache | Neurologist |
Tests Used in Diagnosing Acromegaly3
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. IGF-1 levels are gender and age dependent and are relatively stable throughout the day. In contrast, GH levels can fluctuate throughout the day depending on the patient's age, the time of day, and time since the last meal. There are 2 main approaches to measuring GH levels:
- Multiple tests. To compensate for the variation in levels, the values may be averaged from a series of "random" blood tests3
- 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. Normal patients will experience glucose-suppressed GH levels, while patients with acromegaly will still have elevated GH levels, despite the introduction of glucose3
| Normal GH Levels2 | Normal IGF-1 Levels3 |
|---|---|
Normal GH levels vary,
|
Normal IGF-1 levels depend on the patient's age and gender, and the reference numbers may vary slightly depending on which laboratory provides the results. |
Levels of GH and IGF-1 are often measured in ng/mL. |
|
The Importance of Measuring GH Levels
Since GH is secreted sporadically throughout the day and has a short half-life, a single random GH test 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 OGTT is used to evaluate the response of GH to "glucose challenge." In this test, 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 observed4:
- In normal individuals, administration of glucose suppresses GH levels to <2 ng/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 acromegaly4:
- 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 an 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
The Role of Imaging in Diagnosis3
When it has been established that a patient has elevated GH and IGF-1 levels, MRI or 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 (See images A and B below for examples of MRI scans of a macroadenoma found in an acromegalic patient.)
- 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
Images A and B are examples of magnetic resonance imaging (MRI) studies of an acromegalic patient with a macroadenoma, indicated by the arrows. Image A is a scan taken from the side (sagittal view); image B is a scan taken from the back (coronal view).
Important Safety Information
Carcinoid Syndrome:
Sandostatin® LAR Depot (octreotide acetate for injectable suspension) is indicated for long-term treatment of the severe diarrhea and flushing episodes associated with metastatic carcinoid tumors and for the long-term treatment of the profuse watery diarrhea associated with VIP-secreting tumors in patients in whom initial treatment with immediate release Sandostatin® (octreotide acetate) Injection has been shown to be effective and tolerated.
Important Safety Information:
As with immediate release Sandostatin® Injection, the most frequently reported drug-related adverse events were biliary disorders (62%), gastrointestinal disorders (14% to 38%), and injection-site pain (20% to 50%). Hypoglycemia (4%), hyperglycemia (27%), sinus bradycardia (19%), conduction abnormalities (9%), and arrhythmias (3%) have been reported.
The controlled clinical trials that support the marketing clearance for Sandostatin® LAR Depot did not include determination of effect on tumor size or rate of growth. Sandostatin® LAR Depot is not indicated for tumor shrinkage.
Acromegaly
Sandostatin® LAR Depot (octreotide acetate for injectable suspension) is indicated for long-term maintenance therapy in acromegalic patients who have had an inadequate response to surgery and/or radiotherapy, or for whom surgery and/or radiotherapy is not an option. The goal of treatment in acromegaly is to reduce GH and IGF-1 levels to normal.
Important Safety Information:
As with immediate release Sandostatin® Injection, the most frequently reported drug-related adverse events were biliary disorders (52%), gastrointestinal disorders (7% to 36%), and injection-site pain (2% to 11%). Hypoglycemia (2%), hyperglycemia (15%), and hypothyroidism (2%) have been reported. While not measured in acromegalic patients receiving Sandostatin® LAR Depot, ECG changes have been reported in patients receiving immediate release Sandostatin® Injection; the degree to which these abnormalities are related to octreotide acetate is not clear, as many acromegalics have cardiovascular disease. You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch or call 1-800-FDA-1088.
